Deep brain stimulation (DBS) can significantly decrease symptoms in approximately 60% of patients with refractory obsessive-compulsive disorder (OCD), which affects a fifth of all patients with OCD.1,2,3 The safety and efficacy of DBS, which involves permanent surgically implanted hardware, has been established in patients with severe refractory major depressive disorder. In these cases, DBS may provide long-term relief (>8 years) for patients.4 

However, responses to treatment depend on the target chosen, with 5 targets yielding positive outcomes, including the ventral anterior limb of the internal capsule (vALIC), subthalamic nucleus (STN), nucleus accumbens (NAcc), ventral capsule/ventral striatum (VC/VS), or inferior thalamic peduncle (ITP), all involving fronto-striato-thalamocortical circuits.5 Irrespective of the area targeted for implanted electrodes, 60% of patients who respond to DBS show >35% decreases on the Yale-Brown obsessive-compulsive scale (Y-BOCS),6 while partial responders’ scores decrease from 25% to 34% and non-responders show decreases of <24%.7

Ventral Anterior Limb of the Internal Capsule

Early research focused on the vALIC based on studies demonstrating improvements in patients after anterior capsulotomy,8 with half of patients responding to treatment. A study of 70 patients — the largest cohort of patients to receive DBS for OCD — demonstrated positive outcomes. At 12-month follow up, 52% of patients were responders, and 17% experienced partial relief.7

Subthalamic Nucleus

The STN became a target after DBS in Parkinson disease (PD) demonstrated relief from OCD symptoms in 3 patients with comorbid PD and OCD.9 In 2 of 3 completed studies targeting the STN, all patients reported a mean reduction of as much as 31 points in Y-BOCS scores.10,11 In the largest study (n=16) of the STN, 75% of patients with OCD had decreased Y-BOCS scores. However, this higher response rate may stem from the study’s low threshold for response.12

Nucleus Accumbens

The NAcc is a promising target for DBS based on evidence of reward system dysfunction in OCD.13 In an early study of unilateral, right-sided NAcc implantation in 4 patients with OCD, 3 patients were responders, although the study failed to report Y-BOCS scores.14 A monetary incentive task-functional magnetic resonance imaging (fMRI) study of 18 patients measured outcomes based entirely on NAcc imaging, only using Y-BOCS scores for baseline OCD severity. Patients exhibited reduced NAcc activity, with more hypoactivation in patients with symptoms relating to the fear of contamination than risk avoidance.15 Following DBS, patients showed NAcc activation comparable to healthy controls. Other studies of the NAcc have shown decreases in Y-BOCS scores of as much as 52%16-19 although few patients partially responded to treatment.16,18 While most patients experienced relief from OCD symptoms, anxiety or mood issues remained.16-18

Ventral Capsule/Ventral Striatum

The VC/VS target places DBS leads in the same anterior-posterior plane as the NAcc, stimulating the NAcc and ALIC and aligning with limbic projections from the amygdala, hippocampus, and prefrontal and cingulate cortices.20 In the largest study of this target, 61% of patients experienced >35% reductions in Y-BOCS scores, with improvements seen across 36 months. Notably, 100% of responders reported major reductions in obsessions and checking, 55.6% in symmetry and ordering, and 45.5% in cleanliness and washing. As researchers refined VC/VS placement across the study period, more patients experienced greater symptom relief.21 While the STN may play a role in improved cognitive flexibility, the VC/VS might ameliorate anxiety and mood symptoms.22,23

Anterior Limb of the Internal Capsule and Nucleus Accumbens

Researchers have attempted to more broadly cover the striatal region by simultaneously targeting the ALIC and the NAcc. In a study of DBS for both the ALIC and NAcc (n=20), 40% of patients experienced a full response and 70% at least a partial response at 12-month follow-up.24 A study using a similar treatment (n=22) found that patients’ connectivity profiles between the ALIC and NAcc stimulation sites and their medial and lateral prefrontal cortices significantly predicted patient response rates.25

Inferior Thalamic Peduncle

The ITP, involved in depression and OCD pathophysiology, connects the circuitry of the nonspecific thalamic system and the orbitofrontal cortex. In an early study (n=8), 75% of patients were full responders at 3-month follow-up, although researchers reported an unusually high number of serious adverse events in the surgery and active stimulation periods.26 A later study (n=6) demonstrated promising results and few adverse events, with 66% of patients fully responding to treatment; 1 patient with OCD and depression experienced almost complete relief from all symptoms 5 years later.27 The attractiveness of the ITP in attenuating OCD symptoms led to a phase 1 pilot study, in which all 5 patients responded completely to treatment. However, at 2-year follow-up, 3 adverse events occurred, 1 resulting in the removal of the DBS.28

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DBS: Still Rare in the Treatment of OCD

