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Mental health

Depression

Last revised in April 2025

Depression is characterised by persistent low mood and/or loss of pleasure in most activities and a range of associated emotional, cognitive, physical

Depression: Summary

  • Depression is characterised by the absence of a positive affect (a loss of interest and enjoyment in ordinary things and experiences), low mood, and a range of associated emotional, cognitive, physical, and behavioural symptoms.
  • The severity of depression is defined by the National Institute for Health and Care Excellence (NICE) as:
    • 'Less severe depression' encompassing subthreshold and mild depression.
    • 'More severe depression' encompassing moderate and severe depression.
  • A diagnosis of depression should be considered if a person has risk factors, non-specific symptoms, or symptoms such as disturbed sleep; decreased or increased appetite and/or weight; fatigue or loss of energy; agitation or slowing down; poor concentration; worthlessness or guilt; suicidal ideas or plans.
  • Assessment of a person with depression includes:
    • Assessing the onset, duration, pattern, and severity of symptoms; current lifestyle; past depression and/or self-harm; coexisting mental or physical health conditions; risk factors including family history and personal, social, or environmental factors; suicidal ideas or plans; current and previous medication.
    • Using a validated depression questionnaire to assess severity of symptoms, functioning, and response to treatment.
    • Assessing the person's mental state and cognitive function.
    • Considering a physical examination and arranging additional investigations if indicated.
  • Initial management of a person with depression includes:
    • Providing advice on sources of information and support, including activities to improve sense of wellbeing.
    • Developing a treatment plan using shared decision-making depending on the person's wishes and needs.
    • Discussing treatment options such as active monitoring, guided self-help, antidepressant treatment, and/or cognitive behavioural therapy (CBT) or other psychological interventions.
    • Providing advice on the risks and benefits of antidepressants, if indicated, including adverse effects and withdrawal symptoms, recommended duration of treatment, and how to switch or stop treatment safely (gradually tapering dose with regular monitoring for withdrawal symptoms and signs of relapse).
    • Arranging regular monitoring and follow-up, depending on the person's age, risk of suicide, and clinical judgement.
  • Follow-up of a person with depression includes:
    • Asking about symptom response, adverse effects, concordance with treatment, risk factors for relapse, and any suicidal thoughts or ideas.
    • Managing any modifiable risk factors and reconsidering the diagnosis if clinically appropriate.
    • Giving advice about relapse prevention.
  • Options for further-line management if there is no symptom improvement include:
    • Switching to an alternative psychological therapy.
    • Adding in an antidepressant (if not already taking).
    • Increasing the antidepressant dose or switching to a drug in the same class or different class (using cross-tapering when clinically indicated).
    • Changing to a combination of psychological intervention and antidepressant medication.
    • Seeking specialist advice or arranging referral.
  • Referral to specialist mental health services for co-ordinated multidisciplinary care should be arranged if a person has:
    • More severe depression and is at signficant risk of self-harm or suicide, harm to others, or self-neglect.
    • Psychotic symptoms or suspected bipolar disorder.
    • More severe depression or chronic depressive symptoms affecting personal and social functioning, which have not responded to treatment in primary care.

Have I got the right topic?

From age 18 years onwards.

This CKS topic covers the assessment and management of adults with depression in primary care.

This CKS topic does not cover the management of pregnant or breastfeeding women with depression, or people with other primary mental health disorders such as psychosis, schizophrenia, or bipolar disorder. It also does not cover the management of psychotic depression or depression in people with a coexisting diagnosis of personality disorder. It also does not cover the use of lithium, oral antipsychotics, or other specialist drugs or electroconvulsive therapy (ECT) for depression.

There are separate CKS topics on Alcohol - problem drinking, Bipolar disorder, Depression - antenatal and postnatal, Depression in children, Eating disorders, Generalized anxiety disorder, Poisoning or overdose, Post-traumatic stress disorder, Psychosis and schizophrenia, and Self-harm.

The target audience for this CKS topic is healthcare professionals working within the NHS in the UK, and providing first contact or primary healthcare.

How up-to-date is this topic?

Changes

April 2025 — minor update. QOF indicators removed in line with NHS England's 2025 Quality and Outcomes Framework.

Previous changes

February 2025 — minor update. Added detail relating to the NICE guidance Gambling-related harms: identification, assessment and management.

June 2024 — minor update. An adverse effect of hypoglycaemia relating to venlaflaxine has been added in line with an update to the manufacturer’s SPC.

April 2024 — minor update. Minor typographical error corrected. 

April 2024 — minor update. An adverse effect of serotonin syndrome relating to reboxetine has been added in line with an update to the manufacturer's SPC. 

December 2023 — minor update. An adverse effect of leukopenia relating to paroxetine has been added in line with an update to the manufacturer's SPC. Revisions have been made to the Stopping antidepressants section following comments from an expert reviewer. 

November 2023 — minor update. Hyperprolactinaemia added as a posssble adverse effect of citalopram in line with updated SPC. Added additional information about assessing suicide risk. 

July 2023 — minor update. The quality standards have been updated in line with NICE guidance.  

April 2023 — minor update. Added more detailed information about stopping antidepressants based on the NICE [NG215] Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults [NICE, 2022a]. Also added an additional patient resource provided by the Royal College of Psychiatrists, Stopping antidepressants [RCPsych, 2020].  Revised the wording on timing of the review for people after starting antidepressant medication in line with an update the NICE guideline [NG222] Depression in adults: treatment and management [NICE, 2022b]. 

August to September 2022 — reviewed. A literature search was conducted in July 2022 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. The recommendations have been updated in line with the updated National Institute for Health and Care Excellence (NICE) guideline Depression in adults: treatment and management (2022) and other evidence in the literature. The definitions of depression severity and options for treatment have been amended, in line with the NICE guideline. The topic has undergone minor restructuring to improve clarity and navigation.

June 2022 — minor update. Telephone number for Samaritans has been updated. 

February 2022 — minor update. Links to key therapeutic topic guidance remove as service has been retired.

March 2021 — minor update. Suicide/suicidal thoughts and aggression in patients during discontinuation of venlafaxine has been added in line with updated manufacturer's SPC. A typographical error has also been corrected. 

February 2021 — minor update. SSRI drug interactions updated in line with manufacturer's SPC for sertraline.

January 2021 — minor update. A typographical error has been corrected.

September 2020 — minor update. Gastrointestinal adverse effects of SSRIs have been updated in line with manufacturer's SPC for paroxetine.

August 2020 — minor update. Broken URL links updated.

July 2020 — minor update. SNRI cardiac adverse effects updated in line with manufacturer's SPC for venlafaxine.

May 2020 — minor update. SSRI drug interactions updated in line with manufacturer's SPC for citalopram.

March 2020 — minor update. Takotsubo cardiomyopathy has been added as an adverse effect of SNRIs in line with updated manufacturer's SPC.

March 2020 —  minor update. A typo in the table in the section on prescribing antidepressants in people with chronic physical health problems has been removed.

February 2020 — minor update. Reference to a clinical guideline has been removed from the basis for recommendation in the diagnosis section of this topic.

December 2019 — reviewed. A literature search was conducted in December 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of the topic. Structural changes have been made, but there have been no changes to the recommendations in this topic.

October 2015 — minor update. Based on an update to the manufacturer's Summary of Product Characteristics (SPC). Gynaecological haemorrhage and severe and potentially fatal allergic reactions (very rare) have been included as possible adverse effects of paroxetine. The Drug interaction section has been updated to include the possible interaction between selective serotonin reuptake inhibitors (SSRIs) and pravastatin.

July 2015 — minor update. Based on an update to the manufacturer's SPC, severe hepatic disorders (with potential fatal outcome) have been included as possible adverse effects of trazodone.

March 2015 — minor update. Addition of rhabdomyolysis and urinary retention as adverse effects of mirtazapine.

October 2014 — minor update. Addition of constipation as a common adverse effect of mirtazapine.

April 2014 — minor update. Update to the link for the BDI depression questionnaire.

December 2013 — minor update. Text in management rewritten to clarify that antidepressants should be continued for at least 6 months following remission of symptoms. Typographical errors also corrected.

July to August 2013 — reviewed. Literature searches were conducted in July 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The structure of this topic has been changed to improve clarity; however, there are no changes to the recommendations.

June 2011 — minor update. The NICE quality standards on the management of depression have been added. 

December 2010 — minor update. Expert opinion from UK Medicines Information (UKMI) on the choice of antidepressant in people with epilepsy has been added to the Prescribing information section on Chronic physical health problems.

October 2010 — minor update. Information on fitness to drive from the Driver and Vehicle Licensing Agency's guidance for medical practitioners, At a glance guide to the current medical standards of fitness to drive has been added. 

June 2010 — minor update. The Medicines and Healthcare products Regulatory Agency (MHRA) has advised that epidemiological data show that SSRIs and TCAs are associated with a small increased risk of fractures. However, the mechanism leading to this increased risk is unclear. 

March 2010 — minor update to correct a typographical error in the prescribing information text.

August 2009 to February 2010 — reviewed. The evidence-base has been reviewed in detail, and recommendations are more clearly justified and transparently linked to the supporting evidence.

April 2009 — minor update. The Quality and Outcomes Framework (QOF) indicators for depression have been updated in the Goals and outcome measures section. Hypopituitarism following traumatic brain injury has also been included as an underlying cause of depression. 

September 2008 — minor correction to the Changes section. 

November 2007 — updated to include recommendations from NICE technology appraisal Computerised cognitive behavioural therapy for depression and anxiety.

June 2006 — updated to include amended NICE guidance regarding venlafaxine.

February 2006 — updated to include recent advice from the MHRA regarding the safety of paroxetine in pregnancy. Quality and outcomes framework indicators for depression included. 

May 2005 — rewritten. Validated in September 2005 and issued in November 2005.

July 2004 — updated to include recent advice from the Committee on Safety of Medicines that the recommended target dosage of paroxetine is 20mg daily. Maintenance prescriptions for higher doses have been removed. 

November 2002 — updated to include the management of postnatal depression. Validated in March 2003 and issued in April 2003.

September 2001 — reviewed. Validated in November 2001 and issued in April 2002. This guidance will be rewritten when the National Institute for Health and Care Excellence (NICE) publishes its guidance on the primary care management of depression, which is anticipated in September 2003.

August 1998 — written, replacing the guidance Single major depressive episode and Recurrent major depressive episode.

Update

New evidence

Evidence-based guidelines

  • NICE (2022) Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults. National Institute for Health and Care Excellence https://www.nice.org.uk/ [Free full-text]
  • NICE (2025) Gambling-related harms: identification, assessment and management National Institute for Health and Care Excellence Homepage | NICE [Free full-text]

HTAs (Health Technology Assessments)

NICE (2023) Digitally enabled therapies for adults with depression: early value assessment. www.nice.org.uk. [Free Full-text]

Economic Appraisals

No new economic appraisals relevant to England since 1 July 2022.

Systematic reviews and meta-analyses

  • Oliva, V., Possidente, C., De Prisco, M., et al. (2024) Pharmacological treatments for psychotic depression: a systematic review and network meta-analysis. The Lancet Psychiatry. [Free Full-text]
  • Dobrescu, A.I., Persad, E., Klerings, I., and Gartlehner, G. (2024) Update Alert: Nonpharmacologic and Pharmacologic Treatments of Adult Patients With Major Depressive Disorder: A Systematic Review and Network Meta-analysis for a Clinical Guideline by the American College of Physicians. Annals of Internal Medicin. https://www.acpjournals.org/journal/aim [Free Full-text]
  • Metaxa, A.M. and Clarke, M. (2024) Efficacy of psilocybin for treating symptoms of depression: systematic review and meta-analysis. BMJ. https://www.bmj.com/ [Free Full-text]

Primary evidence

  • Pillinger, T., Arumuham, A., McCutcheon, R.A., et al. (2025) The effects of antidepressants on cardiometabolic and other physiological parameters: a systematic review and network meta-analysis. The Lancet. https://www.thelancet.com [Free Full-text]

New policies

No new national policies or guidelines since 1 July 2022.

New safety alerts

No new safety alerts since 1 July 2022.

Changes in product availability

  • New Product Enalto (escitalopram) orodispersible tablets. This new formulation, available in 5, 10, 15 and 20mg strengths, is licensed for the treatment of depression. See more here.

Goals and outcome measures

Goals

To support primary healthcare professionals to:

  • Make a diagnosis of depression.
  • Offer management in primary care where appropriate, including active monitoring if a person does not wish for treatment, antidepressant drug treatment and/or psychological interventions, depending on the person's preferences, symptoms, previous treatments, comorbidities, and hopes and expectations of treatment.
  • Give advice on measures to prevent relapse.
  • Arrange regular review in primary care, the frequency depending on clinical judgement.
  • Arrange referral to specialist mental health services, or seek specialist advice, where appropriate.

Outcome measures

No outcome measures were found during the review of this topic.

Audit criteria

No audit criteria were found during the review of this topic.

QOF indicators

No QOF indicators were found during the review of this topic.

QIPP - Options for local implementation

No QIPP indicators were found during the review of this topic.

NICE quality standards

The NICE quality standards relevant to this CKS topic are:

  • Statement 1 Adults with suspected depression have a comprehensive assessment. 
  • Statement 2 Adults with a new episode of depression have a discussion with their healthcare professional about the full range of treatment options. 
  • Statement 3 Adults with depression who are at a higher risk of relapse have relapse prevention interventions. 
  • Statement 4 Adults with depression who are stopping antidepressant medication have the dose reduced in stages.
  • Statement 5 Adults from minority ethnic backgrounds with depression are supported to access mental health services.

[NICE, 2011]

Background information

What is it?

  • Depression is characterised by the absence of a positive affect (a loss of interest and enjoyment in ordinary things and experiences), low mood, and a range of associated emotional, cognitive, physical, and behavioural symptoms [NICE, 2022b].
    • It is defined in the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM-5) by the presence of at least five out of a possible eight defining symptoms, during the same two-week period, where at least one of the symptoms is depressed mood or loss of interest or pleasure [APA, 2013].
  • The severity of depression depends on the intensity and frequency of symptoms, their duration, and impact on personal and social functioning. The National Institute for Health and Care Excellence (NICE) guideline classifies new episodes of depression according to severity on the PHQ-9 scale [NICE, 2022b]:
    • 'Less severe depression' —  this encompasses subthreshold and mild depression, defined as depression scoring less than 16 on the PHQ-9 scale.
    • 'More severe depression' — this encompasses moderate and severe depression, defined as depression scoring 16 or more on the PHQ-9 scale.
  • Chronic depressive symptoms are defined by the NICE guideline in people with [NICE, 2022b]:
    • 'Symptoms which continually meet the criteria for the diagnosis of a major depressive episode for at least two years, or have persistent subthreshold symptoms for at least two years, or who have persistent low mood with or without concurrent episodes of major depression for at least two years'.
  • Seasonal affective disorder describes episodes of depression which recur annually at the same time each year with remission in between (usually appearing in winter and remitting in spring) [NICE, 2022b].

How common is it?

The prevalence of depression varies in the literature, depending on the study population country and region, definitions of depression, and study methodology, and there is a lack of large-scale longitudinal general population studies in the literature [Kessler, 2013].

