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Pharmacologic Cotreatment in Patients With Schizophrenia

Pharmacologic Cotreatment in Patients With Schizophrenia

  • Which psychotropic combinations unlock the door to successful treatment? View the slides in PDF format.

  • • Many patients with schizophrenia have residual symptoms despite ongoing antipsychotic treatment
    • Adding medications to antipsychotics is a common treatment strategy in schizophrenia, but no combination is approved for this indication

  • • Many (generally small) randomized controlled trials (RCTs) have studied pharmacologic combination strategies in schizophrenia
    • Meta-analyses of these strategies have led to evidence-based recommendations; however, these approaches have not been quantitatively compared with antipsychotic monotherapy
    • Moreover, the quality of these meta-analyses (and their individual studies) have not been examined

  • • Correll and colleagues[1] performed a systematic review of meta-analyses of pharmacologic combination strategies in schizophrenia to facilitate decision-making
    • They searched PubMed and PsycINFO from inception until May 2016
    • Meta-analyses of RCTs that reported effect sizes for pharmacologic agents plus antipsychotics versus antipsychotic monotherapy in schizophrenia were included

  • • The primary outcome measure was change in total psychopathology rating scale scores
    • Key secondary outcomes were positive and negative symptom subscale scores, and the recommendation for or against combination treatment
    • Data for combination strategies involving clozapine were analyzed separately

  • • Methodological quality of included meta-analyses was assessed using A Measurement Tool to Assess Systematic Reviews (AMSTAR)
    • Study authors developed additional items to assess content quality of these meta-analyses
    • The authors conducted random-effects meta-analyses of effect sizes for combination treatments versus monotherapy
    • They also performed meta-regression analyses of study quality scores and sample size on associations with psychopathology

  • • Twenty-nine meta-analyses were included, representing 381 meta-analyzed trials and 19,321 patients, and 42 different psychotropic cotreatment strategies
    • The individual meta-analyses included a mean of 8 studies and a mean of 50 subjects per study
    • Subjects had a mean age of 38 and illness duration of 13 years, and 65% were male

  • • Fourteen of 32 agents combined with antipsychotics were significantly superior to controls for total psychopathology, generally with medium to large effect sizes (compared with 6 of 25 agents for positive symptoms, 12 of 26 for negative symptoms, and 0 of 5 for studies with clozapine)
    • Twenty augmentation strategies were at least partially recommended by authors, including 12 for which there were not significantly different effects between combination treatments and controls

  • • Of 37 comparisons, 33 (89%) had good study quality (AMSTAR scores of > 7) and 18 (49%) had the maximum AMSTAR score of 11
    • However, evidence for most combination treatments was exposed to potential inconsistencies, including small cumulative sample size, between-study heterogeneity, and potential publication bias
    • Effect sizes for total psychopathology were positively correlated with author recommendations and negatively correlated with study quality

  • • Fourteen of 37 pharmacologic combination strategies outperformed controls for reducing total psychopathology
    • However, effect sizes were inversely correlated with meta-analytic study quality, reducing confidence in recommendations

  • • The authors called for higher-quality trials and patient-based meta-analyses to determine if certain subpopulations might benefit from specific combination treatments
    • No single combination treatment strategy can be recommended for patients with schizophrenia based on the current literature

View the slides in PDF format.


It is not known what agents were more effective,and what agents were used,to me this information is not useful.

abid @

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