A Public Health Concern: The Rising Off-Label Use of Low-Dose Mirtazapine in Swedish Adolescents. Off-Label Sedative Use and Unfavorable Risk-Benefit in Swedish Adolescents (2007–2017)
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Background
Mirtazapine is contraindicated for individuals under 18 by the Swedish Medical Products Agency (Läkemedelsverket), yet recent data reveals its increasing off-label prescription to adolescents for insomnia and anxiety symptoms. This practice occurs despite established safety concerns and contradicts the drug’s approved indication for major depressive disorder requiring 30-45 mg/day.
Methods
We analyzed nationwide prescription data from 2007-2017 using CSV files from Swedish, Danish, and Norwegian registries, complemented by a mini systematic review of 42 peer-reviewed studies. Dose-response relationships, discontinuation rates, and adverse event profiles were examined.
Results
Swedish adolescents received mirtazapine at a mean dose of 8.84-10.76 mg/day (95% CI), significantly below the therapeutic range for depression but optimal for sedation [3, 11, 22]. This pattern contrasts with Nordic neighbors, with Sweden demonstrating 184.1% higher mirtazapine prescription rates for 15–19-year-olds compared to Denmark (6.05% vs. 2.99% of total prescriptions). The practice represents a deliberate clinical strategy within Sweden’s centralized healthcare system, where specialists use mirtazapine as a benzodiazepine alternative under “therapeutic freedom” [6, 28]. Critically, this off-label use exposes adolescents to significant risks including weight-independent metabolic damage (2.8-fold higher prediabetes incidence) [16, 24], movement disorders [17, 29], and rebound insomnia with 57.3% discontinuation rates driven by anxiety/agitation rather than metabolic side effects [21, 30].
Conclusion
Mirtazapine’s off-label use in Swedish adolescents represents a concerning therapeutic paradox: while increasing nighttime sleep by approximately 30 minutes [4, 45], it simultaneously induces daytime sleepiness and cognitive impairment [7, 46], directly undermining the primary goal of insomnia treatment. The evidence demonstrates an intentional clinical practice rather than prescribing error, highlighting a critical regulatory gap that requires immediate attention. Policy interventions should include revised prescribing guidelines with mandatory monitoring protocols for adolescents receiving mirtazapine, alongside public health campaigns to address the growing off-label use of antidepressants for sleep disorders.
