Zolpidem for persistent insomnia in SSRI-treated depressed patients

Background: Depressed individuals effectively treated with selective seroto nin reuptake inhibitors (SSRIs) often report persistent insomnia and requir e adjunctive sleep-promoting therapy. Method: Men (N = 40) and women (N = 150) with a mean age of 41.6 years who had persistent insomnia in the presence of effective and stable treatment ( at least 2 weeks) with fluoxetine (less than or equal to 40 mg/day), sertra line (less than or equal to 100 mg/day), or paroxetine (less than or equal to 40 mg/day) for DSM-IV major depressive disorder, dysthymic disorder, or minor depressive disorder of mild-to-moderate severity (and score of less t han or equal to 2 on item 3 of the Hamilton Rating Scale for Depression [HA M-D]) participated in this randomized, double-blind, parallel-group study. At study entry, patients were required to score less than or equal to 12 on the HAM-D. During a 1-week single-blind placebo period, patients had to re port on at least 3 nights a latency of greater than or equal to 30 minutes or a sleep time of < 6.5 hours and clinically significant daytime impairmen t. Patients received either placebo (N = 96) or zolpidem, 10 mg (N = 94) ni ghtly, for 4 weeks and single-blind placebo for 1 week thereafter. Sleep wa s measured with daily questionnaires and during weekly physician visits. Results: Compared with placebo, zolpidem was associated with improved sleep : longer sleep times (weeks 1 through 4, p <.05), greater sleep quality (we eks 1 through 4, p <.01), and reduced number of awakenings (weeks 1, 2, and 4; p <.05), together with feeling significantly more refreshed, less sleep y, and more able to concentrate. After placebo substitution, the zolpidem g roup showed significant worsening relative to pretreatment sleep on the fir st posttreatment night in total sleep time and sleep quality, reverted to p retreatment insomnia levels on the other hypnotic efficacy measures, or mai ntained improvement (fewer number of awakenings). There was no evidence of dependence or withdrawal from zolpidem (DSM-IV criteria). Incidence rates o f adverse events were similar in both treatment groups (74% and 83% for pla cebo and zolpidem, respectively), but 7 zolpidem patients discontinued comp ared with 2 placebo patients. Conclusion: In this defined patient population, zolpidem, 10 mg, was effect ively and safely coadministered with an SSRI, resulting in improved self-ra ted sleep, daytime functioning, and well-being.