STUDY THE THERAPEUTIC ROLE OF BILATERAL TRANSCRANIAL MAGNETIC STIMULATION IN A SAMPLE OF PATIENTS WITH OBSESSIVE COMPULSIVE DISORDER ATTENDING AL-AZHAR UNIVERSITY HOSPITALS

STUDY THE THERAPEUTIC ROLE OF BILATERAL TRANSCRANIAL MAGNETIC STIMULATION IN A SAMPLE OF PATIENTS WITH OBSESSIVE COMPULSIVE DISORDER ATTENDING AL-AZHAR UNIVERSITY HOSPITALS

By

Bahaa Mahmoud Abd El-Wahed, Mohamed Abd El-Fattah Soliman, Amgad Ahmed Meshref

Department of Psychiatry, Faculty of Medicine, Al-Azhar University

Corresponding Author: Bahaa Mahmoud Abd El-Wahed,

Mobile: 01064691668, E-mail: bahaa.mahmoud11@gmail.com

ABSTRACT

Background: Obsessive-compulsive disorder (OCD) is  a mental disorder in which a person has certain thoughts repeatedly or feels the need to perform certain routines repeatedly to an extent that generates distress or impairs general functioning, affects approximately 2-3% of the world population. The first-line treatments are selective serotonin reuptake inhibitors and cognitive behavioral therapy. Despite that, approximately 40- 60% of patients remain treatment refractive.

Objective: Evaluating the efficacy of low frequency repetitive transcranial magnetic stimulation (rTMS) applied over the supplementary motor area (SMA) on both sides as an adjunctive treatment for OCD.

Methods: Twenty-four patients with OCD were randomly assigned to 2 weeks either active LF (1 Hz, n=12) with parameters (25-minute trains, 1,500 pulses/day each side at 100% of the resting motor threshold RMT, 5 sessions/week) or sham (n=12) (same LF parameters with coil tilting). OCD symptoms were assessed using: Yale-Brown Obsessive Compulsive Scale (Y-BOCS) before and immediately after sessions.

Results: A repeated-measures analysis of variance (ANOVA) revealed a significant reduction in Y-BOCS scores in the active groups compared with the sham group after 2 weeks. There were no reports of serious adverse effects following the active or sham rTMS treatments.

Conclusion: LF rTMS over the supplementary motor area (SMA) on both sides appeared to be superior to sham rTMS for relieving OCD symptoms in patients with OCD. Further trials with larger sample sizes should be conducted to confirm the present findings.

Key words: Bilateral Transcranial magnetic stimulation; Obsessive-compulsive disorder; supplementary motor area.

INTRODUCTION

     Obsessive-compulsive disorder (OCD) is a chronic and highly debilitating neuropsychiatric disorder characterized by obsessions and/ or compulsions; that lead to significant distress to the patients and their families (American Psychiatric Association, 2014). Obsessions are persistent, intrusive ego dystonic thoughts, urges or images, while compulsions are repetitive and time-consuming behaviors or mental acts that usually done to prevent the occurrence or limit the distress caused by the obsession. The prevalence of OCD in the general population is estimated at 2 to 3%, and it affects both sexes equally (Ruscio A et al., 2010).

      High doses of SSRIs and clomipramine in addition to CBT are considered as first-line treatments for OCD at present (Stein DJ et al., 2012). Recently, treatment regimens have expanded to include other psychotropic drugs, particularly antipsychotics.5Despite that, 40-60% of patients fail to respond to those medications appropriately or unable to tolerate their side effects (Rehn S et al., 2018). Therefore, it was important to develop new treatment strategies based on understanding the abnormalities that contribute to OCD (Elbeh KA et al., 2016).

     Repetitive Transcranial Magnetic Stimulation (rTMS) is one of the potential additional treatments for OCD. It is a non-invasive neuromodulator technique in which strong electrical currents are passed through a coil that is placed directly on the scalp to induce magnetic field pulses with sufficient intensity able to pass through the skull and form an electrical current in the cortical region below the coil; consequently, depolarizing or hyperpolarizing the axons of the neurons (Shayganfard M et al., 2016).

