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Background: Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive neuromodulation technique that uses rapidly changing magnetic fields to induce electrical currents in targeted cortical regions, thereby modulating cortical excitability and synaptic plasticity. The efficacy, tolerability, and safety of several rTMS protocols have been established in double-blind, sham-controlled randomized trials and meta-analyses of treatment-resistant depression. Depression and insomnia are among the most common psychiatric comorbidities of narcolepsy, while hypersomnia symptoms occur in up to half of patients with depression. However, the relationship between hypersomnia and depression remains incompletely understood. Narcolepsy and depression appear to have a bidirectional association, and their comorbidity rate has been estimated to exceed one-third. Pharmacological management is often challenging because antidepressant response may be suboptimal, and psychotropic adverse effects may aggravate excessive daytime sleepiness, nocturnal sleep disruption, or cognitive impairment. Therefore, rTMS may offer a clinically meaningful non-pharmacological treatment option for patients with narcolepsy and comorbid depression.
Methods: We designed a randomized, single-blind, case-controlled, parallel-group study with an additional major depressive disorder (MDD) comparison group. Adults aged 20–45 years who met the ICSD-3 criteria for narcolepsy and had comorbid depression diagnosed according to DSM-5 criteria. Participants with narcolepsy and depression were assigned to one of three interventions: high-frequency rTMS using intermittent theta-burst stimulation (iTBS). Treatment was delivered two to three times weekly for two to four consecutive weeks, for a total of 10 sessions, targeting the left dorsolateral prefrontal cortex. Outcomes included depressive symptom severity measured using the Beck Depression Inventory-II, daytime sleepiness assessed using the Epworth Sleepiness Scale and a visual analogue scale, subjective sleep quality assessed using the Pittsburgh Sleep Quality Index, and objective sleep–wake parameters measured by actigraphy. Outcomes were evaluated after treatment and during follow-up for up to six months.
Results: rTMS was associated with improvements in depressive symptoms, excessive daytime sleepiness, subjective nighttime sleep quality, and actigraphy-derived sleep parameters. The therapeutic response appeared particularly prominent in patients with narcolepsy type 2 and comorbid depression. Improvements in selected clinical and sleep-related outcomes were sustained for up to six months after treatment. These findings suggest that improvements were not limited to mood symptoms but extended to clinically relevant sleep and daytime functional domains in this difficult-to-treat population over extended follow-up periods. No treatment-related adverse events were observed during the study period.
Conclusions: Left dorsolateral prefrontal rTMS may improve both depressive and sleep-related symptoms in patients with narcolepsy and comorbid depression, particularly those with narcolepsy type 2. Its potential benefits across mood, daytime alertness, nighttime sleep, and daily functioning suggest that rTMS may serve as an additional treatment option.
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