Antipsychotic drugs

Antipsychotic drugs are also known as ‘major tranquillisers’ or ‘neuroleptics’. There are now two distinct groups of antipsychotics: the older ‘typical’ drugs such as chlorpromazine and haloperidol, and the newer ‘atypical’ drugs, such as risperidone and olanzapine. They are used to treat psychotic disorders, such as schizophrenia, psychotic depression and mania, and to calm severe agitation. The atypical antipsychotic drugs also have mood stabilising effects, and are increasingly used in the treatment of bipolar disorder, both in the acute phase and prophylactically.

Antipsychotic drugs were first discovered in the 1950s. The tranquillising properties of chlorpromazine were noticed when it was used as a sedative prior to surgery, and this led to trials of its effects in patients with mental illness. The results were startling, with patients who had been chronically ill and untreatable in some cases able to recover normal functioning. The use of chlorpromazine, and other drugs that were rapidly developed, became widespread. The impact of this, the first effective treatment for schizophrenia, was profound. It made possible the closure of psychiatric inpatient beds, and the move to treatment of patients with serious mental illness in their own homes, that continues today. In the 1990s the atypical drugs were developed, and in general were better tolerated, and therefore more acceptable to patients. They are now more commonly prescribed than typical antipsychotics. Typicals are still used in depot medications, as there are limited atypical alternatives, and for patients who have been well on typical medications over many years. It is now considered to be good practice to offer atypicals to patients starting on antipsychotic drugs for the first time. The most effective antipsychotic, clozapine, is an atypical that was first discovered in the 1950s, but was thought to be too dangerous to use because it can cause agranulocytosis. The development of effective systems for monitoring patients on clozapine has allowed this drug to be reintroduced for the treatment of patients who do not respond to other antipsychotic drugs.

All antipsychotics have a calming effect which begins quickly, and they can provide rapid relief for an extremely distressed patient. The action on psychotic symptoms is slower, over a period of one or two weeks. In treatment of acute symptoms low doses are used initially, either orally or by intramuscular injection, and increased according to the patient’s response, and side effects. In the long-term treatment of chronic schizophrenia, antipsychotics control continuing symptoms and prevent acute relapse.

How do antipsychotics work?

The older antipsychotics act by blocking dopamine receptors in the brain. The mechanism of action of the atypical antipsychotics varies from drug to drug. They generally have a specific dopaminergic action, blocking a subtype of dopamine receptors known as D2. They also have serotonergic and alpha-adrenergic effects, and some work selectively in the mesolimbic cortex. This gives them a significant advantage over the older drugs in that they produce few or no extrapyramidal effects (see below). However they do have other side effects that can limit their use in some patients, and are significantly more expensive than typical antipsychotics. In general the atypicals are no more effective than the older drugs in treating psychotic symptoms. The important exception to this is clozapine, which is reserved for treatment-resistant schizophrenia (see below).

Side effects

Typical antipsychotics have a characteristic side-effect profile, as follows:

Extrapyramidal effects. There are four types:

Acute dystonia: severe muscle spasms occur, often affecting the neck or eyes (oculogyric crisis). This can be painful and distressing and occurs in up to 10% or patients, usually in the first few days of treatment.

Parkinsonian symptoms: lack of facial expression, increased muscle tone and tremor, occurring in about a third of patients.

Akathisia: a distressing side effect characterised by physical and psychological restlessness. It is present in up to a third of patients.

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