iACT & iTBS for Sleep Quality in Depressed Adolescents

This was a four‐arm, parallel‐group, randomized controlled superiority trial conducted inthe outpatient department of a psychiatric hospital in Anhui Mental Health Center. Thestudy was retrospectively registered on the Open Science Framework in May 2024. The studyprotocol was approved by the institutional review board (Approval No.:CCNU‐IRB‐202306017b). Written informed consent was obtained from a parent or legalguardian, 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 disorderconfirmed by independent evaluations from two board‐certified psychiatrists usingsemistructured clinical interviews; had a Hamilton Depression Rating Scale, 17‐itemversion (HAMD‐17) score of at least 8; and reported a concurrent subjective sleepdisturbance, such as difficulty initiating sleep, frequent nighttime awakenings, ornonrestorative sleep. Participants were required either to be receiving stableantidepressant pharmacotherapy for at least 2 weeks or to be taking no antidepressantmedication. Participants could not be receiving another systematic psychological orphysical treatment and were required to be right‐handed.Participants were excluded for a history of epilepsy, a major neurological disorder, acontraindication to transcranial magnetic stimulation, acute suicide risk, a substanceuse disorder within the preceding year, severe somatic illness, or current use oftargeted hypnotic or sedative medication.Participants were randomly assigned in a 1:1:1:1 ratio using a computer‐generatedpermuted‐block randomization sequence. Allocation was managed by personnel independent ofoutcome assessment. Independent HAMD‐17 raters were masked to treatment assignment.Participants and intervention‐delivery personnel were not masked because the treatmentformats and waitlist condition were distinguishable. Self‐report outcome measures werecompleted by participants.The internet‐delivered Acceptance and Commitment Therapy program was provided through acustom‐developed WeChat mini‐program. The program included an introduction, sixsequential treatment modules, and a concluding session. The content was delivered over 12days and covered psychoeducation, acceptance, cognitive defusion, mindfulness, valuesclarification, 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 totalplanned exposure was approximately 120 minutes. All modules were completed on site duringdaily hospital visits. Online records and staff monitoring were used to document modulecompletion and practice activities. A crisis hotline was embedded in the program.Intermittent theta burst stimulation was administered once daily for 12 consecutive daysusing a Magstim Rapid2 stimulator with a 70‐mm figure‐of‐eight coil. The individualizedstimulation target was located over the left dorsolateral prefrontal cortex usingintegrated neuronavigation. Resting motor threshold was measured before treatment. Eachsession delivered 1,800 pulses in three 600‐pulse blocks. Stimulation consisted ofthree‐pulse 50‐Hz bursts repeated at 5 Hz, delivered in 2‐second trains separated by8‐second intervals. Stimulation intensity was 100% of the participant's resting motorthreshold.Participants in the combined group received both interventions. On days when a newAcceptance and Commitment Therapy module was available, theta burst stimulation wasdelivered first and was immediately followed by the module. On intervening days,participants received theta burst stimulation only. Participants in theinternet‐delivered therapy‐only group followed the module schedule without theta burststimulation. Participants in the stimulation‐only group received theta burst stimulationwithout the therapy program during the intervention period. Participants assigned to thewaitlist received no targeted intervention during the 42‐day study period and completedassessments on the same schedule as the active‐treatment groups. Access to theinternet‐delivered Acceptance and Commitment Therapy program was offered to participantsin the waitlist and stimulation‐only groups after the final follow‐up assessment.Assessments were conducted at baseline, immediately after the 12‐day intervention, and ata 30‐day follow‐up. The primary outcome was subjective sleep quality, measured with the19‐item Pittsburgh Sleep Quality Index, with total scores ranging from 0 to 21 and higherscores indicating worse sleep quality. Secondary outcomes were depressive symptomseverity, measured with the 17‐item Hamilton Depression Rating Scale, and psychologicalflexibility, measured with the 12‐item flexibility subscale of the MultidimensionalPsychological 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 participantreports during and after the intervention procedures. Examples included headache andscalp discomfort associated with intermittent theta burst stimulation.The primary analyses examined changes from baseline to post‐treatment and follow‐upacross the four groups. Repeated‐measures models were used to account for the correlationamong observations from the same participant. The main comparisons evaluated the combinedintervention against the waitlist and against each monotherapy, as well as eachmonotherapy against the waitlist. Analyses adjusted for age, gender, and only‐childstatus. Additional analyses examined clinical response in sleep quality, the robustnessof findings under alternative model specifications, and whether the combined interventionshowed evidence of greater‐than‐additive change relative to the two monotherapies. All152 participants completed the three scheduled assessments.This study was registered retrospectively after participant recruitment and datacollection had begun.