Clinical Review - Schizophrenia

Contributed by Dr Jenny Morgan, consultant psychiatrist, Hampshire Partnership NHS Foundation Trust, Tadley and Cathy Morgan, final year medical student, University of Bristol Medical School

PET scan of the temporal lobe in a hallucinating schizophrenic patient (Photograph: SPL)
PET scan of the temporal lobe in a hallucinating schizophrenic patient (Photograph: SPL)

Section 1: Epidemiology and aetiology
Schizophrenia is characterised by symptoms that include cognitive, behavioural and perceptual disturbances.

The word schizophrenia is derived from the Greek words skhizein meaning 'to split' and phren meaning 'mind', which is unfortunate because this fuels the misconception that it is characterised by a 'split personality'.

The diagnosis of schizophrenia is still associated with a considerable amount of stigma, fear and public misunderstanding not helped by often misleading media coverage. This article hopes to dispel some myths and give advice on how to assess and manage patients.

The prevalence of schizophrenia is about 1 per cent and, with small variations, is generally the same in every ethnic group. The incidence is much lower as the condition tends to be lifelong. The male to female risk ratio is 1.4:1. Males usually present before the age of 25 and females before the age of 35.

The cause of schizophrenia is not yet fully understood. It is thought of as multifactorial in aetiology, with environmental stressors acting on genetic vulnerability. Positive family history is the strongest risk factor. The relative risk of developing the condition is about 7 per cent in a first-degree relative and 40-50 per cent in monozygotic twins. Many genes are implicated.

Other risk factors include cannabis use, particularly early in adolescence, which increases the risk fourfold.1, 2 There may also be a dose relationship, making the type of cannabis known as skunk - which has a high percentage of tetrahydrocannabinol - particularly harmful.

But only a small percentage of cannabis users develop schizophrenia. Urban living, migrant status and obstetric complications increase the risk. Schizophrenia is increasingly understood as a neurodevelopmental condition and is associated with mild congenital anomalies.3

Research has shown that various changes in brain morphology, including increase in size of the lateral ventricles and other grey matter deficits, are present during the first episode.4

Section 2: Making the diagnosis
The WHO ICD-105 and DSM-IV classifications of schizophrenia are comprehensive and specific. In Britain, the ICD-10 is more commonly used amongst psychiatrists (see box below). Both are currently under revision.

Patients may present with florid psychoses but often symptoms are vague and are brought to the attention of the GP by worried relatives who know the patient is 'not right'.

It is vital to recognise this prodromal illness, which may manifest itself with affective or anxiety symptoms, social withdrawal, behavioural changes or difficulty concentrating.

In psychotic patients, positive symptoms including auditory hallucinations and persecutory or other bizarre delusions are common; for example, the patient believing they are being watched by computers.

Patients may experience delusions of control when they feel their actions, feelings or thoughts are being controlled by an external force or person.

They may hear their thoughts spoken out loud and worry that others can hear them. It can be described as if their brain is a 'leaky sieve' and they have little control over thoughts entering or leaving their brain.

They often have ideas or delusions of reference when they infer that common events refer to them directly (such as personal messages from television and newspapers). Lack of insight is difficult to manage. On the whole it is best to be truthful but if possible avoid confrontation over their beliefs. Patients are more likely to reveal their psychotic symptoms if not challenged early in the consultation.

Negative symptoms include social withdrawal, self-neglect, loss of motivation and initiative, emotional blunting and paucity of speech. Symptoms of disorganisation include thought disorder, manifested by distorted or illogical speech where connections between ideas are difficult to follow.

Patients may exhibit catatonic symptoms, including mannerisms or posturing. There are often subtle cognitive changes as the condition progresses.

Symptoms of psychosis are difficult to elicit but listening to what the patient wants to talk about and picking up on things which sound odd can reveal underlying beliefs.

It is rare for an acutely psychotic person to 'hold it together' for long without revealing some psychotic symptoms. The box below outlines some helpful screening questions.

Differential diagnosis

  • Organic psychosis: prescribed drugs, drug withdrawal (including from benzodiazepines or alcohol), epilepsy, tumours, HIV, neurosyphilis, carbon monoxide or heavy metal poisoning and hyper/hypothyroidism.
  • Drug-induced psychosis: cannabis, amphetamines and cocaine.
  • Other functional psychoses: affective disorders, schizoaffective disorder, persistent delusional disorder and acute and transient psychoses (symptoms last less than one month).
  • Dementia.
  • Post-traumatic stress disorder.
  • Personality disorder (schizotypal).

