Epidemiology

Incidence is around 7-17/100 000/year using DSM-III criteria. A recent study in London has shown a large increase in the incidence of schizophrenia (both broadly or narrowly defined); mainly in younger people.^[1] Prevalence is approximately 1% of the population.^[2] It is highest in inner city areas, figures such as 7.2 per 1000 have been quoted.^[1][3]

It can develop at any age but starts most commonly in late adolescence and the early twenties (uncommon before puberty). Peak age of onset is later in women. Men are also more likely to have negative symptoms and more serious forms of schizophrenia.^[3] Schizophrenia is also higher in migrants and this probably reflects a mixture of environmental and social factors. It is also being increasingly recognised that a schizophrenia prodrome exists. This usually becomes apparent during adolescence with features such as poor attention and withdrawal. However, the management and diagnosis of this entity is currently unclear and further work is being performed in this area.^[4]

Aetiology of schizophrenia

Multiple factors are involved in schizophrenia eg genetic, environmental and social. Short-lived illnesses similar to paranoid schizophrenia are associated with cocaine, amphetamines and cannabis. Cannabis use especially, has been noted to be a culprit in both established schizophrenia and in enhancing future risk of schizophrenia in those who have not yet developed psychotic symptoms.^[3]

Risk factors

• Family history - strongest predictor with relatively high concordance amongst monozygotic twins (40%); individual genes, however, cannot currently be implicated^[5]
• Intrauterine and peri-natal complications eg premature birth, low birth weight
• Intrauterine infection, particularly viral
• Abnormal early cognitive/neuromuscular development
• Social isolation, migrants^[3]
• Abnormal family interactions eg hostile or overly critical parents
• Heavy cannabis use in adolescence combined with susceptibility (probably genetic)^[6][7]

Presentation

Acute symptoms

The hallmark symptoms of a psychotic illness are:

• Delusions
• Hallucinations
• Thought disorder
• Lack of insight

These 'first rank' or "positive" symptoms of schizophrenia are rare in other psychotic illnesses (eg mania or organic psychosis). The presence of only one of the following symptoms is strongly predictive of the diagnosis:

• Lack of insight
• Auditory hallucinations, especially the echoing of thoughts, or a third person 'commentary' on one's actions, eg 'Now he's putting on his coat'
• Thought insertion, removal or interruption - delusions about external control of thought
• Thought broadcasting - the delusion that others can hear one's thoughts
• Delusional perceptions - ie abnormal significance for a normal event, eg 'The rainbow came out and I realised I was the son of god.'
• External control of emotions
• Somatic passivity - thoughts, sensations and actions are under external control

Hallucinations in other sensory modalities (visual, olfactory) also occur but much less commonly. Organic causes of psychosis should be actively sought when these hallucinations are reported. Delusions tend to be grandiose or persecutory, but these symptoms are also seen in other psychotic illnesses.

Chronic symptoms (also called 'negative' symptoms)

• Under activity - which also effects speech
• Low motivation
• Social withdrawal
• Emotional flattening
• Self neglect

Patients may manifest symptoms of other psychiatric diseases (eg depression, anxiety, obsessions and compulsions). There is significant co-morbidity with alcohol and substance misuse.^[8][9]

Signs

Conduct a full physical examination to exclude/support possibility of organic psychosis.

In the mental state examination be alert for:

• Appearance and behaviour - withdrawal, suspicion, or (rarely) stereotypical behaviours (repetition of purposeless movements) and mannerisms (eg saluting)
• Speech - interruptions to the flow of thought (thought blocking), loosening of associations/ loss of normal thought structure (knight's move thinking)
• Mood/affect - flattened, incongruous or 'odd'
• Abnormal beliefs - delusional percepts, delusions concerning thought control or broadcasting, passivity experiences
• Abnormal experiences - hallucinations, especially auditory
• Cognition - attention, concentration, orientation and memory should be assessed (significant impairment suggests delirium or severe dementia)

See also our dedicated article Psychosis - Diagnosis and Management.