  • The World Health Organization (WHO) states that depression is common and a leading causes of disability worldwide [WHO, 2021].
  • The international World Mental Health Survey Initiative epidemiological study of 'major depressive episode' population-based data from 18 countries (n = 89,037) found [Bromet, 2011]:
    • The average lifetime prevalence estimate was 14.6% for adults in high-income countries.
    • The average 12-month prevalence estimate was 5.5% for adults in high-income countries.
    • The average age of onset was 25.7 years in adults in high-income countries.
    • The female-male ratio was about 2:1.
    • There were methodological limitations including sampling issues and variable response rates which affected data interpretation.
  • Expert opinion in a review article notes a peak in prevalence occurs in the second and third decades of life, with a subsequent smaller peak in the fifth and sixth decades [Malhi, 2018].

What are the risk factors?

The underlying cause of depression is unknown, but is likely to result from a complex interaction of genetic, environmental, biological, cultural, and psychological factors [Ferenchick, 2019].

  • Risk factors for depression include [Bromet, 2011] [Cleare, 2015] [Malhi, 2018] [Ferenchick, 2019] [NICE, 2022b]:
    • Female sex.
    • Older age.
    • Past history of depression.
    • Personal, social, or environmental factors, such as relationship issues or breakdown, bereavement, stress, poverty, unemployment, homelessness, social isolation, or past history of child maltreatment. See the CKS topic on Child maltreatment - recognition and management for more information.
    • Postpartum period. See the CKS topic on Depression - antenatal and postnatal for more information.
    • Past history of depression.
    • Family history of depressive illness (first-degree relatives of a person with a 'major' depressive episode have a three-fold increased risk of depression) or suicide.
    • History of other mental health conditions and/or substance misuse. See the CKS topic on Alcohol - problem drinking for more information.
    • Other chronic physical health conditions associated with functional impairment (such as diabetes mellitus, chronic obstructive pulmonary disease, cardiovascular disease, chronic pain syndromes, epilepsy, stroke disease).
  • Risk factors for relapse of depression include [Cleare, 2015] [Malhi, 2018] [NICE, 2022b]:
    • Older age of onset.
    • History of recurrent episodes of depression, particularly if frequent or within the past two years.
    • Incomplete response to previous treatment, including residual symptoms.
    • Unhelpful coping styles or behaviours, such as avoidance or rumination.
    • History of severe depression (including severe functional impairment).
    • Other chronic physical or mental health conditions, especially in the elderly.
    • Ongoing personal, social, or environmental factors (see above).

What are the complications?

Possible complications of depression include:

What is the prognosis?

The prognosis of depression varies between individuals in terms of the duration, number, and pattern of episode(s) over a lifetime [Malhi, 2018].

  • Expert opinion in a review article notes that for most people, the course of illness is episodic, and they feel well in between acute depressive episodes. Depressive episodes typically last 3–6 months with treatment, and most people recover within 12 months [Malhi, 2018].
  • A sub-analysis of data from a longitudinal Dutch cohort study of adults with anxiety and depression (n = 903) with a 6-year follow-up found [Verduijn, 2017]:
    • At 2 years' follow-up of major depressive symptoms only, the recovery rate was 58% and 21% of participants reported a chronic episode with ongoing symptoms after 2 years.
    • At 6 years' follow-up of major depressive symptoms and comorbid anxiety, the recovery rate was 17% and 55% of participants reported a chronic episode with ongoing symptoms after 2 years.
    • Recovery rates were lower for participants followed up for longer time periods, and if comorbid conditions such as anxiety were included in the analysis.
  • Expert opinion in a review article notes that the recurrence risk is high, increases with each depressive episode, and cites evidence that nearly 80% of people have at least one further depressive episode in their lifetime [Malhi, 2018]. Similarly, the British Association for Psychopharmacology (BAP) guidelines state that people with a history of a major depressive episode have a median of four episodes in a lifetime, and about 12% of people have chronic depressive symptoms [Cleare, 2015].

Diagnosis

When should I suspect a diagnosis of depression?

Consider a diagnosis of depression if a person has possible risk factors, non-specific symptoms, or any of the symptoms of depression listed below.

  • Be aware that a person with depression may present with non-specific symptoms rather than low mood.
    • In particular, older people may only present with physical symptoms or a deterioration in cognitive functioning.
  • Ask the two 'depression identification questions':
    • During the last month, have you often been bothered by feeling down, depressed, or hopeless?
    • During the last month, have you often been bothered by having little interest or pleasure in doing things?
  • If the person answers 'yes' to one of the questions and symptoms have been present most days, most of the time, for at least 2 weeks, ask about associated symptoms of depression:
    • Disturbed sleep (decreased or increased compared to usual). See the CKS topic on Insomnia for more information.
    • Decreased or increased appetite and/or weight.
    • Fatigue or loss of energy. See the CKS topic on Tiredness/fatigue in adults for more information.
    • Agitation or slowing down of movements and thoughts.
    • Poor concentration or indecisiveness.
    • Feelings of worthlessness or excessive or inappropriate guilt.
    • Recurrent thoughts of death, recurrent suicidal ideas, or a suicide attempt or specific plan. See the CKS topic on Self-harm for more information.

Basis for recommendation

The recommendations for diagnosis are based on the National Institute for Health and Care Excellence (NICE) guidelines Depression in adults: treatment and management [NICE, 2022b] and Depression in adults with a chronic physical health problem: recognition and management [National Collaborating Centre for Mental Health, 2009]; the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], expert opinion in review articles on depression [Malhi, 2018; Ferenchick, 2019] and on the prognosis of depression [Kraus, 2019], and expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021].

  • The recommendation on when to suspect depression is based on the NICE guideline on depression in adults [NICE, 2022b] and expert opinion in a review article [Ferenchick, 2019].
    • Expert opinion in a review article notes that early recognition of depression is important, as duration of untreated depression correlates with a poorer prognosis [Kraus, 2019].
  • The information that depression may present as non-specific or physical symptoms rather than specifically low mood is based on expert opinion in a review article [Ferenchick, 2019].
  • The recommendation to use the two 'depression identification questions' is based on the two NICE guidelines [National Collaborating Centre for Mental Health, 2009; NICE, 2022b].
  • The information on associated symptoms of depression is largely based on the NICE guideline on depression in adults [NICE, 2022b] together with expert opinion in review articles [Malhi, 2018; Ferenchick, 2019].
    • The NICE guideline on depression in adults notes that the criteria for diagnosis of depression are based on two main classification systems: the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and the 11th revision of the International Classification of Diseases (ICD-11) [NICE, 2022b].

How should I assess a person with suspected depression?

If a person has a suspected diagnosis of depression:

  • Ask about:
    • The onset, duration, pattern, and severity of symptoms, including impact on daily functioning at work, on carer role(s), and on relationships including any safeguarding concerns for children or vulnerable adults in their care. See the CKS topic on Child maltreatment - recognition and management for more information.
    • Current lifestyle including diet, physical activity, sleep; gambling, alcohol and/or substance misuse. See the CKS topics on Alcohol - problem drinking and Insomnia for more information.
    • Any past history of depression and/or episodes of self-harm. See the CKS topic on Self-harm for more information.
    • Any current symptoms or past history of coexisting mental health conditions, including mood elevation or psychotic symptoms suggesting bipolar disorder or psychotic depression, psychosis, anxiety, post-traumatic stress disorder (PTSD), or eating disorders. See the CKS topics on Bipolar disorder, Eating disorders, Generalized anxiety disorder, Post-traumatic stress disorder, and Psychosis and schizophrenia for more information.
    • Any learning disability or acquired cognitive impairment including dementia, traumatic brain injury, or Parkinson's disease. See the CKS topics on Dementia, Head injury, Learning disabilities, and Parkinson's disease for more information.
    • Any risk factors for depression including family history of depression, suicide, or self-harm; chronic physical health conditions; history of domestic violence.
    • Current or previous supportive relationships including partner, other family, friends, carers; and support from any other statutory or voluntary organisations.
    • Any recent or past stressful or traumatic life events, including difficult interpersonal relationships or relationship breakdown including divorce; job stress or redundancy; debt or financial difficulties; bereavement or other trauma; housing and living conditions; immigration status; social isolation.
    • Any current or previous forensic history.
    • Current medication, any previous treatments for depression, symptom response and any adverse effects.
    • Always ask about any thoughts, ideas, plans, or intent to self-harm or commit suicide, and any protective factors.
    • If there is a risk of self-harm or suicide:
      • Assess the person's level of social support and awareness of sources of help.
      • Arrange help appropriate to their level of need
      • Advise the person to seek further help if their situation deteriorates.
      • See the CKS topic on Self-harm for more information.
  • Consider using a validated depression questionnaire to assess for depression, severity of symptoms, functioning, and response to treatment.
  • Assess the person's mental state and cognitive function.
  • Consider performing a physical examination including neurological examination and arranging additional investigations, depending on clinical judgement, particularly if a coexisting condition or alternative cause for symptoms is suspected.

Depression questionnaires

  • Depression questionnaires which are validated for use in primary care include:
    • PHQ-9 (Patient Health Questionnaire-9)
      • A nine-item, self-administered scale, which reflects the DSM-5 (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) criteria.
      • It classifies current symptoms on a scale of 0 (not at all) to 3 (nearly every day) — the maximum score is 27.
      • It can be downloaded free of charge from www.phqscreeners.com.
    • HADS (Hospital Anxiety and Depression Scale) 
    • BDI-II (Beck Depression Inventory-II)
      • A 21-item, self-administered scale that uses DSM-5 criteria.
      • Each question is rated from 0 to 3 — the maximum score is 63.
      • Scores of 14–19, 20–28, and 29–63 can be interpreted as mild, moderate, and severe depression respectively.  
      • It is available to purchase from www.pearsonassessments.com.
  • In people who have concerns about gambling the NHS gambling questionnaire may be helpful https://www.nhs.uk/live-well/addiction-support/gambling-addiction/. 

Basis for recommendation

The recommendations for assessment are based on the National Institute for Health and Care Excellence (NICE) guidelines Depression in adults: treatment and management [NICE, 2022b], the NICE guideline Gambling-related harms: identification, assessment and management [NICE, 2025] the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], and expert opinion in review articles on depression [Malhi, 2018; Ferenchick, 2019].

Clinical features on history-taking

  • These recommendations are based on the NICE guideline [NICE, 2022b], the BAP guidelines [Cleare, 2015], expert opinion in review articles [Malhi, 2018; Ferenchick, 2019], and are also pragmatic, based on what CKS considers to be good clinical practice.
    • The BAP guidelines note that the use of antidepressants in people with undiagnosed bipolar disorder can trigger hypomania/mania.

Using a validated depression questionnaire

  • This recommendation is based on the NICE guideline [NICE, 2022b] and expert opinion in review articles [Malhi, 2018; Ferenchick, 2019].
    • The NICE guideline notes that a validated questionnaire can help to assess symptoms, functioning, impairment, and evaluate treatment.

 Assessing mental state and cognitive function

  • This recommendation is based on the NICE guideline [NICE, 2022b] and expert opinion in a review article [Ferenchick, 2019].
    • Cognitive testing can help to assess for coexisting or alternative conditions that may present with depressive symptoms, including neurological conditions and dementia [Ferenchick, 2019].

Performing a physical examination and arranging additional investigations

  • This recommendation is based on expert opinion in a review article [Ferenchick, 2019]. It is also pragmatic, based on what CKS considers to be good clinical practice.

What else might it be?

Other conditions that may present similarly to, or coexist with, depression include:

  • Bereavement — depressive symptoms may be transiently present in normal grief. Uncomplicated bereavement may present with sadness and dysphoria, but active suicidal thoughts, psychotic symptoms, persistent hopelessness, worthlessness, and excessive feelings of guilt are rare with normal bereavement.
  • Anxiety disorders — this frequently coexists with depression. See the CKS topics on Generalized anxiety disorder and Post-traumatic stress disorder for more information.
  • Bipolar disorder — depressive episodes may be accompanied by, or interspersed with mania, hypomania, or mixed episodes. See the CKS topic on Bipolar disorder for more information.
  • Psychotic disorder including schizophrenia — more severe depression may present with psychosis. See the CKS topic on Psychosis and schizophrenia for more information.
  • Premenstrual dysphoric disorder — this is a severe form of premenstrual syndrome (PMS) characterized by depressed mood, anxiety, and irritability during the luteal phase of the menstrual cycle which impacts on daily functioning. See the CKS topic on Premenstrual syndrome for more information.
  • Neurological conditions, such as dementia, multiple sclerosis, and Parkinson's disease — may have symptoms that overlap with depression. See the CKS topics on Dementia, Multiple sclerosis, and Parkinson's disease for more information.
  • Substance misuse — such as alcohol, anabolic steroids, cannabis, cocaine, and opioids. See the CKS topics on Alcohol - problem drinking and Opioid dependence for more information.
  • Gambling-related harms — these can vary over time and recent onset or short periods of less intense gambling can lead to severe harms in some people resulting in becoming a dominant risk factor for suicidal ideation and suicide attempts, even in the absence of other risk factors.
  • Other drug adverse effects — these are an uncommon cause of depressive symptoms, but may be secondary to centrally-acting antihypertensives (such as methyldopa), lipid-soluble beta-blockers (such as propranolol), hormonal contraceptives, proton pump inhibitors such as omeprazole, gabapentin, opioids, and isotretinoin.
  • Other medical conditions such as anaemia, hypothyroidism, and obstructive sleep apnoea syndrome (OSAS) — may present with non-specific symptoms such as fatigue. See the CKS topics on Anaemia - iron deficiency, Anaemia - B12 and folate deficiency, Hypothyroidism, and Obstructive sleep apnoea syndrome for more information.

Basis for recommendation

The information on differential diagnosis is based on the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], the NICE guideline Gambling-related harms: identification, assessment and management [NICE, 2025] expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021], a US cross-sectional population-based prevalence study of depression caused by drug adverse effects [Qato, 2018], expert opinion in the British National Formulary (BNF) [BNF, 2022], and expert opinion in review articles on depression [Malhi, 2018; Ferenchick, 2019] and on the management of grief and depression at the end of life [Widera and Block, 2012].

Management

Scenario: New or initial management

From age 18 years onwards.

How should I initially manage a person with depression?

