Previous changes

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

February 2024 — minor update. An adverse effect of hyperprolactinaemia relating to Citalopram 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.

November 2023 — reviewed. A literature search was conducted in October 2023 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

August 2022 — minor update. Typographical error corrected. 

October 2020 — minor update. Broken URL links have been updated.

August 2020 — minor update. Broken URL link updated.

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

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

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

January 2019 — reviewed. A literature search was conducted in January 2019 to identify evidence-based guidelines, UK policy, systematic reviews, and key randomized controlled trials published since the last revision of this topic. The topic has undergone restructuring. No major changes to the recommendations have been made.

June 2013 — reviewed. A literature search was conducted in May 2013 to identify evidence-based guidelines, UK policy, systematic reviews, and key RCTs published since the last revision of the topic. There are no major changes to the recommendations.

April to July 2010 — this is a new CKS topic. The evidence-base has been reviewed in detail, and recommendations are clearly justified and transparently linked to the supporting evidence.

New evidence

• NICE (2025) Gambling-related harms: identification, assessment and management National Institute for Health and Care Excellence Homepage | NICE [Free full-text]

Evidence-based guidelines

No new evidence-based guidelines since 1 October 2023.

HTAs (Health Technology Assessments)

No new HTAs since 1 October 2023.

Economic appraisals

No new economic appraisals relevant to England since 1 October 2023.

Systematic reviews and meta-analyses

• Bertolini, F., Robertson, L., Bisson, J. I., Meader, N., Churchill, R., Ostuzzi, G., ... & Barbui, C. (2024). Early pharmacological interventions for prevention of post‐traumatic stress disorder (PTSD) in individuals experiencing acute traumatic stress symptoms. Cochrane Database of Systematic Reviews, (5). [Abstract]

Primary evidence

No new primary evidence which reaches the CKS threshold for inclusion published since 1 October 2023.

New policies

No new policies since 1 January 2019.

New safety alerts

No new safety alerts since 1 January 2019.

Changes in product availability

No changes in product availability since 1 January 2019.

Screening questionnaires

• In primary care, the Trauma Screening-Questionnaire (TSQ) may be helpful to identify people with post-traumatic stress disorder. It:
  • Consists of 10 questions which measure re-experiencing and arousal symptoms.
  • Takes only a few minutes to administer.
  • Is designed for use three weeks or more following exposure to a traumatic event to identify people who are likely to be currently suffering from post-traumatic stress disorder.
  • Asks the person to indicate which symptoms they have experienced at least twice in the past week.
    • If the person has six or more positive responses, they are at risk of having post-traumatic stress disorder and should be referred for further assessment (using a structured interview for post-traumatic stress disorder).
  • Is freely available to download.
• Other questionnaires may be used, but some are not as freely available, and as they are longer and often more complex, they may not be as suitable for use in primary care. They include:
  • Impact of Events Scale-Revised
    • A 22-item self-report measure that assesses subjective distress caused by traumatic events.
  • Davidson Trauma Scale
    • A 17-item self-report measure that assesses the 17 DSM-IV (Diagnostic and Statistical Manual of Mental Disorders, fourth edition) symptoms of post-traumatic stress disorder.
  • Post-Traumatic Stress Disorder Checklist for DSM-V
    • A 17-item self-report measure of the 17 DSM-IV symptoms of post-traumatic stress disorder.

Differential diagnosis

• Depression — suggested by low mood, lack of energy, loss of interest, and suicidal ideation. For more information, see the CKS topics on Depression, Depression in children, and Depression - antenatal and postnatal.
• Generalized anxiety disorder — suggested by excessive anxiety and worry (apprehensive expectation) about a number of events or activities (for example, possible job responsibilities, finances, health of family members, misfortunes that may befall their children) which occurs on more days than not, for at least 6 months. The anxiety and worry must be accompanied by at least three additional symptoms (restlessness, being easily fatigued, difficulty concentrating, irritability, muscle tension, or disturbed sleep). For more information, see the CKS topic on Generalized anxiety disorder.
• Panic disorder — suggested by recurrent, unexpected panic attacks not triggered by stimuli that recall a specific trauma.
• Specific phobias — suggested by fear and avoidance restricted to certain situations.
• Adjustment disorder — suggested by variable symptoms of low mood, anxiety, worry, traumatic stress symptoms, and feelings of inability to cope, plan ahead, or carry on. Symptom intensity is usually less than with PTSD.
• Dissociative disorders — suggested by persistent and recurrent feelings of detachment and estrangement from oneself (depersonalisation disorder) and/or gaps in recall, often related to traumatic events (dissociative amnesia). There is an absence of the re-experiencing and hyper-arousal symptoms of PTSD.
• Psychosis — suggested by hallucinations and delusions. Flashbacks and vivid intrusive images are accompanied by perceptual and cognitive disorganisation. For more information, see the CKS topics on Bipolar disorder and Psychosis and schizophrenia.