Differential diagnosis

Organic disorders

• Drug induced psychosis - amphetamine, LSD, cannabis
• Temporal lobe epilepsy
• Encephalitis
• Alcoholic hallucinosis
• Dementia
• Delirium due to: infection; metabolic or toxic disturbance; neurological disease; endocrine etc.
• Cerebral syphilis (still rare, although worldwide incidence of syphilis has been increasing)^[10]

Psychiatric conditions

• Mania
• Psychotic depression
• Some personality disorders
• Panic disorders

Associated conditions^[2]

• Depression
• Anxiety
• Post-traumatic stress disorder
• Personality disorder
• Substance misuse
• Obesity
• Diabetes mellitus (usually type II associated with weight gain of anti-psychotic use)^[11]
• Infections
• Cardiovascular disease
• Continuing disability

Investigations^[2]

When a patient presents with their first episode consider the need for the following investigations:

• Abnormal LFTs and macrocytosis on FBC are highly suggestive of alcohol abuse.
• Serological tests for syphilis should not be forgotten. Screening for AIDS should be preceded by counselling.
• Urine screen for drugs of abuse. Light recreational use of cannabis can produce a positive test for the next fortnight. Heavy and chronic use can produce a positive results for months after the last use. Patients with already diagnosed schizophrenia may also present with a deterioration - consider intercurrent physical illness as a possible cause.^[12]

Also consider the following in new patients and already established patients presenting with psychosis or deterioration:

• Intoxication - alcohol, cannabis, amphetamines
• Drug overdose - suicidal, or accidental

Management

Initial management

• NICE guidelines emphasise the importance of early assessment and engagement in a therapeutic relationship, including assessment of social circumstances and involvement of family where possible.^[2]
• For initial assessment and management see our dedicated article Psychosis - Diagnosis and Management.
• NICE recommend that GPs should only prescribe anti-psychotics if they are on familiar territory. Protocols should be established with local mental health services as the wait to see a psychiatrist will vary from district to district. An atypical antipsychotic is the drug of choice. NICE have not found any difference between the various types. The drug's SPC and the BNF should be used to calculate dosages.

Multidisciplinary support^[2][13]

• The care of the schizophrenic patient is a joint effort between secondary care and primary practice. The latter are important as they are likely to see patients more often and for other physical diseases. Multidisciplinary support is essential to ensure support and early recognition of problems.
• A combination of in and outpatient care, hospital consultant, community psychiatric nurses, GPs, crisis support, day care, home treatment teams, social workers, voluntary organisations and involvement of carers is essential.
• Rates of associated physical diseases are high.
• Use of anti-psychotic drugs may cause additional problems eg weight gain and increased incidence of type II diabetes mellitus.^[11]
• Awareness of health promotion such as diet, smoking cessation and screening for other diseases is important in general practice.
• Compliance is improved with regular monitoring and attention to side effects. A useful resource here is the Liverpool antipsychotic side effect scale.^[14][15]

Social factors^[2][13]

• Rates of homelessness, poverty, and economic deprivation are increased.
• Most patients live at home (55%) with or without a carer, 16% live in sheltered accommodation, whereas 16% are inpatients.
• Social support for help with housing, vocational support, social isolation,employment and financial aid is important.
• Use of the Recovery Action Plan should also be promoted. This has foundations of recovery which include hope, responsibility for self and education.

Psychological support^[2][13]

• Information and education
• Voluntary organisations and support groups
• Information and support for carers is also essential
• Specialist "family interventions in psychosis" teams provide important support to both the patient and family and should be part of initial management
• Furthermore, family therapy has been shown to reduce relapse and admission rates^[3]
• Cognitive behavioural therapy is helpful

Drugs^[2][13]

• First-line treatment in suspected schizophrenia now involves the use of the newer atypical antipsychotics eg risperidone or olanzapine is first line but haloperidol is still used.
• Depot formulations should be considered if the patient prefers this after an acute episode or if there is non-compliance with medication.
• Benzodiazepines have little role other than in rapid tranquilisation. This may be required if the patient is violent or aggressive and refuses admission.

