How effective are second-generation antipsychotic drugs? A meta-analysis of placebo-controlled trials

Abstract

We conducted a systematic review and meta-analysis of randomized controlled trials that compared second-generation antipsychotic (SGA) drugs with placebo in schizophrenic patients and which considered 13 different outcome measures. Thirty-eight randomized controlled trials with 7323 participants were included. All SGA drugs were more effective than placebo, but the pooled effect size (ES) for overall symptoms (primary outcome) was moderate (À0.51). The absolute difference (RD) in responder rates was at 18% (41% responded to drug compared with 24% to placebo, number needed to treat = 6). Similar ESs were found for the other efficacy parameters: negative symptoms (ES = À0.39), positive symptoms (ES = À0.48), depression (ES = À0.26), relapse (RD 20%) and discontinuation due to inefficacy (RD 17%). Curiously, the efficacy of haloperidol for negative and depressive symptoms was similar to that of the SGA drugs. In contrast to haloperidol, there was no difference in terms of EPS between any SGA drugs and placebo, and there was also no difference in terms of dropouts due to adverse events. Meta-regression showed a decline in treatment response over time, and a funnel plot suggested the possibility of publication bias. We conclude that the drug versus placebo difference of SGA drugs and haloperidol in recent trials was moderate, and that there is much room for more efficacious compounds. Whether methodological issues account in part for the relatively low efficacy ESs and the scarcity of adverse event differences compared with placebo needs to be established.

Efficacy of Antimanic Treatments: Meta-analysis of Randomized, Controlled Trials

“…Exclusion of two small studies of tamoxifen with large drug-placebo differences did not change these results (RD ¼ 0.17, Hedges' g ¼ 0.41, NNT ¼ 6). The close similarity of these computed measures of drugover-placebo efficacy to the meta-analytically pooled efficacy of SGAs in schizophrenia is noteworthy (Leucht et al, 2009).…”

“…For example, in their evaluation of antidepressants for major depressive disorder (MDD), Moncrieff and Kirsch (2005) found only a two point difference between drug and placebo on the Hamilton rating scale for depression. Leucht et al (2009) in a metaanalytic review of 38 studies reported a difference of only nine points on the brief psychiatric rating scale between SGAs and placebo in patients diagnosed with schizophrenia. The few previous meta-analytic assessments of relative efficacy of treatments for mania usually involved selective consideration of agents of particular interest, and none has considered outcomes of all available RCTs, as identified through clinical trial registries (Emilien et al, 1996;Perlis et al, 2006b;Scherk et al, 2007;Smith et al, 2007;Tohen et al, 2001).…”

Impaired integration of disambiguating evidence in delusional schizophrenia patients

“…Such cognitive-focused interventions are crucial because of the limited effectiveness of pharmacological treatments (Elkis, 2007;Leucht et al 2009) and low medication compliance in psychosis (Byerly et al 2007). Thus, the BADE represents a promising area of focus for cognitive-based interventions and assessing treatment responsiveness in psychosis.…”

Frontale Hirnvolumenminderung durch Antipsychotika?

“…Durch ergänzende längerfristige Einzeltherapie und vor allem Familieninterventionen lässt sich die Anzahl der Rück-fälle gemäß Studienlage deutlich reduzieren [9,123]. 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.…”