Meta-analysis finds minimal cognitive gains from antipsychotic medications

A systematic review and network meta-analysis of 68 studies found no clear evidence that a specific antipsychotic significantly improves cognitive function in patients with schizophrenia spectrum disorders compared to placebo.

Cognitive deficits are a core component of schizophrenia spectrum disorders (SSD), affecting memory, attention, and overall cognitive function, contributing significantly to the disease burden. Antipsychotics, widely used to manage SSD, are not considered or expected to improve cognitive functions.

Antipsychotics are primarily used to manage the core symptoms of SSD, such as hallucinations, delusions, reduced emotional expression, and social withdrawal. Since cognitive improvement is not the goal of these medications, it remains an understudied aspect of drug interactions.

Researchers led by the Technical University of Munich, Germany, wanted to determine the association between treatment with various antipsychotics and cognitive function in patients with SSD.

In a metadata review study, “Antipsychotic Drugs and Cognitive Function: A Systematic Review and Pairwise Network Meta-Analysis,” published in JAMA PsychiatryResearchers compared the effects of different antipsychotic medications with a placebo to assess whether these medications improve cognitive performance in patients with SSD.

The team searched for unblinded, randomized clinical trials of at least three weeks duration using standardized cognitive assessment tools, primarily the MATRICS Consensus Cognitive Battery. Data obtained from 9,525 participants determined that although antipsychotics as a group showed small cognitive benefits, no individual drug demonstrated a substantial benefit over placebo. Secondary analyzes revealed minimal effects on quality of life and social functioning.

First-generation antipsychotics, such as haloperidol and fluphenazine, as well as clozapine, achieved poor cognitive outcomes. Some second-generation antipsychotics, including paliperidone and sertindole, have shown slightly better cognitive outcomes, but without significant advantages over placebo.

Antipsychotics grouped by their receptor binding properties showed minor improvements in cognitive function, with standardized mean difference (SMD) effect sizes ranging from 0.21 to 0.40, but none demonstrated a Robust cognitive improvement. The SMD between drugs and placebo for different receptor binding profiles included: adrenergic/low dopaminergic (0.21), serotonergic/dopaminergic (0.26), muscarinic (0.28), and dopaminergic (0.40). ).

First-generation antipsychotics, such as haloperidol (0.04) and fluphenazine (0.15), ranked low in cognitive performance, as did clozapine, a second-generation antipsychotic often used to treat dementia. treatment-resistant schizophrenia, also ranked low (0.12).

For reference, a significant or noticeable SMD result would be equal to or greater than 0.5, with 0.8 considered a substantial difference.

Results for molindone and thioridazine were ranked higher, but were considered less reliable due to small sample sizes (15 to 22 participants) and use of only one measure, processing speed, to determine cognitive results.

These results suggest that antipsychotics provide limited cognitive benefits to patients with SSD. New or additional treatments specifically targeting the cognitive component of the disease are needed. The authors recommend avoiding first-generation dopamine antagonists and clozapine when cognitive deficits are of concern and highlight the need to standardize cognitive assessments across trials to improve comparability of results.

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