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Antipsychotics

5. Key points

Checklist

  • Antipsychotics are used to treat symptoms of psychotic illness and have other licensed uses such as treatment of anxiety and agitation
  • Antipsychotics have commonly been divided into first-generation (‘conventional’ or ‘typical’) antipsychotics eg chlorpromazine and second-generation (‘atypical’) antipsychotics eg olanzapine. The classification may help to predict some adverse effects, but its value should not be overestimated as all antipsychotics show a range of potential therapeutic and adverse effects
  • Clozapine may have a distinct therapeutic profile but its use is restricted by its adverse effects
  • An antipsychotic should be continued at optimum dose for 4–6 weeks before assessing response to treatment. Poor adherence (common in antipsychotic use) may sometimes explain lack of improvement in symptoms
  • Although adverse effects vary between antipsychotics, more common adverse effects include nausea, dry mouth, constipation, headache, sedation, postural hypotension, weight gain, and raised prolactin; several adverse effects diminish with continuing treatment
  • Extrapyramidal side effects of antipsychotics—acute dystonia1, akathisia2, parkinsonism3 and tardive dyskinesia4—can occur with varying frequency
  • Less frequent but serious adverse effects include: metabolic effects (including hyperglycaemia and raised blood lipids), blood disorders, QT-interval5 prolongation and tachyarrhythmia
  • Neuroleptic malignant syndrome, a rare risk of antipsychotics, is characterised by muscle rigidity, raised temperature and it may also feature altered mental status, autonomic instability, leucocytosis6 and raised creatine kinase7. Neuroleptic malignant syndrome is a medical emergency.
  • Important adverse effects of clozapine include agranulocytosis8, myocarditis, cardiomyopathy, gastrointestinal obstruction, and hypersalivation
  • Antipsychotics are thought to act principally by antagonism at the dopamine D2 receptor, but other mechanisms are also involved; adverse effects involve dopamine D2 receptors (eg extrapyramidal effects and hyperprolactinaemia) as well as others such as acetylcholine muscarinic receptors (eg constipation) and histaminergic receptors (eg sedation)
  • The elderly are especially prone to adverse effects of antipsychotics. The risk of stroke and other cerebrovascular adverse events may be raised three-fold in elderly patients with dementia receiving an antipsychotic; mortality rate is also raised
  • An antipsychotic should not be used for behavioural or psychological symptoms of dementia in the elderly unless other therapies have been unsuccessful and there is immediate risk of harm to the patient or others; only short-term use of risperidone is licensed for this purpose
  • Antipsychotics do not cause psychological dependence but physical dependence can result in withdrawal effects especially on abrupt discontinuation after prolonged use
  • Important drug interactions include drugs that: increase sedation (eg alcohol, benzodiazepines); increase the risk of arrhythmias associated with QT-interval9 prolongation (eg anti-arrhythmics); increase hypotension risk (eg antihypertensives); increase seizure risk (eg tramadol); and increase the risk of neuroleptic malignant syndrome (eg lithium). Antipsychotics inhibit the effect of dopamine agonists used for Parkinson’s disease
  • Use of antipsychotics in pregnancy and breast-feeding requires careful assessment of risk and benefit. Antipsychotic use in the third trimester can cause adverse effects in the newborn including neonatal withdrawal syndrome
  • Patients on antipsychotics may need to be monitored for weight, blood pressure, blood glucose, lipids, cholesterol, prolactin level, liver function, cardiac conduction (ECG), movement disorders and blood count. Close adherence to monitoring guidelines is recommended.
  1. A neurologically based movement disorder involving sustained contraction of the affected muscles, leading to abnormal posturing or repetitive movements or both↩
  2. Sensation of restlessness and a compulsion to move constantly↩
  3. A clinical triad involving tremor, muscle rigidity and bradykinesia (slow movements) The symptoms often characterise Parkinson’s disease, but can also be caused by drugs, particularly antagonists of dopamingeric transmission in the nigrostriatal region of the brain.↩
  4. Involuntary, repetitive, purposeless movements, involving the face, jaw, neck, trunk and other parts, which can follow long-term use of an antipsychotic↩
  5. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩
  6. An increase in the number of white cells in the blood, usually in response to inflammation. Leucocytosis can also be abnormally triggered by drugs.↩
  7. An enzyme found in many body tissues. Raised concentration is a marker for muscle damage and disorders such as myocardial infarction, muscular dystrophy and renal failure. Creatine kinase (CK) is also referred to as creatine phosphokinase (CPK)↩
  8. Marked deficiency of a type of white blood cells (granulocytes) essential for immune functioning↩
  9. The period between the start of the QRS complex (on an electrocardiogram [ECG]) to the end of the T wave. Prolongation of the QT interval is associated with potentially very serious rhythm disorders such as torsades de pointes↩