Patterns of hypnotic prescribing for residual insomnia and recurrence of major depressive disorder: a retrospective cohort study using a Japanese health insurance claims database

Major depressive disorder (MDD) is highly prevalent in Japan and frequently accompanied by insomnia that may persist even with MDD remission. Hypnotics are used for the pharmacological treatment of insomnia, but their influence on MDD recurrence or residual insomnia following MDD remission is unclear. This retrospective, longitudinal, cohort study utilized a large Japanese health insurance claims database to investigate patterns of hypnotic prescriptions among patients with MDD, and the influence of hypnotic prescription pattern on MDD recurrence.

Eligible patients (20–56 years) were those registered in the Japan Medical Data Center database between 1 January 2005 and 31 December 2018, and prescribed antidepressant and hypnotic therapy after being diagnosed with MDD. Patients who had ceased antidepressant therapy for > 180 days were followed for 1 year to evaluate depression recurrence, as assessed using Kaplan-Meier estimates. Logistic regression modelling was used to analyze the effect of hypnotic prescription pattern on MDD recurrence.

Of the 179,174 patients diagnosed with MDD who initiated antidepressant treatment between 1 January 2006 and 30 June 2017, complete prescription information was available for 2946 eligible patients who had been prescribed hypnotics. More patients were prescribed hypnotic monotherapy (70.8%) than combination therapy (29.2%). The most prescribed therapies were benzodiazepine monotherapy (26.2%), non-benzodiazepine monotherapy (28.9%), and combination therapy with two drugs (21.1%). Among patients prescribed multiple hypnotics, concomitant prescriptions for anxiolytics, antipsychotics, mood stabilizers and sedative antidepressants were more common. The 1-year recurrence rate for MDD was approximately 20%, irrespective of hypnotic mono- versus combination therapy or class of hypnotic therapy. Being a spouse (odds ratio [OR], 1.44; 95% confidence interval [CI], 1.03–2.02) or other family member (OR, 1.46, 95% CI, 0.99–2.16) of the insured individual, or being prescribed a sedative antidepressant (OR, 1.50, 95% CI, 1.24–1.82) conferred higher odds of MDD recurrence within 1 year of completing antidepressant therapy.

Benzodiazepines are the most prescribed hypnotic among Japanese patients with MDD, though combination hypnotic therapy is routinely prescribed. Hypnotic prescription pattern does not appear to influence real-world MDD recurrence, though hypnotics should be appropriately prescribed given class differences in efficacy and safety.