Feasibility and Safety of Accelerated Sequential Theta Burst Stimulation for Adolescent Obsessive-compulsive Disorder: A Case Report

Abstract

Repetitive transcranial magnetic stimulation (rTMS) has been shown to be effective for treatment-resistant obsessive-compulsive disorder (OCD) in adults; however, it has not yet been studied in adolescents with OCD. This report details the feasibility and safety of administering sequential accelerated theta burst stimulation (sequential aTBS) in an adolescent with treatment-resistant OCD. Despite completing 29 continuous TBS sessions over the right dorsolateral prefrontal cortex (DLPFC) and an additional 15 intermittent TBS sessions on the left DLPFC, our patient did not show any symptom improvement. This case represents the first documentation of the feasibility, safety, and tolerability of sequential aTBS in adolescents with OCD. The patient tolerated the aTBS sessions well, experiencing only mild tingling and local muscle twitches.

Introduction

Obsessive-compulsive disorder (OCD) is one of the most disabling neuropsychiatric disorders among children and adolescents. The evidence-based treatment options include cognitive behavioral therapy, and serotonin reuptake inhibitors (SRIs). In cases of moderate to severe OCD, a combination of CBT and SRIs is recommended; however, even after adequate trials, approximately 10% of the children may not respond. ¹ Repetitive transcranial magnetic stimulation (rTMS) has emerged as an option in treatment-resistant OCD in adults and recently received FDA approval. ² Accelerated TMS (aTMS), where multiple sessions are administered on a single day, was found to be beneficial in depression as well as OCD for adults. ³ The safety and tolerability of TMS in children are established for depression, attention deficit hyperactivity disorder, and autism spectrum disorders.^4-6 However, there is limited research on the use of TMS for the treatment of OCD among children and adolescents. Here, we describe the feasibility and safety of administering sequential accelerated theta burst stimulation (sequential aTBS) in an adolescent with treatment-resistant OCD.

Case Report

Master Y, a 17-year-old boy born second in birth order to a non-consanguineous marriage, had neurotypical development and a slow-to-warm temperament. He presented with a 2-year history of illness characterized by repetitive thoughts and magical thinking, believing that specific aversive outcomes might be associated with certain tasks. Additionally, he had repeated thoughts about cleanliness, dust, germs, and an increased significance placed on the number three. He engaged in several repetitive behaviors, including cleaning, thinking of God’s images, listening to devotional songs, checking, and avoidance. Over the past year, he also complained of low mood, loss of interest, and loss of pleasure. He has a family history of OCD and depression in a first-degree relative.

A mental status examination confirmed the presence of multiple obsessions and compulsions, as well as pervasive sad mood, anhedonia, amotivation, death wishes, and feelings of hopelessness and helplessness. Physical examination and routine biochemical investigations did not show any abnormalities. He was diagnosed with OCD with poor to absent insight and single-episode depressive disorder, severe without psychotic symptoms, according to ICD-11 criteria. At the time of admission, his Children’s Yale-Brown Obsessive-Compulsive Scale (CY-BOCS) score was 33, and his Children’s Depression Rating Scale (CDRS) score was 54.

Initially, we managed him as an outpatient, but he failed to respond adequately to trials of desvenlafaxine 100 mg/day, fluoxetine 80 mg/day, and risperidone augmentation. Due to nonresponse and the development of severe depressive symptoms, we admitted him for treatment optimization. Sertraline was started and titrated up to 200 mg/day, and risperidone dose was increased to 2 mg/day. We planned to add rTMS to his treatment regimen to further augment the response. He refused psychological and occupational interventions.

After obtaining informed consent from the father, we planned to start continuous TBS (cTBS) targeting the right dorsolateral prefrontal cortex (DLPFC), as right inhibitory TMS was found to be most efficacious in adults with OCD. ² The TMS adult safety screen assessed the safety of undergoing TMS treatment. ⁷ The right DLPFC was localized using the Beam F3 method, and resting motor threshold (RMT) was estimated from the right motor cortex using the ML PEST method by observing movements of the left thumb and index finger. ⁸ We administered the treatment using the Magventure Magpro-X100 with mag options and the Cool-B70 coils, positioned at 45 degrees with the handle directed posteriorly. He received thrice daily cTBS sessions (except for the first day, which had two sessions only), consisting of 50Hz pulses repeated as 5Hz bursts for 40 seconds totaling 600 pulses), at 100% of RMT with an inter-session intervals of 1 hour. Adverse effects of cTBS were monitored after each session using a TMS adverse effect questionnaire. At the end of the first week (post 14 sessions of cTBS), the CY-BOCS and CDRS scores were 31 and 64, respectively, indicating nonresponse of OCD symptoms and worsening of depression. Considering a protocol targeting both OCD and depression, we added intermittent TBS (iTBS) sessions targeting the left DLPFC alongside right DLPFC cTBS and continued with three sessions/day for another 15 sessions. ⁹ However, his symptoms did not improve after adding iTBS (CY-BOCS score 29, CDRS score 63), leading us to discontinue TMS sessions. Throughout both protocols, the patient tolerated the stimulation well, reporting only mild tingling and tapping sensations at the stimulation site and eyebrow twitches. He was discharged with sertraline 200 mg, risperidone 2 mg, and clonazepam 0.5 mg. At the 2-week follow-up, his OCD symptoms remained worsened (CY-BOCS score 35), but there was some improvement in depressive symptoms (CDRS score 45).

Discussion

While rTMS has been used in adult OCD treatment with established safety, its application in children and adolescents is limited, raising concerns about its use in developing brains. ¹⁰ However, recent safety guidelines have reported that rTMS can be safely administered to children, with no reported serious adverse effects or changes in hearing. ¹¹ In the sole available case report, Das et al. ¹² employed once-daily high-frequency deep TMS (20Hz, 100% RMT, 2000 pulses per session) targeting the medial prefrontal cortex in an adolescent girl with OCD. They observed a 66% reduction in symptoms, with the treatment well tolerated. Our case represents the first report on the feasibility, safety, and tolerability of sequential aTBS among adolescents with OCD. The patient tolerated aTBS sessions well, experiencing only mild tingling and local muscle twitches.

Despite undergoing 29 cTBS sessions over the right DLPFC and 15 iTBS sessions targeting the left DLPFC, our patient showed no improvement in symptoms. Several factors may have contributed to this nonresponse, including poor prognostic indicators such as adolescent onset, severe symptoms at presentation, and comorbid depression, compounded by genetic predisposition. ¹³ Additionally, previous studies have suggested that higher obsession subscores and interference due to obsessions are poor predictors of response to TMS, potentially contributing to our patient’s lack of improvement. ¹⁴ Furthermore, the involvement of non-DLPFC circuits, such as the deeply seated orbitofrontal cortex (OFC), which may not be effectively modulated by standard figure-of-eight coils, could have contributed to the nonresponse. ¹⁴ Moreover, the possible role of brain state and the development of homeostatic metaplasticity due to the sequential administration of two types of TBS should also be considered. ¹⁵ Future approaches could involve more individualized TMS techniques, utilizing functional MRI to identify the implicated neural networks, and employing brain simulation models to determine the optimal dose and orientation of rTMS, which may lead to improved treatment outcomes. ³