It is well established that maintenance treatment with antipsychotic medication decreases relapse rates in patients with schizophrenia. However, a substantial proportion of patients will relapse or stop taking their medication. This may be caused by adverse effects associated with the drugs. It is postulated that newer, atypical antipsychotics, which have a different spectrum of receptor effects and a lower frequency of extrapyramidal side effects, may improve treatment compliance and reduce the risk of relapse.

To investigate this premise, Dr Stefan Leucht from the Technical University in Munich and colleagues reviewed prospective, randomized, controlled trials studying the relapse of schizophrenia in patients taking new antipsychotic medication.

Data on relapse, general treatment failure and dropout due to adverse events was collected and subjected to meta-analysis.

Overall, 17 studies involving 3,015 participants, aged between 34-63 years were analyzed. Most patients had DSM-III-R schizophrenia, although some trials did include patients with schizoaffective or schizophreniform disorders. All trials were of six months duration or longer.

Compared to placebo, the new antipsychotic drugs had significantly lower raw relapse rates and reduced relapse rates estimated from survival curves.

The researchers found that overall treatment failure with the new antipsychotics was significantly lower compared to placebo. They also observed that the tolerability of new antipsychotics was not significantly different from placebo during the 6-12 month period of these studies.

Overall, 43 per cent of patients on new antipsychotics compared to 72 per cent of those on placebo left the studies early because of relapse, adverse events and loss to follow-up.


Eleven studies with a total of 2,032 patients provided comparative data on relapse/treatment failure for the new generation and conventional psychotics.

Statistical analysis revealed that the rates of relapse and overall treatment failure were modestly but significantly lower with the newer drugs. No significant difference in drop out rates was identified between newer and conventional drugs.

Dr Leucht, writing in the American Journal of Psychiatry says, “ The available data do not allow for any conclusion about whether this superiority for new antipsychotics in relapse prevention is related to enhanced efficacy, better adherence or a combination of these factors. Although adherence is a critical issue in the maintenance treatment of schizophrenia, it was poorly monitored in the trials.”

And the team conclude that although the meta-analysis is subject to limitations resulting from methodological problems, there is a modest reduction in relapse rates and treatment failure with the new antipsychotics. The absolute reduction of the relapse risk by 8 per cent per year by newer antipsychotic medication is as strong evidence as that supporting the use of aspirin to prevent vascular events, they say.

Reference: Leucht et al, American Journal of Psychiatry 2003;160:1209-1222

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