     Although pathophysiology of OCD is not fully understood, many studies suggested that OCD is associated with dysfunction in the orbitofronto -striato- pallido-thalamic circuitry. This includes dorsolateral prefrontal cortex (DLPFC), anterior cingulate gyrus, supplementary motor area (SMA), orbitofrontal cortex (OFC) and caudate nucleus (Seo HJ et al., 2016).

     The aims of the present study are evaluating the therapeutic effect low frequency (1 Hz) repetitive transcranial magnetic stimulation (rTMS) applied over the supplementary motor area (SMA) on both sides versus sham stimulation in the treatment of OCD patients.

MATERIALS AND METHODS

     The present study has included 24 patients with a primary diagnosis of OCD according to DSM-5 criteria from those attending psychiatric clinic at Sayed Galal Hospital, Faculty of Medicine, Al-Azhar University and accepted to participate in this study by obtaining prior informed consent during the period from March 2020 to September 2020. The ethical Committee of the Faculty of Medicine, Al-Azhar University approved the experimental protocol.

Inclusion criteria:

      Patients aged from 18 to 65 years old of both sexes with Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score: ≥ 16.

Exclusion criteria:

     Patients with history of other comorbid neuropsychiatric disorder; drug abuse, history of epilepsy, serious head injury or neurosurgical procedure; metal implants and pacemakers.

Procedure:

     The stimulation was carried out using an 8-figure shape coil (Magstim rapid 2), which placed with its center Parallel above the optimal position of the supplementary motor area (SMA) on both sides.

     The supplementary motor area (SMA) on both sides was identified at points 3-cm anterior to the leg motor area in the sagittal midline. The Resting Motor Threshold (RMT) has been determined using visualization method via the stimulation of the primary motor cortex area for leg muscles in 5 successful trials of 10 TMS.

     The patients were randomly classified into two groups to receive either a sham or active LF rTMS.

The 1^st group: included 12 patients received rTMS with (1 Hz frequency, 1500 pulses/session at 100% of RMT applied in 150 trains, with 5 seconds inter-train interval). The 2^nd (sham) group: included 12 patients received stimulation with the same parameters of the 1st group and the coil was placed over the same area but perpendicular to the scalp.

     Every patient received 10 sessions, each session lasting 25 minutes, 1 session/ day for 5 consecutive days for two weeks and continued pharmacological treatments with the same doses throughout the study. Neither the patient nor the rater knew whether the patients were receiving real or sham rTMS.

     All patients were assessed before rTMS procedure, after 2 weeks later with Yale-Brown obsessive compulsive scale (Y-BOCS) (Goodman WK et al., 1989).

Statistical analysis:

     Data was analyzed using SPSS version 23.0. Quantitative data were expressed as mean ± standard deviation (SD). Qualitative data were expressed as percentage. The demographic and clinical data were compared using t-tests, chi-square tests. A repeated-measures analysis of variance (ANOVA) was used to evaluate the group- and time-dependent effects of rTMS on the mean scores of the psychometric scales. Patients with a reduction ≥25% in Y-BOCS score were classified as responders. P value ＜0.05 was considered to indicate statistical significance.

RESULTS

     Of the 24 patients who were initially included in this study, 12 patients in each group. All patients completed treatment sessions, and the procedure was well tolerated.

      The difference between the active and the sham groups according to demographic data wasn’t statistically significant (Table 1-a, b, c, d, e).

Table (1-a):    Age of the studied patients

Table (1-b):   Sex of the studied patients

X²: Chi square test

Table (1-c):    Marital state of the studied patients

X²:  Chi square test

Table (1-d):   Working state of the studied patients

X²:  Chi square test

Table (1-e):    Handedness of the studied patients

X²:  Chi square test

Table (2):  Y-BOCS of the studied patients before sessions

     The comparison between the 2 groups according to mean Y-BOCS isn’t significantly different immediately after sessions (P=0.641) (Table 3).

