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Treatment of obsessive-compulsive disorder with frontopolar multifocal transcranial direct current stimulation and exposure and response prevention: A case Series

Open AccessPublished:September 23, 2021DOI:https://doi.org/10.1016/j.brs.2021.09.008

      1. Background

      Exposure and response prevention (ERP) is the most effective psychotherapy for obsessive-compulsive disorder (OCD). However, about 1 in 3 OCD patients receive no significant benefit from ERP, many who benefit continue to exhibit clinically significant symptoms, and therapeutic response typically takes 2–3 months [
      • Schruers K.
      • Koning K.
      • Luermans J.
      • et al.
      Obsessive–compulsive disorder: a critical review of therapeutic perspectives.
      ]. Alternative intervention strategies are urgently needed.
      Evidence suggests that the default mode network (DMN) and, in particular, the medial prefrontal cortex (mPFC), a key hub of the DMN, supports adaptive safety learning (e.g., fear extinction) that is considered a key mechanism of exposure-based treatments [
      • Marin M.F.
      • Camprodon J.A.
      • Dougherty D.D.
      • et al.
      Device-based brain stimulation to augment fear extinction: implications for PTSD treatment and beyond.
      ]. Our group recently demonstrated that frontopolar multifocal transcranial direct current stimulation (tDCS) modulates DMN and mPFC functional connectivity in community volunteers and accelerates therapeutic safety learning in OCD patients [
      • Adams T.G.
      • Cisler J.M.
      • Kelmendi B.
      • et al.
      Transcranial direct current stimulation targeting the medial prefrontal cortex modulates functional connectivity and enhances safety learning in obsessive-compulsive disorder: results from two pilot studies.
      ]. OCD patients who received Active (real) tDCS reported 53% greater reduction in subjective distress within a single 50-min exposure session, compared to patients who received Sham (placebo) tDCS [
      • Adams T.G.
      • Cisler J.M.
      • Kelmendi B.
      • et al.
      Transcranial direct current stimulation targeting the medial prefrontal cortex modulates functional connectivity and enhances safety learning in obsessive-compulsive disorder: results from two pilot studies.
      ].
      Motivated by these exciting laboratory findings, we recently treated two OCD patients, IB and DC, with 12 sessions of integrated frontopolar multifocal tDCS and manualized ERP [
      • Foa E.B.
      • Yadin E.
      • Lichner T.K.
      Exposure and response (ritual) prevention for obsessive compulsive disorder: therapist guide.
      ].

      2. Methods

      After providing informed consent (IRB#57153) and eligibility screening, including tDCS safety screen and structured clinical interview [
      • Tolin D.F.
      • Gilliam C.
      • Wootton B.M.
      • et al.
      Psychometric properties of a structured diagnostic interview for DSM-5 anxiety, mood, and obsessive-compulsive and related disorders.
      ], two OCD patients began the 10-week treatment study. Twelve 90-min treatment sessions were delivered, in person, over six weeks (twice weekly). Treatment involved four planning sessions – psychoeducation, treatment planning (e.g., hierarchy development [see Supplemental Table 1 for examples]), and in vivo and imaginal exposure demonstrations – followed by eight tDCS + ERP sessions. 20-minutes of frontopolar tDCS (1.5mA, 30-s ramp in/out, Supplemental Figure 1) was administered at the beginning of these sessions and was followed by 50-min of ERP practice, which was primarily in vivo and therapist assisted. Between-session exposures were encouraged. Psychiatric assessments were completed prior to the first treatment session, every four treatment sessions, and one and four weeks post-treatment. Symptom change was measured with the Yale-Brown OCD Scale (YBOCS) [
      • Goodman W.K.
      • Price L.H.
      • Rasmussen S.A.
      • et al.
      The Yale-Brown obsessive compulsive scale: I. Development, use, and reliability.
      ], which was completed by an independent evaluator. Self-reports of OCD symptoms and depression were also collected [
      • Abramowitz J.S.
      • Deacon B.J.
      • Olatunji B.O.
      • et al.
      Assessment of obsessive-compulsive symptom dimensions: development and evaluation of the dimensional obsessive-compulsive scale.
      ,
      • Kroenke K.
      • Spitzer R.L.
      The PHQ-9: a new depression diagnostic and severity measure.
      ]. Patients were debriefed, provided unstructured feedback, and compensated $250 for their participation after completing the final follow-up assessment.

