Since clozapine was introduced about 10 years ago, several new drugs have been marketed for the treatment of schizophrenia. Most of these drugs are designed to control negative symptoms and produce fewer extrapyramidal side effects than conventional medications. Geddes and colleagues reviewed the literature on the efficacy and side effect profile of the new, atypical antipsychotic agents and compared these findings with the performance of conventional medications.

The authors used systematic search strategies to identify randomized, controlled trials comparing atypical with conventional antipsychotic medications in the treatment of schizophrenia. Drug companies and leading experts were also asked to provide details of any unpublished comparative trials completed before December 1998. Each trial was analyzed for inclusion and exclusion criteria, characteristics of the patients studied, outcome measures and duration of follow-up. Specific data extracted for each trial included symptom scores or rating scales, quality-of-life measures, drop-out numbers, number and type of side effects, and costs. Authors of trials were contacted for missing information. The quality of each study was assessed on the basis of bias, such as information on blinding and details about completeness of patient follow-up.

In the 52 trials identified, more than 12,600 patients met inclusion criteria. Most trials compared atypical antipsychotic medications with haloperidol, were of short duration (median: 6.5 weeks follow-up) and had significant drop-out rates. The drugs studied included clozapine, olanzapine, quetiapine, risperidone and sertindole. The effect of the atypical medications on negative symptoms compared with haloperidol depended on the dosage of haloperidol used. At up to 12 mg daily, atypical antipsychotics had no significant advantage over haloperidol in control of symptoms and tolerance. With dosages of 12 mg or more of haloperidol daily, atypical antipsychotics had significant benefits in efficacy or tolerability, and caused fewer extra-pyramidal side effects. No reliable evidence could be found of differential effects between the atypical agents studied.

The authors conclude that the initial impression of significant benefit from atypical antipsychotics was too simplistic. The effect on symptoms was similar between atypical agents and haloperidol up to 12 mg daily. Overall tolerability was similar between the two classes of drugs, but atypical agents caused fewer extra-pyramidal side effects. They recommend that conventional agents, such as haloperidol, remain the first line of treatment, but the choice for an individual patient can now include several agents, depending on the potential for side effects.