Clinical Review - Schizophrenia

The latest advice and guidance on diagnosing and managing schizophrenia. By Dr Jonathan Mitchell and Dr Clive Travis

Coloured PET scan of schizophrenia patient's brain during hallucination (orange areas: brain activity) (Photograph: SPL)
Coloured PET scan of schizophrenia patient's brain during hallucination (orange areas: brain activity) (Photograph: SPL)

Section 1: Epidemiology and aetiology

The terms schizophrenia and psychosis 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.

A study conducted in three centres in the UK found incidence rates of 12.8 per 100,000 for schizophrenia, 23.2 per 100,000 for non-affective psychosis and 34.8 per 100,000 for all psychotic disorders (including mood bipolar disorder and psychotic depression).1

Rates at the three sites varied - those in London were nearly double the rates in Nottingham and Bristol. The highest incidence rate was in men aged 20-24, with the highest rate for women being five years later. The majority experienced their first psychotic episode by the age of 40. Rates were three times higher in the black and minority ethnic population than in the white population.

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

The model suggests that biological, psychological and social factors can affect a patient's vulnerability to schizophrenia and that acute episodes can be precipitated by environmental stressors.

For patients with a high vulnerability, low levels of stress may cause psychotic symptoms, whereas those with less vulnerability only develop psychosis under greater levels of stress. 

Dopamine was linked to schizophrenia in the 1970s, the 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, 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.

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 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 patient well.

Biological tests are not used to confirm the diagnosis, but can help to exclude other diagnoses, ensuring safe prescribing and monitoring for the development of associated physical health problems.

Before the onset of clear psychotic symptoms, many patients experience a prodromal period in which they may experience difficulties with changes in mood, perception, behaviour and concentration, which may affect interactions with others and ability to work or study.

Over the past decade or so, there has been much interest in attempts to detect those at risk of developing psychosis, to try to prevent the development of schizophrenia.

Although criteria have been developed that can detect patients at high risk of transition to psychosis,2 it is not clear which treatments might prevent this in those at risk.

The use of antipsychotic drugs is not recommended in this group because the risks outweigh the benefits, and although cognitive therapy has shown promising short-term results in some trials, the largest trial of cognitive therapy in an at-risk population to date showed no reduction in rates of patients' transition to psychosis.3

Recognising symptoms
GPs have an important role in the early recognition of emerging schizophrenia and referral to a psychiatrist to confirm the diagnosis and initiate a multidisciplinary treatment plan.

Even after the onset of clear psychotic symptoms, there may be diagnostic uncertainty because symptoms can be changeable in the early phases of schizophrenia and duration of symptoms form part of the diagnostic criteria.

Patients with schizophrenia can experience positive, negative or affective symptoms (see box below).

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, so depression with psychotic symptoms needs to be considered as an alternative diagnosis.

Bipolar disorder
Patients with bipolar disorder can 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 part of the patient's way of coping.


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.

For patients experiencing a first episode of schizophrenia, early intervention from psychosis teams has been shown to improve outcomes compared with generic CMHTs.4

GPs have a vital role in monitoring the physical health of patients who have schizophrenia (Photograph: SPL)

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

Although antipsychotics have in the past been divided into typical and atypical groups, the use of these groups is probably not helpful because there is no clear division between them in terms of chemical structure, receptor profile, efficacy, side-effects or tolerability, and 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 choice of drug should be made jointly by prescriber and 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 the 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.

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

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 20 years less than the general population. Increased suicide rates explain much 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.

Patients 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 check focusing on cardiovascular and metabolic risks is recommended, with appropriate interventions, such as support with smoking cessation and treatment of hypertension.

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.

Self-harm is common in schizophrenia and suicide rates are higher (Photograph: SPL)

However, relapse rates are high, with up to 80% 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 compliance.7

Section 5: Case study

A 34-year-old man was diagnosed with paranoid schizophrenia in 1994. His psychotic symptoms developed after a prodromal period in which he experienced panic attacks and symptoms of mania, and caused damage to some property.

