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Keywords:

11 Medical and Health Sciences, 17 Psychology and Cognitive Sciences, Psychiatry, 3202 Clinical sciences

Abstract:

BACKGROUND: Antipsychotic cotreatment (APCT), frequent in clinical care, has been criticized for lack of supportive evidence and additive adverse effects, but improved side effects have also been described. METHODOLOGY: Metaanalysis of randomized placebo controlled trials (RPCTs) of APCT vs. placebo in schizophrenia. Primary outcome was change in weight or BMI. Secondary outcomes included other cardiometabolic, prolactin and psychopathology outcomes. For dichotomous data relative risk (RR) and for continuous data Hedges’s g was calculated as effect size measures, each with 95% Confidence Intervals (CIs), and with number-needed-to-treat (NNT) and standardized/weighted mean difference (SMD/WMD) as appropriate. RESULTS: 8 RCPTs (n=786) lasting 8-16 weeks were analyzed. Compared with placebo, only adding aripiprazole to clozapine or olanzapine (N=3, n=283) was associated with significant weight loss [SMD=-0.5 (CI:-0.8,-0.3), p<0.0001; WMD=-1.7kg (-2.8,-0.6, p=0.003], greater weight loss >7% [N=1, n=206, RR:4.9 (CI:1.5,16.4), p=0.009; NNT=9 (CI:6-25)] and significant reduction in total cholesterol [N=2, n=246, SMD=-0.4 (CI:-0.7,-0.2), p=0.0009)], LDL-cholesterol [N=2, n=241, SMD=-0.3 (CI:-0.6,-0.1), p=0.002)] and triglycerides [N=3, n=273, SMD=-0.4 (CI:-0.7,-0.0), p=0.05)], but not of HDL-cholesterol (p=0.95) or glucose (p=0.41). No significant cardiometabolic effects were found with risperidone or fluphenazine augmentation of clozapine (N=3, n=119), aripiprazole augmentation of quetiapine or risperidone (N=1, n=290) or aripiprazole augmentation of haloperidol (N=1, n=54). Groups were similar regarding total (p=0.25-0.94), positive (p=0.30-0.99) and negative symptoms (p=0.19-0.94). Side effects were similar across groups, except for prolactin decrease when adding aripiprazole to clozapine (p=0.0005) or quetiapine/risperidone (p<0.0001), while adding risperidone to clozapine raised prolactin (p<0.0001]. CONCLUSION: Specific APCTs differ in their cardiometabolic effects. Short-term addition of aripiprazole to a high metabolic risk antipsychotic (olanzapine, clozapine), but not to a medium (quetiapine, risperidone) or low risk (haloperidol) agent significantly improved body weight and lipid parameters. Adding risperidone or fluphenazine to clozapine was not beneficial, and none of the combinations benefited or worsened psychopathology or short-term adverse effects, except for increased prolactin when adding risperidone to clozapine, while aripiprazole addition to clozapine, quetiapine or risperidone lowered prolactin.