If a person has been diagnosed with depression in primary care following initial assessment:

  • Provide advice on the nature and course of depression, recovery, and sources of information and support including self-help materials, support groups, and peer support, such as:
  • Provide advice on activities to improve sense of wellbeing, such as:
    • Physical activitity including walking, jogging, swimming, dance, gardening, particularly if outdoors.
    • Maintaining a healthy lifestyle through diet, alcohol intake, and sleep.
  • Offer social support including for any family and/or carers who are supporting the person.
  • Arrange urgent referral to specialist mental health services if the person has:
    • More severe depression and is at signficant risk of self-harm or suicide, harm to others, or self-neglect — crisis resolution and home treatment (CRHT) team input may be needed. See the CKS topic on Self-harm for more information.
    • Psychotic symptoms — CRHT team or specialist psychiatry input may be needed. See the CKS topic on Psychosis and schizophrenia for more information.
      • Note: be aware that voluntary or compulsory admission under the Mental Health Act (1983) may be needed in specific circumstances following specialist assessment.
  • Follow local safeguarding procedures if:
  • Discuss the options for treatment of depression and develop a treatment plan, depending on the person's wishes, any physical or mental health comorbidities, experiences with previous treatment(s), hopes and expectations of treatment, involving family/carers in shared decision-making where appropriate.
  • If a person has a new episode of less severe depression and does not want treatment, or feels that symptoms are improving:
    • Offer active monitoring, with the option to consider treatment at any time if needed.
    • Ensure the person has adequate social support and is aware of sources of help if symptoms worsen.
    • Arrange an initial review, usually within 2–4 weeks, and ensure follow-up if the person does not attend.
  • If a person has a new episode of less severe depression and wishes to consider treatment, match treatment to their clinical needs and wishes:
    • Consider offering guided self-help first-line.
    • Do not routinely offer an antidepressant as first-line treatment. If the person wishes to start drug treatment, offer a selective serotonin reuptake inhibitor (SSRI) first-line.
    • Offer other treatment options, depending on the person's preferences, their previous experience of treatment(s), and local referral pathways and service provision.
      • See the National Institute for Health and Care Excellence (NICE) summary of first-line treatment options, which include cognitive behavioural therapy (CBT), group exercise, group mindfulness and meditation, and counselling.
      • Arrange an initial review usually 2–4 weeks after starting treatment, and ensure follow-up if the person does not attend.
      • Detailed information on the key features, other factors, and delivery of each treatment option is available in the full NICE guideline on Depression in adults.
  • If a person has a new episode of more severe depression, match treatment to their clinical needs and wishes:
    • Offer any treatment option first-line, depending on the person's preferences, their previous experience of treatment(s), and local referral pathways and service provision.
      • See the National Institute for Health and Care Excellence (NICE) summary of first-line treatment options, which include individual CBT, antidepressant treatment, individual behavioural activation, counselling, guided self-help, and group exercise.
      • Arrange an initial review usually 2–4 weeks after starting treatment, and ensure follow-up if the person does not attend.
      • If a person wishes to start an antidepressant, offer an SSRI or serotonin noradrenaline reuptake inhibitor (SNRI) first-line. See the section on Initiating antidepressants for more information if starting antidepressant treatment.
      • Detailed information on the key features, other factors, and delivery of each treatment option is available in the full NICE guideline on Depression in adults.
    • Advise the person they must not drive and must notify the Driver and Vehicle Licensing Agency (DVLA) if they have significant memory or concentration problems, agitation, behavioural disturbance, or suicidal thoughts.
  • Do not recommend taking the over-the-counter preparation St John's wort for management of depression.
  • For people who have gambling-related harms.
    • Consider referring people to an NHS triage service, for triage and allocation to an appropriate level of service.
    • Self-referral via an NHS triage service or the national gambling helpline, is also an option.
    • Consider referring any affected others to gambling treatment or support services, depending on their level of need.
  • Arrange appropriate management of any associated mental and physical health condition(s).
    • See the section on Differential diagnosis for more information on other conditions that may coexist with depression.
  • Arrange regular monitoring and follow-up, depending on clinical judgement.

Mental Health Act (1983)

  • The Mental Health Act (MHA) 1983 allows compulsory admission of people who: 
    • Have a mental disorder of a nature or degree that warrants assessment or treatment in hospital, and
    • Need to be admitted in the interests of their own health or safety, or for the protection of other people.
  • If a person needs to be admitted to hospital for specialist mental health input, every attempt should be made to persuade them to go voluntarily. If admission is necessary but the person declines, compulsory admission may be arranged under sections 2, 3, or 4 of the MHA.
    • Section 2 allows compulsory admission for up to 28 days for assessment.
    • Section 3 allows compulsory admission for up to 6 months for treatment. 
      • Sections 2 and 3 require an application from an approved mental health professional (AMHP), or the person's nearest relative, and written recommendations from two doctors, one of whom is section 12 approved (usually a psychiatrist) and one who has previous acquaintance with the person (usually the person's GP if at all practicable). 
      • For admission under section 2, where there is no obvious person to provide the second medical recommendation (for example because the person is not registered with a GP or is not known to local mental health services), another section 12-approved doctor is usually asked to assess the person. However, in cases where this is not practicable, any registered medical practitioner may provide the second recommendation as long as there are no potential conflicts of interest (for example, they work in the same hospital as the doctor providing the first recommendation). 
      • The person can be examined jointly or separately by the two doctors.
    • Section 4 is used in exceptional cases to permit compulsory admission for up to 72 hours if there is urgent necessity, and undesirable delay would occur while trying to arrange admission under normal procedures. 
      • It requires an application from an AMHP (or the person's nearest relative) and just one medical recommendation, preferably from a doctor with previous acquaintance (usually the person's GP).
      • Where the person has been compulsorily admitted under an emergency section 4, this section is usually converted to a section 2 (usually requiring further involvement of the GP).
    • Section 136 may be used by police to take people from a public place to a place of safety so they can be assessed.
  • See the Department of Health and Social Care's 2015 publication Mental Health Act 1983: reference guide on the GOV.UK website, for more detailed information on how the MHA operates.

Basis for recommendation

The recommendations for initial management are based on the National Institute for Health and Care Excellence (NICE) guidelines  Depression in adults with a chronic physical health problem: recognition and management [National Collaborating Centre for Mental Health, 2009] and Depression in adults: treatment and management [NICE, 2022b]; the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], the Department of Health and Social Care publication Mental Health Act 1983: reference guide [Department of Health and Social Care, 2015], the Driver and Vehicle Licensing Agency (DVLA) document Assessing fitness to drive: a guide for medical professionals [DVLA, 2022], and expert opinion in review articles on depression [Malhi, 2018; Ramanuj, 2019].

Advising on sources of information and support 
  • These recommendations are based on the two NICE guidelines [National Collaborating Centre for Mental Health, 2009; NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The NICE guideline notes that providing appropriate information helps people to self-monitor their symptoms and feel involved in their own recovery. It notes a lack of evidence on the effectiveness of peer support [NICE, 2022b].
    • The recommendation to advise on activities to improve wellbeing is based on the NICE guideline committee's knowledge and experience [NICE, 2022b].
    • The recommendation to offer social support, including to carers is based on the NICE guideline on depression in adults [NICE, 2022b].
Arranging urgent referral to specialist mental health services
  • These recommendations are based on the NICE guideline on depression in adults [NICE, 2022b], the BAP guidelines [Cleare, 2015], and expert opinion in a review article [Ramanuj, 2019].
    • The NICE guideline notes that following crisis resolution and home treatment (CRHT) team referral, a person may need inpatient treatment if they have more severe depression and cannot be adequately supported by CRHT team input.
    • The information that admission under the Mental Health Act (1983) may be needed is based on the Department of Health and Social Care publication [Department of Health and Social Care, 2015].
Developing a treatment plan based on severity of symptoms
  • The recommendation to develop a treatment plan based on shared decision-making is based on the NICE guideline on depression in adults [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The NICE guideline states that when discussing treatment options, include information on potential benefits and harms, waiting times, expected outcomes, and how and where they will be delivered, where possible.
    • NICE advises to ask about experiences with previous treatments, to try to optimize engagement with any proposed treatment plan.
    • The NICE recommended first-line treatment options are based on the NICE committee's consensus 'interpretation of their clinical and cost-effectiveness, and consideration of implementation factors'.
    • The NICE guideline recommends initial review, usually within 2–4 weeks, and advises to check for suicidal ideas at review, especially in the early weeks of treatment.
  • The NICE recommendations on first-line treatment options for less severe depression were based on limited evidence from studies. 
    • There was some evidence for the effectiveness of guided self-help, which was recommended first-line for most people as it was felt to be easily accessible, pragmatic, and cost-effective.
    • There was good evidence for the effectiveness of group and individual cognitive behavioural therapy (CBT) and group and individual behavioural activation (BA), which were also felt to be cost-effective options.
    • The recommendation not to offer antidepressant treatment first-line is based on evidence that some psychological therapies are more effective than antidepressants, and there are risks of potential adverse effects with medication. The NICE guideline recommends the use of a selective serotonin reuptake inhibitor (SSRI) first-line if the person prefers antidepressant treatment, due to their safety profile and tolerability.
    • NICE found some evidence for the effectiveness of short-term psychodynamic psychotherapy and counselling, but noted these treatments are not so cost-effective compared with other options. It also noted considerable uncertainty in the effectiveness and cost-effectiveness of psychological interventions.
  • The NICE recommendations on first-line treatment options for more severe depression were based on limited evidence from studies.
    • There was good evidence for the effectiveness and cost-effectiveness of combination CBT with antidepressant treatment, individual CBT, and individual BA.
    • The recommendation to use an SSRI or serotonin noradrenaline reuptake inhibitor (SNRI) first-line if the person wishes to start antidepressant treatment, is based on their tolerability, but NICE notes that a tricyclic antidepressant (TCA) may be preferred if a person has responded well to this in the past and there are no contraindications.
    • There was some evidence for the effectiveness of other treatment options such as counselling and individual problem-solving therapy, which were also noted to be cost-effective.
    • The guideline committee noted that psychological interventions such as interpersonal psychotherapy and short-term psychodynamic psychotherapy showed some evidence for effectiveness, but were not so cost-effective compared with other treatment options.
    • The guideline committee expressed some concerns that although guided self-help and group exercise may provide benefit, a person should ideally be monitored regularly by a healthcare professional to ensure symptoms are improving, so other treatment options may be more appropriate for this clinical population.
  • The recommendations on when to stop driving and when to notify the Driver and Vehicle Licensing Agency (DVLA) are based on the DVLA document on fitness to drive [DVLA, 2022].
Not recommending use of St John's wort
  • The recommendation not to use St John's wort is based on the NICE guideline on depression in adults [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • NICE notes that although this may be of benefit in less severe depression, it is not recommended due to 'uncertainty about appropriate doses, persistence of effect, variation in the nature of preparations and potential serious interactions with other drugs'. Furthermore, the BAP guidelines note a lack of long-term and relapse prevention data for this preparation.
Managing associated mental and physical health conditions
  • This recommendation is based on the NICE guideline on depression in adults [NICE, 2022b] and expert opinion in a review article [Malhi, 2018].
    • A history of coexisting chronic physical or mental health conditions can increase the risk of relapse of depression, especially in the elderly.
Arranging regular monitoring and follow-up
  • This recommendation is based on the NICE guideline on depression in adults [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The NICE guideline recommends initial review, usually within 2–4 weeks, and advises to check for suicidal ideas at review, especially in the early weeks of treatment.
    • The NICE guideline also recommends that for people aged 18-25 years or those where there is a particular concern for risk of suicide follow up should be 1 week after starting antidepressant medication [NICE, 2022b].
    • The NICE guideline and BAP guidelines advise to consider using a validated depression questionnaire, such as PHQ-9, to help monitor symptoms at reviews.

How should I start an antidepressant?

If antidepressant drug treatment is being considered for a person with depression, use shared decision-making to agree an appropriate treatment plan.

  • Match the choice of antidepressant drug to the person's needs, taking into account the following factors:
    • The person's preferences for treatment.
    • Potential toxicity in overdose. If the person is at risk of suicide:
      • Avoid tricyclic antidepressants ([TCAs] except for lofepramine) and venlafaxine (a serotonin noradrenaline reuptake inhibitor [SNRI]) due to their risk of death from overdose. See the section on Antidepressant toxicity in overdose in Prescribing information for more information.
      • Consider limiting the amount of medication available to the person, to reduce the risk of death or medical complications if taken in overdose, depending on clinical judgement.
    • Tolerability and potential adverse effects and withdrawal symptoms.
    • Any associated mental health conditions or physical health conditions which may affect prescribing.
      • If the person has a chronic physical health condition, sertraline or citalopram may be preferred first-line, as they have a lower likelihood of drug interactions. See the section on Co-prescribing with other medication for more information.
    • Any current drug treatment(s) or substances that may potentially interact with an antidepressant.
      • This includes over-the-counter medication, herbal remedies, alcohol, or recreational drugs. See the sections on drug interactions for different antidepressant drug classes in Prescribing information for more information.
  •  Counsel the person when starting antidepressant drug treatment. 
    • Advise that symptoms of anxiety, agitation, hopelessness, or suicidal ideas may increase when starting treatment, and advise when to seek urgent review.
      • Arrange to review the person's treatment if needed, depending on clinical judgement. See the section on Follow-up in the section Scenario: Ongoing management for more detailed information.
      • Ensure the person has a crisis plan identifying potential triggers and strategies to help.
    • Advise that medication usually starts to work within 4 weeks (if the antidepressant is going to work).
    • Advise that medication may be needed for at least 6 months after the remission of symptoms, to reduce the risk of relapse. People who are at high risk of relapse may need to take medication for longer.
    • Reassure that antidepressant drugs are not addictive but withdrawal symptoms may occur if medication is stopped abruptly, doses are missed, or the full dose is not taken as directed.
    • Advise that some antidepressant drugs may affect alertness and concentration, affecting the person's ability to drive. This is particularly relevant when starting treatment or after increasing the dose.
  • Arrange to review the person after starting antidepressant medication to check symptom response, concordance with treatment, any adverse effects or harms of treatment, or suicidal ideas.  This will usually be within 2 weeks to check their symptoms are improving and for side effects.
    • Arrange initial review 1 week after starting antidepressant medication if the person is aged 18–25 years or there is a particular concern for risk of suicide, and ensure a risk management strategy is in place.
      • Ensure the person has a crisis plan identifying potential triggers and strategies to help.
      • Consider limiting the amount of medication available, depending on clinical judgement.
      • Arrange subsequent reviews as needed and within 4 weeks of starting antidepressant treatment. See the section on Follow-up in the section Scenario: Ongoing management for more information on ongoing care.
    • Arrange review usually within two weeks of starting an antidepressant for most other people.
    • Consider using a validated depression questionnaire to monitor response to treatment, such as PHQ-9.
    • Ensure the person has adequate social support and is aware of sources of help if symptoms worsen.
  • If there is no improvement in symptoms after four weeks of antidepressant medication at a recognized therapeutic dose:
    • Check concordance with treatment and assess for any adverse effects, harms of treatment, or suicidal ideas.
    • See the section on Follow-up in the section Scenario: Ongoing management for more information on further-line treatment options.

Co-prescribing with other medication

  • See Table 1 below for information on antidepressant drug options if a person is taking medication for a comorbid condition.
    • See the sections in Prescribing information for more detailed information on potential contraindications, cautions, adverse effects, and drug interactions of different antidepressant drug classes.

Table 1. Antidepressant options if a person is taking medication for a comorbid condition.

Medication being taken for a comorbid physical health conditionAntidepressants that should not normally be offeredSuitable antidepressant options 
Nonsteroidal anti-inflammatory drugs (NSAIDs)Selective serotonin reuptake inhibitor (SSRI) or a serotonin noradrenaline reuptake inhibitor (SNRI) due to increased risk of gastrointestinal (GI) bleeding. If no suitable alternative can be found, offer gastroprotection.Mirtazapine, reboxetine, or trazodone, or moclobemide (specialist initiation).
WarfarinTricyclic antidepressants (TCAs), SSRIs, or SNRIs.*Mirtazapine, reboxetine, or trazodone.
HeparinSSRI or an SNRI.Any alternative (for example mirtazapine, trazodone, reboxetine, or a TCA).
AspirinSSRIs (use with caution) and SNRIs. If no suitable alternative can be found, offer gastroprotection.

Mirtazapine.

When aspirin is used alone, consider trazadone, mianserin, or reboxetine.

Anti-epileptic drugs All antidepressants lower the seizure threshold — consider seeking specialist advice. Consider whether depression may be worsened by the anti-epileptic drug 

SSRIs: citalopram, sertraline, escitalopram.

