Factors associated with the long-term use of benzodiazepine receptor agonists as hypnotics among patients with major depressive disorder and comorbid insomnia

Background: Patients with major depressive disorder (MDD) and comorbid insomnia are often co-prescribed benzodiazepines (BZDs) or Z-drugs as hypnotics with antidepressants to manage persistent insomnia. However, factors associated with their long-term use remain unclear among MDD patients. Methods: We retrospectively analyzed data from 351 MDD patients who started antidepressants with co- prescribed hypnotics (BZDs/Z-drugs) and investigated the prevalence of and factors associated with their long-term use at 12 months. We conducted logistic regression analyses of their long-term use, and compared insomnia severities between the continued and discontinued groups of hypnotics in 32 patients whose insomnia severities had been longitudinally assessed. Results: 66.1% of patients had continued hypnotics for 12 months. Multiple logistic regression analysis revealed that the diazepam-equivalent dose of hypnotics at the start of the combined treatment (>5 mg), the presence of chronic insomnia prior to MDD, and hospitalization correlated with their long-term use (all p < 0.01). We also found the relationship between the insufficient amelioration of insomnia severities and their long-term use. However, confidence in these results is tempered by various factors, including the dependence on hypnotics, the patient's attitude about hypnotic treatment, and the exclusion of subjects treated with other drugs such as sedative antidepressants or antipsychotics. Conclusions: These clinical indicators may facilitate the selection of treatment strategies for MDD with comorbid insomnia. To avoid the long-term use of hypnotics, their dose at the start of the combined treatment needs to be adequate (<= 5 mg) and alternative treatments to BZDs/Z-drugs are required for refractory insomnia.