A systematic review and meta-analysis of 68 studies with a total sample size of over 9,500 participants found that first-generation dopamine antagonists, such as haloperidol and fluphenazine, as well as clozapine with its anticholinergic properties, were less effective than other medications in slowing cognitive decline in patients with psychosis. However, the researchers found no significant difference between the medications. The results were published in JAMA Psychiatry.
Cognitive impairments constitute an independent, core component of schizophrenia spectrum disorders. They play a significant role in the course of the illness and significantly impact patients' quality of life. Specifically, patients experience impairments in attention, concentration, and memory.
Existing antipsychotics have varying effects on cognitive function in patients with schizophrenia. For example, some second-generation antipsychotics have been reported to have a more positive impact on cognitive performance than first-generation antipsychotics, such as haloperidol. However, most previous reviews and meta-analyses have been limited in terms of relevance, inclusion of new medications, and methodological quality.
Therefore, a team 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 were men and 30 percent were women.
The primary analysis showed no clear differences in their effects on cognitive function between antipsychotics. Overall, molindone and thioridazine performed better in assessing cognitive function in patients. 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 cognitive function in patients, although the total number of participants was small. In contrast, clozapine, fluphenazine, and haloperidol performed worst and were associated with lower cognitive performance. These results remained unchanged in most meta-regressions and sensitivity analyses.
A secondary analysis revealed that molindone and thioridazine were associated with a positive effect on processing speed, while brexpiprazole was associated with a small positive effect on visual learning. Paliperidone may be associated with improved cognitive performance in verbal learning. Haloperidol, fluphenazine, and clozapine, however, again consistently ranked lower in various cognitive domains.
The authors acknowledge that the results of this meta-analysis do not allow for the recommendation of a specific antipsychotic for the treatment of cognitive impairment in schizophrenic disorders. However, first-generation dopamine blockers, such as haloperidol or fluphenazine, and the anticholinergic clozapine should likely be avoided. However, improved clinical trial methodology in this area (e.g., the development of a comprehensive standardized assessment of cognitive functioning) is needed to ensure that meta-analyses and reviews are more reliable.
You can read more about schizophrenia and how far medicine has advanced in its treatment in the article "The Mind Thief."