Fluoxetine and fluvoxamine (not first-line due to increased risk of drug interactions)

SNRIs: duloxetine is preferred.

TCAs – try to avoid as they lower the seizure threshold; if needed, doxepin is preferred.

Moclobemide (specialist initiation)

TriptansSSRIs.Mirtazapine, trazadone, mianserin, or reboxetine.
MAO-B inhibitors (such as selegiline and rasagiline)SSRIs.Mirtazapine, trazadone, mianserin, or reboxetine.
Clozapine, methadone, tizanidine

Fluvoxamine.

Sertraline or citalopram. 
TheophyllineFluvoxamine.

Sertraline or citalopram.

Flecainide or propafenoneCitalopram or escitalopram.

Sertraline (preferred option).

Mirtazapine or moclobemide may also be used (specialist initiation for latter).

AtomoxetineFluoxetine, paroxetine, citalopram, or escitalopram.A different SSRI.

Data from: [National Collaborating Centre for Mental Health, 2009; SPS, 2019a; Taylor, 2021; BNF, 2022] * INR may increase slightly. 

Basis for recommendation

The recommendations for starting antidepressants are based on the National Institute for Health and Care Excellence (NICE) guidelines Depression in adults: treatment and management [NICE, 2022b] and Depression in adults with a chronic physical health problem: recognition and management [National Collaborating Centre for Mental Health, 2009], the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], the Driver and Vehicle Licensing Agency (DVLA) document Assessing fitness to drive: a guide for medical professionals [DVLA, 2022], and expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021].

Factors affecting choice of antidepressant
  • These recommendations are largely based on the NICE guideline on depression in adults [NICE, 2022b], the BAP guidelines [Cleare, 2015], and the Maudsley prescribing guidelines [Taylor, 2021].
    • The recommendations to avoid tricyclic antidepressants (TCAs, except lofepramine which has a better safety profile) and venlafaxine if there is an increased risk of suicide are based on the respective NICE guidelines on depression in adults [NICE, 2022b] and depression with physical health problems [National Collaborating Centre for Mental Health, 2009]. These note that TCAs carry the greatest risk in overdose, and venlafaxine is associated with a greater risk of death from overdose compared with other equally efficacious antidepressants.
    • The recommendation to use selective serotonin reuptake inhibitors (SSRIs) first-line for most people due to their good safety profile and tolerability is based on the NICE guideline on depression in adults. This approach is supported by the Maudsley prescribing guidelines [Taylor, 2021].
    • The recommendation to use sertraline or citalopram first-line if the person has an associated chronic physical health condition is based on the NICE guideline on depression with physical health problems, as these drugs are less likely to interact with other drugs [National Collaborating Centre for Mental Health, 2009].
Providing information when starting antidepressants
  • The recommendations on information to provide when starting antidepressants are largely based on the NICE guideline on depression in adults [NICE, 2022b] and the Maudsley prescribing guidelines [Taylor, 2021].
    • NICE advises to be vigilant about symptoms such as mood changes, agitation, hopelessness, and suicidal ideation, particularly during high-risk periods such as starting or changing antidepressants and at times of increased personal stress [NICE, 2022b].
    • CKS notes that the Maudsley prescribing guidelines state that an antidepressant effect is usually seen by two weeks after starting medication [Taylor, 2021].
    • The recommendation to advise when to stop driving and when to notify the Driver and Vehicle Licensing Agency (DVLA) is based on the DVLA document on fitness to drive [DVLA, 2022].
Arranging regular reviews
  • The recommendations on when and how to review a person after starting antidepressants are largely based on the NICE guideline on depression in adults [NICE, 2022b]. They are supported by the BAP guidelines [Cleare, 2015].
    • The NICE guideline advises early review after one week for younger adults and those at risk of suicide, as there is an increased risk of suicidal ideas, self-harm, and suicide in the early stages of antidepressant treatment.
    • The recommendation to consider using a validated depression questionnaire, such as PHQ-9, to help monitor symptoms at reviews is based on the NICE guideline and the BAP guidelines.
Management if no symptom response
  • These recommendations are based on the NICE guideline on depression in adults [NICE, 2022b] and the Maudsley prescribing guidelines [Taylor, 2021].
    • The Maudsley prescribing guidelines note that any person likely to be responsive to an antidepressant will have started to show at least some sign of symptom improvement at four weeks. If this has not occurred, it is unlikely the person will respond to the drug at that specific dose.

Scenario: Ongoing management

From age 18 years onwards.

How should I follow-up a person with depression after initial management?

Following initial management, arrange to review and monitor a person with depression in primary care if appropriate.

  • Ask about and manage:
    • Any ongoing symptoms of depression, impact on daily functioning including work, relationships, and any carer role for a child or vulnerable adult(s).
    • Response of symptoms to any psychosocial intervention(s) or antidepressant drug treatment, including adherence to treatment, and any adverse effects.
      • Consider using a validated depression questionnaire to assess for depression, severity of symptoms, and response to treatment, such as PHQ-9. See the section on Depression questionnaires for more information.
    • Any thoughts, plans, or intent to self-harm or commit suicide and any other risks to others or risk of self-neglect.
    • Any new symptoms of other mental health disorders, including anxiety, eating disorders, bipolar disorder, or psychosis.
    • Any new or ongoing personal, social, or environmental factors that may impact on symptoms and recovery.
  • Follow local safeguarding procedures if:
  • Offer support to the family and/or carers who are supporting a person with depression, particularly if there are severe or chronic symptoms.
  • If there is no improvement in symptoms at follow-up after 4 weeks of antidepressant medication at a recognized therapeutic dose, or after 4–6 weeks of psychological therapy or combined psychological therapy with antidepressant medication:
    • Assess and manage any modifiable risk factors for depression.
    • Assess and manage any issues affecting concordance with treatment (including stopping or reducing the dose of antidepressant due to adverse effects; or explore reasons for missed sessions with psychological therapy).
    • Consider whether an alternative diagnosis or comorbid condition may be limiting the person's response to or engagement with treatment.
  • Discuss the options for further-line treatment, depending on the person's wishes, experiences with previous treatment(s), hopes and expectations of treatment, involving family/carers in shared decision-making where appropriate.
  • If there is limited or no improvement with psychological interventions alone, options include:
    • Switching to an alternative psychological therapy.
    • Adding in a selective serotonin reuptake inhibitor (SSRI) antidepressant.
    • Switching to an SSRI alone.
  • If there is limited or no improvement with antidepressant medication alone, options include:
    • Augmenting with group exercise.
    • Switching to a psychological intervention.
      • See the section on Initial management for more information on choices of psychological intervention.
    • Increasing the antidepressant dose or switching the antidepressant to a drug in the same class or different class.
      • Advise that antidepressant dose increases may not be more effective and may increase adverse effects. Arrange regular monitoring and follow-up.
      • Advise that options to switch antidepressant include to an SSRI or SNRI. See the section on Switching antidepressants  for more information.
    • Changing to a combination of psychological intervention and antidepressant medication.
      • See the section on Initial management for more information on choices of psychological intervention.
  • If there is limited or no improvement with a combination of psychological intervention and antidepressant medication, options include:
    • Switching to an alternative psychological therapy.
      • See the section on Initial management for more information on choices of psychological intervention.
    • Increasing the antidepressant dose or switching the antidepressant to a drug in the same class or different class.
    • Seeking specialist advice or arranging referral for consideration of an additional antidepressant drug or other specialist augmentation of treatment, depending on clinical judgement.
      • Advise that adding in another antidepressant may not be more effective and may increase adverse effects.
      • See the section on Referral for more information on specialist treatment options.
  • If a person has features of chronic depression, see the section on Managing chronic depression for more information on management options.

Basis for recommendation

The recommendations for follow-up are largely based on the National Institute for Health and Care Excellence (NICE) guideline Depression in adults: treatment and management [NICE, 2022b], the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], and expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021].

Assessing reasons for lack of response to treatment
  • The recommendation to assess for reasons for lack of response to treatment is based on the knowledge and experience of the NICE committee which noted this may be due to a number of different reasons which should be assessed before considering further-line treatment [NICE, 2022b].
  • The BAP guidelines note that a lack of significant improvement after 2–4 weeks of antidepressant treatment substantially reduces the probability of an eventual sustained response [Cleare, 2015].
  • The Maudsley prescribing guidelines highlight the importance of considering alternative diagnoses such as bipolar disorder in a person who has not responded to treatment, as this condition is often unresponsive to standard antidepressant treatment [Taylor, 2021].
Options for further-line treatment 
  • The recommendations for further-line treatment options if a person has had psychological interventions alone first-line are based on the NICE guideline committee's knowledge and experience [NICE, 2022b].
  • The recommendations for further-line treatment options if a person has tried antidepressants alone first-line are based on some evidence identified by NICE for the effectiveness of augmenting with group exercise; very limited evidence for effectiveness of switching antidepressant or increasing antidepressant dose; and some evidence for combination psychological therapy and antidepressant medication [NICE, 2022b].
  • The recommendations for further-line treatment options if a person has tried combination psychological intervention and antidepressants is based on the NICE guideline [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The NICE guideline committee noted combination antidepressant treatment or other specialist treatment may be needed, including the addition of a second-generation antipsychotic drug or lithium, or augmentation with electroconvulsive therapy (ECT).

What should I advise to prevent relapse of depression?

During follow-up of a person with depression, advise that continuation of treatment (antidepressant or psychological intervention) after full or partial remission of symptoms, may help reduce the risk of relapse.

  • Discuss with the person the relative risks and benefits of continuing or stopping treatment, taking into account:
    • Possible risk factors for relapse.
    • Possible risks of continuing antidepressants long-term, such as adverse effects and withdrawal symptoms on stopping treatment.
      • Advise a person taking an antidepressant that treatment should be taken for at least six months following remission of symptoms, to prevent relapse.
      • See the sections on adverse effects for each drug class in Prescribing information for more information.
  • If a person has been taking an antidepressant alone and is in remission but at higher risk of relapse, discuss options to prevent relapse, such as:
    • Continuing antidepressant medication, maintaining the dose that led to full or partial remission of symptoms, or
    • Engaging with a psychological intervention, such as group cognitive behavioural therapy (CBT) or mindfulness-based cognitive therapy (MBCT), or
    • Continuing antidepressant medication and engaging with a psychological intervention (CBT or MBCT).
  • If a person has been taking an antidepressant in combination with a psychological intervention and is in remission but at higher risk of relapse, discuss options to prevent relapse, such as:
    • Continuing with one or both treatments.
  • If a person has engaged with a psychological intervention alone and is in remission but at higher risk of relapse, discuss options to prevent relapse, such as:
    • Continuing to engage with psychological intervention with a focus on relapse prevention skills.
  • If a person is taking antidepressant medication longterm to prevent relapse:
    • Arrange review at least every six months, to monitor symptoms, check concordance with medication, assess for adverse effects, risk factors for relapse, any suicidal ideas, and their wishes for ongoing treatment.
      • Consider using a validated depression questionnaire to monitor response to treatment, such as PHQ-9. See the section on Depression questionnaires for more information.
    • Ensure the person has adequate social support and is aware of sources of help if symptoms worsen.
  • If a person is continuing with a psychological intervention to prevent relapse:
    • Arrange for review when they are finishing treatment to monitor symptoms, assess risk factors for relapse, and arrange ongoing follow-up and treatment depending on clinical judgement.
  • See the National Institute for Health and Care Excellence (NICE) summary of strategies to prevent relapse for more information.

Basis for recommendation

The recommendations for relapse prevention are based on the National Institute for Health and Care Excellence (NICE) guideline Depression in adults: treatment and management [NICE, 2022b] and the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015].

Discussing continuation of treatment for relapse prevention
  • The information that continuation of treatment after full or partial remission may reduce the risk of relapse is based on the NICE guideline [NICE, 2022b].
  • The recommendations to discuss the relative risks and benefits of continuing treatment, and to continue antidepressants for at least six months following remission, are based on the NICE guideline [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The BAP guidelines note there is a high risk of relapse after a depressive episode, especially in the first six months, and this risk declines with time in remission. CKS notes these guidelines advise to take antidepressant treatment for at least 6–9 months after full remission if the person is at lower risk of relapse (first episode of depression with no risk factors for relapse).
 Management options if at higher risk of relapse
  •  The recommendations on management options if a person is at higher risk of relapse are based on the NICE guideline [NICE, 2022b].
    • The NICE committee found good evidence that antidepressants, group cognitive behavioural therapy (CBT) and mindfulness-based cognitive therapy (MBCT) were effective for relapse prevention and were cost-effective for people at higher risk of relapse for up to two years.
    • It noted that MBCT should include relapse prevention components such as consolidation of changes and strategies used to stay well; identifying stressful life events and warning signs or unhelpful behaviours with contingency plans of action if these recur; and making plans for anticipated challenges over the next 12 months.
 Arranging follow-up if on longterm treatment
  • The recommendations on follow-up for a person taking antidepressants longterm are based on the NICE guideline [NICE, 2022b].
  • The recommendations on follow-up for a person continuing with psychological therapy were based on the knowledge and experience of the NICE guideline committee [NICE, 2022b].

How should I advise to switch an antidepressant?

If a person is taking an antidepressant, ideally at a recognized therapeutic dose, but wishes to switch treatment due to lack of response, adverse effects, or personal preference:

  • If treatment is needed for a recurrent episode of depression:
    • Consider prescribing an antidepressant that the person has previously found helpful or prefers.
    • Try to avoid prescribing an antidepressant that the person has previously failed to respond to or could not tolerate due to adverse effects.
    • Advise that symptoms of mood changes, anxiety, agitation, hopelessness, or suicidal thoughts or ideas may increase when changing treatment. Advise to seek urgent review if symptoms worsen significantly or the person/carers are concerned.
      • Arrange to review the person's treatment, depending on clinical judgement. See the section on Follow-up for more information.
  • When switching to a different treatment, match the antidepressant drug choice to the person's needs, taking into account the following factors:
    • The person's preferences for treatment.
    • Potential toxicity in overdose. If the person is at risk of suicide:
      • Avoid tricyclic antidepressants ([TCAs] except for lofepramine) and venlafaxine (a serotonin noradrenaline reuptake inhibitor [SNRI]) due to their risk of death from overdose. See the section on Antidepressant toxicity in overdose in Prescribing information for more information.
      • Consider limiting the amount of medication available to the person, to reduce the risk of death or medical complications if taken in overdose, depending on clinical judgement.
    • Tolerability and potential adverse effects and withdrawal symptoms.
      • Advise on the risk of serotonin syndrome when combinations of serotonergic antidepressants are prescribed. See the sections on adverse effects and drug interactions for SSRIs and SNRIs in Prescribing information for more information.
    • Any drug treatment for associated mental health or physical health conditions which may affect prescribing.
    • Any current drug treatment(s) or substances that may potentially interact with an antidepressant.
      • This includes over-the-counter medication, herbal remedies, alcohol, or recreational drugs. See the sections on drug interactions for different antidepressant drug classes in Prescribing information for more information.
  • Advise on how to switch to a new antidepressant safely, depending on the drug class(es), potential drug interactions, and recommended washout period.
    • Explain that cross-tapering usually involves gradually reducing the dose of the current antidepressant while starting the new antidepressant at a low dose, and gradually increasing the new drug dose as the previous drug is withdrawn.
      • Note: it may be possible to switch abruptly by withdrawing the current antidepressant and starting the new drug the next day, for example when switching from one selective serotonin reuptake inhibitor (SSRI) to another SSRI or an SNRI — the exception to this is fluoxetine, due to its long half-life, where a 'washout' period is needed.
    • See Table 1 for information on how to switch between different antidepressant drug classes.

