A systematic review and meta-analysis of 68 studies with a total sample of more than 9.5 thousand people showed that first-generation dopamine antagonists, such as haloperidol and fluphenazine, as well as clozapine with its anticholinergic properties, were worse than other drugs at slowing down the decline in cognitive functions in patients with psychosis. However, scientists did not find any significant difference between the drugs. The results were published in JAMA Psychiatry.
Cognitive impairments are an independent major part of schizophrenia spectrum disorders. They play a significant role in the course of the disease and greatly affect the quality of life of patients. In particular, patients experience impairments in attention, concentration and memory.
Existing antipsychotics have different effects on cognitive function in patients with schizophrenia: for example, some second-generation antipsychotics have been reported to have a more positive effect on cognitive abilities than first-generation drugs, such as haloperidol. However, most previous reviews and meta-analyses were quite limited in terms of relevance, inclusion of new drugs, and methodological quality.
Therefore, a group of scientists led by Stefan Leucht from the Medical School of the Technical University of Munich conducted a systematic review and meta-analysis of the most recent studies on the effects of antipsychotic drugs on cognitive function. The analysis included 68 studies, which involved a total of 9,526 participants. The studies were published between 1958 and 2022, and the average study duration was 12 weeks. The average age of the participants was 35.1 years, 70 percent of the participants were men and 30 percent were women.
The primary analysis showed that there were no clear differences in the effects on cognitive function between the antipsychotics. Overall, molindone and thioridazine ranked higher in patients’ cognitive function. However, the results for both drugs were based on a single study, each with a small sample size. Similarly, chlorpromazine also had a positive effect on patients’ cognitive function, although the total number of participants was small. In contrast, clozapine, fluphenazine, and haloperidol ranked lowest and were associated with lower cognitive performance. These results were not significantly changed in most meta-regressions and sensitivity analyses.
Secondary analyses showed that molindone and thioridazine were associated with a positive effect on processing speed, and brexpiprazole with a small positive effect on visual learning. Paliperidone may be associated with improved cognitive performance on verbal learning. Haloperidol, fluphenazine, and clozapine were again consistently inferior across cognitive domains.
The authors acknowledge that the results of this meta-analysis do not allow a specific antipsychotic drug to be recommended for the treatment of cognitive impairment in schizophrenic disorders. However, first-generation dopamine blockers such as haloperidol or fluphenazine and the anticholinergic clozapine should probably be avoided. However, the methodology of clinical trials in this area should be improved (e.g., development of a comprehensive standard assessment of cognitive functioning) so that meta-analyses and reviews can be more reliable.
You can read more about schizophrenia and how far medicine has advanced in its treatment in the article “The Mind Thief.”