Diagnostic criteria

To meet the DSM-5 criteria for post-traumatic stress disorder (PTSD) the person must have:

• Been exposed to actual or threatened death, serious injury, or sexual violence in one (or more) of the following ways:
  • Directly experiencing the traumatic event.
  • Witnessing, in person, the event as it occurred to others.
  • Learning that the traumatic event occurred to a close family member or friend. In cases of actual or threatened death of a family member or friend, the events must have been violent or accidental.
  • Experiencing repeated or extreme exposure to aversive details of the traumatic event (e.g. first responders collecting human remains; police officers repeatedly exposed to details of child abuse).
• Persistently re-experience at least one of the following intrusive symptoms:
  • Recurrent, involuntary, and intrusive memories.
  • Recurrent traumatic nightmares (children may have frightening dreams not related to the trauma).
  • Dissociative reactions (e.g. flashbacks) in which the person feels or acts as if the traumatic event is recurring. These reactions may occur as brief episodes or the person may lose consciousness (children may re-enact the traumatic event through play).
  • Intense or prolonged distress after exposure to traumatic reminders.
  • Marked physiologic reactivity after exposure to trauma-related stimuli.
• Persistently avoid stimuli associated with the traumatic event, such as:
  • Trauma-related thoughts or feelings, or
  • Trauma-related external reminders (e.g., people, places, conversations, activities, objects, or situations).
• Experience at least two of the following negative changes in mood or thoughts that began or worsened after the traumatic event:
  • Unable to recall key features of the traumatic event.
  • Persistent (usually distorted) negative beliefs and expectations about themselves or the world.
  • Persistent distorted blame of self or others for causing the traumatic event or for resulting consequences.
  • Persistent negative emotional state (e.g. fear, horror, anger, guilt or shame).
  • Markedly diminished interest in (pre-traumatic) significant activities.
  • Feelings of detachment or estrangement from others.
  • Persistent inability to experience positive emotions (happiness, satisfaction, or love).
• At least two of the following trauma-related alterations in arousal and reactivity that began or worsened after the traumatic event:
  • Irritable or aggressive behaviour (with little or no provocation).
  • Self-destructive or reckless behaviour.
  • Hypervigilance.
  • Exaggerated startle response.
  • Problems in concentration.
  • Sleep disturbance.
• The above symptoms should:
  • Cause significant distress or functional impairment (e.g. social, occupational).
  • Not be caused by medication, substance use, or other illness.
  • Be persistent for more than one month.
• PTSD with delayed expression is diagnosed when the full diagnostic criteria are not met until at least 6 months after the traumatic event (although the onset of some symptoms may be immediate).
• PTSD with dissociative symptoms is diagnosed if they meet the DSM 5 criteria and they experience high levels of either of the following in reaction to trauma-related stimuli:
  • Depersonalization: experience of being an outside observer of or detached from oneself (e.g., feeling as if "this is not happening to me" or one were in a dream).
  • Derealization: experience of unreality, distance, or distortion (e.g. "things are not real").

To meet the ICD-11 criteria, the person must:

• Have been exposed to a traumatic event or situation (either short or long-lasting) of exceptionally threatening or catastrophic nature, which would be likely to cause pervasive distress in almost anyone.
• Experience persistent remembering or 'reliving' the stressor in intrusive flashbacks, vivid memories, or recurring dreams; or experience distress when exposed to circumstances resembling or associated with the stressor.
• Exhibit an actual or preferred avoidance of circumstances resembling or associated with the stressor, which was not present before exposure to the stressor.
• Experience either of the following:
  • Inability to recall, either partially or completely, some important aspects of the period of exposure to the stressor.
  • Persistent symptoms of increased psychological sensitivity and arousal (not present before exposure to the stressor) are shown by any two of the following: difficulty in falling or staying asleep, irritability or outbursts of anger, difficulty in concentrating, hypervigilance, and exaggerated startle response.
• Symptoms should manifest within 6 months, although in some cases, there may be a delayed onset.

