A comprehensive analysis of 68 studies found that no antipsychotic significantly outperformed placebo in improving cognitive function in schizophrenia spectrum disorders.
A systematic review and network meta-analysis evaluated the effects of antipsychotic medications on cognitive function in schizophrenia spectrum disorders (SSDs), involving 68 studies and 9,525 participants (mean [SD] age, 35.1 [8.9] years; 70% male). The analysis showed minimal differences in cognitive outcomes among antipsychotics. First-generation dopamine antagonists, including haloperidol (standardized mean difference [SMD], 0.04; 95% confidence interval [CI], −0.25 to 0.33) and fluphenazine (SMD, 0.15; 95% CI, −0.39 to 0.69), along with clozapine (SMD, 0.12; 95% CI, −0.23 to 0.48), ranked low for cognitive improvement.
No individual antipsychotic was linked to significantly better cognitive outcomes than placebo, although antipsychotics as a class showed small effect sizes across receptor profiles. The mean SMDs were as follows: adrenergic/low dopamine, 0.21; serotonergic/dopaminergic, 0.26; muscarinic, 0.28; dopaminergic, 0.40. These small effects may reflect general symptom reduction rather than specific cognitive enhancement.
The analysis, published in JAMA Psychiatry, noted substantial heterogeneity in the measurement of cognitive performance across trials, limiting definitive conclusions. The researchers indicated that standardizing cognitive assessments—such as consistently using the MATRICS Consensus Cognitive Battery (MCCB)—in clinical trials could enhance result consistency. Additionally, findings suggested that first-generation dopamine antagonists and clozapine may be less beneficial when cognitive deficits are a concern.
Full disclosures can be found in the published analysis.