He was treated with an antipsychotic, but stopped taking it due to intolerable side- effects. He was detained under the Mental Health Act on an annual basis over the following decade, initially after further incidences of damage to property and later as a result of written material he had posted.

Living on the street
He had escaped and absconded from the hospital on two occasions and had been missing for more than a year on another, living with his condition elsewhere in the country, sometimes on the street. He drank around 70 units of alcohol per week.

The patient had tried numerous antipsychotics and while they rectified his delusional thoughts, he failed to reach recovery because he found the side-effects of akathisia, depression and suicidal ideation intolerable, so after discharge from hospital, he always stopped taking his medication.

He was most fearful of the power wielded over him using the Mental Health Act and he had previously preferred to spend the months after discharge gradually returning to the psychotic state, which he said he usually enjoyed.

The GP's role
In 2004 he was discharged by the hospital managers' panel. After discharge he visited his GP's surgery, where he told the GP: 'It does not take a genius to see that if I am not on anything I will be back in hospital within six months,' and asked to try olanzapine, explaining that he wanted the hospital managers who released him to know he had tried it.

He was prescribed olanzapine 5mg by his GP and the dose was later increased at his request to 10mg with 20mg fluoxetine. He has now avoided hospital for more than eight years.

He shows no weight gain and has returned to employment, now working as a freelance expert patient on a schizophrenia website.

Section 6: Evidence base

Clinical trials

  • Lieberman JA, Stroup TS, McEvoy JP et al; Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE) Investigators. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia. N Engl J Med 2005; 353: 1209-23.

This large multicentre pragmatic RCT conducted in the US included a comparison of firstand second-generation antipsychotics among almost 1,500 patients and found no clinically significant differences between the groups.


  • NICE. Core interventions in the treatment and management of schizophrenia in primary and secondary care (update). CG82; March 2009.

Chapter 9 covers the interface between primary and secondary care services and physical healthcare. Chapter 6 covers pharmacological treatment.

Chapter 5 has a care pathway and a section on primary care.

  • Barnes TRE, Schizophrenia Consensus Group of the British Association for Psychopharmacology. Evidence-based guidelines for the pharmacological treatment of schizophrenia: recommendations from the British Association for Psychopharmacology. J Psychopharmacol 2011; 25(5): 567-620.

A review of evidence and recommendations for the pharmacological treatment of different stages of schizophrenia.


Contains links to information for the public, including leaflets for patients and carers in different languages.

An international web-based resource with links to information about schizophrenia.

Visit MIMS Learning for an updated version of this article

CPD IMPACT: EARN more credits

These further action points may allow you to earn more credits by increasing the time spent and the impact achieved.

  • Familiarise yourself with the initial symptoms of schizophrenia and make a short presentation to colleagues, with the aim of ensuring timely referral.
  • Audit your patients with schizophrenia and ensure they have received a physical health check within the past year.
  • Consider whether your patients are on optimal medical therapy and whether you can offer them access to additional therapies that may be beneficial, such as art therapy or CBT.

Contributed by Dr Jonathan Mitchell, consultant psychiatrist, Sheffield Health and Social Care NHS Foundation Trust, and Dr Clive Travis, a service user and expert patient.

1. Kirkbride JB, Fearon P, Morgan C et al. Arch Gen Psychiatry 2006; 63(3): 250-8.

2. Chuma J, Mahadun P. Br J Psychiatry 2011; 199: 361-6.

3. Morrison AP, French P, Stewart SL et al. BMJ 2012; 344: e2233.

4. Bird V, Premkumar P, Kendall T et al. Br J Psychiatry 2010; 197: 350-6.

5. Roberts L, Roalfe A, Wilson S et al. Fam Pract 2007; 24: 34-40.

6. Cem Atbasoglu E, Schultz SK, Andreasen NC. J Neuropsychiatry Clin Neurosci 2001; 13: 336-41.

7. Hawton K, Sutton L, Haw C et al. Br J Psychiatry 2005; 187: 9-20.

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