      3. Case 1: IB

      IB is a 24-year-old, middle-class, African-American female. At intake, she met DSM-5 criteria for OCD, agoraphobia, recurrent major depressive disorder (MDD), and posttraumatic stress disorder (PTSD); OCD was primary. IB was on stable (>4 weeks) doses of sertraline (100mg) and amphetamine-dextroamphetamine (10mg) at intake and through study completion. She previously received counseling and cognitive-behavioral therapy (CBT) for depression and anxiety, but not for OCD specifically. As reflected by her baseline severity ratings (Fig. 1A), she reported limited benefits from sertraline or past therapy.
      Fig. 1
      Fig. 1Symptoms of OCD (YBOCS) and depression (PHQ-9) dramatically improved after four sessions of tDCS + ERP (mid-treatment) and further improved at one-week and one-month follow-up (after eight session of tDCS + ERP) for two patients with a principal diagnosis of OCD. The first patient treated reported an 80% reduction in OCD symptoms (A) and the second patient reported a 57% reduction in OCD symptoms (B). Both patients reported similar reductions in depressive symptoms (74% and 73%, respectively).
      IB's primary obsessions included aggressive fears (e.g., that she may unintentionally hurt others), the need to know insignificant facts (e.g., the definition of medical terms from TV shows), and symmetry/exactness. Her primary compulsions included checking, reassurance-seeking, and ordering/rearranging. IB's baseline YBOCS Severity score was in the extreme range (YBOCS = 35), which was corroborated by a self-reported Dimensional Obsessive-Compulsive Scale (DOCS) score of 58. Additionally, IB reported moderately severe symptoms of depression at baseline (Patient Health Questionnaire [PHQ-9] = 19).
      After treatment planning sessions (1–4), IB's YBOCS Severity score decreased to 29. After four sessions of tDCS + ERP (session 8), YBOCS decreased to 19. One week after treatment completion (eight sessions of tDCS + ERP), IB's YBOCS score was reduced to the subclinical/mild range (YBOCS = 10). Symptom reductions were maintained at one-month follow-up (YBOCS = 7) and reflected an 80% total reduction in OCD severity from baseline. This was corroborated by a 69% reduction in self-reported OCD symptoms at one-month follow-up (DOCS = 18). IB's self-reported symptoms of depression were reduced by 74% at one-month follow-up (PHQ-9 = 5). See Fig. 1A.

      4. Case 2: DC

      DC is a 23-year-old, middle-class, Hispanic female. At intake, she met DSM-5 criteria for OCD, agoraphobia, and generalized anxiety disorder; OCD was primary. DC was treatment naïve; she denied previous psychiatric or psychological treatment. DC's primary obsessions included aggressive fears (e.g., something bad might happen to family member [s]), the need to remember insignificant things (e.g., scenes in television shows), and contamination fears (e.g., fear that food would make her sick). Her primary compulsions included the repeating rituals (e.g., taking shoes on/off), symmetry, and counting. DC's baseline YBOCS Severity score was in the moderate range (YBOCS = 23), as was her baseline self-reported OCD severity (DOCS = 29). Despite not meeting criteria for MDD during the structured clinical interview, DC reported moderate symptoms of depression at baseline (PHQ-9 = 11).
      After treatment planning sessions (1–4), DC's YBOCS Severity score increased by one point (YBOCS = 24). After four sessions of tDCS + ERP, her YBOCS decreased to 16. One week after treatment completion (eight sessions of tDCS + ERP), DC's YBOCS score was reduced to the subclinical/mild range (YBOCS = 12). Symptom reductions were maintained at one-month follow-up (YBOCS = 10) and reflected a 57% total reduction in OCD severity from baseline. This was corroborated by a 72% reduction in self-reported OCD symptoms at one-month follow-up (DOCS = 8). DC's self-reported symptoms of depression were reduced by 73% at one-month follow-up (PHQ-9 = 3). See Fig. 1B.

