There is no clear evidence that atypical antipsychotics are more effective or better tolerated than conventional antipsychotics, according to the authors of a meta-analysis published last week (British Medical Journal 2000;321:1371).
Dr John Geddes (senior clinical research fellow, department of psychiatry, University of Oxford) and colleagues say that conventional antipsychotic drugs should remain as the first treatment option for schizophrenia although atypicals are of value especially when extrapyramidal side effects are a problem.
The researchers reviewed 52 trials which included 12,649 patients. Most of the trials compared the effectiveness of atypicals with haloperidol, although occasionally chlorpromazine, flupenthixol, perphenazine and zuclopenthixol were the comparators. Most trials were short term but five provided follow-up data for one year or more.
The researchers identified a significant advantage, in terms of efficacy and drop-out rates, for atypical antipsychotics as the dose of the comparator, haloperidol, increased. However, these advantages were not seen in trials where haloperidol was used at recommended doses of 12mg/day or less.
The researchers say that, overall, no evidence was identified to suggest that any atypical antipsychotic had a specific effect on either positive or negative symptoms. "Benefits seemed evenly spread, " they say.
In an accompanying leading article, Professors Shitij Kapur and Gary Remmington (associate professors of psychiatry, schizophrenia program and PET centre, Toronto, Canada) say that the article provides sobering evidence that questions the optimism surrounding the use of atypical antipsychotics. However, they point out that meta-regression analyses often miss the enhanced efficacy of drugs that can be shown in carefully designed controlled trials (ibid, p1360).
Dr David Taylor (chief pharmacist, Maudsley hospital, London) told The Journal on December 6 that three points needed to be raised about the review. First, the review pointed out that conventional antipsychotics are tolerated at low doses. Dr Taylor commented that there was evidence to show that such doses were too low to be effective. Secondly, the paper recommended the use of atypicals after conventional drugs had failed. "The available evidence does not bear this out. Only clozapine can be recommended properly for people not responding to conventional drugs, " he said.
The third point raised by Dr Taylor was that the review did not address the common practice of co-prescribing. Atypicals were often co-prescribed with conventional antipsychotics and so, in practical terms, arguments about tolerability were not relevant, he said.