Professor/Research Scientist Wegmans School of Pharmacy, St John Fisher College Rochester, United States
Background: Benztropine is a long-acting M1 muscarinic receptor antagonist/dopamine reuptake inhibitor for the extrapyramidal effects of antipsychotics and Parkinson's Disease (PD). It was associated with reduced risk of suicide attempts (OR=0.50, 95% CI=0.37, 0.68) in a new statistical drug-safety signal-generation system.
Objectives: To test the association between benztropine and suicidal behavior in North American adults, including commercially insured veterans.
Methods:
Design: Within-person exposure-only cohort study in MarketScan (IBM Watson) (164 million unique patients, including veterans). Subjects (N=62,493) were adults with an index benztropine fill in 2011–2019 (after at least 12 months with none) followed for 12 months or until disenrollment (including death), suicide attempt, or intentional self-harm. Setting: US privately insured adults. Most were prescribed benztropine with antipsychotics (n = 51,055, 82%). Exposure: The first benztropine prescription fill after at least 12 months with none was considered the index prescription. Common doses were 1mg (55%), 0.5 mg (29%) and 2mg (16%). Main Outcome: Suicidal behavior defined as suicide attempt or self-harm and coded in outpatient, inpatient or emergency department settings using International Statistical Classification of Diseases and Related Health Problems codes (ICD-9-CM and ICD-10-CM). Statistical Analysis: We used a discrete-time survival model based on a logistic regression with complementary log-log link function such that the exponential of the estimated regression coefficient is a hazard ratio. Month was the unit of analysis and a categorical variable for the 12-month follow-up. Within each subject we compared suicidal events in months with and without coverage from a benztropine filled prescription. Covariates were age, sex, PD, Charlson Comorbidity Index, suicide attempt history, time-varying antipsychotic use, and baseline diagnoses and medications.
Results: Suicidal events (N= 486) occurred in 0.8% of subjects after the index benztropine prescription. Benztropine was associated with fewer suicidal events (HR=0.63, 95% CI = 0.50, 0.80). Similar associations were observed in patients with or without antipsychotics, with bipolar disorder or schizophrenia, and in those treated with newer versus older antipsychotics. A significant dose-response relation was found: 6% reduction in suicidal events per 1 mg benztropine equivalent dosage per month (similar in those with and without antipsychotics).
Conclusions: Benztropine was associated with lower suicidal event rates within individuals with commercial insurance, including those receiving or not receiving antipsychotic medications.