Basis for recommendation

The recommendations on the diagnosis of post-traumatic stress disorder (PTSD) are largely based on expert opinion in the National Institute of Health and Care Excellence (NICE) guideline Post-traumatic stress disorder [NICE, 2018], expert opinion in review articles A Review of PTSD and Current Treatment Strategies [Schrader, 2021], the British Medical Journal (BMJ) Best Practice guide Post-traumatic stress disorder [BMJ Best Practice, 2023] and Posttraumatic Stress Disorder[Mann, 2023].

PTSD symptoms in children

• The information on PTSD symptoms in children is based on expert opinion in the Royal College of Psychiatrists leaflet Post Traumatic Stress Disorder (PTSD) [RCPSYCH, 2021].

Screening questionnaires

• NICE suggests the use of 'a validated, brief screening instrument for PTSD' for people at high risk of PTSD including following a major disaster, and for some refugees and asylum seekers [NICE, 2018]. Previous expert reviewers of this CKS topic suggested that a PTSD screening questionnaire may also be helpful for general use in primary care.
• In the absence of any recommendations from NICE relating to specific PTSD screening tools, CKS has suggested the Trauma Screening Questionnaire (TSQ) as it is simple and quick to administer and score (10 yes or no answers), is easy to access online, and is free to download.
  • The TSQ was used in the 2007 Adult Psychiatric Morbidity Survey, and has been validated [Brewin, 2002; McManus, 2009]. Other screening questionnaires may also be used, but they may not be as easily accessible/suitable for primary care.
  • The Harvard Trauma Questionnaire and the Posttraumatic diagnostic scale were found to be the most popular and equally sensitive in a 2020 systematic review [Mughal, 2020].
  • Comprehensive details of PTSD screening questionnaires are provided in the BMJ Best Practice guideline post-traumatic stress disorder [BMJ Best Practice, 2023].

Diagnostic criteria 

• Details of the criteria used to confirm a diagnosis of PTSD were derived from the fifth edition of the American Psychiatric Association's Diagnostic and Statistical Manual of Mental Disorders (DSM 5) [APA, 2022]  and the International Classification of Diseases (ICD-11)[WHO, 2022]. 

How do I manage someone with post-traumatic stress disorder?

Note: The role of a general practitioner (GP) in the initial management of a person with symptoms of PTSD is to determine the need for emergency physical and mental health assessment and to coordinate care. Where a referral is being made to confirm a diagnosis of PTSD, it is likely that psychological therapy or drug treatment will be arranged directly by the specialist involved. However, whilst awaiting referral, the person should be assessed as described below. Where confirmation of the diagnosis has taken place in primary care, specialist referral is required for any further management. Once any interventions are established by a specialist, a GP may again become involved in a person’s care via a shared-care arrangement. If there is difficulty finding a specialist locally, the UK Psychological Trauma Society website lists trauma centres that provide a specialist mental health service with expertise in managing PTSD.