To date, DBS for OCD remains rare, treating fewer than 300 patients worldwide and with most studies enrolling <5 patients.29 Larger studies in the future will prove invaluable in assessing the efficacy of DBS for OCD and identifying the most efficacious placement of leads. Meta-analyses across targets yield different outcomes, depending on the criteria for clinical improvement and the unilateral or bilateral placement of electrodes.30 Some researchers have challenged the accuracy of the Y-BOCS in capturing the multidimensional nature of OCD symptoms, suggesting that a Maudsley’s challenge test during fMRI can reveal the best DBS placement and the extent of improvement after activation.30 This test enables clinicians to target dysfunctional circuits specific to each patient by breaking their presentation of OCD into 4 dimensions: contamination and washing; hoarding; symmetry and repeating or ordering; and forbidden thoughts and checking.29

The promise of DBS in attenuating the impact of severe refractory OCD resulted in the US Food and Drug Administration granting a Humanitarian Device Exemption.21 Notably, 75% of a random sample of American Psychiatric Association members stated that they would consider referring patients for neurosurgical treatment of severe refractory OCD.31 Nevertheless, few patients can experience the potential relief of DBS, as private insurers have chosen not to cover costs. Currently, DBS is mostly available to patients enrolled in studies.

“The US healthcare system fails patients with mental illness,” notes Kelly Foote, MD, a professor of neurosurgery at the University of Florida in Gainesville and co-investigator on multiple studies on the impact of DBS on refractory OCD, “These patients’ quality of life could be salvaged because DBS is a cost-saving intervention [that works] after all other treatments have proven ineffective.”

References

1. Skapinakis P, Caldwell DM, Hollingworth W, et al. Pharmacological and psychotherapeutic interventions for management of obsessive-compulsive disorder in adults: a systematic review and network meta-analysis. Lancet Psychiatry. 2016;3:730–9. doi:10.1016/S2215-0366(16)30069-4

2. Alonso P, Cuadras D, Gabriëls L, et al. Deep brain stimulation for obsessive-compulsive disorder: a meta-analysis of treatment outcome and predictors of response. PloS One. 2015:10:e0133591. doi:10.1371/journal.pone.0133591

3. Kisely S, Hall K, Siskind D, et al. Deep brain stimulation for obsessive-compulsive disorder: a systematic review and meta-analysis. Psychol Med. 2014;44:3533-3542. doi:10.1017/S0033291714000981

4. Crowell AL, Riva-Posse P, Holtzheimer PE, et al. Long-term outcomes of subcallosal cingulate deep brain stimulation for treatment-resistant depression. Am J Psychiatry. 2019;176(11): 949-956. doi:org/10.1176/appi.ajp.2019.18121427

5. Senova S, Clair A-H, Palfi S, et al. Deep Brain Stimulation for refractory obsessive-compulsive disorder: towards an individualised approach. Front Psychiatry. 2019;10:905. doi:org/10.3389/fpsyt.2019.00905

6. Goodman WK, Price LH, Rasmussen SA, et al. The Yale-Brown obsessive compulsive scale: I. Development, use, and reliability. Arch Gen Psychiatry 1989;46:1006-1011. doi:org/10.1001/archpsyc.1989.01810110048007

7. Denys D, Graat I, Mocking R, et al. Efficacy of deep brain stimulation of the ventral anterior limb of the internal capsule for refractory obsessive-compulsive disorder: a clinical cohort of 70 patients [published online January 7, 2020]. Am J Psychiatry.  doi:org/10.1176/appi.ajp.2019.19060656

8. Mindus P, Rasmussen SA, Lindquist C. Neurosurgical treatment for refractory obsessive-compulsive disorder: implications for understanding frontal lobe function. J Neuropsychiatry Clin Neurosci. 1994;1:26-36.

9. Mallet L, Mesnage V, Houeto JL, et al. Compulsions, Parkinson’s disease and stimulation. Lancet. 2002;360:9342:1302-1304. doi:org/10.1016/S0140-6736(02)11339-0

10. Fontaine D, Mattei V, Borg M, et al. Effect of subthalamic nucleus stimulation on obsessive-compulsive disorder in a patient with Parkinson’s disease: Case report. J Neurosurg. 2004;100(6):1084-1086. doi:org/10.3171/jns.2004.100.6.1084

11. Le Jeune F, Verin M, N’Diaye K, et al. Decrease of prefrontal metabolism after subthalamic stimulation in obsessive-compulsive disorder: a positron emission tomography study. Biol Psychiatry. 2010;68:1016-1022. doi:org/10.1016/j.biopsych.2010.06.033

12. Mallet L, Polosan M, Jaafari N, et al. Subthalamic nucleus stimulation in severe obsessive-compulsive disorder. N Engl J Med. 2008;359(20):2121-2134. doi:org/10.1056/NEJMoa0708514

