Study Question: Are the newer antipsychotic medications more effective than the older ones? Do they cause fewer extrapyramidal symptoms?

Setting: Various (meta-analysis)

Study Design: Meta-analysis (randomized controlled trials)

Synopsis: In this meta-analysis, investigators included studies that directly compared new generation antipsychotics (NGAs, such as clozapine and olanzapine) with conventional low-potency antipsychotics (LPAs, such as chlorpromazine and thioridazine). The primary intent of the study was to compare side effects, with a secondary goal to evaluate efficacy.

The investigators accessed numerous databases and the Cochrane register of randomized schizophrenia trials, and contacted manufacturers and first authors of included papers to track down unpublished studies. The Jadad scale was used to assess the quality of the 31 included trials (total of 2,320 patients). All data were extracted independently by two investigators, but they do not describe their process of conflict resolution. The mean Jadad score was 3.4 (on a scale of zero to 5), and no study had a score lower than 2. A funnel plot (a method of assessing potential publication bias) suggests that studies demonstrating no benefit of NGAs, with respect to extrapyramidal symptoms, may not have been found. No such bias occurred with any of their other outcomes.

The investigators converted the dosing of the LPAs to the equivalent dosage of chlorpromazine and then stratified the studies by those using less than 600 mg chlorpromazine equivalent per day and those using 600 mg or more. In 11 studies of clozapine, fewer extrapyramidal effects occurred in patients receiving clozapine than in those receiving LPAs (number needed to treat [NNT] = seven; 95 percent confidence interval, four to 25). No difference was found in extrapyramidal effects in other comparisons.

In the studies that compared lower dosages of LPAs, 295 of 584 patients taking NGAs had no clinically significant response, compared with 314 of 538 patients taking LPAs (51 percent versus 58 percent; NNT = 13; P =.02). In the studies using higher dosages of LPAs, the response was 156 of 234 patients and 218 of 248 patients showing no clinically significant response, respectively (67 versus 88 percent; NNT = five; P =.004). Even stratifying by dosage, there was significant variability between studies.

Bottom Line: In head-to-head trials, newer antipsychotic agents are slightly more effective than the older LPAs. Among the newer agents, only clozapine has fewer extrapyramidal side effects. (Level of Evidence: 1a–)