This study evaluated whether combining an internet-delivered Acceptance and Commitment Therapy program with intermittent theta burst stimulation improves subjective sleep quality in adolescents with depressive disorders and sleep disturbances. Acceptance and Commitment Therapy is a psychological treatment that teaches skills for accepting difficult thoughts and feelings, reducing unhelpful struggle with them, and taking actions consistent with personal values. Intermittent theta burst stimulation is a brief, noninvasive form of brain stimulation delivered over the left dorsolateral prefrontal cortex. A total of 152 adolescents aged 11 to 19 years were randomly assigned to one of four groups: combined internet-delivered Acceptance and Commitment Therapy plus intermittent theta burst stimulation, internet-delivered Acceptance and Commitment Therapy alone, intermittent theta burst stimulation alone, or a waitlist control group. Treatment was provided over 12 consecutive days. Participants completed assessments before treatment, immediately after treatment, and 30 days later. The study was registered retrospectively after participant recruitment and data collection had begun. The primary outcome was subjective sleep quality, measured with the Pittsburgh Sleep Quality Index. Secondary outcomes were depressive symptom severity and psychological flexibility. The study also assessed treatment exposure and adverse events, including headache or scalp discomfort associated with brain stimulation.
This was a four-arm, parallel-group, randomized controlled superiority trial conducted in the outpatient department of a psychiatric hospital in Anhui Mental Health Center. The study was retrospectively registered on the Open Science Framework in May 2024. The study protocol was approved by the institutional review board (Approval No.: CCNU-IRB-202306017b). Written informed consent was obtained from a parent or legal guardian, and written assent was obtained from each adolescent participant. Participants were recruited by convenience sampling between August 2023 and January 2024. Eligible participants were 11 to 19 years old; had a primary DSM-5 depressive disorder confirmed by independent evaluations from two board-certified psychiatrists using semistructured clinical interviews; had a Hamilton Depression Rating Scale, 17-item version (HAMD-17) score of at least 8; and reported a concurrent subjective sleep disturbance, such as difficulty initiating sleep, frequent nighttime awakenings, or nonrestorative sleep. Participants were required either to be receiving stable antidepressant pharmacotherapy for at least 2 weeks or to be taking no antidepressant medication. Participants could not be receiving another systematic psychological or physical treatment and were required to be right-handed. Participants were excluded for a history of epilepsy, a major neurological disorder, a contraindication to transcranial magnetic stimulation, acute suicide risk, a substance use disorder within the preceding year, severe somatic illness, or current use of targeted hypnotic or sedative medication. Participants were randomly assigned in a 1:1:1:1 ratio using a computer-generated permuted-block randomization sequence. Allocation was managed by personnel independent of outcome assessment. Independent HAMD-17 raters were masked to treatment assignment. Participants and intervention-delivery personnel were not masked because the treatment formats and waitlist condition were distinguishable. Self-report outcome measures were completed by participants. The internet-delivered Acceptance and Commitment Therapy program was provided through a custom-developed WeChat mini-program. The program included an introduction, six sequential treatment modules, and a concluding session. The content was delivered over 12 days and covered psychoeducation, acceptance, cognitive defusion, mindfulness, values clarification, and values-consistent action. The modules were unlocked on days 1, 3, 5, 7, 9, and 11, with approximately 15 minutes required for each component. The total planned exposure was approximately 120 minutes. All modules were completed on site during daily hospital visits. Online records and staff monitoring were used to document module completion and practice activities. A crisis hotline was embedded in the program. Intermittent theta burst stimulation was administered once daily for 12 consecutive days using a Magstim Rapid2 stimulator with a 70-mm figure-of-eight coil. The individualized stimulation target was located over the left dorsolateral prefrontal cortex using integrated neuronavigation. Resting motor threshold was measured before treatment. Each session delivered 1,800 pulses in three 600-pulse blocks. Stimulation consisted of three-pulse 50-Hz bursts repeated at 5 Hz, delivered in 2-second trains separated by 8-second intervals. Stimulation intensity was 100% of the participant's resting motor threshold. Participants in the combined group received both interventions. On days when a new Acceptance and Commitment Therapy module was available, theta burst stimulation was delivered first and was immediately followed by the module. On intervening days, participants received theta burst stimulation only. Participants in the internet-delivered therapy-only group followed the module schedule without theta burst stimulation. Participants in the stimulation-only group received theta burst stimulation without the therapy program during the intervention period. Participants assigned to the waitlist received no targeted intervention during the 42-day study period and completed assessments on the same schedule as