A double blind randomised sham controlled study for effect of deep repetitive transcranial magnetic stimulation in treatment of patients with somatic symptom disorder

Somatic Symptom Disorder (SSD) is characterized by the presence of one or more persistent somatic symptoms associated with excessive thoughts, emotions, and behaviors related to these symptoms. These symptoms may or may not be explained by medical conditions and arise from a heightened awareness of bodily sensations, with a tendency to interpret these sensations as indicative of some medical illness. Symptoms include dizziness, abdominal pain/discomfort, nausea, palpitations, headache, etc. The global prevalence of SSD is 5-7%, with a much higher female predilection, exhibiting a male-to-female ratio of 1:10 (D’Souza et al., 2022). While the etiology of

SSD is unclear, studies have identified risk factors including childhood neglect, sexual abuse, chaotic lifestyle, and history of alcohol and substance abuse.

Psychosocial stressors, such as unemployment and impaired occupational functioning, have also been implicated. The pathophysiology of SSD is unknown. Autonomic arousal from endogenous noradrenergic compounds may cause tachycardia, gastric hypermotility, heightened arousal, muscle tension, and pain associated with muscular hyperactivity in patients with SSD. Additionally, there may be a genetic component and environmental factors contributing to the disorder. The symptoms of SSD overlap with those of chronic pain but exhibit a distinct psychopathology. The DSM-5 classifies SSD as a separate entity, highlighting the wider range of symptoms and a preoccupation with somatic symptoms characterized by heightened sensitivity and affective-laden perception. Incorporating affective, cognitive, and behavioral components into the criteria for SSD provides a more comprehensive and accurate reflection of the true clinical picture. Failure to recognize this disorder may lead physicians to perform unnecessary2 investigations or diagnostic procedures, resulting in iatrogenic complications. It also poses a significant financial burden on healthcare services. SSD is frequently comorbid with depression and anxiety. However, the treatment outcome in SSD depends on the total number of bodily symptoms rather than the burden of comorbidities. Therefore, newer modalities of treatment must target the distinct neural circuitry of SSD.

Repetitive Transcranial Magnetic Stimulation (rTMS) is a non-invasive brain stimulation modality that allows for selective activation or inhibition of neural circuits . TMS works on the principle of “electromagnetic induction.” There is induction of a brief and pulsed magnetic field which is perpendicular to the electric current. Studies have shown that repeated stimulation at low frequency produces long-lasting inhibition, known as long-term depression (LTD), whereas repeated high-frequency stimulation can produce excitation through long-term potentiation (LTP). rTMS has been used to study cortical and subcortical functions, neural plasticity, and brain mapping in normal individuals and in various neuropsychiatric disorders. TMS of the dorsolateral prefrontal cortex (dlPFC) is FDA approved for treatment- resistant depression and obsessive-compulsive disorder. TMS in medically unexplained symptoms, fibromyalgia, and complex regional pain syndrome has shown encouraging results mediated by endogenous opioid-mediated functional improvement in fronto-cingulo-limbic connections. The medial PFC has been successfully targeted in depression, tinnitus, and substance use disorders to modulate anterior cingulate cortex (ACC) activity. ACC is the critical integrator where affectively laden information (insula, amygdala), visceral somatic information (thalamus, brainstem), motivated behavior (striatum, PFC, amygdala), and cognitive control (PFC) converge. Therefore, ACC can be explored as a potential candidate for neuromodulation.

Patients will be approached from AIIMS Psychiatry Outpatient setting, diagnosed with Somatic Symptom Disorder as per DSM-5 criteria. Patients meeting the inclusion criteria will be approached on the day of their visit to the OPD. Inclusion and exclusion criteria will be applied. Informed consent will be obtained from patients who agree to participate in the study. Assessment of the patients will be carried out using a short clinical performa for sociodemographic history and clinical history and then using the following instruments - Patient Health Questionnaire-15 (PHQ-15), Hamilton Depression Rating Scale (HAMD), Hamilton Anxiety Rating Scale (HAMA), World Health Organization Quality of Life Brief Version (WHOQOL-BREF), and Global Assessment of Functioning (GAF). Assessment will be completed in one single session. The assessment will take about 1.9 hours. The patients will be randomized using the computer generated randomisations into either deep rTMS treatment group or sham rTMS group. Allocation concealment using sealed envelopes and double blinding will be done to prevent selection bias and observer bias. The patients in the treatment rTMS group will receive deep rTMS at the mPFC at 20 Hz stimulation with 50 trains of 2 seconds and an inter-train interval of 20 seconds. The protocol will take 18 minutes. Treatment sessions will be administered once daily over a period of 15 days. Conversely, patients in the sham rTMS group will undergo sham procedures for the same duration. At the conclusion of the 15-session treatment period, patients in both groups will undergo a reassessment using the aforementioned instruments to evaluate any improvements in their symptoms.