Insomnia Moderates Outcome of Serotonin-Selective Reuptake Inhibitor Treatment in Depressed Youth

Objective: Insomnia is evident in the majority of youth with depression, and is associated with poorer outcomes. There are limited data on the impact of insomnia in response to acute treatment, which is particularly relevant with serotonin-selective reuptake inhibitors, given their tendency to worsen sleep architecture. Methods: Three hundred nine children and adolescents (ages 7-18 years) were randomized to fluoxetine (n = 157) or placebo (n = 152) for 8-9 weeks (Emslie et al. 1997, 2002). Substantial insomnia at baseline was defined as a child's depression rating scale-revised [CDRS-R] sleep item >= 4. Outcome measures were CDRS-R, response, and remission. Results: Insomnia was reported in 172/309 (55.7%) youth, and was associated with higher depression severity and greater fatigue, suicidal ideation, physical complaints, and decreased concentration. While response rates were similar in those with or without insomnia overall (51.7% vs. 55.7%), there is a significant difference by age group. Among adolescents, those with insomnia were less likely to respond to fluoxetine (39.2%; 20/51) than those without (65.9%; 27/41; p = 0.013), while in children on fluoxetine, those with insomnia were more likely to respond to fluoxetine (69.4%; 25/36) than those without insomnia (41.4%; 12/29; p = 0.027). Insomnia did not impact the response to placebo in either age group. Within adolescents, the overall least squares means for CDRS-R total score (across the 8 weeks of treatment) were significantly different between those who had insomnia versus those who did not within the fluoxetine group (43.65 [SE = 1.31] vs. 36.58[SE = 1.45], F = 12.69, df = 1, 169, p = 0.0005; d = 0.82), but not within the placebo group (44.91[SE = 1.34] vs. 43.75[SE = 1.68], F = 0.29, df = 1, 179, p = 0.591; d = 0.15). Conclusions: While adolescents reporting substantial insomnia were less likely to respond to antidepressant treatment than those without insomnia, children were more responsive to fluoxetine when they had insomnia. Additional intervention targeting sleep disturbance may be warranted in adolescents.