Schizophrenia: clinical review

Incidence of psychosis and schizophrenia, recognition of signs and symptoms, the role of medication and CBT, plus positive outcomes to work towards.

Section 1: Epidemiology and aetiology

The terms psychosis and schizophrenia are used to describe a related group of psychotic disorders including paranoid schizophrenia, schizophreniform psychosis, schizoaffective disorder and delusional disorder. These disorders alter a person’s perception, cognition, affect and behaviour.

The use of the general term ‘psychosis’ has become more common over the last few years. This is partly due to the stigma associated with specific diagnoses, but also to recognise that diagnostic uncertainty is common and treatment decisions are based on the level of distress and dysfunction associated with psychotic symptoms rather than diagnosis.

The overall incidence of psychosis in people aged 16-65 in England between 1950 and 2009 is 32 per 100,000.1 The incidence has been stable over time, but varies markedly by age, sex, place and ethnicity. For men and women the incidence is highest in their 20s and then declines, though women have a second smaller peak in onset in their 40s. Incidence of psychosis increases with urbanicity and is significantly higher in people of black African, black Caribbean and Asian ethnicity compared with white British people.

An online tool has been developed to allow commissioners and services to predict local rates of first episode psychosis. It can be found at:


No definitive cause has been found for schizophrenia. The stress vulnerability model is often used to explain the development of a first episode of psychosis and subsequent relapses.

The model suggests that biological, psychological and social factors affect vulnerability to psychosis and relapses can be precipitated by environmental stressors. For people with a high vulnerability for psychosis low levels of stress may cause psychotic symptoms, whereas those with less vulnerability may develop psychosis under greater levels of stress.


Dopamine was linked to schizophrenia in the 1970s with key evidence being that amphetamine use can precipitate a schizophrenia-like disorder and that antipsychotics are dopamine receptor antagonists, with the clinically effective dose correlating with D2-receptor affinity. It has also been proposed that other neurotransmitters (for example, serotonin, glutamate and gamma-aminobutyric acid) may have a role.

Other factors

Schizophrenia can run in families and evidence of a genetic basis comes from twin and adoption studies. The genetics of schizophrenia is complicated; it seems likely inheritance is through the combined effect of several genes of small effect, and a number of susceptibility genes have been identified.

Development of schizophrenia in adult life has been associated with factors as diverse as winter birth, obstetric complications and maternal viral infection. Evidence has been found that social adversity, being born and brought up in a city, trauma and migration all raise the risk of psychosis and schizophrenia.

Stimulants, hallucinogens and cannabis can induce psychosis and precipitate relapse. Heavy cannabis use in adolescence has been associated with increased schizophrenia rates.

Section 2: Making the diagnosis

The diagnosis of schizophrenia is made on the basis of a detailed psychiatric, medical and personal history and mental state examination, supplemented where possible with additional information from someone who knows the person well.

Biological tests are not used to confirm a diagnosis of psychosis or schizophrenia, but can be useful where the history is suggestive of an organic cause, for example psychotic-like symptoms may occur in delirium or traumatic brain injury.

At-risk mental state

Before the onset of clear psychotic symptoms many people go through a period in which they have changes in mood, perception, behaviour and concentration which impact on their interactions with others and ability to work or study.

Criteria have been developed that can help to identify people with an at-risk mental state (ARMS) who are at high risk of transition to psychosis (see box 1), with about a third developing psychosis in three years.2

At-risk mental state groups
  1. Family history of schizophrenia and personal history of recent decline in functioning.
  2. Transient psychotic symptoms with spontaneous remission within a week.
  3. Attenuated positive symptoms such as ideas of reference, paranoid ideas, perceptual disturbance.

Treatment with an antipsychotic drug is not recommended for people at high risk of psychosis because the risks outweigh the benefits. CBT is the most effective treatment and can reduce the risk of transition to psychosis.3

First episode psychosis

Even after the onset of clear and persistent psychotic symptoms there may be diagnostic uncertainty because symptoms can be changeable in the early phases of psychosis and duration of symptoms is part of the diagnostic criteria. For example, a diagnosis of schizophrenia requires psychotic symptoms to persist for a month.

Recognising symptoms

GPs have an important role in the recognition of people with an at-risk mental state and those who have first episode psychosis. Early treatment can improve outcomes and so GPs should urgently refer people who may have an at-risk mental state or first episode psychosis to an early intervention in psychosis team to confirm the diagnosis and initiate a multidisciplinary treatment plan.

Patients with schizophrenia can experience positive, negative and affective symptoms (see box 2).

Box 2: symptoms

Positive symptoms
Hallucinations, delusions, thought disorder

Negative symptoms
Anhedonia, anergia, poverty of speech and thought, social withdrawal

Affective symptoms
Depression, mania

Differential diagnoses

Psychotic depression
Depressive symptoms are common in the period before the onset of psychotic symptoms, during acute episodes and in the period of recovery after an acute episode. Depression with psychotic symptoms needs to be considered as an alternative diagnosis.

Bipolar disorder
People with bipolar disorder may experience psychotic symptoms during episodes of depression or mania.

Substance-induced psychosis
Stimulants, hallucinogens, cannabis and alcohol can cause psychotic symptoms that last longer than the acute effects of the drug. It is important to remember that substance misuse may be the cause of a psychotic episode, coincidental to it or may be part of the patient’s way of coping.

Section 3: Managing the condition

The management of schizophrenia can be complicated and usually requires liaison between primary care services and community mental health teams (CMHTs). For some patients, psychiatric inpatient and/or substance misuse services may be involved.

