Adjunctive Triple Chronotherapy in the Treatment of Adolescent Major Depressive Disorder: A Randomized Controlled Pilot Trial

Introduction: This randomized controlled pilot trial examined whether adjunctive triple chronotherapy (TCT) in adolescents hospitalized with major depressive disorder (MDD) was (1) feasible, and (2) suggested to be more effective in managing depression and accompanying symptoms at 60 days postdischarge, compared to adolescents with depression who received treatment-as-usual (TAU). Methods: TCT participants underwent sleep deprivation for up to 36 hours, sleep phase advancement for four days, and daily exposure to light therapy. Both arms received medication management and group therapy during the inpatient stay. Outpatient visits occurred on Days 7/10, 30, and 60. Outcomes included depression, anxiety, insomnia, self-harm, suicidality, and quality of life. Results: Sixty-four adolescents were enrolled, 32 into TCT, 32 into TAU. The mean age was 15 years, the majority were female, Caucasian, and non-Hispanic/non-Latino. Compared to baseline, both TCT and TAU participants showed a significantly lower Patient Health Questionnaire-Adolescent (PHQ-A) score by Day 4 (TCT: N = 31, X¯=20.4 ± 3.54 vs. N = 17, X¯=9.12 ± 6.98, p < 0.001; TAU: N = 32; X¯=20.1 ± 3.99 vs. N = 10; X¯=8.6 ± 5.93, p < 0.001) and by Day 60 (TCT: N = 11, X¯=7.45 ± 5.22, p < 0.001; TAU: N = 14, X¯=13.36 ± 7.25, p < 0.001). For between-group differences, TCT participants reported significantly lower PHQ-A scores at Day 60 compared to TAU participants (N = 11, X¯=7.45 ± 5.22 vs. N = 14, X¯=13.36 ± 7.25, p = 0.03). Anxiety and insomnia were significantly lower at treatment end in the TCT arm (N = 11, X¯=1.91 ± 1.97 vs. N = 14; X¯=4.64 ± 2.79, p = 0.009) and (N = 11, X¯=6.55 ± 6.64 vs. N = 14; X¯=12.21 ± 6.76, p = 0.05), respectively. Retention was a challenge; approximately 2/3 of the sample dropped out by study end. Conclusions: TCT is a potentially effective adjunctive treatment for MDD in adolescents.