In distinguishing schizophrenia from its differentials, visual and olfactory hallucinations are uncommon, while clouding of consciousness does not occur. No investigation is diagnostic.

ICD-10 diagnostic criteria for schizophrenia5

At least one of the following present most of the time for one month

  • Thought echo, insertion or withdrawal, or thought broadcast.
  • Delusions of control referred to body parts, actions, sensations or thoughts; delusional perception.
  • Hallucinatory voices giving a running commentary, discussing the patient, or coming from a part of the patient's body.
  • Persistent bizarre or culturally inappropriate delusions.

Or at least two present most of the time for one month

  • Persistent daily hallucinations accompanied by delusions.
  • Incoherent or irrelevant speech.
  • Catatonic behaviour such as stupor or posturing.
  • Negative symptoms such as marked apathy, blunted or incongruous mood.


Useful screening questions14

1. Have you felt that something odd might be going on that you cannot explain?

2. Have you been feeling that people are talking about you, watching you or giving you a hard time for no reason?

3. Have you been feeling, seeing or hearing things that others cannot?

4. Have you felt especially important in some way, or that you have powers that let you do things which others cannot?

Section 3: Managing the condition
If an emerging or frank psychosis is suspected it is important to refer promptly to secondary care with as much information as possible. This will be either to the local early intervention in psychosis service, the crisis resolution and home treatment (CRHT) service or the community mental health team.

Managing patients
Patients presenting with acute psychosis should be seen within 48 hours. In drug-naive patients, offer a benzodiazepine if the patient is very agitated. In an emergency call the police and the CRHT service.

If there is concern of risk to self or others, and the patient refuses to consider hospital admission, a Mental Health Act assessment should be made.

Studies show that early intervention improves prognosis6 but it is unclear whether patients who present later are those who have a worse prognosis anyway.7 Always listen to and work with the patient's family because they are the most sensitive to change from normal. It is also important to listen to the patient, explain what you are doing - as far as possible - and encourage autonomy.

Patients with longstanding schizophrenia managed in primary care, may need referral back to secondary care if there is an exacerbation of their symptoms, intolerable side-effects, poor compliance, substance misuse or risk to self or others.

The standardised mortality ratio is about 1.5 times that of the general population. The GP role in managing the physical health of the patient is very important because patients are at increased risk of diabetes and cardiovascular disease, further increased by smoking, hypertension and hyperlipidaemia.

If possible, it is helpful to carry out a baseline screening of BP, weight, waist circumference, FBC, U&Es, LFTs, plasma glucose and lipids before starting antipsychotics.

The updated NICE guideline8 recommends an ECG prior to starting an antipsychotic if there are any cardiovascular risk factors, including a family history of prolonged QT.

For established illness, NICE recommends an annual physical review in general practice.

Pharmacological therapy
Second-generation antipsychotics (SGAs/atypicals) such as risperidone, olanzapine, quetiapine and aripiprazole are recommended because they are less likely than first-generation antipsychotics (FGAs/typicals) to cause hyperprolactinaemia, extrapyramidal side-effects or tardive dyskinesia.

However, recent large studies9,10 have highlighted adverse effects of SGAs and the pendulum may swing back in favour of FGAs such as haloperidol and trifluoperazine. If a patient has established illness, information on previous treatments, dosage, duration and response to medication is invaluable.

If non-compliance has been an issue, intramuscular depots can be considered. Antipsychotics may cause side-effects (see below) and the smallest effective dose should be used.

Clozapine is effective for 20-30 per cent of patients who have not responded to antipsychotics and is especially effective in treating negative symptoms.11 There is a less than 1 in 5,000 chance of developing agranulocytosis, thus FBC is monitored. Suicide risk is reduced by treatment and energetic follow-up.

Psychosocial management
NICE recommends all patients with schizophrenia should be offered cognitive behavioural therapy for psychosis, family intervention and art therapy.8 Vocational advice is important, though this is often offered by non-statutory agencies.

Section 4: Prognosis
Eighty per cent of patients recover from their first episode of illness, although only 20 per cent never have another episode. About 10 per cent suffer a chronic debilitating illness with poor functioning while most function fairly well.

Poor prognostic features include substance misuse, slow insidious presentation, and long duration of untreated psychosis. Family dynamics with high expressed emotion which is critical or hostile are unhelpful.

