0416 The Effect of Doxepin 3 Mg on Sleep Latency: Results from a Meta-analysis of Two Phase 3 Trials

Introduction Doxepin 3 and 6 mg are FDA-approved treatments for insomnia characterized by sleep maintenance symptoms. A large, randomized, placebo-controlled trial has confirmed the sleep latency effects of doxepin 6 mg in a phase advance model of healthy adults. The antihistaminic effects of doxepin 3 mg may also lead to sleep latency benefits in adults with insomnia symptoms. Methods Two randomized, double-blind, parallel group, placebo-controlled phase 3 trials involving doxepin 3 mg in subjects with chronic insomnia were used to assess the sleep latency effects on night 1/day 2. Meta-analysis methods were used to assess latency to sleep onset (LSO) and latency to persistent sleep (LPS), each on a log scale, for subjects with evaluable data in the intent to treat analysis set. Subgroup analyses were performed for both LSO and LPS for subjects above and at or below the median baseline values. Fixed and random effects models were performed using generic inverse variance methods. Results The analysis included a total of 460 subjects. Among these subjects, 68.5% were female, 65.2% were White and 20.0% were African American. The mean age was 58.5 years (median 65 years). The baseline median LSO was 55 minutes and median LPS was 35 minutes. We observed limited evidence for heterogeneity (all p-values > 0.2) and therefore present fixed effects estimates only. Doxepin 3 mg improved LSO by 12% (RR=0.88; 95% CI [0.73 to 1.05]) and LPS by 22% (RR=0.78; 95% CI [0.64 to 0.94]) when compared to placebo. There was a non-statistically significant 6% improvement in LSO observed among subjects above the median (RR=0.94) and a 15% non-statistically significant improvement among subjects below the median (RR=0.85). A statistically significant 29% improvement in LPS was observed for subjects above the median (RR=0.71; 95% CI [0.56 to 0.91]) and a non-statistically significant 6% improvement for those below the median (RR=0.94). All subgroup data reflect results compared to placebo. Conclusion Doxepin 3 mg may be an effective option to treat sleep latency in adults with insomnia symptoms, especially those with a long latency to persistent sleep. Support (if any) This work was supported by Haleon and Currax.