The effect of doxepin 3 mg on sleep latency: a pooled analysis of two phase 3 trials.

Introduction: Most pharmacologic treatments with clinical data for insomnia symptoms are controlled substances. An exception is doxepin, an antihistamine that has shown efficacy for the treatment of difficulties with sleep maintenance. This analysis assessed the utility of doxepin 3 mg in the treatment of difficulties with sleep onset.

Patients and methods: A pooled analysis of two phase 3, randomized, controlled trials was conducted. Patients with primary insomnia received doxepin 3 mg or placebo 30 min before bedtime. Latency to persistent sleep (LPS) was assessed by polysomnography at screening (baseline), night 1 following a single dose (the main outcome of interest), and nights 15 and 29. Patient-reported latency to sleep onset (LSO) was recorded in a diary the following morning.

Results: A total of 310 patients, 153 randomized to placebo and 157 randomized to doxepin 3 mg, were included. Doxepin 3 mg resulted in a small but statistically significant 22% improvement in LPS compared with placebo on night 1 following a single dose (risk ratio: 0.78; 95% CI: 0.64, 0.94). A similar improvement was seen in a subgroup of patients with baseline LPS > 35 min. This subgroup had an 11-min reduction in LPS, compared with a 6.4-min reduction for the overall population. There was a nonsignificant 12% reduction in LSO in the overall population (risk ratio: 0.88; 95% CI: 0.73, 1.05).

Conclusions: Doxepin 3 mg has a statistically significant effect on sleep latency on the first night of treatment in adults with insomnia that did not reach the clinical significance threshold.