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

Abstract

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. 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 ( 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.

Developing a Brief Suicide Prevention Intervention and Mobile Phone Application: A Qualitative Report

“…Though past research has shown the clear need for interventions geared toward both sobriety and improving sleep in the treatment of suicidal youth (Emslie et al, 2012; Goldstein, Bridge & Brent, 2008; Goldstein et al, 2009; McMakin, et al 2011), there is a need for further research to effectively assess how sleep problems and drug and alcohol use may relate to maintaining safety during transition of care.…”

Protecting Adolescents From Self-Harm: A Critical Review of Intervention Studies

“…59–62 Finally, insomnia is a negative moderator of treatment response to antidepressants in adolescents, meaning that in patients with insomnia, antidepressants are no more efficacious than placebo. 63 While intervention studies have linked improvement in sleep to improvements in mood, social relationships, and academic performance, no study has yet tested whether improvement in sleep quality will reduce suicidal ideation or risk for suicide re-attempt. 60 …”

“…44,64 Prioritizing the improvement of sleep early in treatment intervention may attenuate suicidal risk, given the strong relationship between sleep difficulties and emotional lability, suicidal ideation, suicidal behavior, and suboptimal treatment response. 56–58,60,63 …”

Pre-treatment insomnia as a predictor of single and combination antidepressant outcomes: A CO-MED report

“…Similarly, in another study comparing the acute efficacy of three different antidepressant agents (fluoxetine, sertraline, and paroxetine), no difference in response was observed for depressed outpatients with- and without pre-treatment insomnia 14 . No difference in overall response rates was found for a sample of 309 children and adolescents with- and without pre-treatment insomnia who were treated with 10-20mg of fluoxetine for 8-9 weeks 15 . However, adolescent participants with pre-treatment insomnia showed a poorer response to fluoxetine, whereas child participants with pre-treatment insomnia showed higher response rates on the same medication regimen.…”