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Watching for red flags in psychosis

By being alert for the prodromal phase in psychosis, pharmacists can help patients receive the help and support they need. So what are the signs to look out for?

Psychosis, where people “lose some contact with reality”1 is “relatively common”, according to NICE.2 Some people with psychosis hold unusual and false beliefs, such as that they alone know God’s absolute, specific truth. They may experience unusual thoughts and altered perceptions. 

The psychosis can range from specific, isolated eccentricities to disorders that potentially devastate every aspect of life. Importantly, psychotic episodes can occur independently of disorders such as schizophrenia.3 “There are also many people with psychosis who live productive lives and whose symptoms are well controlled,” says Dr Jon Van Niekerk, a fellow of the Royal College of Psychiatrists and group medical director at Cygnet Health Care.

People with psychosis experience ‘positive’ symptoms, such as hallucinations and delusions, and ‘negative’ symptoms, including apathy, social withdrawal and impaired emotions.4 Many people with psychosis also report cognitive problems with, for instance, working memory and attention.4 About 80-90 per cent of people show a prodromal phase before full-blown psychotic episodes4, so pharmacists should watch for indications that a person should speak to their GP or community psychiatric team. It is also important to be aware of some triggers for psychosis, including recreational stimulants and several common medicines.5

Psychotic episodes are relatively common. A meta-analysis of 31,261 adults from 18 countries reported that 6.6 per cent of women and 5.0 per cent of men experienced at least one psychotic episode.6 Most of these people had one (32.2 per cent) or between two and five (31.8 per cent) psychotic episodes. In the UK, about 0.7 per cent of people develop schizophrenia at some time.2

“The prevalence of psychosis in the UK has been stable for a long time,” says Van Niekerk. However, the prevalence of people who exper-ience a single psychotic episode varies over time.

Psychosis triggers

In predisposed people, factors that can trigger psychosis include: chronic stress; racial discrimination; socio-economic problems (e.g. access to food, money and housing); high air pollution; drug dependence; bullying, neglect and physical violence.3,5,7-9 For example, sexual assault doubled the risk of hallucinations, delusional beliefs and raised the risk of psychotic disorders more than five-fold.7 

“People from certain groups might not present with psychosis and access services as early as others, as is the case with many other mental disorders. For instance, people from some ethnic minorities are more likely to present in crisis and more likely to be sectioned than those from a white background,” Van Niekerk says. 

“High-risk Black and ethnic minority people are less likely to access services and misdiagnosis is more common than in white people. Black people, particularly men, are especially likely to encounter some risk factors for psychosis. So it is imperative that clinicians are culturally competent and ensure they are sensitive to differences when providing a differential diagnosis.”

In addition, common medicines, including antibiotics, antihistamines, antimalarials and corticosteroids, can trigger psychosis.5 For instance, between 1.1 and 2.5 per cent of children and adolescents who take methylphenidate for attention deficit hyperactivity disorder (ADHD) develop psychosis.10 

People with Parkinson’s disease who take levodopa can experience psychosis, such as: complex, well-formed hallucinations of people, especially children, or animals; a vivid impression that a non-existent person is nearby; or hallucinate a glimpse of a person or animal passing through their peripheral vision.11

“Psychosis isn’t just a dopaminergic condition: the interplay of a lot of neurotransmitters seems to be involved”

Certain recreational drugs, especially amphetamines and other stimulants, and cannabis high in tetrahydrocannabinol [skunk], can increase the risk of psychosis or trigger an acute episode,” Van Niekerk comments. Other drugs to watch for include cocaine, ecstasy, ketamine, synthetic cathinones (‘bath salts’) and synthetic cannabinoids (spice).5,8,9 One individual who was using spice and developed psychosis “slashed himself to remove the ‘wires’ in his body”.8

There is, Van Niekerk argues, a need for more research into whether drug abuse causes psychosis. “Cannabidiol and other alkaloids have shown promise in reducing symptoms of psychosis, but these have not translated into clinically-validated antipsychotic medication,” he says. Nevertheless, chronic drug abuse may have a ‘kindling’ effect: in other words, rather than tolerance, repeated administration progressively increases psychosis risk. 

“People with a history of psychosis should avoid stimulants and skunk,” Van Niekerk comments. “When they stop these drugs, the occurrence of psychotic episodes usually reduces.”

These drugs actually offer insights into the neurochemistry underlying psychosis. Methylphenidate and levodopa are dopamine agonists. Tetrahydrocannabinol, methamphetamine, cocaine and levodopa can increase dopaminergic activity.5,9 “But it is clear that psychosis isn’t just a dopaminergic condition: the interplay of a lot of neurotransmitters seems to be involved,” Van Niekerk says. 

For example, about 3-7 per cent of patients with psychosis show autoantibodies to NMDA receptors, which bind glutamate. Many people who do not have psychosis also show auto-antibodies to NMDA receptors, so other factors, such as inflammation, probably contribute to this ‘autoimmune psychosis’.4

The sub-types of psychosis could differ in their neurochemistry. “Mood disorders, such as severe depression and bipolar disorder, can trigger acute psychosis,” Van Niekerk comments. People with schizoaffective disorder can show psychosis as well as mania or depression.5 People with psychotic depression tend to have delusions and hallucinations that are consistent with their mood disorder5, so insistent, vehement voices may reinforce their guilt and feelings of isolation and worthlessness.

