Effect of Transcranial Direct Current Stimulation on Sertraline Composition on the Severity of Symptoms of Obsessive-Compulsive Disorder

EXTENDED ABSTRACT

Background

Obsessive-compulsive disorder (OCD) is a disabling neuropsychiatric disorder characterized by recurrent intrusive thoughts, images, or impulses and repetitive behaviors or mental acts performed to reduce the distress associated with these obsessions [1]. Its worldwide prevalence is approximately 1-2%, and the disorder can substantially impair quality of life and daily functioning [3, 4, 6]. Selective serotonin reuptake inhibitors (SSRIs), including sertraline, and cognitive-behavioral therapy are established first-line treatments [7]. Nevertheless, up to 40% of patients do not respond adequately to SSRIs, and approximately one-third remain symptomatic despite optimized pharmacotherapy and cognitive-behavioral treatment [8–10]. Augmentation or switching strategies are available for treatment-resistant cases, but they may provide incomplete benefit and can increase adverse effects [11–13]. Transcranial direct current stimulation (tDCS) is a noninvasive neuromodulation technique that applies weak direct electrical current to targeted cortical regions. It has shown therapeutic potential in neuropsychiatric disorders and preliminary OCD studies, but findings regarding efficacy, optimal electrode placement, and timing of response have been inconsistent [14–18]. The present study therefore evaluated whether active tDCS added to stable sertraline therapy reduced overall OCD severity and specific dimensions of obsessive and compulsive symptoms compared with sham stimulation.

Methods

This double-blind randomized clinical trial enrolled 50 consecutive patients attending the psychiatry clinic of Amir Kabir Hospital in Arak who met DSM-5 clinical criteria for moderate-to-severe OCD and were receiving sertraline. Eligible participants were 15-65 years old, had at least basic literacy, were taking a stable sertraline dose of at least 100 mg, and agreed not to change the medication dose during the study. Important exclusion criteria included recent brain surgery; neurologic disorders associated with structural brain abnormalities, recent stroke, or brain tumor; implanted cranial devices; a non-removable hearing aid; active scalp lesions; migraine, epilepsy, or seizure history; unstable medical or psychiatric conditions including psychosis, bipolar disorder, recent suicidal ideation or attempt; current use of benzodiazepines, anticonvulsants, lithium carbonate, psychostimulants, dextromethorphan, pseudoephedrine, or recreational substances; and neuromodulation treatment within the preceding 3 months. Participants were randomly allocated by a lottery-based allocation method to active tDCS (n=25) or sham tDCS (n=25). Both groups continued sertraline. For stimulation, a saline-soaked sponge anode was placed over the left dorsolateral prefrontal cortex and the cathode over the right orbitofrontal region. Active and sham procedures were administered for 20 minutes per session over 16 sessions. The patient and the psychiatry resident who assessed outcomes were blinded to treatment assignment. OCD symptoms were assessed with the Padua Inventory at baseline, after 8 sessions (week 4), after 16 sessions (week 8), and 1 month after completion of treatment. Sample size estimation was based on prior treatment-response data reported by Silva et al. [19], yielding a minimum of 23 participants per group; 25 per group were enrolled. Data were analyzed in SPSS version 26 using Student's t test, Mann-Whitney U test, chi-square test, and repeated-measures analysis of covariance as appropriate, with P<=0.05 considered statistically significant. The study received ethics approval from Arak University of Medical Sciences (IR.ARAKMU.REC.1402.115) and was registered in the Iranian Registry of Clinical Trials (IRCT20230922059487N1). Written informed consent was obtained from all participants.

Results

The intervention and control groups were comparable at baseline. Mean age was 32.36±10.76 years in the intervention group and 30.44±6.63 years in the control group (P=0.452). Mean duration of illness was 2.80±2.06 and 2.56±1.15 years, respectively (P=0.614). Men accounted for 10 participants (40%) in the intervention group and 11 (44%) in the control group, while women accounted for 15 (60%) and 14 (56%), respectively (P=0.774). Baseline total Padua Inventory scores were also similar (63.64±14.2 versus 67.08±16.3; P=0.333). After treatment began, clinically and statistically important separation between groups emerged. At week 4, the total OCD score decreased to 46.96±24.0 in the active-tDCS group compared with 64.12±19.4 in the sham group (P<0.001). At week 8, scores were 36.20±31.1 and 62.40±21.7, respectively (P<0.001). One month after treatment ended, the intervention group retained a substantially lower total score (37.36±32.7) than the control group (64.36±21.2; P<0.001). Bonferroni post-hoc analysis showed a significant reduction across the first three assessment stages, whereas the slight increase at the 1-month follow-up relative to week 8 was not significant.

Table 1. Comparison of changes in obsessive-compulsive disorder symptom severity across four assessment stages between the two groups.

A similar pattern was observed for major symptom domains. Contamination-obsession scores were comparable at baseline (16.80±6.21 versus 18.12±4.41; P=0.654), but were lower with active tDCS at week 4 (11.80±6.57 versus 16.92±4.83), week 8 (8.48±8.30 versus 16.16±5.38), and 1-month follow-up (8.68±8.36 versus 16.80±5.34), with significant between-group differences after treatment. Thoughts of harming others likewise fell from 15.44±13.18 at baseline to 11.72±12.32 at week 4, 10.04±12.59 at week 8, and 10.40±12.89 at follow-up in the intervention group, while remaining higher in controls. Checking-compulsion scores decreased from 16.72±9.47 at baseline to 12.52±9.18 after 8 sessions and 9.72±10.24 after 16 sessions, with a value of 10.00±10.51 one month later; corresponding control values were 18.60±8.33, 18.00±8.60, 17.72±9.03, and 18.12±9.08. The groups did not differ at baseline for this domain (P=0.189), but differed significantly at all subsequent assessments (P<0.001). Both active and sham procedures were well tolerated, and no serious adverse event leading to treatment discontinuation was reported.

Table 4. Comparison of changes in checking-compulsion severity across four assessment stages between the two groups.

Conclusion

Adding active tDCS to stable sertraline therapy produced a greater reduction in overall OCD severity and in contamination, harm-related, and checking symptoms than sham stimulation. Improvement was evident after 8 sessions, became more pronounced after 16 sessions, and remained apparent one month after treatment cessation. Within the conditions of this study, tDCS was a tolerable, noninvasive adjunct for patients with persistent moderate-to-severe OCD symptoms despite sertraline treatment.

Keywords: Obsessive-Compulsive Disorder (OCD), Sertraline, Transcranial Direct Current Stimulation (TDCS)

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