A Meta-Analysis of Head-to-Head Comparisons of Second-Generation Antipsychotics in the Treatment of Schizophrenia

Review of Leucht, S., Komossa, K., Rummel-Kluge, C., Corves, C., Hunger, H., Schmid, F., Lobos C., Schwarz, S. & Davis, J. (2009).  “A Meta-Analysis of Head-to-Head Comparisons of Second-Generation Antipsychotics in the Treatment of Schizophrenia.”  Am. J. Psychiatry, 166, 152 – 163.

One of the earliest drugs to treat schizophrenia was chlorpromazine (thorazine), discovered by the French surgeon Henri Laborit in 1952.  Chlorpromazine is what is referred to as a “typical antipsychotic.”  A leading hypothesis is that one of the main causes of schizophrenia is too much dopamine.  Chlorpromazine works by blocking dopaminergic receptors (mesolimbic and nigrostriatal) in the central nervous system.  Chlorpromazine was tremendously successful and brought significant relief to millions of patients.  Unfortunately it has a significant side effect (among others).  Not enough dopamine causes muscle tremors known as tardive dyskinesia, which in turn resemble Parkinson’s Disease (ameliorated by L-dopa, a dopamine precursor).  In a way schizophrenia and Parkinson’s are reciprocals.

These and other issues lead to the development of “second generation” antipsychotics such as olanzapine, aripiprazole, quetiapine, risperidone and ziprasidone.  They have the same molecular action of chlorpromazine but without some of its side-effects.  This meta-analysis reviewed 78 clinical trials enrolling a total of 13,558 patients – an impressive level of participation.  It reviewed the efficacy of second-generation antipsychotics and analyzed their side effects.  The authors concluded olanzapine was better than aripiprazole, quetiapine, risperidone and ziprasidone; risperidone was better than quetiapine and ziprasidone; and clozapine was better than zotepine.  These differences mainly were due to improvement in “positive symptoms” (as defined in the DSM) rather than negative ones.  Subject to the caveats pertaining to all meta-analyses (such as whether the underlying data truly is comparable), this study is the most recent and comprehensive one in the literature and provides a useful guide