Improvement in Hypersomnia with High Frequency Repetitive Transcranial Magnetic Stimulation in Depressed Adolescents: Preliminary Evidence from an Open-label Study

Study Objectives: Sleep disruption is a significant symptom of major depressive disorder (MDD). To our knowledge, no prior work has examined the impact of repetitive transcranial magnetic stimulation (rTMS) on sleep disturbances in adolescents with MDD.

Methods: Seventeen adolescents with treatment-resistant depression received 30 daily sessions of 10-Hz rTMS applied to the left dorsolateral prefrontal cortex (L-DLPFC). Clinical symptoms were assessed at baseline; after 10, 20, and 30 treatments; and at a 6-month follow-up visit. Insomnia was measured with a 3-item subscale of the Quick Inventory of Depressive Symptomatology-Adolescent (17 Item)-Self Report (QIDS-A-SR). Hypersomnia was measured with a single QIDS-A-SR item. Depression severity was rated with the Children's Depression Rating Scale, Revised (CDRS-R). The effect of rTMS on sleep was examined via linear mixed model analyses, with fixed effects of time (as a proxy of treatment), depression severity, age, and hypnotic medication use.

Results: No significant main effect of time was observed on the insomnia subscale (F = 1.078, p = 0 .379). However, there was a significant main effect of time on the QIDS-A-SR hypersomnia score (F = 2.733, p = 0 .040), with significant improvement from baseline to treatment 10 (p = 0.019) and from baseline to 6-month follow-up (p = 0.044). In exploratory sensitivity analyses, response/nonresponse to rTMS for overall depressive symptoms had no significant effect on sleep outcomes.

Conclusions: rTMS may have intrinsic effects on hypersomnia apart from its antidepressant effects in depressed adolescents. Future work should utilize sham controls and objective, quantitative measurements of sleep architecture to assess effects of rTMS in depressed adolescents.

Clinical Trial Registry: Clinicaltrials.gov identifiers are NCT00587639, NCT01502033, NCT01804270.