Placebo Response and Practice Effects in Schizophrenia Cognition Trials

Area of Science:

• Neuroscience and Clinical Psychology
• Psychiatric Clinical Trials

Background:

• Cognitive impairment associated with schizophrenia (CIAS) clinical trials are susceptible to practice effects from repeated cognitive testing.
• Distinguishing practice effects from true placebo effects is challenging in CIAS trials.

Purpose of the Study:

• To systematically evaluate the magnitude of practice effects on the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MCCB) battery in CIAS.
• To identify demographic, clinical, and cognitive factors associated with improvement in placebo conditions.

Main Methods:

• A blinded review of data from 813 patients with schizophrenia treated with placebo across 12 randomized controlled trials.
• Utilized data from 779 patients with baseline and follow-up MCCB composite scores.
• Seven trials included prebaseline assessments to directly compare practice and placebo effects.

Main Results:

• The mean MCCB composite score at baseline was 22.8 points below normative standards.
• The mean change in MCCB score during placebo treatment was 1.8 T-score points (0.18 SD), indicating minimal placebo effect.
• Practice effects were similar to placebo effects, and baseline depression, anxiety, and motivation were associated with greater MCCB improvement.

Conclusions:

• Placebo effects in CIAS trials are minimal and not responsible for the failure of active treatments to separate from placebo.
• The observed improvements are unlikely due to ceiling effects, as patients started significantly below normative scores.
• Understanding practice effects is crucial for accurately interpreting cognitive outcomes in CIAS clinical trials.