• For all people with symptoms of PTSD, ask about the effects on work or school, relationships, social life, and quality of life, and assess their degree of distress and functional impairment as mild, moderate, or severe:
  • Mild — distress caused by the symptoms is manageable, and the person's social and occupational functioning are not significantly impaired.
  • Moderate — distress and impact on functioning lie somewhere between mild and severe, and there is not considered to be a significant risk of suicide, harm to self, or harm to others. 
  • Severe — distress caused by the symptoms is felt to be unmanageable, and/or there is significant impairment in social and/or occupational functioning, and/or there is considered to be a significant risk of suicide, harm to self, or harm to others.
• Note: Clinically important symptoms of PTSD can be defined as those causing at least moderate functional impairment and/or those scoring above a clinical threshold on a validated scale (where this has been assessed). Where symptoms are deemed to be ‘moderate’, use clinical judgement to determine the need for intervention.
• Be aware that PTSD commonly co-exists with other mental health disorders, including depression, anxiety disorders, gambling-related harms, and alcohol or substance misuse. For more information on managing these conditions, please see the CKS topics on Depression, Generalized anxiety disorder, Insomnia,  Alcohol - problem drinking, and Opioid dependence.
• If the person is exhibiting severe distress and/or functional impairment, co-morbid depression or another mental health disorder, or there are other concerns, assess their risk of suicide and self-harm. For more information on assessing risk of suicide, see the section on 'assessing risk of suicide' in the CKS topic on Depression. 
• If the person is considered to be at high risk of suicide, refer urgently (same day) to the crisis resolution and home treatment team. For more information, see the section on 'managing risk of suicide' in the CKS topic on Depression. For information on what action to take if admission is thought to be necessary but the person refuses, see the 'compulsory admission' section in the CKS topic on Depression. Follow local policy when referring to specialist mental health services.
  • Also assess for safeguarding concerns for children or vulnerable adults (if applicable). Follow local safeguarding procedures if appropriate.
• For people not requiring same-day referral:
  • If the person has co-morbid depression, be aware that treating the PTSD first is often associated with an improvement in depression. However, if depression is severe enough to make psychological treatment of PTSD difficult, the depression should be treated first. For more information, see the CKS topic on Depression.
  • If there are concerns relating to the person's physical health, arrange or carry out an emergency physical health assessment using clinical judgement to determine the appropriate investigations.
  • Assess the person's social needs (including asking about employment or accommodation problems). Make any appropriate social care referrals.
• For all people with subclinical PTSD symptoms, consider active monitoring and arrange regular follow-up (within one month if the person has reported symptoms in the first month following the trauma).
• For people with clinically important PTSD symptoms where the traumatic event occurred within the last month:
  • For adults, arrange specialist referral for psychological therapy or drug treatment.
  • For children and young adults aged 18 years and under, use clinical judgement to determine whether active monitoring or specialist referral are required. Seek specialist advice where there is any doubt.
• For all people with clinically important PTSD symptoms that have continued for more than one month after a traumatic event, offer referral to a specialist mental health service for psychological therapy or drug treatment.
  • Armed forces veterans with service-related post-traumatic stress disorder can be referred to secondary care more rapidly than civilians under the veterans' priority scheme.
  • Availability and arrangements for accessing trauma-focused psychological treatments may vary locally, and there may sometimes be a significant delay before treatment begins.
• Consider treatment with an antidepressant such as venlafaxine or an SSRI in an adult if:
  • The person expresses a preference for drug treatment.
  • The person declines referral for psychological therapies.
  • Referral is significantly delayed.
    • Discuss the potential for adverse effects and withdrawal symptoms before drug treatment is initiated. Explain that adverse effects early in treatment with an SSRI or SNRI may include increased anxiety, agitation, and sleeping problems.
    • Review the effectiveness and adverse effects of the drug every 2 to 4 weeks during the first 3 months of treatment and every 3 months thereafter. Dose adjustment may be required. Bear in mind that the full efficacy of the drug may take several weeks to be realised.
    • Be aware that in a minority of people under 30 years of age, SSRIs and SNRIs are associated with an increased risk of suicidal thinking and self-harm. Anyone in this age group receiving an SSRI or SNRI should therefore be seen within 1 week of first prescribing, and the risk of suicide and self-harm should be monitored weekly for the first month. 
    • For more information on prescribing venlafaxine or an SSRI, see the section on prescribing information.
  • Note: Do not offer drug treatments for PTSD in children and young people aged under 18 years.
• For people with problems sleeping:
  • Advise on sleep hygiene and consider prescribing a hypnotic for short-term use. For more information, see the CKS topic on Insomnia.
• Enquire about any other family members who have been affected by the trauma to determine if they require assessment and treatment.
• Provide information and support to people with PTSD (and their family members or carers as appropriate) covering:
  • Common reactions to traumatic events, including the symptoms of PTSD and its course.
  • Reassurance that PTSD is a treatable condition.
  • Treatment options, including information about which treatments may be offered by a specialist — for more information, see the section on psychological therapies and drug treatments.
  • Where their care will take place.
  • Information about support groups, and written patient information, such as leaflets from the Mental health Foundation, Mind, Rethink, and the Royal College of Psychiatrists.
• Arrange follow-up for monitoring of the person's symptoms, functioning, and response to treatment at intervals determined by clinical judgement and as part of any shared care arrangement (if applicable). Where management is being shared between primary and secondary care, there should be a written agreement confirming which party is responsible for monitoring. Any such decisions should also involve the person and, if appropriate, their family or carers. 

Choice of SSRI

Note: Only paroxetine and sertraline are licensed in the UK for the treatment of post-traumatic stress disorder (PTSD). Use of other SSRIs for this indication, therefore, constitutes off-licence use.

