Schizophrenia

What is schizophrenia?

Schizophrenia is the most common form of psychosis. It is a lifelong condition, which can take on either a chronic form or a form with relapsing and remitting episodes of acute illness. It is a disorder which not only affects patients but also family and close friends.

How common is schizophrenia? (Epidemiology)

In the UK the 2014 adult psychiatric morbidity survey found that around 0.5% of people aged 16 years or older in England had received a diagnosis of a psychotic disorder (schizophrenia, schizoaffective disorder, or affective psychosis) in the preceding year.¹ The next psychiatric morbidity survey is planned for 2023-24.

Worldwide the pooled incidence of all psychotic disorders has been found to be 26.6 per 100,000 person-years. Men are at higher risk of all psychotic disorders than women. Ethnic minorities were also at excess risk of all psychotic disorders.²

Schizophrenia can develop at any age but starts most commonly in adolescence and the early 20s.³ In young people aged 10-18 it accounts for 24.5% of all psychiatric admissions, with a marked rise after the age of 15.⁴ Peak age of onset is later in women.

What causes schizophrenia? (Aetiology)

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.⁵

Risk factors

• Family history - specific genetic variants and pathways that increase susceptibility to schizophrenia have been identified.⁶

• Intrauterine and perinatal complications - eg, premature birth, low birth weight.

• Intrauterine infection, particularly viral.

• Abnormal early cognitive/neuromuscular development.

• Social isolation, migrants. The higher level of schizophrenia in migrants probably reflects a mixture of environmental and social factors.

• Abnormal family interactions - eg, hostile or overly critical parents.

Schizophrenia symptoms (presentation)

Acute symptoms

The hallmark symptoms of a psychotic illness are:⁷

• 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)⁸

• Underactivity - which also affects speech.

• Low motivation.

• Social withdrawal.

• Emotional flattening.

• Self-neglect.

In children and adolescents, there may be a prodromal period in which family and friends may notice subtle changes in behaviour and personality. Transient or attenuated first-rank symptoms may occur but these are not pathognomonic. Many young people with such symptoms do not go on to develop schizophrenia but there is a higher risk of it developing in the presence of such a condition within ten years of initial presentation.⁴

Patients may manifest symptoms of other psychiatric diseases (eg, depression, anxiety, obsessions and compulsions). There is significant comorbidity with alcohol and substance misuse.

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 perceptions, 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 the separate Psychosis - Diagnosis and Management article.

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 cause, etc.

• Cerebral syphilis (still rare, although worldwide incidence of syphilis has been increasing).

Psychiatric conditions

• Mania.

• Psychotic depression.

• Some personality disorders.

• Panic disorders.

• Dissociative identity disorder.

Associated conditions⁹

• Depression.

• Anxiety.

• Post-traumatic stress disorder.

• Personality disorder.

• Substance misuse.

• Obesity.

• Diabetes mellitus (usually type II, associated with clozapine and olanzapine).

• Infections.

• Cardiovascular disease.

• Continuing disability.

Investigations⁹

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

• LFTs and FBC. 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 subsequent fortnight. Heavy and chronic use can produce a positive result for months after the last use.

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.

Schizophrenia treatment and management

Initial management

• National Institute for Health and Care Excellence (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.⁹

• Early intervention is particularly important in the case of young people, including the involvement of Child and Adolescent Mental Health Services (CAMHS).⁴

• For initial assessment and management see the separate Psychosis - Diagnosis and Management article.

• NICE recommends that GPs should only prescribe antipsychotics prior to specialist assessment if they are instructed to do so by a consultant psychiatrist.⁷ Secondary care should lead on care for at least the first 12 months. Protocols should be established with local mental health services/early intervention teams/psychiatrists, depending on local arrangements. An atypical antipsychotic is the drug of choice. NICE has not found any difference between the various types. The drug's Summary of Product Characteristics (SPC) and the British National Formulary (BNF) should be used to calculate dosages.

Multidisciplinary support⁹

• The care of a patient who has schizophrenia is a joint effort between secondary care and primary care. The latter is important, being 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 inpatient and outpatient care, hospital consultant, community psychiatric nurses, GPs, crisis support, daycare, home treatment teams, social workers, voluntary organisations and involvement of carers is essential.

• Rates of associated physical diseases are high - particularly cardiovascular disease.¹⁰

• Use of antipsychotic drugs may cause additional problems - eg, weight gain and increased incidence of type 2 diabetes mellitus.