What to watch for

During the prodromal phase, people experience similar, but milder, symptoms to full-blown psychosis including: social withdrawal; uncharacteristic and unusual behaviour; feeling sounds are louder and colours are more intense; disturbed communication and emotions; bizarre ideas; poor personal hygiene; and less interest in daily activities.2,4,5 Some people with sub-syndromal psychosis never experience a full episode but, without treatment, about 20 per cent develop full-blown psychosis within two years.4

So, what should pharmacists watch for?

The first signs of someone presenting with psychosis include poor attention and memory loss. “Their speech may be jumbled. They may suddenly jump between subjects, stop mid-sentence or repeat certain words,” Van Niekerk says. “Also, a person who shows a gradual deterioration in their appearance and self-care may be prone to psychosis.” Various mood changes, depression, irritability, anxiety, sleep disturbance and suicidal thoughts can present in the prodromal phase.12  

In the meta-analysis, hallucinations were more common than delusions.6 Psychotic hallucinations are usually auditory. “People hear voices, which can seem very real and very frightening. The voices seem to come from inside or just outside the head, which can seem very loud, even drowning out voices in the immediate surroundings,” Van Niekerk says. “The voices tell the person to do something. Often it is something neutral but the instruction can also be risky. The voices may keep up a running commentary on what the person is doing or be highly derogatory, which can be deeply distressing.” 

Auditory hallucinations can be difficult to treat. “Sometimes, we can’t get rid of the hallucinations but we can often reduce their impact. In addition to psychopharmaceuticals, cognitive behavioural therapy and ‘hearing voices’ groups can normalise the experience and offer coping strategies,” Van Niekerk says. 

Early detection offers the best chance of a good outcome. Dr Van Niekerk suggests watching for people who pause and seem to listen, who are very preoccupied or who begin answering back to unheard voices. “People with delusions may have unusual beliefs that aren’t shared by the people around them, such as that they are being spied on or have a special purpose,” he says. “They talk about and are increasingly preoccupied by the delusion. Over time, it can become fixed.”

Psychosis is terrifying for patients and their families. To make matters worse, during an episode the patient may lose insight: they may really believe their delusions or feel the hallucination is real. By watching for the prodrome, pharmacists can help people at risk receive the help and support they need.

Bill’s story...

Bill, a 57-year-old research physiologist, has lived with severe depression for almost 40 years, with persistent thoughts of suicide and self-harm, which he traces to severe bullying and distant, unaffectionate parents. He is taking a serotonin and noradrenaline reuptake inhibitor (SNRI), which eases but does not resolve the low mood and suicidal ideation. 

Since sixth form, several times a month Bill has experienced voices “at the back of his head” deriding him and calling his ideas and efforts futile, telling him that he’s a joke to the people around him. His drug treatment reduces the volume, but not the frequency, insistence or content.

About 15 years ago, Bill experienced a full-blown psychotic episode that lasted several weeks. Since then, he’s experienced intermittent episodes, such as believing that the walls are as malleable as plasticine, that the police and intelligence services are tracking him online, and that a cougar-sized cat was creeping past in the corner of his eye. Over the years, his scruffy appearance became more unkempt, despite occasional attempts to improve his sartorial image.

Recently, Bill endured chronic financial and work stress, which exacerbated his depression. After a major travel delay late at night due to a person under a train, Bill heard a loud voice telling him that he won’t get home, that he’d freeze on the streets and be savagely assaulted, so wouldn’t it be better for everyone if he also took his own life...

Suddenly, Bill felt he’d jumped several feet to the right and watched his physical body pace up and down. Bill doesn’t know how long the out-of-body experience lasted. He’s worried this could herald another full-blown psychotic attack but is concerned about a referral and the cognitive impact of neuroleptics. Three months later he still hasn’t told his GP.  


1. NHS – psychosis 

2. NICE. National Clinical Guideline 178 (full version)

3. Anglin DM. Annual Review of Clinical Psychology 2023; DOI:10.1146/annurev-clinpsy-080921-074730

4. Coutts F et al. Nature Reviews Neurology 2023; DOI:10.1038/s41582-023-00779-1

5. Griswold KS et al. American Family Physician 2015; 91:856-863

6. McGrath JJ et al. JAMA Psychiatry 2015; 72:697-705

7. Yates K et al. Schizophrenia Research 2022; 241:78-82

8. Slomski A. JAMA 2012; 308:2445-2447

9. Yeruva RR et al. Innovations in Clinical Neuroscience 2019; 16:31-32

10. Pasha K et al. Cureus 2023; 15:e34299

11. Beaulieu-Boire I et al. Movement Disorders 2015; 30:90-102

12. George M et al. Indian Journal of Psychiatry 2017; 59:505-509

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