• NICE states that there is no evidence for significant differential efficacy of specific SSRIs in the treatment of PTSD, so prescribers can decide which SSRI to use. However, they noted that of the two drugs licensed for this indication, paroxetine is more likely to be associated with discontinuation symptoms [NICE, 2018].
• The NICE guideline Depression in adults recommends that the choice of drug treatment can be based on factors including the person's preference, the drug's adverse effect profile, the risk of toxicity in overdose, the possibility of interaction with any other drug treatments, and any previous response/tolerance (or otherwise) to treatment (if applicable) [NICE, 2016].

Dosage

Note: Only paroxetine and sertraline are licensed in the UK for the treatment of post-traumatic stress disorder (PTSD). Use of other SSRIs for this indication therefore constitutes off-licence use.

• For citalopram: prescribe a starting dose of 10 mg daily, increased gradually in steps of 10 mg if required, usual dose 20–30 mg daily; maximum 40 mg per day.
  • Note: as citalopram is not licensed for use in PTSD, the recommended doses are licensed doses for panic disorder.
• For escitalopram: prescribe a starting dose of 10 mg once daily. Dose may be increased to a maximum of 20 mg a day (except in elderly people and those with reduced hepatic function).
  • Note: as escitalopram is not licensed for use in PTSD, the recommended doses are licensed doses for generalized anxiety disorder.
• For fluoxetine: prescribe a starting dose of 20 mg daily. Increase gradually to a maximum of 60 mg daily if required. Consider the long half-life of fluoxetine when adjusting dosage.
  • Note: as fluoxetine is not licensed for use in PTSD, the recommended doses are licensed doses for major depression and obsessive-compulsive disorder.
• For paroxetine: prescribe a starting dose of 20 mg a day to be taken in the morning. The maximum licensed dose for the treatment of PTSD is 50 mg/day in adults, with 40 mg/day recommended in the elderly.
• For sertraline: prescribe a starting dose of 25 mg daily for one week, then increase to 50 mg daily. Dose may be further increased if required/tolerated in steps of 50 mg at intervals of at least one week. The maximum licensed dose for the treatment of PTSD is 200 mg a day.

[EMC, 2022; BNF, 2023; EMC, 2023a; EMC, 2023b; EMC, 2023c; EMC, 2023d]

Contraindications and cautions

• Do not prescribe SSRIs to people:
  • In a manic phase of bipolar disorder.
  • Taking monoamine oxidase inhibitors (MAOIs) or who have recently discontinued a MAOI.
  • Taking pimozide.
  • With uncontrolled epilepsy or new onset seizures.
• Do not prescribe citalopram/escitalopram to people with:
  • Known QT interval prolongation or taking medication known to prolong the QT interval.
  • Congenital long QT syndrome.
• Do not prescribe fluoxetine to people taking metoprolol to treat heart failure.
• Prescribe SSRIs with caution to people with:
  • Cardiac disease
  • Epilepsy (discontinue if convulsions develop).
  • A history of bleeding disorders, especially gastrointestinal bleeding.
    • Older people or people taking drugs that can damage the gastrointestinal mucosa or interfere with clotting (for example, NSAIDS or aspirin) may also be at risk. Consider prescribing a gastroprotective drug in these circumstances.
  • Diabetes mellitus.
  • History of mania.
  • Susceptibility to angle-closure glaucoma.
  • Also, prescribe with caution to those undergoing concurrent electroconvulsive therapy.
• Prescribe citalopram/escitalopram with caution to people at a higher risk than average of developing Torsade de Pointes. This includes people with:
  • Congestive heart failure.
  • Recent myocardial infarction.
  • Bradyarrhythmias.
  • Concomitant illness or medication causing a predisposition to hypokalemia or hypomagnesaemia.
• Prescribe fluoxetine and sertraline with caution to people with risk factors for QTc prolongation.

[BNF, 2023; EMC, 2022; EMC, 2023a; EMC, 2023b; EMC, 2023c; EMC, 2023d]