Antipsychotic use
Antipsychotics are recommended for one to two years after first presentation, although patients should be encouraged to keep taking medication because ongoing antipsychotic treatment protects against further relapse. Rate of relapse at one year is 20 per cent with medication compared with 57 per cent without.

Relapse risk
At least 50 per cent of patients have stopped their medication at one year and 75 per cent at two years. Discontinuation of anti-psychotics increases the risk of relapse fivefold.12 After each episode of illness, recovery tends to be less complete indicating that psychosis in itself is damaging.

The lifetime suicide risk is 10 per cent and is highest in the first five years. Substance and alcohol misuse increase the risk. Fifty per cent of those with schizophrenia suffer depressive symptoms at presentation.

Treatment with antidepressants may be beneficial but further research is needed.13

There is a popular misconception that all people with schizophrenia are violent. Violence is rare.

Approximately 10 per cent are responsible for 90 per cent of all fear-inducing and violent acts by this patient group, but only about one per cent will carry out potentially lethal or seriously injurious behaviours.

Side-effects of drugs
  • Weight gain
  • Sedation
  • Sexual dysfunction
  • Reduced seizure threshold
  • Cardiotoxicity (including prolonged QT)

First-generation antipsychotics (typicals)
Anticholinergic effects:
  • Blurred vision
  • Dry mouth
  • Urinary retention
Extrapyramidal effects:
  • Dystonia
  • Pseudoparkinsonism
  • Akathisia
  • Tardive dyskinesia
  • Neuroleptic malignant syndrome (rare)
  • Hyperprolactinaemia

1. Arseneault L, Cannon M, Poulton R et al. Cannabis use in adolescence and risk for adult psychosis. BMJ 2002; 325: 1212-3.

2. Henquet C, Murray R, Linszen D et al. The environment and schizophrenia: the role of cannabis use. Schizophr Bull 2005; 31: 608-12.

3. Chan RC, Ting Xu R, Heinrichs W et al. Neurological soft signs in non-psychotic first-degree relatives of patients with schizophrenia: a systematic review and meta-analysis. Neurosci Biobehav Rev 2010; 34: 889-96.

4. Steen RG, Mull C, McClure R et al. Brain volume in first-episode schizophrenia, systematic review and meta-analysis of magnetic resonance imaging studies. Br J Psychiatry 2006; 188: 510-8.

5. WHO. The ICD-10 classification of mental and behavioural disorders: clinical descriptions and diagnostic guidelines. Geneva, WHO, 1992.

6. Perkins DO, Hongbin G, Boteva K et al. Relationship between duration of untreated psychosis and outcome in first episode schizophrenia: a critical review and meta-analysis. Am J Psychiatry 2005; 162: 1785-804.

7. Marshall M, Rathbone J. Early intervention for psychosis. Cochrane Database Syst Rev 2006; Issue 4. Art No: CD004718. DOI: 10.1002/14651858.

8. NICE. Core interventions in the treatment and management of schizophrenia in adults in primary and secondary care (update). London, NICE, 2009.

9. McEvoy JP, Lieberman JA, Stroup TS et al. Effectiveness of clozapine versus olanzapine, quetiapine, and risperidone in patients with chronic schizophrenia who did not respond to prior atypical antipsychotic treatment. Am J Psychiatry 2006; 163: 600-10.

10. Jones PB, Barnes TR, Davies L et al. Randomized controlled trial of the effect on quality of life of secondvs first-generation antipsychotic drugs in schizophrenia: Cost Utility of the Latest Antipsychotic drugs in Schizophrenia Study (CUtLASS 1). Arch Gen Psychiatry 2006; 63: 1079-87.

11. Kerwin RW, Bolonna AA. Is clozapine antisuicidal? Expert Rev Neurother 2004; 4(2): 187-90.

12. Robinson D, Woerner MG, Alvir J et al. Predictors of relapse following response from a first episode of schizophrenia or schizoaffective disorder. Arch Gen Psychiatry 1999; 56: 241-7.

13. Whitehead C, Moss S, Cardno A et al. Antidepressants for people with both schizophrenia and depression. Cochrane Database Syst Rev 2002, Issue 2. Art No: CD002305. DOI: 10.1002/14651858.

14. Care Services Improvement Partnership. Emerging psychosis and young people: what you need to know. London, CSIP, 2008.

  • Contributed by Dr Jenny Morgan, consultant psychiatrist, Hampshire Partnership NHS Foundation Trust, Tadley and Cathy Morgan, final year medical student, University of Bristol Medical School.

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