Table (3):  Y-BOCS of the studied patients after sessions

     As regard OCD symptoms according to Y-BOCS, there is reduction in the active groups immediately after sessions with statistically significant difference (p=0.027) (Table 4).

Table (4):  Y-BOCS of the active group patients before and after sessions

DISCUSSION

     The present study aimed to evaluate the effect of low frequency repetitive transcranial magnetic stimulation (rTMS) applied over the supplementary motor area (SMA) on both sides as an adjunctive treatment for OCD compared to sham TMS. This was in line with studies which indicated that rTMS of the supplementary motor area (SMA) on both sides was more effective for treating OCD than sham stimulation (Shivakumar V et al., 2019).

     The study included 24 OCD patients whom divided into a sham or active rTMS groups. The demographical and clinical data of the 2 groups were monitored at the baseline and there was no significant difference in the scores of Y-BCOS. The side effects of the rTMS were acceptable as what was mentioned in many previous studies (Seo HJ et al., 2016).

     It was clear that OCD more common among males (58.3% males) also most of the patients were in the third and fourth decade of life as the most representative age category in the two groups was (21-38 years). The difference between groups according to sex (p =0.682) and age (p =0.265) has no statistical significance (Table 1a, b).

     This is consistent with Kang et al. study (17 males/ 3 females) with mean age (28.6), Sarkhel et al., 2010 (male/female 23/19), mean age (30.67) and many other studies which indicate that symptoms in more than 80% of casas started before the age of 35 Years (Rehn Set al., 2018).

     Regarding the marital and occupation status, the percentage of non-workers people were higher in the 2 groups without statistical significance difference (p = 0.653) (Table 1-d). This can be explained by the presence of OCD as a mental disorder that causes a deterioration of social and occupational performance (Elbeh KA et al., 2016).

     Our result found that LF-rTMS (1 Hz) applied over the supplementary motor area (SMA) improves symptoms and severity of OCD with significant reduction of Y-BOCS score at the end of 2^nd week of treatment (Table 4) (P=0.027) and three patients were considered as responders to the treatment (defined as having decrease in the score of Y-BOCS ≥ 25% of the baseline) versus none in the sham group. The difference between groups in Y-BOCS wasn’t statistically significant at the end of sessions (Table 3) (p=0.641).

     Our results are consistent with that of Mantovani et al., study, where they found that LF-rTMS over the supplementary motor area (SMA) produces significant improvement of OCD (P <0.01). Also results agreed with that of Gomes et al. as there were significant differences over 2nd weeks between the active and sham groups on Y-BOCS (P <0.0001) (Mantovani et al.).

     While Pelissolo et al. who studied the effect of LF-rTMS over SMA in OCD for 4 weeks and there were no statistically significant differences between the active and sham groups on Y-BOCS at the end of the 4th week. Perhaps this is due to the difference in the stimulation period as well as the nature of sham stimulation.

     In our study there were statistically significant differences between the active and the sham groups, patients treated with active rTMS had a somewhat greater reduction in OCD symptoms.

     The obstacles that we have met may be related to many limitations such; the short stimulation period (two weeks), dependence on the manual targeting in  coil localization, relying on the tilting method in sham stimulation, relatively small sample size, the nature of the target group with OCD in COVID restrictions and finally choosing SMA as the target region for stimulation which is only one of the neural circuits involved in the occurrence of OCD symptoms, or a starting point to induce remote stimulation of other circuits also involved in OCD and persistence of symptoms, such as OFC and  DLPFC which can't be stimulated directly using rTMS techniques used in the present study.

     So, we recommend that; Conducting more studies involving larger numbers of patients with a less chronic form of OCD, taking into account that there are other regions involved in the occurrence of OCD, the impact of psychiatric drugs, neuroimaging and computer modeling of TMS to determine optimal stimulation targets and the change in brain activity in OCD during rest than exposure to stimuli.

CONCLUSION

     The two-week treatment with rTMS applied over the SMA on both sides as an adjunctive treatment does outweigh the sham stimulation in relieving OCD symptoms, reducing clinical severity or improving treatment response.

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