Adverse effects

• The most common adverse effects associated with use of an SSRI are:
  • Gastrointestinal effects — these are dose-related and include nausea, vomiting, abdominal pain, dyspepsia, constipation, and diarrhoea.
  • Central nervous system effects — including dizziness, agitation, anxiety, insomnia, headache, and tremor.
  • Drowsiness — may impair performance of skilled tasks such as driving and operating machinery.
    • Advise the person that it is illegal in England and Wales to drive while taking a prescribed drug if it impairs driving [DVLA, 2015].
  • Sexual dysfunction — this is also a common symptom of generalized anxiety disorder.
• Other adverse effects include:
  • Increased risk of bleeding, especially in older people or people taking other drugs that can damage the gastrointestinal mucosa or interfere with clotting (for example, nonsteroidal anti-inflammatory drugs [NSAIDs]).
  • Leukopenia — has been reported as an uncommon adverse drug reaction in people prescribed paroxetine. 
  • Increased risk of fractures — the Medicines and Healthcare products Regulatory Agency (MHRA) has advised that SSRIs are associated with a small increased risk of fractures; however, the mechanism leading to this is unclear and may be multifactorial. 
  • Hyponatraemia — risk factors for developing hyponatraemia include a history of hyponatraemia, extreme old age (greater than 80 years of age), female sex, low body weight, diuretics, diabetes mellitus, hypertension, reduced renal function, volume depletion, and chronic obstructive pulmonary disease.
    • Monitor the person for signs and symptoms of hyponatraemia (such as dizziness, lethargy, nausea, confusion, cramps, and seizures).
  • Increased suicide risk — this is most likely in younger people (less than 30 years of age) when starting an SSRI.
    • Monitor people carefully during the first few weeks of SSRI treatment; in particular, be alert for signs of suicidal ideation, akathisia, and increased anxiety and agitation.
  • Discontinuation symptoms (such as dizziness, sensory disturbances [including paraesthesia], sleep disturbances [including insomnia and intense dreams], agitation or anxiety, nausea and/or vomiting, tremors, and headache).
    • The risk of discontinuation symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction. 
    • Generally, these symptoms are mild to moderate; however, in some people, they may be severe.
    • They usually occur within the first few days of discontinuing treatment.
    • Generally, these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals, they may be prolonged (2 – 3 months or more).
    • It is therefore advised that an SSRI should be gradually tapered over a period of several weeks or months, according to the person's needs.
    • Paroxetine is associated with a higher incidence of discontinuation symptoms compared with other selective serotonin reuptake inhibitors.
  • For citalopram and escitalopram, QT prolongation and/or ventricular arrhythmias, especially in women, people with hypokalaemia, or people with pre-existing QT prolongation or other cardiac disease.
  • Hyperprolactinaemia is an effect of unknown frequency with Citalopram use.

[EMC, 2022; BNF, 2023; EMC, 2023a; EMC, 2023b; EMC, 2023c; EMC, 2023d; EMC, 2023e; EMC, 2024a]

Drug interactions

• Key drug interactions with SSRIs as a class include:
• 5HT₃- receptor agonists/antagonists (such as dapoxetine, duloxetine, fenfluramine, fentanyl, triptans, St John's Wort, tramadol, tryptophan) — possible increased serotonergic effects including serotonin syndrome.
  • The manufacturer of dapoxetine advises SSRIs should not be started until 1 week after stopping dapoxetine and to avoid dapoxetine for 2 weeks after stopping SSRIs.
• Antiepileptics — SSRIs antagonise the anticonvulsant effect of antiepileptics (convulsive threshold lowered).
• Aspirin, dabigatran, and NSAIDs — increased risk of bleeding.
• Coumarins — SSRIs possibly enhance the anticoagulant effect of coumarins.
  • Consider frequent monitoring of the INR. Any change in the person's clinical condition, particularly liver disease, intercurrent illness, or drug administration, necessitates more frequent monitoring of the INR. 
• Cyproheptadine — antidepressant effect of SSRIs possibly antagonised by cyproheptadine.
• Drugs that can cause hyponatremia (e.g. diuretics, desmopressin, carbamazepine and oxcarbazepine) — exercise caution when prescribing concurrently as the combination may further increase the risk.
• Lithium — increased risk of CNS effects when SSRIs are given with lithium (lithium toxicity reported).
  • Advise the person to be alert for symptoms such as decreased appetite, diarrhoea, vomiting, ataxia, nystagmus, dysarthria, confusion, and seizures. Consider frequent monitoring of lithium levels.
• MAOIs — CNS effects of SSRIs increased by MAOIs (risk of serious toxicity).
• Methylphenidate — metabolism of SSRIs possibly inhibited.
• Pimozide — SSRIs possibly increase plasma concentration of pimozide (increased risk of ventricular arrhythmias—avoid concomitant use).
• Rasagiline — increased risk of CNS toxicity.
• Ritonavir — plasma concentration of SSRIs possibly increased.
• Tricyclic antidepressants — SSRIs increase the plasma concentration of some tricyclics
• Vortioxetine — possible increased risk of convulsions.

