Mental Health | Stopping and Switching antipsychotic drugs is Serious

Mental Health HelpMental Health | In general, specialist advice should be sought when stopping or switching antipsychotics.

While antipsychotics are often needed long term, there are circumstances when clinicians, patients and families should reconsider the benefits versus the harms of continuing treatment. Consideration should always involve your prescriber.

Withdrawal syndromes, relapse and rebound can occur if antipsychotics are discontinued, especially if they are stopped abruptly. Generally, they should be reduced and stopped slowly, ideally over weeks to months

Relapse of psychosis and exacerbation occur in most patients with psychotic disorders, occasionally with drastic consequences. Sometimes this occurs many months after stopping anti-psychotics

Switching from one antipsychotic to another is frequently indicated due to an inadequate treatment response or unacceptable adverse effects. It should be carried out cautiously and under close observation

Stopping antipsychotic drug therapy is feasible and appropriate in a number of clinical circumstances. For patients who require long-term treatment, switching to another antipsychotic may be needed if their response to treatment has been inadequate, or unacceptable adverse effects have occurred.

For patients with serious psychiatric illness, stopping or switching antipsychotics requires referral to a specialist if possible. However, for patients on small off-label doses of antipsychotics for behavioral disturbance in dementia or for sleep problems, it may be reasonable for the GP to taper the dose and stop treatment with careful monitoring.

Off-label uses and consequences

Psychiatrists also use some antipsychotics such as olanzapine, quetiapine and risperidone for off-label indications. An example would be adjunctive initial treatment of severe major depression when rapid relief of agitation, insomnia and suicidality is needed while waiting for antidepressants to take effect. As a consequence, GPs are seeing a broad spectrum of patients (not merely those with schizophrenia) who have been started on antipsychotics, often in combination with other psychotropic drugs.

It has been common practice to continue these antipsychotics long term, especially when treatment of an acute episode has been reasonably successful. However, long-term antipsychotic use can have serious consequences including tardive dyskinesia, weight gain, metabolic syndrome, diabetes and cardiovascular complications.

Withdrawing antipsychotics

When stopping an antipsychotic, individual circumstances must be carefully considered including illness severity and history, risk of relapse and its consequences, treatment response and prognostic factors, and the patient’s social situation. If possible, antipsychotics should be stopped very slowly under close medical observation. Abrupt discontinuation can result in rebound psychosis which can be more severe than before treatment was started. This is not uncommon when stopping clozapine as a result of complications such as agranulocytosis or myocarditis. Depending on the pharmacological action of the antipsychotic, several withdrawal syndromes can occur.

Direct switch

While it is possible to stop the first drug and start the second drug the next day, this may result in withdrawal symptoms and possible drug interactions. When the first antipsychotic is aripiprazole or brexpiprazole, a direct switch can be made as both these drugs have very long half-lives and no anticholinergic effects.

Cross titration

Evidence indicates there may be little difference in the risk of relapse with immediate and gradual antipsychotic stopping or switching.11 Most psychiatrists use the cross-titration strategy. This involves a reduction of the first antipsychotic while introducing the second drug.
Continuation with slower titration and discontinuation

Mental HealthA slower approach to titration is to continue the first antipsychotic for a period at its usual dose while gradually increasing the therapeutic dose of the second antipsychotic. The first antipsychotic can then be gradually reduced and stopped. The risk of relapse is minimised with this approach, but there may well be additive adverse effects during the process.

There are a variety of clinical circumstances in which stopping an antipsychotic should be considered and undertaken if appropriate. When it is necessary to switch from one antipsychotic to another during the course of treating psychoses, clinicians need to have some understanding of the pharmacokinetics and dynamics of antipsychotic drugs in order to plan and carefully monitor a switching regimen. This usually involves a period of both drugs being used simultaneously.

Stopping and switching antipsychotics can result in serious consequences, particularly a relapse of psychosis which may entail serious risks and worsen long-term prognosis. Withdrawal syndromes related to cholinergic and dopaminergic effects may occur depending on the characteristics of the antipsychotics involved.


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