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Study reaffirms treatment effects for cognition in schizophrenia

Recent findings indicated placebo effects in schizophrenia cognition trials were not large enough to impact a treatment effect with small or medium effect size.

“Cognitive enhancement studies have typically used a regulatory pathway that was developed during the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative. Central to this method has been the assessment of cognition with a set of performance-based tests referred to as the MATRICS Consensus Cognitive Battery (MCCB),” Richard S. E. Keefe, PhD, of Duke University, Durham, North Carolina, and colleagues wrote. “However, the MCCB validation study used a single test-retest assessment, which does not reflect the complexity of standard clinical trials that have more than two assessments performed with the MCCB and multiple treatment conditions.”

To evaluate the impact of practice effects on the MCCB in cognitive impairment associated with schizophrenia, researchers conducted a blinded review of data for 813 individuals with schizophrenia treated in 12 randomized placebo-controlled trials.

At baseline, the mean MCCB score was 22.8 points below the normative mean, with a mean total change in MCCB during receipt of placebo of 1.8 T-score points or 0.18 standard deviation.

In the seven studies with prebaseline assessment, practice effects were “essentially identical” to postbaseline placebo changes, according to researchers.

Baseline factors associated with greater improvement in MCCB during receipt of placebo included depression and anxiety (P = .02), increased motivation (P = .03) and less improvement from screening to baseline (P < .001).

“In 12 double-blind, placebo-controlled, clinical trials for cognitive impairment associated with schizophrenia, the magnitude of placebo effects on the MCCB was small and not different from the retesting effects during the pretreatment screening period when patients knew that they were not receiving treatment,” the researchers wrote. “The magnitude of the placebo effect was not large enough to obscure a treatment effect with a small to medium effect size. There are patient and study characteristics that have a modest influence on postbaseline retest changes, and the number of reassessments is minimally associated with changes in performance on the MCCB.” – by Amanda Oldt

Disclosure: Keefe reports receiving investigator-initiated research funding support from the Department of Veterans Affairs, the NIMH, and the Singapore National Medical Research Council; receiving honoraria and serving as a consultant, speaker, or advisory board member for Abbvie, Acadia, Akebia, Akili, Alkermes, Astellas, Asubio, Avanir, AviNeuro/ChemRar, Axovant, Biogen, Boehringer Ingelehim, Cerecor, CoMentis, FORUM, Global Medical Education, GW Pharmaceuticals, Intracellular Therapeutics, Janssen, Lundbeck, MedScape, Merck, Minerva Neurosciences Inc, Mitsubishi, the Moscow Research Institute of Psychiatry, Neuralstem, Neuronix, Novartis, the New York State Office of Mental Health, Otsuka, Pfizer, Reviva, Roche, Sanofi, Sunovion, Takeda, Targacept, the University of Moscow, the University of Texas Southwest Medical Center, and WebMD; receiving royalties from the Brief Assessment of Cognition in Schizophrenia (BACS) testing battery and the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Battery (BACS Symbol Coding); and being a shareholder in NeuroCog Trials and Sengenix. Please see the study for a full list of relevant financial disclosures.