Key drug interactions with specific SSRIs include:

• Citalopram, escitalopram: Drugs that prolong the QT interval (including some antiarrhythmics (such as amiodarone), antipsychotics (such as haloperidol), antihistamines (such as mizolastine), and antiretrovirals (such as ritonavir, saquinavir, and lopinavir). Do not prescribe concurrently due to the potential for additive effects. Fluconazole and citalopram-  the manufacturer advises that concomitant use should only be undertaken when necessary and with caution. 
• Fluoxetine:
  • Metoprolol used for heart failure — do not prescribe concurrently. 
  • Tamoxifen — avoid concurrent use. Fluoxetine is a potent inhibitor of the liver enzyme CYP2D6 and may reduce the plasma concentration of tamoxifen, leading to reduced efficacy.
  • Mequizatine — do not prescribe concurrently. The risk of mequitazine adverse events (such as QT prolongation) may be increased because of inhibition of its metabolism by fluoxetine.
  • Drugs that prolong the QT interval — prescribe with caution as an additive effect cannot be excluded.
  • Phenytoin — prescribe concurrently with caution. Changes in phenytoin blood levels and, in some cases, toxicity have been observed. Consider using conservative titration schedules and monitoring clinical status.
• Paroxetine:
  • Thioridazine — do not prescribe concurrently as this can lead to elevated plasma levels of thioridazine, increasing the risk of QTc interval prolongation with associated serious ventricular arrhythmia such as torsades de pointes and sudden death.
  • Tamoxifen — avoid concurrent use. Paroxetine is a potent inhibitor of the liver enzyme CYP2D6 and may reduce the plasma concentration of tamoxifen, leading to reduced efficacy.
  • Aripiprazole, clozapine, darifenacin, galantamine, methadone, metoprolol, pitolisant, procyclidine, ranolazine, risperidone and vortioxetine — exercise caution as paroxetine may increase the plasma concentrations of these drugs.
  • Atomoxetine, perphenazine, and propafenone — exercise caution as paroxetine may inhibit the metabolism of these drugs.
  • Asenapine, darunavir, fosphenytoin, phenobarbital, phenytoin, primidone, ritonavir, and terbinafine — exercise caution as plasma concentration of paroxetine may be altered by these drugs.
• Sertraline: Drugs that prolong the QT interval — exercise caution when using concurrently as the risk of QTc prolongation and/or ventricular arrhythmias may be increased.

[EMC, 2022; BNF, 2023; EMC, 2023a; EMC, 2023b; EMC, 2023c; EMC, 2023d]

Dosage

Note: venlafaxine is not licensed for the treatment of post-traumatic stress disorder, and use for this indication, therefore, constitutes an off-licence use.

• Modified-release products are recommended for anxiety disorders.
• The recommended starting dose is 75 mg once daily, increased if necessary up to 225 mg once daily. Dose to be increased at intervals of at least 2 weeks, maximum 225 mg per day.

[BNF, 2023; EMC, 2023f]

Contraindications and cautions

• Do not prescribe venlafaxine to people:
  • With uncontrolled hypertension.
  • Taking a monoamine oxidase inhibitor (MAOI), or who have recently discontinued an MAOI.
  • With conditions associated with high risk of cardiac arrhythmia.
• Prescribe venlafaxine with caution to people with:
  • Bleeding disorders.
    • Older people or people taking drugs that can damage the gastrointestinal mucosa or interfere with clotting (for example, NSAIDS or aspirin) may also be at risk. Consider prescribing a gastroprotective drug in these circumstances.
  • Cardiac disease.
  • Diabetes.
  • A recent history of myocardial infarction.
  • A history of mania.
  • Narrow-angle glaucoma or increased intraocular pressure.
  • History of seizures.
  • Hypertension.
    • For venlafaxine, all people should therefore be screened for high blood pressure, and preexisting hypertension should be controlled before initiation of treatment. Blood pressure should be reviewed periodically, after initiation of treatment and after dose increases.
    • With use of venlafaxine, caution should be exercised in people whose underlying conditions might be compromised by increases in blood pressure, such as those with impaired cardiac function.