Table 1. Switching between different antidepressant drugs.

 Switching to:
Switching from: TCA (except clomipramine)SSRI (citalopram, escitalopram, paroxetine or sertraline)SNRI (duloxetine, venlafaxine)FluoxetineMirtazapineReboxetineTrazodone
TCA (except clomipramine)Direct switch possible

Gradually reduce the dose of TCA to 25–50 mg daily or half the usual dose. Start SSRI then slowly withdraw TCA over next 5–7 days

Cross-taper cautiously starting with low dose SNRIHalve dose of TCA, add fluoxetine and then slowly withdraw TCACross-taper cautiouslyCross-taper cautiouslyHalve dose of TCA, add trazodone and then slowly withdraw TCA
SSRIs (citalopram, escitalopram, paroxetine or sertraline)

Cross-taper cautiously with low dose of TCA

Direct switch possibleDirect switch possible (caution if paroxetine used)Direct switch possibleCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously
SNRIs (duloxetine, venlafaxine)Cross-taper cautiously with low dose of TCADirect switch possibleDirect switch possibleDirect switch possibleCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously
FluoxetineStop fluoxetine, start TCA at a low dose 4–7 days later and increase dose very slowlyStop fluoxetine, start SSRI at a low dose 4–7 days laterStop fluoxetine, start SNRI at a low dose 4–7 days later—Cross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously
MirtazapineCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously—Cross-taper cautiouslyCross-taper cautiously
ReboxetineCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously—Cross-taper cautiously
TrazodoneCross-taper cautiously with low dose of TCACross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously—
Sources: [SPS, 2019b; Taylor, 2021]

A cross-tapering regimen

  • See Table 1 for an example of a cross-tapering regimen using a weekly schedule. For some people the schedule may need to be fortnightly or longer [SPS, 2019b].

  • Table 1. An example of a cross-tapering regimen switching from citalopram to mirtazapine.

     Pre-switch dosageWeek 1Week 2Week 3Week 4
    Withdrawing citalopram40 mg daily20 mg daily10 mg daily5 mg daily2.5 mg daily
    Introducing mirtazapineNil15 mg daily30 mg daily30 mg daily45 mg daily (if required)
    Data from: [Taylor, 2021].

 

Basis for recommendation

The recommendations for switching antidepressants are largely based on the National Institute for Health and Care Excellence (NICE) guidelines Depression in adults: treatment and management [NICE, 2022b] and Depression in adults with a chronic physical health problem: recognition and management [National Collaborating Centre for Mental Health, 2009]; the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021], and the UK Specialist Pharmacy Service (SPS) publication How do you switch between tricyclic, SSRI and related antidepressants? [SPS, 2019b].

Advising on switching antidepressants
  • The recommendations to use response to previous antidepressant treatment to guide choice of new treatment is largely based on the BAP guidelines [Cleare, 2015].
  • The NICE guideline on depression notes the need to be vigilant for symptoms such as agitation, hopelessness, and suicidal ideation, particularly during high-risk periods such as starting or changing antidepressants and at times of increased personal stress [NICE, 2022b]. The information on how to manage symptoms is based on the NICE guideline [NICE, 2022b] and is supported by the BAP guidelines [Cleare, 2015].
Factors affecting choice of antidepressant
  • These recommendations are based on the NICE guidelines on depression [NICE, 2022b] and depression with a physical health condition [National Collaborating Centre for Mental Health, 2009], the BAP guidelines [Cleare, 2015], the Maudsley prescribing guidelines [Taylor, 2021], and the SPS publication [SPS, 2019b].
    • The recommendations to avoid tricyclic antidepressants (TCAs, except lofepramine which has a better safety profile) and venlafaxine if there is an increased risk of suicide are based on the respective NICE guidelines on depression in adults [NICE, 2022b] and depression with physical health problems [National Collaborating Centre for Mental Health, 2009]. These note that TCAs carry the greatest risk in overdose, and venlafaxine is associated with a greater risk of death from overdose compared with other equally efficacious antidepressants.
    • The recommendation to consider limiting the amount of medication if the person is at risk of suicide is based on the NICE guideline on depression [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The information on the risk of serotonin syndrome if combinations of serotonergic antidepressants are prescribed is based on the NICE guideline on depression with a physical health condition [National Collaborating Centre for Mental Health, 2009], the Maudsley prescribing guidelines [Taylor, 2021], and the SPS publication [SPS, 2019b].
Advising on cross-tapering
  • The recommendations on how to cross-taper are largely based on the BAP guidelines [Cleare, 2015], the Maudsley prescribing guidelines [Taylor, 2021], and the SPS publication [SPS, 2019b].
    • The Maudsley prescribing guidelines recommend cross-tapering wherever possible when switching antidepressants, which usually involves the gradual reduction of the current drug and simultaneous gradual introduction of the new drug.
    • CKS notes that the BAP guidelines state that switching drugs abruptly is generally preferable unless there is a potential drug interaction, in which case follow the recommended taper/'washout' period, for example when switching from fluoxetine which has a long half-life.

How should I advise stopping an antidepressant?

Do not stop antidepressants suddenly unless there are exceptional medical circumstances, such as the occurrence of serious side effects (for example upper gastrointestinal bleeding). In these circumstances, consider scheduling more frequent reviews. Antidepressants should not be stopped suddenly as this may increase the risk of experiencing severe, debilitating, and long-lasting withdrawal symptoms.

 

  • Take into account:
    • The urgency of the withdrawal, for example, gradual withdrawal of a medicine that is no longer effective or necessary, or more rapid withdrawal of a medicine that is causing significant harm.
    • Whether the initial goal should be complete withdrawal or, for people who find complete withdrawal too difficult, whether dose reduction with ongoing review is a more realistic initial aim.
    • Factors that might increase the person's risk of problems during withdrawal, including:
      • Long duration of antidepressant use.
      • High dose of antidepressant.
      • A previous history of withdrawal symptoms.
      • A previous history of problems associated with dependence.
      • Taking an antidepressant recognised to be high risk of withdrawal, such as paroxetine or serotonin and norepinephrine reuptake inhibitors.
    • Any concurrent medicines and how these might affect the person's response to withdrawal.
    • Factors that might influence the timing of the start of the dose reduction, such as the person's circumstances and available support.
  • Give information and support for people withdrawing from a medicine. Before starting withdrawal:
    • Give the person information about the process of withdrawal that is tailored to their situation and the medicine they are taking.
    • Explain the process of withdrawal.
    • Consider providing details of sources of peer support, national and local support groups for people who are withdrawing from a medicine, and information such as that provided by the Royal College of Psychiatrists on Stopping Antidepressants [RCPsych, 2020].      
  • Discuss withdrawal symptoms with the person and tell them about the support that is available. When discussing withdrawal symptoms, explain that:
    • Withdrawal can be difficult and may take several months or longer.
    • Support will be available throughout the withdrawal process.
    • Withdrawal symptoms do not affect everyone, and it is not possible to predict who will be affected.
    • Withdrawal symptoms vary widely in type and severity, can affect both physical and mental health, may occur at any time during withdrawal or be delayed in onset (which could take weeks or longer), and can change over time or persist over a prolonged period of months or years.
    • There are options for managing withdrawal symptoms, including slowing the rate of dose reduction.
    • Some people may experience withdrawal symptoms that can be difficult to distinguish from a re‑emergence of their original symptoms or a new disorder, and it is important to discuss these with a healthcare professional if they occur. 

If a person is taking an antidepressant and wishes to stop treatment due to recovery, lack of response, adverse effects, or personal preference:

  • Advise that treatment can be stopped at any stage, but in general, the dose should be reduced gradually in stages over time ('tapering') with regular monitoring for withdrawal symptoms and signs of relapse, the frequency of follow-up depending on clinical judgement.
    •  When agreeing a dose reduction schedule with the person:
      • Explain the risk of abrupt discontinuation and that the rate of safe withdrawal varies between people and can vary over time for the same person.
      • Balance the risk of adverse events from continued exposure to the medicine with minimising the risk of withdrawal symptoms by slow dose reduction and withdrawal.
      • Ensure that the planned rate of reduction is acceptable to the person.
      • Explain that although withdrawal symptoms are to be expected, the reduction schedule can be modified to allow intolerable withdrawal symptoms to improve before making the next reduction.
      • Consider giving the person additional control over the process of dose reduction (for example by issuing their usual daily dose in a form that allows them to reduce the amount in small decrements at a pace of their choosing, rather than issuing successive prescriptions for reduced daily doses). This could include prescribing a liquid preparation of the antidepressant medication. 
      • Agree on regular intervals for reviewing and adjusting the reduction schedule as needed.
      • Ensure the person knows who to contact if problems occur.
    • Advise a slow step-wise taper of the drug dose proportionate to the existing dose over time, for example, by prescribing 50% of the previous dose. Consider prescribing smaller reductions (such as 25% of the previous dose) as the dose is lowered towards zero.
      • Ensure that any withdrawal symptoms have resolved or are tolerated before prescribing a further dose reduction.
      • Advise that withdrawal may take weeks or months (or longer)  to complete.
  • Reassure the person that relapse of depression does not usually occur soon after stopping or reducing an antidepressant dose.
  • If distressing symptoms occur or worsen after a dose reduction:
    • Assess whether they are withdrawal symptoms or a re‑emergence of symptoms that were relieved by the medicine.
    • If the symptoms are new, think about delaying the next dose reduction, trying a smaller dose reduction, or reverting to the previous dose.
      • Subsequent reduction strategies could include smaller dose reductions or spacing the reductions at greater intervals. 
  • Advise that withdrawal symptoms vary in type and severity, do not affect all people, and may occur within a few days of stopping or reducing the dose of any antidepressant. Be aware that it can be difficult to distinguish between the re‑emergence of underlying conditions and the emergence of withdrawal symptoms. The following may indicate withdrawal symptoms rather than symptoms of an underlying condition:
    • Rapid or early onset of symptoms after a dose reduction or cessation of the medicine.
    • Symptoms of the underlying illness that the person reports as qualitatively different from their underlying condition or more intense than before.
    • New symptoms that the person has not experienced before.
      • Some people have reported that withdrawal symptoms often ascribed to a return of an underlying condition, a new mental health condition, or a psychosomatic condition. 
  • Use clinical judgement to determine the need for further investigation to rule out new pathology.
  • Consider arranging a more rapid drug withdrawal if the person:
    • Has serious or intolerable adverse effects, such as hyponatraemia, cardiac arrhythmias, or upper gastrointestinal bleeding.
    • Wishes to switch antidepressant drugs. See the section on Switching antidepressants for more information.
    • Is taking fluoxetine (due to its long half-life) — if taking fluoxetine 20 mg daily, a period of alternate day dosing may be suitable for drug withdrawal.
      • Note: a more gradual withdrawal schedule is needed for people taking higher doses of fluoxetine.
  • Consider arranging a longer drug withdrawal if the person: 
    • Is taking an antidepressant with a higher risk of withdrawal effects, such as paroxetine or venlafaxine.
    • Is taking long-term maintenance antidepressant treatment — drug withdrawal over months (or longer) may be needed.
    • Has had significant trouble in the past with withdrawal symptoms when trying to discontinue.
  • Do not treat withdrawal symptoms with another medicine that is associated with dependence or withdrawal symptoms.
    • If dose reduction has been unsuccessful (for example because of intolerable withdrawal symptoms or a change in the person's physical, mental or social circumstances) and the current prescription needs to be continued:
      • Aim to stop any further escalation in dose.
      • Make a plan to attempt a more gradual dose reduction at a later date (after a period of stabilisation). 
      • Clearly record the advice given to the person about the potential harms of continuing the medicine, and the reasons for continuing without a reduction, in the management plan.
  • Advise seeking urgent medical review if the person:
    • Has significant, severe, or troublesome withdrawal symptoms.
      • Consider restarting the antidepressant at the previous dose and then prescribing smaller dose reductions at a slower rate after symptoms have resolved, with ongoing monitoring for withdrawal symptoms.
    • Has a relapse of symptoms of depression or a worsening of residual symptoms.
    • If a person develops a protracted withdrawal syndrome following dose reduction or cessation note that some people may not respond to re-instatement of the drug and may experience debilitating neurological, psychological, and somatic symptoms, which can wax and wane over time.
  • See the section on Preventing relapse for more information.

 

 

Basis for recommendation

The recommendations for stopping antidepressants are largely based on the National Institute for Health and Care Excellence (NICE) guidelines Depression in adults: treatment and management [NICE, 2022b] and Medicines associated with dependence or withdrawal symptoms: safe prescribing and withdrawal management for adults [NG215] [NICE, 2022a] and Depression in adults with a chronic physical health problem: recognition and management [National Collaborating Centre for Mental Health, 2009]; the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021], and the UK Specialist Pharmacy Service (SPS) publication How do you switch between tricyclic, SSRI and related antidepressants? [SPS, 2019b].

Advising on tapering antidepressants
  • The information on how to slowly taper the drug dose and the need for regular monitoring for relapse is based on the NICE guideline on depression, which states there is limited evidence that this approach reduces the risk of withdrawal symptoms [NICE, 2022b]. The Maudsley prescribing guidelines note that tapering the dose in small increments to doses much smaller than common therapeutic doses improves the likelihood that a person will tolerate stopping the antidepressant and will remain off it [Taylor, 2021].
  • The information that antidepressant drug withdrawal may take weeks, months (or longer) is based on the NICE guideline [NICE, 2022b], the BAP guidelines [Cleare, 2015]. The Maudsley prescribing guidelines [Taylor, 2021] and information provided by an expert reviewer. 
  • The information that relapse does not usually occur soon after reducing or stopping antidepressants is based on the NICE guideline [NICE, 2022b].
Advising on withdrawal symptoms
  • The information on withdrawal symptoms is largely based on the NICE guideline [NICE, 2022b], the BAP guidelines [Cleare, 2015], the Maudsley prescribing guidelines [Taylor, 2021], the SPS publication [SPS, 2019b] and information provided by an expert reviewer. 
Considering a more rapid withdrawal
  • The recommendations if there are serious or intolerable adverse effects are based on the NICE guideline [NICE, 2022b], the BAP guidelines [Cleare, 2015], and are also pragmatic, based on what CKS considers to be good clinical practice.
  • The recommendation if the person wishes to switch antidepressant is based on the NICE guideline [NICE, 2022b].
  • The recommendation if the person is taking fluoxetine is based on the NICE guideline [NICE, 2022b] and the Maudsley prescribing guidelines, which state that due to its long half-life, withdrawal symptoms may be delayed by weeks, and as the withdrawal period is spread out symptoms may be relatively well tolerated [Taylor, 2021].
Considering a longer withdrawal
  • The recommendation if the person is taking paroxetine or venlafaxine is based on the NICE guideline on depression with a physical health condition [National Collaborating Centre for Mental Health, 2009]. This approach is supported by the Maudsley prescribing guidelines [Taylor, 2021].
  • The recommendation if the person is taking antidepressants longterm is based on the BAP guidelines [Cleare, 2015], the Maudsley prescribing guidelines [Taylor, 2021] and information provided by an expert reviewer. 
Advising on when to arrange urgent review
  • These recommendations are based on the NICE guideline on depression [NICE, 2022b] and the Maudsley prescribing guidelines [Taylor, 2021].

