Schizophrenia

Schizophrenia is the commonest 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.

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% worldwide - being highest in inner city areas, figures such as, 7.2 per 1000 have been quoted.^1,2

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.² 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.³

Multiple factors are involved in schizophrenia e.g. 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.²

Risk factors

• Family history - strongest predictor with relatively high concordance amongst monozygotic twins (40%); individual genes, however, cannot currently be implicated⁴
• Intrauterine and peri-natal complications e.g. premature birth, low birth weight
• Intrauterine infection, particularly viral
• Abnormal early cognitive/neuromuscular development
• Social isolation, migrants²
• Abnormal family interactions e.g. hostile or overly critical parents
• Heavy cannabis use in adolescence combined with susceptibility (probably genetic)^5,6

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 (e.g. 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, e.g. '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, e.g. '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 (e.g. depression, anxiety, obsessions and compulsions). There is significant co-morbidity with alcohol and substance misuse.^7,8

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 (e.g. 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

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)⁹

Psychiatric conditions

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

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

• Infection screen (chest x-ray, urine and blood cultures, full blood count, ESR and CRP)
• Renal and liver function tests
• Drug screen
• Lumbar puncture
• CT brain
• Electroencephalogram (EEG)¹⁰

Patients with already diagnosed schizophrenia may also present with a deterioration - consider intercurrent physical illness as a possible cause.¹¹

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

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.¹²

Multidisciplinary support^12,13

• 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 e.g. weight gain and increased incidence of type II diabetes mellitus.¹⁴
• 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.^15,16

Social factors^12,13

• 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^12,13

• 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 rates²
• Cognitive behavioural therapy is helpful and NICE advise 10 sessions over about 3 months^2,17

Early Intervention in psychosis¹⁸

As mentioned above it is becoming increasingly recognised that a schizophrenia prodrome exists. This has led to the introduction of the Early Intervention Paradigm. This has two basic aspects:

1. Identifying cases prior to their first episode of psychosis and then trying to prevent or reduce progression rate. A number of studies have been performed looking at the role of psychological, social and drug management in these groups and it appears that a combination of all three is probably best in this subset of patients.
2. The second aspect occurs post-onset of psychosis and deals with rapid initiation of treatment, symptomatic and functional recovery and prevention of relapse. Early intensive therapy including family therapy and social skills training has been shown to reduce the duration of the first psychotic episode and improve long term outcome.

Drugs^12,13

Antipsychotics are the main stay of drug therapy in schizophrenia. Examples include Haloperidol, Flupenthixol, Sulpiride, Loxapine and Chlorpromazine. There are two broad groups of antipsychotics: typical antipsychotics and atypical antipsychotics. They differ mostly in terms of the adverse effects profile and for a few drugs there is also a suggestion of differences in terms of efficacy. NICE Guidelines recommend the use of atypical agents in a first episode of schizophrenia, or with patients suffering from unacceptable side effects with conventional antipsychotics.^12,19

Side effects include:

• Extrapyramidal symptoms - worse with typical antipsychotics; mild and transient with atypical antipsychotics
• Other movement disorders e.g. dystonias, akathisia and tardive dyskinesias (especially of the mouth called oro-facial dyskinesia)
• Weight gain - more notorious with atypical antipsychotics (as is risk of developing type 2 diabetes mellitus)
• Apathy
• Agitation
• Sedation
• Headache
• Constipation
• Endocrine effects
• Cardiovascular symptoms
• Neutropenia
• Neuroleptic malignant syndrome - more common with typical antipsychotics

The atypical antipsychotics can also cause bone marrow suppression.

A recent Cochrane systematic review comparing risperidone and olanzapine has shown that there is little difference between them and that both have significant adverse effects. Risperidone tends to cause movement disorders and sexual dysfunction, olanzapine rapid weight gain.²⁰ A long-term follow-up trial comparing risperidone and haloperidol has shown that risperidone reduces relapse in more patients and for a longer time than haloperidol, whilst causing fewer movement disorders.²¹

• Mortality 1.6 times higher than general population
• Suicide risk 9 times higher
• Death from violent incidents twice as high
• 36% substance misuse problem and high rates of cigarette smoking

• Obesity
• Diabetes mellitus (usually type II associated with weight gain of anti-psychotic use)¹⁴
• Infections
• Cardiovascular disease
• Continuing disability¹²

• Two-thirds of adults with chronic schizophrenia had difficulty in at least one activity of daily living
• Half of adult patients were classified as being unable to work
• Only 19% were engaged in employment

However, it is also important to remember that a large number of patients will achieve good functional levels and some recover.

• Anyone with suspected or newly diagnosed schizophrenia should be referred urgently for psychiatric assessment and development of a care plan.¹⁰
• If the diagnosis is clear, refer urgently and consider prescribing an atypical antipsychotic drug e.g. risperidone or olanzapine - (discuss with psychiatrist). Alternatively, in primary practice a benzodiazepine can be prescribed before referral.
• Doses of antipsychotics should be gradually 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.²
• Always consider drug adherence factors for 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).²
• 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.
• Primary and secondary care doctors need to have a close alliance in managing patients with schizophrenia and good communication is the key to success.
• NICE guidance advises the use of mental health registers and regular health check-ups in primary practice.²
• 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).²²
• Regular assessments should include establishing the presence of diabetes mellitus, cardiovascular disease and risk factors, medication related adverse events and endocrine disorders.²
• Also a low threshold for re-referral to secondary care if necessary e.g. failure to respond to current therapy.

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

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.

Generally rates of 80% for recovery after first episode of psychosis have been reported.² For example, one study reported that almost 50% had symptom remission for 2 years and 25% had social functioning to a reasonable level. Unfortunately in the same study only 13% had both.²³ 10% will have ongoing severe problems and the remainder usually have a fluctuating course with reasonable function.¹² Slow, insidious onset and prominent negative symptoms are associated with a worse outcome.
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