Clozapine was the only antipsychotic associated with a decreased risk of attempted or completed suicide in a study involving two nationwide cohorts of patients with schizophrenia. Researchers published the findings in Schizophrenia Bulletin online.
“According to our results, for persons with suicide attempts, clozapine should be the preferred choice of antipsychotic,” researchers wrote. “The main results and sensitivity analyses from both cohorts support this notion.”
The study compared attempted or completed suicide during periods of antipsychotic use and nonuse among 61,889 people with schizophrenia in Finland and 29,823 people with schizophrenia in Sweden. The investigation spanned the 10 most commonly used antipsychotic monotherapies as well as adjunctive pharmacotherapies.
Clozapine stood out as the sole antipsychotic consistently linked with a decreased risk of suicidal outcomes, compared with no antipsychotic use, the study found. The hazard ratio of attempted or completed suicide with clozapine was 0.64 among patients in Finland and 0.66 among patients in Sweden.
“The mechanisms behind the effectiveness of clozapine in preventing suicides and suicide attempts are not entirely clear, but it is known that clozapine’s ability to bind central nervous system receptors is distinct from other second-generation antipsychotics and, in randomized controlled trials, clozapine is substantially more efficacious than other antipsychotics for overall symptoms and, especially, for depressive symptoms that may predispose patients to suicidal behavior,” researchers wrote.
Benzodiazepines and related Z-drugs, on the other hand, were associated with a heightened risk of suicidal outcomes. According to the study, hazard ratios of attempted or completed suicide were between 1.29 and 1.30 for benzodiazepines and between 1.33 and 1.62 for Z-drugs.
“The use of benzodiazepines and related drugs has been linked with reduced impulse control, even after their hypnotic effect wears off, which increases the translation of suicidal ideation to suicidal actions,” researchers wrote. “Our results likely reflect actual risks associated with benzodiazepine use, as our within-individual analysis eliminates selection bias.”
Taipale H, Lähteenvuo M, Tanskanen A, Mittendorfer-Rutz E, Tiihonen J. Comparative effectiveness of antipsychotics for risk of attempted or completed suicide among persons with schizophrenia. Schizophrenia Bulletin. 2020 August 15;[Epub ahead of print].