      5. Conclusions

      To our knowledge, these are the first cases of OCD treated with integrated tDCS and ERP to be reported in the scientific literature. Both OCD patients reported dramatic reductions in OCD symptoms (57–80%) after 12 sessions of treatment, only eight of which included tDCS and significant exposure practice. They reported similarly large reductions in depressive symptoms despite no therapeutic targeting of depression and no changes to psychiatric medications. Consistent with past ERP augmentation research [
      • Chasson G.S.
      • Buhlmann U.
      • Tolin D.F.
      • et al.
      Need for speed: evaluating slopes of OCD recovery in behavior therapy enhanced with d-cycloserine.
      ], both patients reported their largest reductions from baseline to mid-treatment (48–71% after four sessions of tDCS + ERP), which suggests that the administration of frontopolar tDCS prior to exposure practice may accelerate treatment response. This is also consistent with our recently published laboratory findings, which demonstrated that frontopolar tDCS administered before a single session of exposure can accelerate therapeutic safety learning in OCD. These preliminary findings, especially when viewed alongside the growing evidence suggesting that tDCS targeting the mPFC can enhance safety learning [
      • Adams T.G.
      • Cisler J.M.
      • Kelmendi B.
      • et al.
      Transcranial direct current stimulation targeting the medial prefrontal cortex modulates functional connectivity and enhances safety learning in obsessive-compulsive disorder: results from two pilot studies.
      ,
      • Adams Jr., T.G.
      • Wesley M.
      • Rippey C.
      Transcranial electric stimulation and the extinction of fear.
      ], support additional research into this promising treatment augmentation strategy. Well-powered, double-blind, randomized, placebo-controlled clinical trials are needed to determine if the addition of frontopolar tDCS can improve the efficacy or efficiency of ERP for OCD.

      Declaration of interests

      The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
      The authors declare the following financial interests/personal relationships which may be considered as potential competing interests:
      Dr. Adams, Dr. Gold, Mr. Rippey, and Mrs. Kelly have no financial disclosures/conflicts to report. Dr. Pittenger serves as a consultant for Biohaven, Teva, Lundbeck, Brainsway, and CH-TAC, receives royalties and/or honoraria from Oxford University Press and Elsevier, and has filed a patent on the use of NIRS neurofeedback in the treatment of anxiety, which is not relevant to the current work. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.

      Declaration of competing interest

      Dr. Adams, Dr. Gold, Mr. Rippey, and Mrs. Kelly have no financial disclosures/conflicts to report. Dr. Pittenger serves as a consultant for Biohaven, Teva, Lundbeck, Brainsway, and CH-TAC, receives royalties and/or honoraria from Oxford University Press and Elsevier, and has filed a patent on the use of NIRS neurofeedback in the treatment of anxiety, which is not relevant to the current work. The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.

      Acknowledgements

      This publication was supported by the National Center for Research Resources and the National Center for Advancing Translational Sciences, the National Institutes of Health, through Grants UL1TR001998 and the University of Kentucky Center for Clinical and Translational Science. Dr. Adams is supported by the National Institute of Mental Health (NIMH): K23MH111977 and L30MH111037. Dr. Pittenger is supported by the Taylor Family Foundation and the NIMH (R01MH116038 and K24MH121571). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH or other funders.

      Appendix A. Supplementary data

      The following is the Supplementary data to this article:

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