How should I manage chronic depressive symptoms?

If a person presents with chronic depressive symptoms and significant impairment of personal and social functioning, discuss options for management, depending on the person's wishes, hopes and expectations of treatment, involving family/carers in shared decision-making where appropriate.

  • If the person has not received previous treatment for depression, discuss one of the following options for treatment:
    • Cognitive behavioural therapy (CBT) — this should focus on managing factors that may maintain symptoms, such as unhelpful coping styles or behaviours including avoidance or rumination, or interpersonal difficulties.
    • A selective serotonin reuptake inhibitor (SSRI) — if a specific SSRI is not tolerated, consider treatment with an alternative SSRI.
    • A serotonin noradrenaline reuptake inhibitor (SNRI).
    • A tricyclic antidepressant (TCA).
    • Combination therapy with CBT and either an SSRI or TCA.
  • If the person has had, or is still receiving treatment for depression, discuss options for further-line treatments. See the section on Follow-up for more information.
  • Consider arranging referral to the following services, depending on local referral pathways and service provision:
    • A befriending service (typically run by trained volunteers).
    • A rehabilitation or occupational therapy service, with a focus on job opportunities and/or social activities, for example.
  • If there is no improvement in symptoms at follow-up after a trial of SSRIs or SNRIs:
    • Assess and manage any modifiable risk factors for depression.
    • Assess and manage any issues affecting concordance with treatment (including stopping or reducing the dose of antidepressant due to adverse effects; or explore reasons for missed sessions with psychological therapy).
    • Consider whether an alternative diagnosis or comorbid condition may be limiting the person's response to or engagement with treatment.
    • Ensure the person has adequate social support and is aware of sources of help.
    • Offer referral to a specialist mental health service or seek specialist advice.
      • See the section on Referral for more information.

Basis for recommendation

The recommendations for chronic depressive symptoms are based on the National Institute for Health and Care Excellence (NICE) guideline Depression in adults: treatment and management [NICE, 2022b], the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], and expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021].

Management options depending on treatment history
  • The recommended options for management are largely based on the NICE guideline on depression [NICE, 2022b], the BAP guidelines [Cleare, 2015], and the Maudsley prescribing guidelines [Taylor, 2021].
    • The NICE guideline committee found some evidence for the effectiveness of cognitive behavioural therapy (CBT) and some antidepressant drug treatments for the management of chronic depressive symptoms, and very limited evidence that combination antidepressant and psychological therapy may be more effective than either intervention alone.
    • CKS notes that the BAP guidelines state that antidepressants are generally needed for people with chronic depressive symptoms [Cleare, 2015].
    • The Maudsley prescribing guidelines note that if a person has had multiple episodes of depression, there is evidence of benefit from maintenance antidepressant treatment for at least two years, 'but no upper duration of treatment has been identified' [Taylor, 2021].
Arranging referral for befriending or rehabilitation
  • These recommendations are largely based on the NICE guideline on depression [NICE, 2022b].
Management options at follow-up if no improvement
  • These recommendations are extrapolated from the NICE guideline on depression [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The NICE guideline notes that specialist referral for consideration of other drug treatment may be helpful, based on some evidence for the effectiveness of tricyclic antidepressants (TCAs), moclobemide, irreversible monoamine oxidase inhibitors (MAOIs) such as phenelzine, or low-dose amisulpride.

When should I refer?

Arrange referral to specialist mental health services for co-ordinated multidisciplinary care, or seek specialist advice if:

  • Considering adding in an additional antidepressant medication from a different drug class, if there is a limited response or no response to treatment in primary care.
    • Options include adding trazodone or mirtazapine to a selective serotonin reuptake inhibitor (SSRI).
  • The person has more severe depression affecting personal and social functioning, has not responded to treatment in primary care, and has coexisting psychosocial and/or physical health risk factors.
  • The person has chronic depressive symptoms affecting personal and social functioning, has not responded to treatment in primary care, and has coexisting psychosocial and/or physical health risk factors.
  • There is a history, or clinical suspicion of, bipolar disorder. See the CKS topic on Bipolar disorder for more information.
  • Considering switching to or from a monoamine oxidase inhibitor (MAOI).
  • Considering other specialist combination drug treatment or physical therapy (such as electroconvulsive therapy [ECT]).
    • Specialist drug options include combining an antidepressant with a second-generation antipsychotic (such as aripiprazole, olanzapine, quetiapine, risperidone), or augmentation with lithium, lamotrigine, or triiodothyronine.
    • The Royal College of Psychiatrists (RCPsych) patient information Mental health services and teams in the community may be helpful.

Basis for recommendation

The recommendations on referral are based on the National Institute for Health and Care Excellence (NICE) guideline Depression in adults: treatment and management [NICE, 2022b], the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015], expert opinion in a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021], and expert opinion in review articles on depression [Malhi, 2018; Ramanuj, 2019].

  • The recommendation regarding adding in an additional antidepressant from a different drug class is based on the knowledge and experience of the NICE guideline committee [NICE, 2022b].
  • The recommendation for a person with more severe depression is based on the knowledge and experience of the NICE guideline committee [NICE, 2022b], is extrapolated from the BAP guidelines [Cleare, 2015], and is supported by expert opinion in a review article [Ramanuj, 2019].
    • The NICE guideline notes that this population group need a multidisciplinary care plan and a crisis plan.
  • The recommendation for a person with chronic depressive symptoms is based on the knowledge and experience of the NICE guideline committee [NICE, 2022b], the BAP guidelines [Cleare, 2015], and is supported by expert opinion in a review article [Ramanuj, 2019].
    • The NICE guideline notes that specialist referral for consideration of other drug treatment may be helpful, based on some evidence for the effectiveness of tricyclic antidepressants (TCAs), moclobemide, irreversible monoamine oxidase inhibitors (MAOIs) such as phenelzine, or low-dose amisulpride. It also notes that this population group need a multidisciplinary care plan and a crisis plan.
  • The recommendation if a diagnosis of bipolar disorder is suspected is based on the BAP guidelines, as the use of antidepressants in people with undiagnosed bipolar disorder can trigger hypomania/mania [Cleare, 2015].
  • The recommendation regarding considering treatment with an MAOI is based on the knowledge and experience of the NICE guideline committee [NICE, 2022b] and the BAP guidelines [Cleare, 2015].
    • The NICE guideline highlights that some combinations of antidepressants are potentially dangerous and should be avoided, such as a selective serotonin reuptake inhibitor (SSRI), serotonin noradrenaline reuptake inhibitor (SNRI), or tricyclic antidepressant (TCA) with a MAOI.
  • The recommendations if considering specialist combination treatment or other specialist treatments are based on the knowledge and experience of the NICE guideline committee [NICE, 2022b], the BAP guidelines [Cleare, 2015], and expert opinion in a review article [Ramanuj, 2019].
    • The NICE guideline notes that specialist augmentation with an antipsychotic drug may cause loss of interest and motivation, which needs careful monitoring in a person with depression.
    • The NICE guideline states there is limited evidence for the use of electroconvulsive therapy (ECT) if there is no or inadequate response to other treatment. The BAP guidelines note that ECT may be used in emergency and urgent situations such as 'depressive stupor', high risk of suicide, extreme levels of distress, and poor fluid intake.

Prescribing information

Important aspects of prescribing information relevant to primary healthcare are covered in this section specifically for the drugs recommended in this CKS topic. For further information on contraindications, cautions, drug interactions, and adverse effects, see the electronic Medicines Compendium (eMC), or the British National Formulary (BNF).

Antidepressant dosing and titration

  • The Maudsley prescribing guidelines advise to prescribe the starting dose of an antidepressant and titrate up to the recognized minimum effective dose [Taylor, 2021].
    • See Table 1 for recommended starting doses, minimum effective doses, and maximum doses of different antidepressants.
    • For selective serotonin reuptake inhibitors (SSRIs), mirtazapine, reboxetine, and venlafaxine, starting doses are often effective and up-titration may not be necessary.
    • For people who show a clear clinical response to a low-dose TCA, this dose may be maintained without further dose increases, providing the person maintains symptom improvement.

Table 1. Recommended starting doses, minimum effective doses, and maximum doses of antidepressants.

AntidepressantStarting dose (per day)Usual minimum effective dose (per day)Max dose in depression (per day)
Serotonin reuptake inhibitors
Citalopram20 mg20 mg40 mg (20 mg in the elderly and in those with reduced hepatic function)
Escitalopram10 mg (5 mg in the elderly and in those with reduced hepatic function)10 mg20 mg (10 mg in the elderly and in those with reduced hepatic function)
Fluoxetine20 mg20 mg60 mg
Fluvoxamine50 mg50 mg300 mg
Paroxetine20 mg20 mg50 mg* (40 mg in the elderly)
Sertraline50 mg50 mg200 mg
Tricyclic antidepressants
Imipramine10–75 mgAt least 75 mg to 100 mg† (possibly 125 mg)150–200 mg
Lofepramine140 mg140 mg210 mg
Others
Duloxetine60 mg60 mg60 mg
Mirtazapine15–30 mg30 mg45 mg
Reboxetine8 mg8 mg12 mg
Trazodone150 mg150 mg300 mg
Venlafaxine75 mg75 mg375 mg
Vortioxetine10 mg (5 mg in the elderly)10 mg20 mg
†Lower doses may be effective.

Data from: [Taylor, 2021; BNF, 2022]

Antidepressant toxicity in overdose

  • Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) have the highest toxicity in overdose.
    • Among TCAs, d​​​​​​dosulepin has particularly high toxicity, while lofepramine has relatively low toxicity.
    • TCAs have potentially fatal cardiovascular effects (tachycardia, postural hypotension, slowed cardiac conduction) when taken in overdose. Overdose can also cause sedation, coma, and seizures. 
    • Moclobemide (an MAOI) prolongs the QT interval and toxic effects in overdose may include hypertensive crisis, serotonin and noradrenaline toxicity, agitation, aggressiveness, and behavioural changes.
  • Venlafaxine and mirtazapine are less toxic than TCAs, but have a higher toxicity compared with selective serotonin reuptake inhibitors (SSRIs).
    • Arrhythmia is rare even after a massive overdose of venlafaxine. Venlafaxine commonly causes vomiting, sedation, tachycardia, hypertension and seizures in overdose. 
    • Duloxetine has low toxicity in overdose. It can cause somnolence, coma, serotonin syndrome, seizures, vomiting, and tachycardia in overdose. 
    • SSRIs have a low toxicity when taken in overdose, but have been reported to prolong the QTc interval. Citalopram and escitalopram have a higher risk of cardiac toxicity than other SSRIs in overdose.
    • There is a risk of serotonin syndrome in overdose of serotonergic drugs such as SSRIs, which may present with insomnia, anxiety, nausea, diarrhoea, hypertension, tachycardia, hyper-reflexia, agitation, myoclonus, tremor, flushing, low-grade fever, hyperthermia, confusion, rigidity, respiratory failure, coma, or death.

[Cleare, 2015; Taylor, 2021]

Selective serotonin reuptake inhibitors (SSRIs)

Contraindications and cautions

  • Do not prescribe selective serotonin reuptake inhibitors (SSRIs) to people:
    • In a manic phase of bipolar disorder.
    • With poorly controlled epilepsy.
    • With known QT interval prolongation, or congenital long QT syndrome (citalopram and escitalopram).
    • Concurrent use of drugs known to prolong the QT interval (citalopram and escitalopram).
    • With severe hepatic impairment (sertraline).
  • Prescribe SSRIs with caution to people with:
    • A history of bleeding disorders (especially gastrointestinal bleeding).
    • A history of mania.
    • Cardiac disease.
    • Diabetes mellitus.
    • Epilepsy (discontinue if convulsions develop).
    • Susceptible to angle-closure glaucoma.
    • Hepatic impairment (prolonged half-life) — manufacturer advises dose reduction or increasing dose interval in mild to moderate impairment.
    • Renal impairment (citalopram and escitalopram).
    • Risk factors for QT-interval prolongation (citalopram and escitalopram) or hyponatraemia.
    • Undergoing concurrent electroconvulsive therapy.

[BNF, 2022]

Adverse effects

Possible adverse effects of selective serotonin reuptake inhibitors (SSRIs) include:

  • Cardiac — palpitations (common); tachycardia (uncommon); QT interval prolongation, torsade de pointes (citalopram or escitalopram).
  • Gastrointestinal — reduced appetite, diarrhoea, nausea (dose-related), dry mouth, abdominal pain, constipation, vomiting, altered taste, weight changes, hepatitis (rare).
  • Central nervous system — headache, dizziness, drowsiness, tinnitus, paraesthesia, tremor, convulsions (uncommon), sleep disorders, visual impairment, movement disorders (uncommon), serotonin syndrome (rare).
    • Clinical features of serotonin syndrome include confusion, delirium, shivering, sweating, changes in blood pressure, and myoclonus. This can occur when combinations of serotonergic antidepressants are prescribed; most severe cases of serotonin syndrome involve an MAOI (including moclobemide) and an SSRI.  
  • Psychiatric —insomnia (very common); agitation, confusion, reduced concentration, anxiety (common), memory loss, depersonalisation, mania (uncommon).
  • Skin — rash, hyperhidrosis (common); alopecia, pruritus, photosensitivity reaction, urticaria (uncommon).
  • Other — haemorrhage, menstrual cycle irregularities, myalgia, sexual dysfunction (may persist after treatment is stopped), urinary disorders, hyponatraemia (rare), syndrome of inappropriate anti-diuretic hormone secretion (SIADH, rare), thrombocytopenia (rare). Leukopenia has also been reported as an uncommon adverse drug reaction in people prescribed paroxetine.
    • Consider hyponatraemia if the person develops dizziness, drowsiness, confusion, nausea, muscle cramps, or seizures. If suspected, stop the antidepressant and manage appropriately.

[Taylor, 2021; BNF, 2022; EMC, 2023]

Drug interactions

Possible drug interactions associated with selective serotonin reuptake inhibitors (SSRIs) include:

  • Antiepileptics — SSRIs can reduce the seizure threshold.
  • Antidiabetic drugs — SSRIs can affect diabetic control. Monitor blood glucose when starting or stopping an SSRI.
  • Aspirin, NSAIDs, anticoagulants, and antiplatelets — increased risk of bleeding if taken concomitantly with SSRIs. Consider additional INR monitoring with warfarin.
  • Carbamazepine — levels of sertraline may be reduced.
  • Cocaine — possibly an increased risk of bleeding with citalopram. Prescribers should enquire about illicit drug use before prescribing SSRIs.
  • Grapefruit juice — levels of sertraline may be modestly increased.
  • HIV protease inhibitors (for example, lopinavir, atazanavir) — efficacy of SSRIs may be reduced. Monitor and adjust dose of SSRI if required.
  • Lithium — concurrent use with SSRI may cause serotonin syndrome or neuroleptic malignant syndrome. In addition, lithium has been associated with QT prolongation and concomitant use may increase this risk. Monitor for adverse effects.
  • Monoamine oxidase inhibitors (MAOIs) — concurrent use is contraindicated. Fatal reactions may occur (serotonin syndrome or neuroleptic malignant syndrome).
  • SNRIs (venlafaxine, duloxetine) — increased risk of serotonin syndrome or neuroleptic malignant syndrome when given concomitantly with an SSRI. Monitor for symptoms (such as fever, tremor, diarrhoea, agitation).
    • Venlafaxine may also increase the risk of QT interval prolongation if taken concomitantly with an SSRI. Consider ECG monitoring.
  • Tamoxifen — avoid concurrent use with fluoxetine or paroxetine. Fluoxetine and paroxetine are potent inhibitors of the liver enzyme CYP2D6 and may reduce the plasma concentration of tamoxifen, leading to reduced efficacy.
  • Other sedative drugs (alcohol, barbiturates, benzodiazepines) — SSRIs are sedating and co-administration with other sedating drugs may have a synergistic effect.
  • Other drugs, which if taken with SSRIs may increase the risk of serotonin syndrome or neuroleptic malignant syndrome, include opioids, St John’s wort (avoid concurrent use), triptans, vortioxetine.
  • QT interval prolongation — some SSRIs are associated with QT interval prolongation and torsade de pointes. Concurrent use with other drugs that prolong the QT interval drugs may increase the risk. These include antiarrhythmics (amiodarone, dronedarone, quinidine); antipsychotics (phenothiazine derivatives, pimozide, haloperidol); tricyclic antidepressants (TCAs, clomipramine, imipramine); sildenafil.
  • Hyponatraemia — increased risk if concurrent use with other drugs known to be associated with hyponatraemia (for example, diuretics, NSAIDs, antipsychotics, carbamazepine, calcium channel blockers, angiotensin‐converting enzyme [ACE]-inhibitors, and laxatives).

