Accelerated deep transcranial magnetic stimulation using iTBS protocol for refractory obsessive-compulsive disorder

Dear Editor,

Obsessive-compulsive disorder (OCD) is a chronic debilitating condition with purported dysfunction in the fronto-striatal circuits [1]. Around half the patients have unsatisfactory response to first-line treatment strategies including serotonin reuptake inhibitors (SRIs) and cognitive-behaviour therapy (CBT) [1]. Non-invasive brain stimulation (NIBS) has proven to be a valuable add-on treatment, especially in non-responders to first line treatments [2]. Deep transcranial magnetic stimulation (dTMS) can stimulate deeper and broader cortical networks compared to standard rTMS coils. The efficacy of dTMS has been demonstrated in a multi-centre randomised controlled trial and is the only FDA approved NIBS intervention for OCD [3]. It has been found to be helpful even in non-responders to multiple medications and CBT [4]. With the standard protocol (5 sessions per week), treatment response is observed around 32 days after treatment initiation [5].

Accelerated protocols may hasten treatment response. For example, a recent open-labelled trial demonstrated the safety and feasibility of accelerated rTMS protocol targeting the left orbitofrontal cortex for resistant OCD, with response noted within 7 days of treatment [6]. In this trial, 10 sessions of continuous theta burst stimulation (cTBS) were administered per day for 5 days, each session consisting of 600 bursts (1800 pulses) amounting to a total of 90,000 pulses. In another study, 2 dTMS per day administered over 2-3 weeks has been found to be safe in patients with depressive disorder [7]. To the best of our knowledge, the safety and clinical utility of a truly accelerated dTMS protocol (with 5 or more sessions per day) has not been assessed previously. We describe our experience with accelerated dTMS in 2 subjects with treatment-resistant OCD which resulted in a rapid clinical improvement with a robust safety profile.

Ms. S (S1), a 31-year-old female with schizotypal traits, presented with history of OCD since the age of 15 years. Her illness was characterised by contamination obsessions, sexual obsessions, obsessive need for symmetry, pathological doubts, and aggressive impulses along with washing compulsions, repeating compulsions, reassurance seeking and mental compulsions. She had a fair insight but avoided social interactions and other activities that triggered her OC symptoms leading to significant socio-occupational dysfunction. She had previously failed to respond to adequate trials of 4 different SRIs, augmentation with risperidone and aripiprazole, and to 26 sessions of low frequency TMS to pre-supplementary motor area, She was diagnosed to have treatment-resistant OCD and was started on venlafaxine up to 225 mg 10 days before the initiation of the accelerated dTMS protocol.

Mr. N (S2), a 24-year-old gentleman with anankastic personality disorder presented with history of OCD since the age of 14 years. His illness was characterized by obsessions of symmetry, just right phenomena, ordering and repeating rituals, ritualistic bathing, reassurance seeking, rereading, rewriting, avoidance and compulsions by proxy with significant socio-occupational dysfunction. He had excellent insight. The patient had previously failed to respond to adequate trials of 3 SRIs, clomipramine, venlafaxine, and to augmentation with risperidone. He had dropped out of CBT due to intolerance of anxiety associated with the treatment. He was also diagnosed to have treatment resistant OCD and was on treatment with Paroxetine 75mg, clonazepam 1 mg and propranolol 20mg with no significant improvement in symptoms.

Both the patients were offered a trial of adjunctive accelerated dTMS for which they provided informed consent. dTMS sessions were administered using the Brainsway H7-coil. Five sessions of intermittent theta burst (iTBS) stimulation were delivered at 100% of foot resting motor threshold with 1 hour interval between the sessions for 5 continuous days (total 25 sessions). Each session consisted of 1200 magnetic pulses delivered in 40 trains with 8 second inter-train interval. Each train consists of 10 bursts of three biphasic pulses delivered at 50 Hz, bursts repeated at 5Hz. This would amount to 6000 pulses per day and a total of 30000 pulses over 5 days of treatment. A personalised symptom provocation paradigm was developed during the baseline assessment and was administered before each session to evoke a moderate level of distress. Both the subjects tolerated the entire protocol without any significant side effects.

Symptoms were rated on Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and Clinical Global Impression-Severity (CGI-S) scale at baseline, at the end of the treatment, at 1-, 2- and 4-week follow-ups. OCD-Visual Analogue Scale (OCD-VAS)[8] was applied at the end of each treatment day to assess the rapid changes in OC symptoms. There was a 40% and 35% reduction in Y-BOCS score after 1 week of the treatment for S1 and S2 respectively with CGI-S score improving from 6 to 4 for both. Subjective severity as rated by OCD-VAS score also decreased (from 10,6 to 2,2 respectively) in both subjects 7 days after treatment initiation. S1 showed a worsening of symptoms post-treatment with YBOCS score increasing to 31 at 2-week follow-up, while S2 maintained improvement at 2- and 4-week follow-ups.

Discussion

These 2 cases demonstrate the safety and potential clinical utility of accelerated dTMS protocol as an adjunctive modality in the treatment of OCD. As opposed to the usual once-daily protocol, an accelerated protocol might lead to a faster clinical improvement. However, it has to be evaluated whether a higher number of sessions may be required for sustained response. The FDA-approved high frequency (HF) dTMS protocol for OCD consists of 50 trains of 2 seconds at 20Hz with 20 seconds inter-train interval and amounts to a total of 2000 pulses per session. This protocol takes 18 minutes to deliver each session. Like the HF protocol, the iTBS protocol is also an excitatory intervention [9]. We used an iTBS protocol with 1200 pulses per session which takes only 6 minutes to deliver and maybe more tolerable.

Though the improvement was modest, it was encouraging to observe rapid changes in treatment-refractory patients. However, S1 relapsed within a few weeks and S2 did not have adequate follow-up data. It has to be evaluated whether there is a need for optimisation of the protocol or maintenance sessions for sustainability of improvement. Overall, the experience with these 2 cases warrants more systematic studies to assess the efficacy and tolerability of accelerated dTMS in OCD.

Figure 1.

Change in clinical symptoms with accelerated dTMS treatment; YBOCS – Yale Brown Obsessive Compulsive Scale, VAS – Visual Analogue Scale (for OCD related emotional distress)