Efficacy and Safety of First-Generation and Second-Generation Anti-Psychotic Drugs for Schizophrenia in Adults: An Overview of Systematic Reviews

Background The Norwegian Medicines Agency asked the Norwegian Knowledge Centre for the Health Services to review the documentation for antipsychotic drugs in order to evaluate differences in efficacy and safety between the various drugs used for schizophrenia in adults.Methods We searched systematically for literature in the Cochrane Library, Medline, Embase and PsychInfo. We evaluated all identified reviews according to predefined inclusion criteria and appraised the methodological quality of the included systematic reviews.Results We included six systematic reviews. We extracted and analyzed results on the efficacy or safety of first generation antipsychotics (typical antipsychotics) versus second generation antipsychotics (atypical antipsychotics) and among the various second generation antipsychotics. Of 99 possible comparisions, data were available on only 30. We found few differences in efficacy. However, haloperidole showed less efficacy than amisulpride and clozapine, and olanzapine led to greater improvement in functional capacity than quetiapine and ziprasidone. With respect to efficacy measured as symptom response among the second generation antipsychotics there were no differences. For adverse events, metabolic adverse events were most obvious for the second-generation antipsychotic drug olanzapine followed by clozapine and quetiapine, and extrapyramidal adverse events were most obvious for the first- generation antipsychotic drugs haloperidole and perfenazine. There were no differences in extrapyramidal symptoms among the second generation antipsychotics, except that quetiapin caused extrapyramidal symptoms in a greater proportion of patients than risperidon. There were no or few differences between the groups regarding cardiovascular, anticholinergic and hormonal adverse events as well as for discontinuation.Conclusion We found few differences in efficacy between first- and second- generation antipsychotic drugs, and among the second generation antipsychotics. For adverse events there were reported differences for at least one type of adverse event for the majority of the comparisons.