S210. COMPARATIVE EFFECTIVENESS OF ANTIPSYCHOTICS FOR RISK OF ATTEMPTED OR COMPLETED SUICIDE AMONG PERSONS WITH SCHIZOPHRENIA
Authors: Taipale Heidi , Lähteenvuo Markku , Tanskanen Antti , Mittendorfer-Rutz Ellenor , Tiihonen Jari 
Published: May 2020

Abstract

Background
Suicidal attempts and suicide are rather common phenomena in persons with schizophrenia whom are 6–14 times more likely to die due to suicide than the general population. Very little is known on effectiveness of antipsychotics in preventing suicide attempts and completed suicides among patients with schizophrenia. Whether all antipsychotics are effective in preventing attempted or completed suicides also remains unclear. The objective of our study was to investigate comparative effectiveness of antipsychotics for risk of attempted or completed suicide among all patients with schizophrenia in Finland and Sweden.

Methods
Two nationwide register-based cohort studies were conducted including all individuals with schizophrenia in Finland (N=61889) and Sweden (N=29823). The Finnish cohort included all persons treated for schizophrenia in inpatient care (1972–2014), with follow-up for drug use and outcomes during 1996–2017. The Swedish cohort included all persons with treatment contact due to schizophrenia in inpatient or specialized outpatient care, sickness absence, or disability pension (2006–2013), with follow-up for drug use and outcomes during 2006–2016. The main exposure included the ten most commonly used antipsychotic monotherapies, and also adjunctive pharmacotherapies (antidepressants, mood stabilizers, lithium, benzodiazepines and related drugs were investigated). The main outcome measure was attempted or completed suicide which was analyzed with within-individual models by comparing use and non-use periods in the same individual. Sensitivity analyses were conducted by between-individual models, with attempted suicide (hospitalization only) as an outcome, and by censoring first 30 days from each exposure. Results are reported as hazard ratios (HRs) with 95 % confidence intervals (95% CI).

Results
Compared with no use of antipsychotics, clozapine was the only antipsychotic therapy consistently associated with a decreased risk of suicidal outcomes. Hazard ratios (HRs) and 95% CI for attempted or completed suicide were 0.64 (95% CI 0.49–0.84) in the Finnish cohort, and 0.66 (0.43–0.99) in the Swedish cohort, and for attempted suicide 0.60 (0.46–0.79) in the Finnish cohort and 0.62 (0.40–0.95) in the Swedish cohort. No other antipsychotic was associated with a reduced risk of attempted and/or completed suicide than clozapine. Regarding adjunctive pharmacotherapies, benzodiazepines and Z-drugs were associated with an increased risk of suicide attempts or deaths (HRs for benzodiazepines 1.29–1.30 and 1.33–1.62 for Z-drugs, not reaching statistical significance in the Swedish cohort).

Discussion
The results from two large nationwide cohorts provide the first evidence on comparative real-world effectiveness of specific antipsychotics in the prevention of severe suicidal behavior. Clozapine was the only pharmacological treatment associated with a substantially decreased risk of attempted or completed suicide and should be considered as a first-line treatment for patients with suicidal ideation or behavior.