Contributed by Dr Nienke Verkuijl, specialist trainee year 2 psychiatry, and Dr Kathleen Kelly, specialist registrar in general adult psychiatry, Warneford Hospital, Oxford.

Section 1: Aetiology and epidemiology
In psychosis there is a loss of contact with reality as a result of delusional beliefs and/or hallucinations.

There are many causes of psychosis: illicit drug use, for example cocaine and amphetamines giving rise to delusional beliefs; prescribed drug use, for example prednisolone-induced mania and isoniazid-induced psychosis; alcohol withdrawal giving vivid visual hallucinations; dementia giving rise to delusions and hallucinations; endocrine disease, such as thyrotoxicosis and mania; and mental illness, for example schizophrenia and mood disorders with psychotic features.

For the purpose of this review we will concentrate on mental illness and psychosis.

Schizophrenia is strongly affected by many different genes that interact with each other and the environment.

Children who go on to develop schizophrenia may have lower IQ scores and developmental delay. Multiple neurochemical changes are associated with schizophrenia (for example dopaminergic and serotinergic hyperacitivity, glutaminergic hypoactivity).

Psychotic depression
The heritability of depression is moderate and a large effect is attributed to the environment.

An altered function of neurotransmitters (for example serotonin and dopamine) and hypercortisolism (dysregulation hypothalamo-pituitary-adrenal axis) play a role in depression.

Bipolar affective disorder
Bipolar affective disorder (BPAD) is a highly heritable disease. Relatives have an increased risk of developing both depression and BPAD (see box).

Some of the genes implicated fpr BPAD are the same as for schizophrenia. Several aetiological theories have been posed, such as abnormal apoptosis in the hippocampus and frontal cortex. The same neurotransmitters as for depression seem to be effected.

Life events have an impact on the first episode but have increasingly less impact on subsequent episodes.

Environmental risk factors for schizophrenia

  • Maternal drug and alcohol use, influenza and malnutrition.
  • Winter birth.
  • Obstetric complications (hypoxia, premature birth, low birthweight).
  • Urban birth (three times higher risk in a large town compared to a rural village).
  • Belonging to particular migrant groups (African-Caribbeans in the UK have a 6 to 8-fold increased risk).
  • Lower social class.
  • Life events.
  • Smoking cannabis (2 to 4-fold increase).
Aetiology and epidemiology of psychotic disorders
  Schizophrenia Bipolar disorder
Lifetime risk
0.8% 0.8% 0.6%
Mean age of onset Male 23 years, female 26 years Early 20s Late 20s
Sex ratio (male:female) 1:1 1:1 1:2
Risk in identical twins 46% 33-90% 40-50%
Risk in first-degree relative 10% 10% (15% risk of depression) 15%

Section 2: Making the diagnosis
When a patient presents with psychotic symptoms, an organic cause needs to be ruled out. This is done with the help of a (third party) history, physical examinations, and blood and urinary investigations.

Psychotic patients rarely present in a straightforward manner, due to anxiety and because they do not experience symptoms as abnormal. An odd affect, strange behaviour, social isolation, bizarre medical conditions and poor self-care should all lead to a suspicion of psychotic illness.

For a diagnosis, symptoms have to be present for at least a month and there should be social and occupational dysfunction over a period of six months.

Psychotic depression
Usually patients show a pervasive depressed mood, often in combination with psychomotor disturbance and delusions.

Bipolar affective disorder
Typically, patients with BPAD have long periods of severe depression alternating with an excessively elated mood (mania).

To diagnose mania the symptoms should be present for a week and have resulted in significant impairment to social and occupational functioning.

Characteristic features of (psychotic) depression

  • Depressed mood (every day, no change with circumstances, worse in the morning).
  • Anhedonia.
  • Weight loss.
  • Decreased sleep.
  • Psychomotor agitation or retardation.
  • Reduced libido.
  • Loss of energy.
  • Reduced concentration.
  • Increased guilt, feelings of worthlessness.
  • Thoughts of suicide.

Psychotic features

  • Delusions (poverty, guilt over presumed misdeeds, illness).
  • Hallucinations: Auditory, eg derogatory voices, Olfactory eg smells of decomposing bodies, Visual: eg scenes of torture.

Characteristic features of mania

  • Elevated mood.
  • Increased energy (pressure of speech, racing thoughts, reduced sleep).
  • Reduced attention.
  • Increased self-esteem (grandiosity).
  • Loss of social inhibitions (reckless, out-of-character behaviour, increased spending, inappropriate sexual encounters).

Psychotic symptoms

  • Delusions.
  • Hallucinations.
  • Inability to communicate (extreme excitement, excessive motor activity, flight of ideas).
  • Violent behaviour (irritability and aggression).
  • Well-formed persecutory delusions (highly suspicious).
  • Catatonia ('manic stupor').
  • Loss of insight.

Characteristic features of schizophrenia

  • Delusions (bizarre).
  • Hallucinations (mostly auditory: running commentary or voices talking).
  • Disorganised speech.
  • Grossly disorganised or catatonic behaviour.
  • Flattened affect, apathy.

Section 3: Management

The choice of antipsychotic is made jointly by the prescriber and the patient; if this is not possible an atypical antipsychotic should be started.

