15th February 2025

Schizophrenia

Epidemiology of schizophrenia

Genetic and environmental factors both play a role in whether someone develops schizophrenia. Possible environmental factors include but are not limited to: complicated pregnancy and birth, early social services contact, neurodevelopmental difficulties, and cannabis use, especially in adolescence.

Schizophrenia is more common among males. Age of onset varies between genders, with more men experiencing the onset of symptoms in their early-to-mid twenties, and more women experiencing onset of symptoms in their late twenties. Early onset schizophrenia is typically associated with a poorer prognosis (as are presentations with mainly negative symptoms).

Clinical features of schizophrenia

Onset of schizophrenia may be acute or insidious. A prodromal phase often precedes the onset of psychotic symptoms, which may include negative symptoms, social withdrawal, self-neglect, inversion of sleep cycles, anxiety or depression. 

As per the ICD-11, for a diagnosis of schizophrenia, symptoms must be present for at least one month. At least two symptoms are needed for diagnosis. At least one of the two symptoms must come from the following list: 

• Persistent delusions
• Persistent hallucinations
• Formal thought disorder (e.g. tangentiality, ‘knight’s move thinking’, ‘word salad’)
• Experiences of influence, passivity, or control (e.g. thought withdrawal/broadcasting)

The second of the two symptoms can come from either the  above list or from the following symptoms: 

• Negative symptoms (e.g. flat affect, poverty or paucity of speech, lack of motivation, social withdrawal and anhedonia)
• Grossly disorganised behaviour that impedes goal-oriented activity
• Psychomotor disturbances (e.g. catatonic restlessness or agitation, posturing, waxy flexibility, negativism, mutism or stupor)

Management of schizophrenia

There is no first-line antipsychotic drug suitable for all patients, and drug choice is shaped by individual circumstances and choices, as well as minimisation of side effects.

There are two main classes of antipsychotic medication:

• First-generation (typical) antipsychotics:
  • D2 antagonists (+ other receptors)
  • E.g. haloperidol, chlorpromazine, fluphenazine
  • Extrapyramidal side effects (EPSEs) are more common
• Second-generation (atypical) antipsychotics 
  • 5HT2A/D2 antagonists (+ other receptors)
  • E.g. aripiprazole, olanzapine, quetiapine, paliperidone, risperidone, lurasidone and clozapine
  • Metabolic side effects more common

Key considerations for maintenance therapy include:

• Establishing the minimal effective dose in order to reduce side effects
• Depots (e.g. paliperidone, olanzapine, zuclopenthixol) may help ensure compliance
• Encourage psychotherapy, e.g. CBT, family therapy and psychoeducation

Side effects of antipsychotics

Common side effects of antipsychotics include:

Extrapyramidal symptoms:

• Includes parkinsonian symptoms (bradykinesia and tremor), akathisia (restlessness) and tardive dyskinesia (abnormal involuntary movements of the lips, tongue, face and jaw that can continue after drug discontinuation). 
• Also includes dystonia (uncontrolled muscle spasms). This can be very acute in onset. Presentations include but are not limited to: oculogyric crisis (prolonged ‘rolling upwards’ of the eyes), torticollis (neck twisting causing the head to tilt), buccolingual crisis (protruding or pulling sensation of tongue), opisthotonic crisis (whole body spasm causing an arched back, flexed arms and extended lower limbs), scoliosis or lordosis, blepharospasm (eyelid spasm preventing eye opening) and torticopelvic crisis (abdominal pain or rigidity). Laryngeal dystonia causes throat pain, shortness of breath and difficulty talking and is rare but potentially life-threatening.

Consider procyclidine to reduce medication side effects and for acute dystonic reactions.

Metabolic symptoms: 

• Weight gain, hypercholesterolemia and diabetes. 

Cardiovascular:

• QTc-interval prolongation, postural hypotension.

Neuroleptic malignant syndrome:

• Rare but potentially fatal side effects. 
• Presents with hyperthermia, sweating, muscle rigidity (‘lead-pipe rigidity’), hyporeflexia, tachycardia, labile blood pressure and fluctuating consciousness. 
• Management includes stopping the antipsychotic, giving IV fluids, cooling, and considering bromocriptine and dantrolene.

Hyperprolactinaemia:

• May cause loss of libido, sexual dysfunction, galactorrhoea and infertility in both sexes. In men may cause oligospermia, reduced ejaculation volume and gynaecomastia. In women may cause oligomenorrhea or amenorrhea, reduced vaginal lubrication, dyspareunia, acne and hirsutism.
• First-line treatment is stopping or reducing the antipsychotic and changing to another medication. If this is not feasible, low-dose aripiprazole can also be used as an add-on medication to treat symptomatic hyperprolactinaemia.

Sexual dysfunction.

Box 1 Key facts about clozapine

Monitoring of antipsychotics

There are specific guidelines on monitoring for different antipsychotics, but NICE recommends the following as a guide, in addition to baseline measurements:

Table 3 NICE guidelines for monitoring with antipsychotics.