[MHRA, 2016; Preston, 2016; ABPI, 2018a; ABPI, 2019a; ABPI, 2019b; ABPI, 2019c; ABPI, 2019d; ABPI, 2020; ABPI, 2021; BNF, 2022]

Serotonin noradrenaline reuptake inhibitors (SNRIs)

Contraindications and cautions

  • Do not prescribe serotonin noradrenaline reuptake inhibitors (SNRIs) to people with:
    • Uncontrolled hypertension.
    • Hepatic impairment (duloxetine).
    • Severe renal impairment – creatinine clearance less than 30 mL/min (duloxetine).
  • Prescribe SNRIs with caution to people with:
    • A history of bleeding disorders.
    • A history of epilepsy.
    • A history or family history of mania or bipolar disorder.
    • Cardiac disease — monitor blood pressure.
    • Conditions associated with high risk of cardiac arrhythmia.
    • Hypertension.
    • Diabetes mellitus — blood sugar control may be affected.
    • Hepatic impairment — manufacturer advises consider dose reduction of 50% in mild to moderate impairment and of more than 50% in severe impairment (venlafaxine).
    • Renal impairment (venlafaxine).
    • Susceptibility to angle-closure glaucoma (duloxetine).

[BNF, 2022]

Adverse effects

Possible adverse effects associated with serotonin noradrenalin reuptake inhibitors (SNRIs) include:

  • Cardiac — palpitations (common); tachycardia, hypertension, supraventricular arrhythmia (uncommon); torsade de pointes, QT interval prolongation (rare), hypotension, syncope.
  • Gastrointestinal — dry mouth, altered taste, decreased appetite, nausea (very common); constipation, vomiting, diarrhoea, dyspepsia, flatulence, abdominal pain (common); gastrointestinal haemorrhage, weight changes, hepatitis (rare), pancreatitis (rare).
  • Central nervous system — headache, somnolence (very common); dizziness, drowsiness, akathisia, lethargy, tremor, paraesthesia (common); akathisia, movement disorders, sleep disorders, tinnitus, vision problems, seizure (rare).
  • Psychiatric — insomnia, confusion, anxiety, abnormal dreams, agitation (common); suicidal thoughts, depersonalisation.
  • Skin — sweat changes, rash (common), photosensitivity reaction (uncommon), alopecia, angio-oedema.
  • Other — dyspnoea, flushing, menstrual cycle irregularities, sexual dysfunction (may persist after treatment stopped); urinary symptoms, hyponatraemia (rare), neuroleptic malignant syndrome (rare), serotonin syndrome (rare), neutropenia (rare), syndrome of inappropriate antidiuretic hormone secretion (SIADH, rare), thrombocytopenia (rare), hyperprolactinaemia.
  • Overdose of venlafaxine can cause hypoglycaemia.

[BNF, 2022; EMC, 2024a]

Drug interactions

Possible drug interactions associated with use of serotonin noradrenaline reuptake inhibitors (SNRIs) include:

  • Antifungals (fluconazole, itraconazole, ketoconazole) — plasma concentration of venlafaxine increased. Manufacturer advises that concomitant use with fluconazole should only be undertaken with caution; for other antifungals monitor for adverse effects and adjust venlafaxine dose if necessary.
  • Aspirin, NSAIDs, anticoagulants, and antiplatelets — increased risk of bleeding if taken concurrently with SNRI. Consider additional INR monitoring if taking warfarin.
  • Bupropion — plasma concentration of SNRI increased. Monitor for adverse effects and adjust SNRI dose if necessary.
  • Carvedilol, metoprolol — levels may be increased by duloxetine. Monitor blood pressure.
  • Ciprofloxacin — avoid concomitant use (metabolism of duloxetine is inhibited by ciprofloxacin).
  • Clarithromycin, erythromycin — levels of venlafaxine may be increased. Possible increased risk of QT interval prolongation.
  • Diltiazem, verapamil — plasma concentration of venlafaxine may be increased. Monitor for adverse effects and adjust venlafaxine dose if necessary.
  • HIV protease inhibitors (for example ritonavir, lopinavir, atazanavir) — levels of venlafaxine may be increased. Monitor for adverse effects and adjust dose of venlafaxine if necessary.
  • Lithium — concurrent use with SNRI may cause serotonin syndrome. In addition, lithium has been associated with QT interval prolongation. Monitor for adverse effects.
  • Monoamine oxidase inhibitors (MAOIs) — concurrent use is contraindicated. Fatal reactions may occur (serotonin syndrome).
  • SSRIs (paroxetine, sertraline) — increased risk of serotonin syndrome when given concurrently with an SNRI. Monitor for symptoms (such as fever, tremors, diarrhoea, agitation).
    • Venlafaxine may also increase the risk of QT interval prolongation if taken concurrently with an SSRI. Consider ECG monitoring.
  • Other sedative drugs (alcohol, barbiturates, benzodiazepines) — SSRIs are sedating and co-administration with other sedating drugs may have a synergistic effect.
  • Other drugs, which if taken with an SNRI may increase the risk of serotonin syndrome include mirtazapine, opioids, St John's wort (avoid concurrent use), triptans, vortioxetine.
  • QT interval prolongation — possible increased risk of QT interval prolongation if venlafaxine is taken with other drugs known to cause QT interval prolongation, including antiarrhythmics (amiodarone, dronedarone, quinidine); antipsychotics (phenothiazine derivatives, pimozide, haloperidol); tricyclic antidepressants (TCAs, clomipramine, imipramine); sildenafil.

[Preston, 2016; ABPI, 2019e; ABPI, 2019f; BNF, 2022]

Tricyclic antidepressants (TCAs)

Contraindications and cautions

  • Do not prescribe tricyclic antidepressants (TCAs) to people:
    • With acute porphyrias (lofepramine).
    • With arrhythmias.
    • With heart block.
    • With severe hepatic impairment.
    • With severe renal impairment (lofepramine).
    • During the manic phase of bipolar disorder.
    • During the immediate recovery period after myocardial infarction.
    • Taking a monoamine oxidase inhibitor (MAOI).
  • Prescribe TCAs with caution to people with:
    • A history of bipolar disorder or psychosis.
    • Increased risk of suicide.
    • Cardiovascular disease.
    • Older age (increased susceptibility to adverse effects).
    • Chronic constipation.
    • Epilepsy.
    • Diabetes mellitus.
    • Mild to moderate hepatic impairment.
    • Hyperthyroidism (risk of arrhythmias).
    • Susceptibility to angle-closure glaucoma.
    • Phaeochromocytoma (risk of arrhythmias).
    • Prostatic hypertrophy.
    • Urinary retention.

[BNF, 2022]

Adverse effects

Possible adverse effects associated with tricyclic antidepressants (TCAs) include:

  • Cardiac — palpitations, arrhythmias, tachycardia (very common); AV block, bundle branch block (common), QT interval prolongation (common), hypertension, myocardial infarction, sudden cardiac death.
  • Vision — accommodation disorder (very common); mydriasis (common); blurred vision.
  • Gastrointestinal — dry mouth, reduced appetite, altered taste, constipation, nausea, diarrhoea, vomiting, abdominal pain, paralytic ileus, weight changes.
  • Central nervous system — somnolence, tremor, dizziness, reduced concentration, confusion, headache, drowsiness, speech disorders, movement disorders, peripheral neuropathy, seizure, sleep disorders, tinnitus.
  • Psychiatric — aggression (very common); confusion, anxiety, agitation, delirium, hallucinations, suicidal behaviours.
  • Skin — skin reactions, alopecia, facial oedema, photosensitivity reactions.
  • Other — bone marrow depression, gynaecomastia, hyperhidrosis, hyponatraemia, neuroleptic malignant syndrome, sexual dysfunction, thrombocytopenia, urinary disorders.

[BNF, 2022]

Drug interactions

Possible drug interactions associated with tricyclic antidepressants (TCAs) include:

  • Clonidine — the antihypertensive effects may be reduced by TCAs. Monitor blood pressure and adjust dose of antihypertensive if required.
  • Lithium — concurrent use with a TCA may cause neurotoxicity, serotonin syndrome, or neuroleptic malignant syndrome. In addition, both drugs have been associated with QT interval prolongation or torsades de pointes. Monitor for adverse effects.
  • Monoamine oxidase inhibitors (MAOIs) — concurrent use is contraindicated. Fatal reactions may occur similar to, or the same as, serotonin syndrome.
  • Other sedative drugs (alcohol, barbiturates, benzodiazepines) — TCAs are sedating and co-administration with other sedating drugs may have a synergistic effect.
  • Phenothiazines (for example thioridazine) — concentrations of both drugs may be increased, increasing the risk of tardive dyskinesia and antimuscarinic adverse effects. In addition, risk of QT interval prolongation if both drugs are taken concomitantly. Avoid concurrent use, but if this is unavoidable, consider ECG monitoring.
  • Selective serotonin reuptake inhibitors (SSRIs) and serotonin noradrenaline reuptake inhibitors (SNRIs) — TCA concentrations may be increased leading to adverse effects. SSRIs and SNRIs are also associated with QT interval prolongation, possibly increasing the risk of arrhythmias if taken with a TCA. Monitor concomitant use.
  • Tramadol — concomitant treatment may increase the risk of serotonin syndrome. Monitor closely for adverse effects.
  • Warfarin — TCAs may affect the prothrombin time.
  • Drugs which may increase the levels of TCAs include antifungals (fluconazole, terbinafine); bupropion; cimetidine; diltiazem, verapamil; HIV protease inhibitors (for example, ritonavir).
  • Drugs which can reduce the levels of TCAs include carbamazepine, phenobarbital, rifampicin.
  • Drugs which prolong the QT interval — these drugs increase the risk of ventricular arrhythmias when a TCA is given concomitantly. Avoid concurrent use with antiarrhythmics (amiodarone, disopyramide, procainamide, and quinidine); antipsychotics (pimozide, sertindole); olanzapine, clozapine (consider ECG monitoring); domperidone, hydroxyzine, mizolastine, sotalol (avoid concurrent use).

[Preston, 2016; ABPI, 2017; ABPI, 2019g; BNF, 2022]

Mirtazapine

Contraindications and cautions

  • Prescribe mirtazapine with caution to people with:
    • Cardiac disorders.
    • Diabetes mellitus.
    • Hepatic impairment (risk of increased plasma concentration).
    • Hypotension.
    • Older age.
    • History of mania (discontinue if person is entering manic phase).
    • History of seizures.
    • History of urinary retention.
    • Psychosis (may aggravate psychotic symptoms).
    • Renal impairment (clearance reduced by 30% if creatinine clearance is less than 40 mL/min; clearance reduced by 50% if creatinine clearance is less than 10 mL/min).
    • Susceptibility to angle-closure glaucoma.
    • Susceptibility to hyponatraemia.

[BNF, 2022]

Adverse effects

Possible adverse effects associated with mirtazapine include:

  • Cardiac — arrhythmias, QT interval prolongation, postural hypotension.
  • Gastrointestinal — dry mouth, increased appetite, nausea, vomiting, diarrhoea, constipation, pancreatitis (rare), increased weight, jaundice (discontinue drug).
  • Central nervous system — somnolence, sedation, headache (on discontinuation); lethargy, dizziness, tremor, paraesthesia, sleep disorders, movement disorders, seizure.
  • Psychiatric — aggression, confusion, anxiety, insomnia (common); nightmares, agitation, hallucinations, mania (uncommon), suicidal behaviours.
  • Skin — skin reactions.
  • Other — arthralgia, back pain, myalgia, oedema, bone marrow disorders, hyponatraemia, serotonin syndrome, urinary retention.

[BNF, 2022]

Drug interactions

Possible drug interactions associated with mirtazapine include:

  • Antiepileptics — mirtazapine can reduce the seizure threshold, and carbamazepine, phenobarbital and phenytoin decrease mirtazapine levels.
  • Chlorpromazine — increased risk of agranulocytosis. Monitor for blood dyscrasias.
  • Monoamine oxidase inhibitors (MAOIs) — increased risk of serotonin syndrome. Avoid concurrent use (and for 2 weeks after stopping either drug).
  • Rifampicin — decreases levels of mirtazapine. Dose adjustments may be necessary.
  • Other sedative drugs (alcohol, barbiturates, benzodiazepines) — mirtazapine is sedating and co-administration with other sedating drugs may have a synergistic effect.
  • Drugs which may increase the risk of serotonin syndrome if taken concurrently with mirtazapine include lithium, opioids (fentanyl, tramadol), SNRIs (venlafaxine, duloxetine), St John’s wort, tricyclic antidepressants (clomipramine, imipramine), triptans (sumatriptan, naratriptan), vortioxetine.
  • Drugs which may increase the levels of mirtazapine include antifungals (itraconazole, ketoconazole, voriconazole), cimetidine, erythromycin, HIV protease inhibitors (ritonavir, saquinavir).

[Preston, 2016; ABPI, 2018b; BNF, 2022]

Reboxetine

Contraindications and cautions

  • Prescribe reboxetine with caution to people with:
    • A history of bipolar disorder.
    • A history of cardiovascular disease.
    • A history of epilepsy.
    • Hepatic impairment (risk of increased exposure).
    • Prostatic hypertrophy.
    • Renal impairment (needs initial dose reduction).
    • Susceptibility to angle-closure glaucoma.
    • Urinary retention.

[BNF, 2022]

Adverse effects

Possible adverse effects associated with reboxetine include:

  • Cardiac — palpitations, tachycardia, (common), hypertension, hypotension.
  • Vision — accommodation disorder (common); mydriasis (uncommon).
  • Gastrointestinal — dry mouth, decreased appetite, altered taste, nausea, constipation (very common); vomiting (common).
  • Central nervous system — dizziness (very common); insomnia, headache, akathisia, paraesthesia, vertigo.
  • Psychiatric — insomnia (very common); anxiety, agitation (common); sleep disorder.
  • Skin — hyperhidrosis (very common); skin reactions.
  • Other — sexual dysfunction, urinary disorders, chills.
  • Serotonin syndrome (frequency not known).