Following the onset of a first episode of psychosis treatment by an early intervention in psychosis team is more effective than treatment in generic CMHTs.4


Antipsychotic drugs have a major role in the treatment of acute psychosis and are effective in preventing relapse.

Before prescribing an antipsychotic drug an assessment of physical health including weight, BMI, blood pressure, pulse should be made and blood samples for blood glucose, HbA1c and lipid profile are also recommended.

Although antipsychotic drugs have previously been divided into typical and atypical groups, the use of these groups is not helpful because there is no clear division between them in terms of chemical structure, receptor profile, efficacy, side effects or tolerability. In fact, for many drugs there is disagreement about whether they should be called typical or atypical. Therefore, each drug is best thought of as an individual drug with an individual side-effect profile.

Where possible, the most suitable drug should be decided upon jointly by the psychiatrist and the patient, with an assessment of side-effect profile being a key factor. The prescription should be seen as an individual therapeutic trial, starting at a low dose with regular assessment of effects and side effects, and increasing dose gradually if necessary.

After a first episode, drug treatment is best continued at the same dose to prevent relapse. It is not yet possible to predict who will be able to stop medication and who will benefit from long-term treatment, so it is important to discuss the risks and benefits of long-term treatment.

If the patient’s priority is to manage without medication, planning to reduce the dose gradually after one or two years of stability may be possible. In this case, using an advance statement and relapse prevention plan to identify early warning signs and manage relapse can be helpful.

Antidepressant and antimanic drugs may have a role in the treatment of patients who experience depressive or manic symptoms during an episode of psychosis, and anxiolytics and hypnotics are commonly used in the short-term for treating agitation, anxiety and insomnia associated with acute episodes of psychosis.

Talking therapies

CBT for psychosis can be helpful and has been shown to reduce symptoms of psychosis and depression. For patients who live with or are in close contact with a carer, ‘family intervention’ can be effective in reducing relapse and readmission rates.

Arts therapies may help to reduce negative symptoms which are often less responsive to medication than positive symptoms.

Physical health

The life expectancy of people with schizophrenia is 15 years less than the general population. Increased suicide rates explain most of the excess mortality in the early years after diagnosis, but over the course of the illness, much of the excess mortality is due to cardiovascular and metabolic illnesses.

Modifiable risk factors in these patients include smoking, sedentary lifestyle, dietary factors and weight gain.

People with schizophrenia are less likely to be offered general physical health screening in primary care than other groups, despite their increased risks.5 An annual physical health review focusing on cardiovascular and metabolic risks is recommended with the aim being to identify risks early and offer appropriate interventions, such as support to stop smoking, advice on lifestyle and diet, and treatment of hypertension or diabetes.

Section 4: Prognosis

Recovery from schizophrenia is possible and treatment and support should be offered with hope and optimism.

In the short-term the prognosis is good - most patients respond to treatment with an antipsychotic, experiencing an improvement in symptoms and social function.

However, relapse rates are high, with up to 80% of patients experiencing a relapse within five years and for many, schizophrenia is a lifelong condition where long-term medication and support may be required.

The course of schizophrenia is unpredictable, but long duration of untreated psychosis, male gender, early age of onset, low level of premorbid psychosocial functioning and comorbid substance misuse have been associated with poor outcomes.

Self-harm is common in schizophrenia and suicide rates are higher than in the general population (with estimates of suicide rates as high as 15%).

Antipsychotic-induced akathisia has been linked with increased suicidality,6 other factors associated with suicide include depression, substance misuse and poor adherence to treatment.7

Section 5: Evidence base


Chapter 5 includes recognition, referral and treatment of people with at risk mental states. Chapter 7 covers interventions to promote physical health and Chapter 10 covers drug treatment. Chapter 12 includes a section on the interface between primary and secondary care.

This guideline relates to the treatment of children and young people. Chapter 5 covers recognition and referral and chapter 7 covers drug treatment.


This website allows healthcare commissioners and services to estimate their local rates of first episode psychosis. Predictions are based on local demographic data and are shown at county or local authority district level.

Dr Jonathan Mitchell is consultant psychiatrist at Sheffield Health and Social Care NHS Foundation Trust

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  1. Kirkbride JB, Errazuriz A, Croudace TJ et al. Incidence of schizophrenia and other psychoses in England, 1950-2009: a systematic review and meta-analyses. PLoS One. 2012; 7:e31660.
  2. Fusar-Poli P, Bonoldi I, Yung AR et al. Predicting psychosis: meta-analysis of transition outcomes in individuals at high clinical risk. Arch Gen Psychiat 2012; 69(3): 220-9.
  3. Stafford MR, Jackson H, Mayo-Wilon E et al. Early interventions to prevent psychosis BMJ 2013; 346:f185.
  4. Bird V, Premkumar P, Kendall T et al. Early intervention services, cognitive–behavioural therapy and family intervention in early psychosis: systematic review. Br J  Psychiat 2010; 197:350-6.
  5. Roberts L, Roalfe A, Wilson S et al. Physical healthcare of patients with schizophrenia in primary care: a comparative study. Family Practice 2007; 24:34-40.
  6. Atbasoglu EC, Schultz SK, Andreasen NC et al The relationship of akathisia with suicidality and depersonalization among patients with schizophrenia. J Neuropsychiatry Clin Neurosci 2001; 13: 336-41.
  7. Hawton K, Sutton L, Haw C et al. Schizophrenia and Suicide: systematic review of risk factorsBr J  Psychiat 2005; 187:9-20.

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