• 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. Useful resources here are the Glasgow Antipsychotic Side-effect Scale (GASS) and the Liverpool University Neuroleptic Side Effect Rating Scale (LUNSERS).¹¹

• Adherence to medication can be improved with several types of strategies, including daily text messages.¹²

Social factors⁹

• 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^{4 9}

• Information and education.

• Voluntary organisations and support groups.

• Information and support for carers are also essential.

• Specialist 'family interventions in psychosis' teams provide important support to both the patient and family and should be part of initial management.

• Family therapy has been shown to reduce relapse and admission rates.

• Cognitive behavioural therapy is helpful.¹³

• NICE recommends art therapy (eg, music, dancing, drama) for the alleviation of negative symptoms in young people

• Exercise therapy has a positive effect on many aspects of schizophrenia.¹⁴

• Research is ongoing as to how video games may have positive effects on cognitive functioning for people with schizophrenia.¹⁵

Medication^{4 9}

• First-line treatment in newly diagnosed schizophrenia now involves the use of the newer atypical antipsychotics - eg, risperidone or olanzapine.

• 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.

• In children and adolescents the evidence base for the use of antipsychotics is less well developed than in adults. NICE recommends that antipsychotics should only be offered once a definitive diagnosis of schizophrenia has been made. It should not be used where the condition is only suspected or to prevent it from developing. In such cases psychological therapies are often an appropriate first-line option.

• The choice of antipsychotic should be made by the patient and those with parental responsibility in conjunction with the doctor after a full discussion about the risks and benefits. Several medications in this area are not licensed for use in children but are nevertheless extensively prescribed and have a good evidence base.

• Aripiprazole is now recommended for patients aged 15 to 17 years who are intolerant of risperidone, where risperidone is contra-indicated, or where risperidone has not proved effective in controlling the schizophrenia. Aripiprazole has good rates of symptom remission.¹⁶

• NICE recommends clozapine for children and young people whose schizophrenia has not responded to adequate doses of at least two different antipsychotics used sequentially for 6-8 weeks. If clozapine fails, a multidisciplinary review followed by a combination of clozapine and a second antipsychotic can be tried for 8-10 weeks.

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

Electroconvulsive therapy (ECT)

This may be appropriate in patients resistant to pharmacological therapy, particularly if rapid reduction in symptoms is required. It may have an adjunctive effect with antipsychotics.¹⁷

The GP's role⁷

• 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 themself or to others.

• Always bear in mind Mental Health and Mental Capacity legislation 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. This is particularly important for children and adolescents. Transient or attenuated symptoms should be referred to CAMHS (up to age 17) or early intervention in psychosis services (14 years or over) depending on availability.⁴

• 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.

• Regular assessments should include establishing the presence of diabetes mellitus, cardiovascular disease and risk factors, medication-related adverse events and endocrine disorders. NICE recommends 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 themself or to 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 eight 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.

• Drug adherence can be a cause of failure of efficacy - depot preparations may need to be considered.

• Clozapine, initiated under the psychiatrist, is used in one third of patients who are resistant to more conventional forms of treatment (risk of agranulocytosis).

• Treatment should continue for 1-2 years after the initial event and with close specialist supervision.

• If patients are well after 1-2 years of treatment then gradually reduce the dose with a plan to stop - but very close monitoring for relapses is needed.

Service options
These should include:

• Crisis resolution team.

• Home treatment team.

• Community mental health team.

• Day hospital.

• Family support service (if available).

Prognosis and recovery

The perception that outcome is necessarily poor has been challenged by prospective studies and there is clearly great heterogeneity. First episode psychosis has a greater complete recovery rate than multiple episode psychosis; 57% in a recent systematic review.¹⁸ It is estimated that 80% of people show some response to treatment within the first year and 20% of people will have no further psychotic episodes within the following five years.⁷ It has been reported that around 15% of people experience persistent psychotic symptoms that are unresponsive to treatment two years after the acute episode.

The majority of those with schizophrenia live independently outside hospital, but many require continuing support either from services or relatives. The relative risk for suicide is increased 12-fold with a lifetime risk of approximately 6.5%.⁸

All-cause mortality is almost twice that of the general population with shorter life expectancy (by 15-20 years) linked to cardiovascular disease, respiratory disease and cancer.^{8 10}

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.

Factors associated with a poor prognosis include:

• Longer duration of untreated psychosis.

• Early or insidious onset of schizophrenia.

• Male sex.

• Negative symptoms.

• Family history of schizophrenia.

• Low IQ, low socio-economic status, or social isolation.

• Significant psychiatric history.

• Continued substance misuse.