[BNF, 2022; EMC, 2024b]

Drug interactions

Possible drug interactions associated with reboxetine include:

  • Diuretics (loops and thiazides) — hypokalaemia may occur if used concomitantly with reboxetine.
  • Monoamine oxidase inhibitors (MAOIs) — increased risk of acute hypertensive crisis.
  • Drugs which may increase levels of reboxetine include antifungals (ketoconazole, itraconazole, miconazole), fluvoxamine, HIV protease inhibitors (ritonavir, atazanavir), macrolide antibiotics (erythromycin or clarithromycin).
  • Drugs which may reduce levels of reboxetine include carbamazepine, phenobarbital, phenytoin, primidone, rifampicin, St John’s wort.

[ABPI, 2015; Preston, 2016; BNF, 2022]

Switching antidepressants

Switching from citalopram, escitalopram, sertraline, or paroxetine to another antidepressant

  • Cross-tapering with a tricyclic antidepressant (TCA) is inadvisable with paroxetine and fluvoxamine — if needed it should be done very cautiously [SPS, 2019b].
  • Clomipramine is a potent inhibitor of serotonin reuptake, and serotonin syndrome is more likely if co-administered with an SSRI or SNRI — cross-tapering is not recommended except under specialist supervision [SPS, 2019b].
    • Clomipramine should be withdrawn before starting an SSRI, venlafaxine, or duloxetine and vice versa.
Switching from citalopram, escitalopram, sertraline, or paroxetine to:Method
A TCA (except clomipramine)Cross-taper cautiously with a low dose of TCA
SSRIs: citalopram, escitalopram, sertraline, or paroxetineDirect switch possible
SNRIs: duloxetine, venlafaxineDirect switch possible (caution if paroxetine used)
FluoxetineDirect switch possible
MirtazapineCross-taper cautiously
ReboxetineCross-taper cautiously
TrazodoneCross-taper cautiously
Sources: [SPS, 2019b; Taylor, 2021]

Switching from fluoxetine to another antidepressant

  • Be aware that interactions with fluoxetine may still occur for 5 weeks after stopping fluoxetine because of its long half-life [SPS, 2019b].
Switching from fluoxetine to:Method
A TCA (except clomipramine)Stop fluoxetine, start TCA at a low dose 4–7 days later and increase dose very slowly
SSRIs: citalopram, escitalopram, sertraline, or paroxetineStop fluoxetine, start SSRI at a low dose 4–7 days later
SNRIs: duloxetine, venlafaxineStop fluoxetine, start SNRI at a low dose 4–7 days later
MirtazapineCross-taper cautiously
ReboxetineCross-taper cautiously
TrazodoneCross-taper cautiously
Sources: [Taylor, 2021]

Switching from trazodone to another antidepressant

Switching from trazodone to:Method
A TCA (except clomipramine)Cross-taper cautiously with a low dose of TCA
SSRIs: citalopram, escitalopram, paroxetine or sertralineCross-taper cautiously
SNRIs: duloxetine, venlafaxineCross-taper cautiously
FluoxetineCross-taper cautiously
MirtazapineCross-taper cautiously
ReboxetineCross-taper cautiously
Source: [Taylor, 2021]

Switching from duloxetine or venlafaxine to another antidepressant

  • Clomipramine is a potent inhibitor of serotonin reuptake, and serotonin syndrome is more likely if co-administered with an SSRI or SNRI — cross-tapering is not recommended except under specialist supervision [SPS, 2019b].
    • Clomipramine should be withdrawn before starting a selective serotonin reuptake inhibitor (SSRI) or selective serotonin and noradrenaline reuptake inhibitor (SNRI) and vice versa.
Switching from duloxetine or venlafaxine to:Method
A TCA (except clomipramine)Cross-taper cautiously with a low dose of TCA
SSRIs: citalopram, escitalopram, sertraline, or paroxetineDirect switch possible
SNRIs: duloxetine, venlafaxineDirect switch possible
MirtazapineCross-taper cautiously
ReboxetineCross-taper cautiously
TrazodoneCross-taper cautiously
Sources: [Taylor, 2021]

Switching from a TCA to a different TCA or another antidepressant

  • Cross-tapering with a tricyclic antidepressant (TCA) is inadvisable with paroxetine and fluvoxamine — if necessary it should be done very cautiously [SPS, 2019b].
  • Clomipramine is a potent inhibitor of serotonin reuptake, and serotonin syndrome is more likely if co-administered with an SSRI or SNRI — cross-tapering is not recommended except under specialist supervision [SPS, 2019b].
    • Clomipramine should be withdrawn before starting a selective serotonin reuptake inhibitor (SSRI) or selective serotonin and noradrenaline reuptake inhibitor (SNRI) and vice versa.
    • Be aware that interactions with fluoxetine may still occur for 5 weeks after stopping fluoxetine because of its long half-life.

Table 1. Switching antidepressants.

 Switching to:
Switching from: TCA (except clomipramine)SSRI ( citalopram, escitalopram, paroxetine or sertraline)SNRI (duloxetine, venlafaxine)FluoxetineMirtazapineReboxetineTrazodone
TCA (except clomipramine)Direct switch possible

Gradually reduce the dose of TCA to 25–50 mg daily or half the usual dose. Start SSRI then slowly withdraw TCA over next 5–7 days

Cross-taper cautiously starting with low dose SNRIHalve dose of TCA, add fluoxetine and then slowly withdraw TCACross-taper cautiouslyCross-taper cautiouslyHalve dose of TCA, add trazodone and then slowly withdraw TCA
SSRIs ( citalopram, escitalopram, paroxetine or sertraline)

Cross-taper cautiously with low dose of TCA

Direct switch possibleDirect switch possible (caution if paroxetine used)Direct switch possibleCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously
SNRIs (duloxetine, venlafaxine)Cross-taper cautiously with low dose of TCADirect switch possibleDirect switch possibleDirect switch possibleCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously
FluoxetineStop fluoxetine, start TCA at a low dose 4–7 days later and increase dose very slowlyStop fluoxetine, start SSRI at a low dose 4–7 days laterStop fluoxetine, start SNRI at a low dose 4–7 days later—Cross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously
MirtazapineCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously—Cross-taper cautiouslyCross-taper cautiously
ReboxetineCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously—Cross-taper cautiously
TrazodoneCross-taper cautiously with low dose of TCACross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiouslyCross-taper cautiously—
Sources: [SPS, 2019b; Taylor, 2021]

Switching from mirtazapine to another antidepressant

Switching from mirtazapine to:Method
A TCA (except clomipramine)Cross-taper cautiously
SSRIs: citalopram, escitalopram, sertraline, or paroxetineCross-taper cautiously
SNRIs: duloxetine, venlafaxineCross-taper cautiously
FluoxetineCross-taper cautiously
ReboxetineCross-taper cautiously
TrazodoneCross-taper cautiously
Sources: [Taylor, 2021]

Switching from reboxetine to another antidepressant

Switching from reboxetine to:Method
A TCA (except clomipramine)Cross-taper cautiously
SSRIs: citalopram, escitalopram, sertraline, or paroxetineCross-taper cautiously
SNRIs: duloxetine, venlafaxineCross-taper cautiously
FluoxetineCross-taper cautiously
MirtazapineCross-taper cautiously
TrazodoneCross-taper cautiously
Sources: [Taylor, 2021]

Supporting evidence

This topic is largely based on the National Institute for Health and Care Excellence (NICE) guidelines Depression in adults: treatment and management [NICE, 2022b] and Depression in adults with a chronic physical health problem: recognition and management [National Collaborating Centre for Mental Health, 2009], the British Association for Psychopharmacology (BAP) guidelines Evidence-based guidelines for treating depressive disorders with antidepressants: a revision of the 2008 British Association for Psychopharmacology guidelines [Cleare, 2015],  and a chapter in a textbook The Maudsley prescribing guidelines in psychiatry [Taylor, 2021]. The rationale for individual recommendations is outlined in the relevant basis for recommendation sections of the topic.

How this topic was developed

This section briefly describes the processes used in developing and updating this topic. Further details on the full process can be found in the About Us section and on the Clarity Informatics website.

Search strategy

A literature search was conducted for guidelines and systematic reviews on primary care management of depression in adults (> 18 years).

Search dates

November 2019 - July 2022

Key search terms

The terms listed below are the core search terms that were used for EBSCOhost MEDLINE (searched 22nd November 2019). These were combined with filters to identify guidelines and primary care relevant literature in EBSCOhost MEDLINE. The strategy was adapted for The Cochrane Library databases. 

 S5    S1 OR S2 OR S3 OR S4
S4    AB "seasonal affective disorder" OR TI "seasonal affective disorder" 
S3    AB ( depressi* or dysthymi* ) OR TI ( depressi* or dysthymi* ) 
S2    (MH "Depressive Disorder+") 
S1    (MH "Depression") 

Sources of guidelines

Sources of systematic reviews and meta-analyses

  • The Cochrane Library:
    • Systematic reviews
    • Protocols
    • Database of Abstracts of Reviews of Effects
  • Medline (with systematic review filter)
  • EMBASE (with systematic review filter)

Sources of health technology assessments and economic appraisals

Sources of randomized controlled trials

  • The Cochrane Library:
    • Central Register of Controlled Trials
  • Medline (with randomized controlled trial filter)
  • EMBASE (with randomized controlled trial filter)

Sources of evidence based reviews and evidence summaries

Sources of national policy

Patient experiences

Sources of medicines information

The following sources are used by CKS pharmacists and are not necessarily searched by CKS information specialists for all topics. Some of these resources are not freely available and require subscriptions to access content.

Stakeholder engagement

Our policy

The external review process is an essential part of CKS topic development. Consultation with a wide range of stakeholders provides quality assurance of the topic in terms of:

  • Clinical accuracy.
  • Consistency with other providers of clinical knowledge for primary care.
  • Accuracy of implementation of national guidance (in particular NICE guidelines).
  • Usability.

Principles of the consultation process

  • The process is inclusive and any individual may participate.
  • To participate, an individual must declare whether they have any competing interests or not. If they do not declare whether or not they have competing interests, their comments will not be considered.
  • Comments received after the deadline will be considered, but they may not be acted upon before the clinical topic is issued onto the website.
  • Comments are accepted in any format that is convenient to the reviewer, although an electronic format is encouraged.
  • External reviewers are not paid for commenting on the draft topics.
  • Discussion with an individual or an organization about the CKS response to their comments is only undertaken in exceptional circumstances (at the discretion of the Clinical Editor or Editorial Steering Group).
  • All reviewers are thanked and offered a letter acknowledging their contribution for the purposes of appraisal/revalidation.
  • All reviewers are invited to be acknowledged on the website. All reviewers are given the opportunity to feedback about the external review process, enabling improvements to be made where appropriate.

Stakeholders

  • Key stakeholders identified by the CKS team are invited to comment on draft CKS topics. Individuals and organizations can also register an interest to feedback on a specific topic, or topics in a particular clinical area, through the Getting involved section of the Clarity Informatics website.
  • Stakeholders identified from the following groups are invited to review draft topics:
    • Experts in the topic area.
    • Professional organizations and societies (for example, Royal Colleges).
    • Patient organizations, Clarity has established close links with groups such as Age UK and the Alzheimer’s Society specifically for their input into new topic development, review of current topic content and advice on relevant areas of expert knowledge.
    • Guideline development groups where the topic is an implementation of a guideline.
    • The British National Formulary team.
    • The editorial team that develop MeReC Publications.
  • Reviewers are provided with clear instructions about what to review, what comments are particularly helpful, how to submit comments, and declaring interests.

Patient engagement

Clarity Informatics has enlisted the support and involvement of patients and lay persons at all stages in the process of creating the content which include:

  • Topic selection
  • Scoping of topic
  • Selection of clinical scenarios
  • First draft internal review
  • Second draft internal review
  • External review
  • Final draft and pre-publication

Our lay and patient involvement includes membership on the editorial steering group, contacting expert patient groups, organizations and individuals.

Evidence exclusion criteria

Our policy

Scoping a literature search, and reviewing the evidence for CKS is a methodical and systematic process that is carried out by the lead clinical author for each topic. Relevant evidence is gathered in order that the clinical author can make fully informed decisions and recommendations. It is important to note that some evidence may be excluded for a variety of reasons. These reasons may be applied across all CKS topics or may be specific to a given topic.

Studies identified during literature searches are reviewed to identify the most appropriate information to author a CKS topic, ensuring any recommendations are based on the best evidence. We use the principles of the GRADE and PICOT approaches to assess the quality of published research. We use the principles of AGREE II to assess the quality of published guidelines.

Standard exclusions for scoping literature:

  • Animal studies
  • Original research is not written in English

Possible exclusions for reviewed literature:

  • Sample size too small or study underpowered
  • Bias evident or promotional literature
  • Population not relevant
  • Intervention/treatment not relevant
  • Outcomes not relevant
  • Outcomes have no clear evidence of clinical effectiveness
  • Setting not relevant
  • Not relevant to UK
  • Incorrect study type
  • Review article
  • Duplicate reference

Organizational, behavioural and financial barriers

Our policy

The CKS literature searches take into consideration the following concepts, which are discussed at the initial scoping of the topic.

  • Feasibility
    • Studies are selected depending on whether the intervention under investigation is available in the NHS and can be practically and safely undertaken in primary care.
  • Organizational and Financial Impact Analysis
  • Studies are selected and evaluated on whether the intervention under investigations may have an impact on local clinical service provision or national impact on cost for the NHS. The principles of clinical budget impact analysis are adhered to, evaluated and recorded by the author. The following factors are considered when making this assessment and analysis.
    • Eligible population
    • Current interventions
    • Likely uptake of new intervention or recommendation
    • Cost of the current or new intervention mix
    • Impact on other costs
    • Condition-related costs
    • In-direct costs and service impacts
    • Time dependencies
  • Cost-effectiveness or cost-benefit analysis studies are identified where available. 

We also evaluate and include evidence from NICE accredited sources which provide economic evaluations of recommendations, such as NICE guidelines. When a recommended action may not be possible because of resource constraints, this is explicitly indicated to healthcare professionals by the wording of the CKS recommendation.

Declarations of interest

Our policy

Clarity Informatics requests that all those involved in the writing and reviewing of topics, and those involved in the external review process to declare any competing interests. Signed copies are securely held by Clarity Informatics and are available on request with the permission of the individual. A copy of the declaration of interest form which participants are asked to complete annually is also available on request. A brief outline of the declarations of interest policy is described here and full details of the policy is available on the Clarity Informatics website. Declarations of interests of the authors are not routinely published, however competing interests of all those involved in the topic update or development are listed below. Competing interests include:

  • Personal financial interests
  • Personal family interest
  • Personal non-financial interest
  • Non-personal financial gain or benefit

Although particular attention is given to interests that could result in financial gains or losses for the individual, competing interests may also arise from academic competition or for political, personal, religious, and reputational reasons. An individual is not obliged to seek out knowledge of work done for, or on behalf of, the healthcare industry within the departments for which they are responsible if they would not normally expect to be informed.

Who should declare competing interests?

Any individual (or organization) involved in developing, reviewing, or commenting on clinical content, particularly the recommendations should declare competing interests. This includes the authoring team members, expert advisers, external reviewers of draft topics, individuals providing feedback on published topics, and Editorial Steering Group members. Declarations of interest are completed annually for authoring team and editorial steering group members, and are completed at the start of the topic update and development process for external stakeholders.

Competing interests declared for this topic:

None.

References

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