Adherence to Psychotropic Medication in Completed Suicide in Sweden 2006-2013: A Forensic-Toxicological Matched Case-Control Study

Abstract

Background: The aim of the study was to investigate how incomplete adherence to psychotropic medication influences the risk of completed suicide by comparing person-level information regarding dispensed prescriptions and postmortem toxicological findings among complete-suicide cases and non-suicide controls in Sweden 2006-2013. Method: Using national registries with full coverage on dispensed prescriptions, results of medico-legal autopsies, causes of death, diagnoses from inpatient care and continuous drug use, estimated by the prescription-based algorithm PRE2DUP, psychotropic drug use was compared with forensic-toxicological findings for 30 commonly prescribed psychotropic medications. Subjects who had died by suicide (cases) were matched (1:2) with subjects who had died from other causes (controls) for age, sex, and year of death. Odds ratios were calculated using logistic regression to estimate risk of completed suicide conferred by partial adherence and non-adherence to pharmacotherapy. Adjustments were made for previous inpatient psychiatric and somatic care, and ratio of initiated and discontinued prescriptions prior to death. Outcome: In data from autopsies performed in 5294 suicide cases and 9879 non-suicide controls, dispensation ratios for psychotropic medications (postulated as a measure of continued need of treatment) increased in cases, yet decreased in controls, the months prior to death. After adjustments for the ratio and other covariates, partial adherence and non-adherence to antipsychotics were associated with 6·7-fold and 12·4-fold risks, respectively, of completed suicide. The effect sizes for antidepressants were smaller and not statistically significant. Interpretation: After adjustment for continued need of treatment, biochemically verified incomplete adherence to antipsychotic pharmacotherapy was associated with markedly increased risks of completed suicide. Funding Statement: The study has in part been funded by Psykiatrifonden. Funders of the study had no role in study design, data collection, analysis, and interpretation, or the writing of the report. The corresponding author had full access to all data and final responsibility for the decision to submit the report for publication. Declaration of Interests: HT, JT and AT have participated in research projects funded by Janssen-Cilag and Eli Lilly, with grants paid to the institution where they were employed. AT is a member of the JanssenCilag advisory board. JT has served as a consultant to the European Medical Agency and the Finnish Medicines Agency and has received lecture fees from Eli Lilly, Janssen-Cilag, Lundbeck, and Otsuka, and grants from the Stanley Foundation and the Sigrid Juselius Foundation. JF and TM have no conflict of interest. All studied pharmacological products in this paper were generic substances without exclusive ownership by any company. Ethics Approval Statement: All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and national research committee and with the 1964 Declaration of Helsinki and its later amendments or comparable ethical standards. In this registry-based postmortem study, all personal information was anonymized, rendering unnecessary the need for formal consent or ethical approval. The study was nonetheless reviewed and approved by the Regional Ethical Review Board in Stockholm (2013/1411‐31/5).