Side effects Extrapyramidal symptoms are less troublesome with the atypical antipsychotics than with older more conventional therapies. The main problem with atypical antipsychotics are weight gain. Rarely they can also cause bone marrow depression. For further details regarding adverse effects see individual drug monographs.

The GP's role

• Rapid tranquilisation may be required at any stage in the patient's illness if their behaviour is so disturbed that they become a danger to themselves or others. For more information, see Rapid Tranquilisation article.
• Always bear in mind the legal framework, consider the Mental Capacity Act and keep a record of any advance directives or statements. Within the framework, liaise with carers and relatives as much as possible.
• Contact with secondary care should be made as soon as possible and close lines of communication should be maintained throughout the patient's illness.
• Patients who are stable may be managed through a shared care approach or almost entirely within primary care. The 'rules of engagement' for such care should be laid down in a Care Programme Approach (CPA) document.
• NICE guidance advises the use of mental health registers and regular health check-ups in primary practice.^[3]
• The Quality & Outcomes Framework (QOF) highlights that primary care practices should have a register of patients with schizophrenia, participate with community mental health services, review patients in the last 15 months with provision of health promotion and disease prevention, and actively chasing up those who fail to attend this evaluation (within 14 days).^[16]
• Regular assessments should include establishing the presence of diabetes mellitus, cardiovascular disease and risk factors, medication related adverse events and endocrine disorders.^[3] NICE recommend a yearly cardiovascular risk assessment including measurement of lipids.
• Also a low threshold for re-referral to secondary care if necessary eg failure to respond to current therapy.
• If the patient's circumstances and/or psychosis do not permit safe and effective management in the community then inpatient assessment and/or care will be needed. If the patient refuses admission and you feel he or she is a danger to themselves or others, they may be 'sectioned' under the mental health act and undergo compulsory hospitalisation. Most local services now include a crisis intervention team.

The role of secondary care

Because it is a specialised field it is expected that secondary care will assess the patient on a regular basis.

• Doses of antipsychotics may need to be adjusted according to patient response.
• At approximately 8 weeks treatment should be reviewed and if there has been an inadequate response the drug should be changed either to another atypical or typical antipsychotic.^[3]
• Drug adherence can be a cause of failure of efficacy - depot preparations may need to be considered.
• Clozapine, initiated under the psychiatrists is used in one third of patients who are resistant to more conventional forms of treatment (risk of agranulocytosis).^[3]
• Treatment should continue for 1-2 years after the initial event and with close specialist supervision.
• If patients are well after 1-2 years duration of treatment then gradually reduce the dose with a plan to stop - but need very close monitoring for relapses.

Service options should include:

• Crisis resolution team
• Home treatment team
• Community mental health team
• Day hospital
• Family support service (if available)

Prognosis and recovery

Generally rates of 80% for recovery after first episode of psychosis have been reported.^[3] Early intervention and more effective treatment mean that the outlook is not as bleak as it once was. NICE cites several studies which reported a moderately good long-term global outcome in over half of people with schizophrenia, with a smaller proportion having extended periods of remission of symptoms without further relapses. Some people who never experience complete recovery manage to sustain an acceptable quality of life.
Good prognostic factors include:

• Absence of family history
• Good premorbid function - stable personality, stable relationships
• Clear precipitant
• Acute onset
• Mood disturbance
• Prompt treatment
• Maintenance of initiative, motivation

Nevertheless it should be remembered that schizophrenia continues to have a poor prognosis in some patients.

• Slow, insidious onset and prominent negative symptoms are associated with a worse outcome.
• Mortality is 1.6 times higher than general population.
• Suicide risk is 9 times higher
• Death from violent incidents is twice as high.
• 36% of patients have a substance misuse problem and there are high rates of cigarette smoking.