Recent randomised trials have shown that, with the exception of clozapine, newer atypical antipsychotics are no more effective than the older typical antipsychotics. Therefore the side-effect profile of the particular drug should determine the choice of antipsychotic.

Side-effects of the typical antipsychotics include weight gain and diabetes, while atypical antipsychotics are associated with extrapyramidal side-effects.

Once recovered from their acute psychosis, patients should remain on antipsychotics for one to two years.

Cognitive behavioural therapy (CBT) has been shown to reduce persistent symptoms and improve insight. Family therapy improves patient compliance, and communication between family members and decreases relapse rates, admission rates and the burden on carers.

Psychotic depression
In treatment-resistant depression, NICE advises to combine antidepressant medication with CBT, lithium or a second antidepressant.

In the case of psychotic depression, an antipsychotic is added to the current regimen or ECT is given.

With regards to suicide risk, SSRIs are safer than tricyclic antidepressants (TCAs) in overdose.

Antidepressants need to be continued for two years after two or more episodes of depression or after one serious episode.

(Mindfulness based) CBT should offered in recurrent depression to prevent relapses.

Bipolar disorder
For the acute treatment of mania with psychotic features, antidepressant medications need to be withdrawn and an atypical antipsychotic commenced.

In psychotic depression in BPAD, short-term SSRI antidepressants are augmented with an antipsychotic such as quetiapine, olanzapine or risperidone. TCAs are not recommended because of the risk of switching to mania.

Long-term treatment of bipolar disorder is recommended after one manic episode in which there was significant risk or harm. Lithium, olanzapine or sodium valproate are then considered. The choice of medication is jointly made with the patient, based on presentation (lithium is more effective in mania), side-effect profile, gender and age (sodium valproate should not be prescribed to women of child-bearing age).

A key part of relapse prevention is helping the patient identify the early manifestations of the illness and then providing rapid access to appropriate care.

Psychological treatments focus on self-monitoring for early warning signs, provide education about the illness and promote regular patterns of eating, sleeping and activity.

Section 4: Prognosis

After a first psychotic episode the majority of patients will have few relapses and function well. About 20 per cent never experience a further episode, while in another 20 per cent the illness will follow a more chronic course with multiple admissions and only brief periods of normal functioning.

Poor prognostic factors are a slow onset, social withdrawal, self-neglect, emotional blunting and long duration of untreated psychosis. At present, in the UK it takes about two years before a patient with full symptoms of psychosis is commenced on antipsychotic medication. To reduce the length of untreated psychosis and to try and improve prognosis early intervention teams have been introduced around the country.

Good prognostic factors are: acute onset, obvious psychosocial precipitants and good premorbid functioning.

The lifetime risk of suicide is around 5 per cent in schizophrenia, the risk being highest in the first five years after onset of the illness.

Psychotic depression
Most patients with psychotic depression will suffer multiple episodes and 10 per cent never fully recover. About 15 per cent of patients with depression that warrants hospital admission will commit suicide.

Other factors that increase mortality include substance misuse, accidents and cardiovascular, respiratory and thyroid disease.

Bipolar affective disorder
BPAD runs a relapsing course in 90 per cent of patients and is an illness with a high morbidity and mortality. Severe mania can lead to loss of employment, relationships and accommodation.

Lithium reduces the risk of manic relapse by 30 per cent.

About 15 per cent of patients with severe illness will commit suicide.

Poor prognostic factors are poor employment history, increased suicidal thoughts, psychotic symptoms, alcohol abuse, depression, male sex, co-morbid physical problems and non-compliance with treatment.

Good prognostic factors are short periods of mania, later age of onset and good treatment response.

Monitoring of physical health in psychosis

Patients with schizophrenia, BPAD and depression have an increased risk of developing cardiovascular disease.

This risk is increased further with the use of medication. Regular health checks should therefore be provided in primary care.

Side-effects of medication

  • Extrapyramidal side-effects/akathisia.
  • Weight gain.
  • Diabetes.
  • Sexual dysfunction.
  • LFTs, FBC.


  • Serotonin syndrome: tachycardia, shivering, sweating, tremor, hyperreflexia, hyperthermia and hypertension.


  • Lithium level (weekly for 4 weeks, then 3- to 6-monthly)
  • TFTs and U&Es (baseline, then 6-monthly).
  • Weight gain.

Sodium valproate

  • LFTs and FBC (baseline, then 6-monthly).
  • Weight gain.




  • Harrison P, Geddes J, Sharpe M. Lecture Notes Psychiatry. 9th Edition. Oxford: Blackwell Publishing, 2005.
  • Palmer B, Pankratz V, Bostwick J, The lifetime risk of suicide in schizophrenia: a reexamination. Arch Gen Psychiatry 2005; 62: 247-53.
  • Picchioni M, Murray R. Clinical Review: Schizophrenia. BMJ 2007; 335: 91-5.
  • Semple D, Smythe R, Burns J, Darjee R, McIntosh A. Oxford Handbook of Psychiatry. Oxford: Oxford University Press, 2005.
  • Taylor D, Paton C, Kerwin R. The Maudsley Prescribing Guidelines (9th edition). London: Informa Healthcare, 2007.

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