Unwanted effects

Antipsychotic drugs have a great many potential unwanted effects. Most common and troublesome are those involving the extrapyramidal nervous system, as follows:

• Parkinsonism, with tremor, rigidity, bradykinesia, and sialorrhoea

• akathisia, with mental agitation and motor restlessness

• acute dystonia, including torticollis, other abnormal postures, and oculogyric crisis.

All these extrapyramidal effects respond to anti-Parkinsonian drugs such as ben-zhexol or procyclidine, but these extra drugs should not be given unless required because they may cause sedation and confusion, and exacerbate psychotic symptoms and anticholinergic effects; moreover, they (especially procyclidine, because of a temporary mood-altering effect) may be abused.

Tardive dyskinesia is another syndrome of abnormal movements that develops in up to 20 per cent of patients on long-term antipsychotic drug treatment. Elderly, female, and brain-damaged patients are most likely to be affected. Involuntary movements of choreiform or athetoid type affect the orofacial muscles and sometimes the limbs or trunk. The cause may be proliferation or hypersen-sitivity of dopamine receptors after prolonged blockade by antipsychotic drugs, or imbalance between dopamine and its antagonists acetylcholine and GABA. There is no effective treatment; anti-Parkinsonian drugs help some patients. Reducing or, paradoxically, increasing the dose of the responsible antipsychotic may help. Prevention is better, and may be achieved by using the lowest anti-psychotic dose that is effective.

Other unwanted effects of antipsychotic drugs include hypotension, cardiac arrhythmia, either dry mouth or excessive salivation (sialorrhoea), constipation, weight gain, reduced fertility, bone marrow depression, blurred vision, retention of urine, impotence, jaundice, rash, photosensitivity, and hypothermia especially in the elderly.

Neuroleptic malignant syndrome is a rare, but potentially fatal, acute complication of antipsychotic drug use. Symptoms include catatonia or extrapyramidal movements, and hyperpyrexia. Affected patients require intensive medical care.

Antipsychotics are mainly metabolized in the liver. Their main drug interaction is to potentiate the sedative effects of other psychoactive substances, most importantly alcohol, antidepressants, and benzodiazepines. Liver damage is the main contraindication. Regarding use in pregnancy, no serious adverse effects on the foetus are known. Antipsychotic drugs enter breast milk in tiny amounts, but usually, if there is clear indication for their use, the benefit of having a healthy mother outweighs any potential risk to the infant. Antipsychotic drugs lower the convulsive threshold slightly, so caution is required in patients with epilepsy. They sensitize the skin to sunburn, so advice and sunblock preparation are needed in sunny periods.

Tolerance and dependence do not occur.

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