Antipsychotics fail to improve cognitive deficit in schizophrenia spectrum disorders: JAMA

A new study published in the Journal of American Medical Association showed that in individuals with schizophrenia spectrum disorders (SSD), not one antipsychotic was linked to superior cognitive results than a placebo. A significant portion of the symptoms of schizophrenia spectrum disorders include cognitive abnormalities, which also significantly increase the burden of the disease. Antipsychotic medications may have varying impacts on cognition because of their distinct receptor-binding characteristics, but they are not cognitive enhancers.

To ascertain if antipsychotic usage is connected with cognitive function in SSDs at all, no prior network meta-analysis compared antipsychotics to placebo. In order to rule out the relationship between therapy with different antipsychotics and cognition in patients with SSDs, Lena Feber and her team carried out this investigation. Through June 25, 2023, this research gathered information from 68 studies published between 1958 and 2022 that were part of the Cochrane Schizophrenia Trials Register. Blinded and unblinded randomized clinical studies that lasted at least 3 weeks and evaluated antipsychotics or antipsychotics vs placebo were included in the review.

Over half of the studies in the study had an overall high risk of bias, and 10 of the trials were open label. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses–Network Meta-analysis reporting guideline, a systematic review and random-effects frequentist network meta-analysis were conducted. The change in the total cognitive score of each study was the main result. Functioning, quality of life, and cognitive domains were secondary objectives.

First-generation dopamine antagonists, like fluphenazine and haloperidol, as well as clozapine, which has anticholinergic effects, ranked poorly in this systematic review and pairwise network meta-analysis, which included 68 studies with a total of 9525 participants. Furthermore, no particular antipsychotic was linked to a definite improvement over a placebo, and cognitive function was measured in a very varied and sometimes incomplete manner.

Despite the paucity of available data, the evidence examined in this study indicates that when cognitive problems are a concern, clozapine and first-generation dopamine antagonists should be avoided. Cognitive medicines are not antipsychotics. Rather than cognitive deficiencies in the traditional sense, the overall slight improvement in results over a placebo might be explained by less disorganized thought patterns linked to less pleasant feelings.

Source:

Feber, L., Peter, N. L., Chiocchia, V., Schneider-Thoma, J., Siafis, S., Bighelli, I., Hansen, W.-P., Lin, X., Prates-Baldez, D., Salanti, G., Keefe, R. S. E., Engel, R. R., & Leucht, S. (2024). Antipsychotic Drugs and Cognitive Function. In JAMA Psychiatry. American Medical Association (AMA). https://doi.org/10.1001/jamapsychiatry.2024.2890