Using antipsychotic medication

Antipsychotic medications need to be well managed, write Dr Kit Wa Chan and Professor Peter Jones.

Antipsychotic medications represent the most effective intervention in the acute stage of schizophrenia and related illnesses.

'Start low, and go slow' is a useful clinical maxim when treating psychotic disorders, particularly in the treatment of the initial episode where patients can be sensitive to the effects.

Antipsychotic drugs take time to reach a threshold of response, although more minor benefits can occur much earlier.

Sometimes, the complete benefit of treatment in terms of functional recovery can take many months.

In the early stages of psychosis, treatment of other features such as agitation and anxiety should be managed separately, perhaps with benzodiazepines, rather than by increasing the antipsychotic dosage and relying on sedative side-effects.

Depot preparation
When prescribing a depot preparation, a test dose should be given to avoid severe and prolonged adverse effects. The depot should be started at the lowest therapeutic dosage and administered at the longest licensed interval. It takes about 6-12 weeks to reach steady plasma level; therefore, the dosage should only be adjusted after an adequate period of assessment.

For risperidone depot, the only second-generation compound currently available in this form, testing of tolerability and efficacy is desirable with the oral medication. The patient should remain on their full-dosage oral medication for at least three weeks after initiating the depot injection because it takes this amount of time to reach the therapeutic plasma level, due to the unique pharmaceutical preparation. As with many others, this depot must be administered every two weeks.

Side-effects
The tolerability of and adherence to antipsychotic treatment are closely linked. Patients will often experience the side-effects of an antipsychotic before they experience the therapeutic effects.

Therefore, it is important to monitor side-effects closely, especially during the initial phase of the treatment. Weight gain, sedation and sexual side-effects are particularly associated with poor compliance so need to be avoided if possible.

Postural hypotension can be a problem in the elderly and is relatively common with all drugs.

Compared with the second generation antipsychotics (SGA), the first generation anti- psychotic (FGA) drugs are more likely to cause extrapyramidal side-effects (EPSE), such as akathesia, dystonias, Parkinsonism and tardive dyskinesia (with long-term use). These effects, other than akathesia and tardive dyskinesia, can be managed with anticholinergic medications if required, and there is evidence to suggest that, on average, the dosages required for an antipsychotic effect are a little lower than those producing EPSE, so careful dosage reduction is an option, particularly with risperidone.

Hyperprolactinaemia is seen with FGAs and risperidone, and can lead to menstrual irregularities and galactorrhoea.

Weight gain and metabolic side-effects such as impaired glucose tolerance and hyperlipidemias are rising to prominence now that EPSE can be avoided, and may contribute to the burden of cardiovascular morbidity and mortality in people with schizophrenia.

Adverse changes should lead to intervention in the normal way. This is an area where liaison between primary care and specialist mental health services are vital.

The prescribing and monitoring of clozapine is more stringent and should be done according to its specific guidelines because of its potentially lethal complications of neutropenia (3 per cent), agranulocytosis (0.8 per cent) and hypersensitivity myocarditis (risk estimated to be increased 1,000-fold in the first month of treatment). 1

Switching medication
When switching antipsychotics, slow cross-tapering over a couple of weeks is the safest approach. Changing from one antipsychotic to another can be high risk in terms of side-effects and uncertainty concerning the efficacy of the new compound.

Many antipsychotic drugs with a long half-life, including SGAs such as olanzapine, show antimuscarinic effects and a cholinergic rebound if they are stopped abruptly. This can be confused with relapse on the new compound (which is also possible) and is best avoided by cross titration and management of emergent effects, as well as patient expectation.

To switch to clozapine, cross tapering should be done carefully because of the additive side-effects (for example, effects on QTc intervals) and the effect on drug levels (risperidone may increase clozapine levels).

All depot medication should be stopped before starting clozapine. When stopping clozapine, rebound psychosis in patients who have severe illness is a possibility.

However, it is important not to leave patients on clozapine with its high side-effect burden if no benefit is apparent after augmentation has been tried.

Stopping treatment
It can be a difficult decision to stop treatment, particularly after a first episode of psychosis where a person may not appreciate the benefits of relapse prevention. Relapse after the first episode is common, particularly where other factors such as substance misuse and non-adherence with prescribed drugs are present.

A second episode of acute psychosis can be devastating. We encourage patients to remain on antipsychotic medication for at least a year, and ideally two, before taking a drug-free trial.

Risk-benefit ratio
Patients with schizophrenia can benefit from taking antipsychotic medication, but one of the major problems is side-effects, which probably have a great deal to do with the poor adherence.

- Dr Chan is a specialist registrar and Professor Jones is professor of psychiatry and head of department at the University of Cambridge.

Reference
1. Lieberman J. Effectiveness of antipsychotic drugs in patients with chronic schizophrenia: efficacy, safety and cost outcomes of CATIE and other trials. J Clin Psychiatry 2007; 68(2): e04.

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