Abstract

In Denmark, as well as in many other countries, consumption of antipsychotics is on the rise, partly due to increasing off-label use. The aim of this study was to analyze and quantify the extent of off-label use and polypharmacy in incident users of antipsychotic medication, and to examine initial antipsychotic prescribing patterns and associated use of mental health care services. Population-based cohort study linking the following Danish national registers: the Central Psychiatric Research Register, the Register of Medicinal Product Statistics, and Statistics Denmark. From 2007 to 2012, 154,351 Danish subjects initiated treatment with antipsychotics. Among these, 71,254 (46 %) subjects had a psychiatric diagnosis recorded. The most frequent diagnoses were reaction to severe stress and adjustment disorders (10,106; 14 %), depressive episode (8876; 12 %), and recurrent depressive disorder (6810; 10 %). We found high antipsychotic discontinuation rates during the first few months (45 % in 4 months) and frequent antidepressant co-prescribing from treatment onset (47 %). Significantly greater likelihood of psychiatric hospitalization was observed for antipsychotic polypharmacy (HR 1.38; 95 % CI 1.32-1.45), whereas antipsychotic discontinuation was associated with decreased hospitalization risk in most off-label conditions. The brief duration of most antipsychotic prescriptions suggests that antipsychotics are prescribed more liberally than recommended. As a consequence of the range of adverse effects associated with antipsychotic drug use, the documented widespread off-label prescribing practices warrant careful monitoring for adverse effects and prompt discontinuation in case of an unfavorable risk-benefit ratio.

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