Head-to-head comparisons of metabolic side effects of second generation antipsychotics in the treatment of schizophrenia: A systematic review and meta-analysis

Abstract

Objective-The metabolic side effects of second-generation antipsychotics (SGA) are serious and have not been compared head to head in a meta-analysis. We conducted a meta-analysis of studies comparing the metabolic side effects of the following SGAs head-to-head: amisulpride, aripiprazole, clozapine, olanzapine, quetiapine, risperidone, sertindole, ziprasidone, zotepine.Method-We searched the register of the Cochrane schizophrenia group (last search May 2007), supplemented by MEDLINE and EMBASE (last search January 2009) for randomized, blinded studies comparing the above mentioned SGA in the treatment of schizophrenia or related disorders. At least three reviewers extracted the data independently. The primary outcome was weight change. We also assessed changes of cholesterol and glucose. The results were combined in a meta-analysis.Results-We included 48 studies with 105 relevant arms. Olanzapine produced more weight gain than all other second-generation antipsychotics except for clozapine where no difference was found. Clozapine produced more weight gain than risperidone, risperidone more than amisulpride, and sertindole more than risperidone. Olanzapine produced more cholesterol increase than aripiprazole, risperidone and ziprasidone. (No differences with amisulpride, clozapine and quetiapine were found). Quetiapine produced more cholesterol increase than risperidone and ziprasidone. Olanzapine produced more increase in glucose than amisulpride, aripiprazole, quetiapine, risperidone and ziprasidone; no difference was found with clozapine. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Conclusions-Some SGAs lead to substantially more metabolic side effects than other SGAs. When choosing an SGA for an individual patient these side effects with their potential cause of secondary diseases must be weighed against efficacy and characteristics of the individual patient. NIH Public Access

Altered reward anticipation: Potential explanation for weight gain in schizophrenia?

“…A recent meta-analysis showed that all antipsychotic drugs are associated with weight gain (Bak et al, 2014). Moreover, antipsychotic medication is not only related to weight gain in schizophrenia but also in other severe mental disorders (Bak et al, 2014;Parsons et al, 2009;Rummel-Kluge et al, 2010). In the following, we will review evidence for a common pharmacological mechanism and a relation to reward anticipation.…”

“…While the amount of weight gain resulting from different antipsychotics may vary, when looking for a common mechanism, we need to consider which specific pharmacological properties olanzapine or clozapine have that ziprasidone or aripiprazole do not (these specific properties are documented in a meta-analysis of head-to-head trials by Rummel-Kluge et al, 2010). One candidate mechanism of increased weight gain is the antihistaminergic property of both olanzapine and clozapine (Deng et al, 2010).…”

“…A meta-analysis of head-to-head randomized trials seems to suggest that the most effective drugs indeed show the strongest weight gain, although the authors did not systematically assess the relation (Rummel-Kluge et al, 2010). In line with this notion, previous studies indicated that weight gain and improving psychopathology during clozapine treatment are linked (Meltzer et al, 2003).…”

Frontale Hirnvolumenminderung durch Antipsychotika?

“…Eine generell anzuwendende, initiale Standardmedikation mit Antipsychotika und ihre jahrelange Fortführung in "wirksamer Dosis" ohne Empfehlungen zur längerfristigen Dosisminderung mit dem Argument der Rückfallprophyla-xe entsprechend vieler Leitlinien [124] ist bei insgesamt minimaler [125] bis mäßi-ger [126] Verbesserung der Symptomatik durch Antipsychotika kritisch zu diskutieren. Die erwünschten Wirkungen der Antipsychotika sind gegen die oft dosisabhän-gigen und teilweise schweren metabolischen Nebenwirkungen [127,128,129], die im Alter noch deutlich zunehmen [130], und angesichts des erhöhten Risikos von Diabetes [131,132] und koronaren Herzerkrankungen [133] abzuwägen. Dies gilt insbesondere für Kinder und Jugendliche, bei denen die Nebenwirkungen oftmals besonders ausgeprägt sind [134,135].…”

Altered metabolic parameters in association with antipsychotic medication use in diabetes: A population based case-control study

“…The type of anti-psychotic drug or illness itself might increase the risk of developing diabetes (Bushe and Leonard, 2004;Melkersson and Dahl, 2004;Rummel-Kluge et al, 2010) and secondary hormonal changes may influence the metabolic changes (Bushe and Leonard, 2004;Melkersson and Dahl, 2004;Rummel-Kluge et al, 2010). .…”