the active-treatment groups. Access to the internet-delivered Acceptance and Commitment Therapy program was offered to participants in the waitlist and stimulation-only groups after the final follow-up assessment. Assessments were conducted at baseline, immediately after the 12-day intervention, and at a 30-day follow-up. The primary outcome was subjective sleep quality, measured with the 19-item Pittsburgh Sleep Quality Index, with total scores ranging from 0 to 21 and higher scores indicating worse sleep quality. Secondary outcomes were depressive symptom severity, measured with the 17-item Hamilton Depression Rating Scale, and psychological flexibility, measured with the 12-item flexibility subscale of the Multidimensional Psychological Flexibility Inventory-24. Demographic information, including age, gender, school grade, only-child status, and urban or rural residence, was collected at baseline. Adverse events and unintended effects were assessed through spontaneous participant reports during and after the intervention procedures. Examples included headache and scalp discomfort associated with intermittent theta burst stimulation. The primary analyses examined changes from baseline to post-treatment and follow-up across the four groups. Repeated-measures models were used to account for the correlation among observations from the same participant. The main comparisons evaluated the combined intervention against the waitlist and against each monotherapy, as well as each monotherapy against the waitlist. Analyses adjusted for age, gender, and only-child status. Additional analyses examined clinical response in sleep quality, the robustness of findings under alternative model specifications, and whether the combined intervention showed evidence of greater-than-additive change relative to the two monotherapies. All 152 participants completed the three scheduled assessments. This study was registered retrospectively after participant recruitment and data collection had begun.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
DOUBLE
Enrollment
160
Participants received a self-guided internet-delivered Acceptance and Commitment Therapy program through a custom-developed WeChat mini-program over 12 consecutive days. The program included an introduction, six sequential treatment modules, and a concluding session. Modules were unlocked on days 1, 3, 5, 7, 9, and 11, and each component required approximately 15 minutes, for a total planned exposure of approximately 120 minutes. Content was based on the ACT hexaflex model and included psychoeducation, acceptance, cognitive defusion, mindfulness, values clarification, and values-consistent action. Participants completed the modules on site during daily hospital visits. Module completion and practice activities were monitored through the mini-program and by research staff. A crisis hotline was embedded in the program.
Intermittent theta burst stimulation was administered once daily for 12 consecutive days using a Magstim Rapid2 stimulator with a 70-mm figure-of-eight coil. The individualized stimulation target was located over the left dorsolateral prefrontal cortex using integrated neuronavigation, and the target coordinates were saved for subsequent sessions. Resting motor threshold was measured before treatment. Each daily session delivered 1,800 pulses in three blocks of 600 pulses. Stimulation consisted of three 50-Hz pulses repeated at 5 Hz in 2-second trains separated by 8-second intervals. Stimulation was delivered at 100% of the participant's resting motor threshold.
Anhui Mental Health Center
Wuhan, Hubei, China
Change in subjective sleep quality measured by the Pittsburgh Sleep Quality Index (PSQI)
Subjective sleep quality will be assessed with the 19-item Pittsburgh Sleep Quality Index (PSQI). Total scores range from 0 to 21, with higher scores indicating poorer subjective sleep quality. The primary outcome is the change in PSQI total score from baseline to immediately after the 12-day intervention and from baseline to the 30-day follow-up. Negative change scores indicate improvement in subjective sleep quality.
Time frame: Baseline to immediately postintervention (day 12) and baseline to 30-day follow-up (day 42)
Change in depressive symptom severity measured by the 17-item Hamilton Depression Rating Scale (HAMD-17)
Depressive symptom severity will be assessed with the 17-item Hamilton Depression Rating Scale (HAMD-17), a clinician-rated measure with scores ranging from 0 to 52. Higher scores indicate more severe depressive symptoms. The secondary outcome is the change in HAMD-17 score from baseline to immediately after the 12-day intervention and from baseline to the 30-day follow-up. Negative change scores indicate improvement in depressive symptoms.
Time frame: Baseline to immediately postintervention (day 12) and baseline to 30-day follow-up (day 42)
Change in psychological flexibility measured by the Multidimensional Psychological Flexibility Inventory-24 (MPFI-24)
Psychological flexibility will be assessed using the 12-item flexibility subscale of the Multidimensional Psychological Flexibility Inventory-24 (MPFI-24). Scores range from 12 to 72, with higher scores indicating greater psychological flexibility. The secondary outcome is the change in the flexibility subscale score from baseline to immediately after the 12-day intervention and from baseline to the 30-day follow-up. Positive change scores indicate improvement in psychological flexibility.
Time frame: Baseline to immediately postintervention (day 12) and baseline to 30-day follow-up (day 42)
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