[BNF, 2023; EMC, 2023f]

Adverse effects

• The most common adverse effects of venlafaxine include nausea, insomnia, dry mouth, somnolence, dizziness, constipation, sweating, nervousness, and asthenia. 
• Other adverse effects include:
  • Drowsiness — may impair performance of skilled tasks such as driving and operating machinery.
    • Advise the person that it is illegal in England and Wales to drive while taking a prescribed drug if it impairs driving [DVLA, 2015] .
  • Hypertension. 
    • Venlafaxine is commonly associated with dose-related increases in blood pressure. Severely elevated blood pressure requiring immediate treatment has been reported in post-marketing experience. 
  • Sexual dysfunction.
  • Increased risk of bleeding, especially in older people or people taking other drugs that can damage the gastrointestinal mucosa or interfere with clotting (for example, nonsteroidal anti-inflammatory drugs [NSAIDs]).
  • Hyponatraemia — risk factors for developing hyponatraemia include a history of hyponatraemia, extreme old age (greater than 80 years of age), female sex, low body weight, diuretics, diabetes mellitus, hypertension, reduced renal function, volume depletion, and chronic obstructive pulmonary disease.
    • Monitor the person for signs and symptoms of hyponatraemia (such as dizziness, lethargy, nausea, confusion, cramps, and seizures).
  • Increased suicide risk — this is most likely in younger people (less than 30 years of age) when starting an SNRI.
    • Monitor people carefully during the first few weeks of SNRI treatment; in particular, be alert for signs of suicidal ideation, akathisia, and increased anxiety and agitation. 
  • Discontinuation symptoms (such as dizziness, sensory disturbances [including paraesthesia], sleep disturbances [including insomnia and intense dreams], agitation or anxiety, nausea and/or vomiting, tremors, and headache).
    • The risk of discontinuation symptoms may be dependent on several factors, including the duration and dose of therapy and the rate of dose reduction. 
    • Generally, these symptoms are mild to moderate; however, in some people, they may be severe.
    • They usually occur within the first few days of discontinuing treatment.
    • Generally, these symptoms are self-limiting and usually resolve within 2 weeks, though in some individuals, they may be prolonged (2 – 3 months or more).
    • It is therefore advised that an SNRI should be gradually tapered over a period of several weeks or months, according to the person's needs.
  • Altered glycaemic control in people with diabetes mellitus. Monitor diabetic control in people taking venlafaxine modified-release as the doses of insulin or oral anti-diabetic drugs may need to be altered.
  • Cardiac adverse effects:
    • Fatal cardiac arrhythmias have been reported, especially in overdose. The balance of risks and benefits should therefore be considered before prescribing venlafaxine to people at high risk of serious cardiac arrhythmia.
    • Takotsubo or stress cardiomyopathy. Venlafaxine has also been associated with takotsubo or stress cardiomyopathy.
  • Overdose of venlafaxine can cause hypoglycaemia.

[BNF, 2023; EMC, 2023f; EMC, 2024b]

Drug interactions

• Key drug interactions with SNRIs as a class include:
  • Monoamine Oxidase Inhibitors (MAOIs) — CNS effects of SSRIs increased by MAOIs (risk of serious toxicity).
  • 5HT1- receptor antagonists, dapoxetine, SSRIs, St John's Wort, tramadol — risk of increased serotonergic effects.
    • The manufacturer of dapoxetine advises SNRIs should not be started until 1 week after stopping dapoxetine, and to avoid dapoxetine for 2 weeks after stopping SNRIs.
  • Aspirin and NSAIDs — increased risk of bleeding.
  • Warfarin — increases in INR values have been reported when SNRIs were co-administered with warfarin.
    • Consider frequent monitoring of the INR. 
• In addition, for venlafaxine:
  • Amiodarone, erythromycin, moxifloxacin, sotalol — avoid concomitant use due to risk of ventricular arrhythmias. 
    • Note: Amiodarone has a long half-life; there is a potential for drug interactions to occur for several weeks (or even months) after treatment has been stopped.
  • Bupropion — plasma concentration of venlafaxine increased by bupropion.
  • Entacapone — caution with venlafaxine advised by the manufacturer of entacapone.
  • Haloperidol — venlafaxine increases plasma concentration of haloperidol.
  • Lithium, mirtazapine — possible increased serotonergic effects.
  • Selegiline — increased risk of hypertension and CNS excitation. Selegiline should not be started until 1 week after stopping venlafaxine, avoid venlafaxine for 2 weeks after stopping selegiline.

[BNF, 2023; EMC, 2023f; Preston, 2023]