13. de Koning PP, Figee M, van den Munckhof P, et al. Current status of deep brain stimulation for obsessive-compulsive disorder: a clinical review of different targets. Curr Psychiatry Reports. 2011;13(4):274-282. doi:org/10.1007/s11920-011-0200-8

14. Sturm V, Lenartz D, Koulousakis A, et al. The nucleus accumbens: a target for deep brain stimulation in obsessive-compulsive- and anxiety-disorders. J Chem Neuroanat. 2003;26:293-299. doi:org/10.1016/j.jchemneu.2003.09.003

15. Figee M, Vink M, de Geus F, et al. Dysfunctional reward circuitry in obsessive-compulsive disorder. Biol Psychiatry. 2011;69(9):867-874. doi:org/10.1016/j.biopsych.2010.12.003

16. Huff W, Lenarz D, Schormann M, et al. Unilateral deep brain stimulation of the nucleus accumbens in patients with treatment-resistant obsessive-compulsive disorder: outcomes after one year. Clin Neurol Neurosurg. 2010;112(2):137-143. doi:org/10.1016/j.clineuro.2009.11.006

17. Aouizerate B, Cuny E, Martin-Guehl C, et al. Deep brain stimulation of the ventral caudate nucleus in the treatment of obsessive-compulsive disorder and major depression. Case report. J Neurosurg. 2004;101:682-686. doi:org/10.3171/jns.2004.101.4.0682

18. Franzini A, Messina G, Gambini O, et al. Deep brain stimulation of the nucleus accumbens in obsessive compulsive disorder: clinical, surgical and electrophysiological considerations in two consecutive patients. Neurol Sci. 2010;31(3):353-359. doi:org/10.1007/s10072-009-0214-8

19. Denys D, Mantione M, Figee M, et al. Deep brain stimulation of the nucleus accumbens for treatment-refractory obsessive-compulsive disorder. Arch Gen Psychiatry. 2010;67(10):1061-1068. doi:org/10.1001/archgenpsychiatry.2010.122

20. Burdick A, Goodman WK, Foote, KD. Deep brain stimulation for refractory obsessive-compulsive disorder. Front Biosci, Landmark Ed 2009;14:1880-1890. doi:org/10.2741/3348

21. Greenberg B, Gabriels L, Malone Jr D, et al. Deep brain stimulation of the ventral internal capsule/ventral striatum for obsessive-compulsive disorder: worldwide experience. Mol Psychiatry. 2010;15:64. doi:.org/10.1038/mp.2008.55

22. Barcia JA, Reneses B and Nombela C. Precision surgery for obsessive compulsive disorder-which is the proper target? Ann Transl Med. 2019;7. doi:org/10.21037/atm.2019.07.65

23. Tyagi H, Apergis-Schoute AM, Akram H, et al., A randomized trial directly comparing ventral capsule and anteromedial subthalamic nucleus stimulation in obsessive-compulsive disorder: clinical and imaging evidence for dissociable effects. Biol Psychiatry 2019;85(9):726-734. doi:org/10.1016/j.biopsych.2019.01.017

24. Huys D, Kohl S, Baldermann JC, et al. Open-label trial of anterior limb of internal capsule–nucleus accumbens deep brain stimulation for obsessive-compulsive disorder: insights gained. J Neurol Neurosurg Psychiatry. 2019;90:805-812. doi:org/10.1136/jnnp-2018-318996

25. Baldermann, JC, Melzer, C, Zapf, A, et al. Connectivity profile predictive of effective deep brain stimulation in obsessive-compulsive disorder. Biol Psychiatry. 2019;85(9):735-743. doi:org/10.1016/j.biopsych.2018.12.019

26. Mallet L, Polosan M, Jaafari N, et al. Subthalamic nucleus stimulation in severe obsessive–compulsive disorder. New Engl J Med. 2008;359(20):2121-2134. doi:org/10.1056/NEJMoa0708514

27. Jiménez F, Nicolini H, Lozano AM, et al. Electrical stimulation of the inferior thalamic peduncle in the treatment of major depression and obsessive compulsive disorders. World Neurosurg. 2013;80 (3-4):S30-e17-S30-e25. doi:org/10.1016/j.wneu.2012.07.010

28. Lee DJ, Dallapiazza RF, De Vloo P, et al. Inferior thalamic peduncle deep brain stimulation for treatment-refractory obsessive-compulsive disorder: A phase 1 pilot trial. Brain Stimulation. 2019;12(2):344-352. doi:org/10.1016/j.brs.2018.11.012

29. Lipsman N, Neimat JS, Lozano AM. Deep brain stimulation for treatment-refractory obsessive-compulsive disorder: the search for a valid target. Neurosurgery. 2007;61:1-11. doi:org/10.1227/01.neu.0000279719.75403.f7

30. Barcia JA, Reneses B and Nombela C. Precision surgery for obsessive compulsive disorder—which is the proper target? Ann Transl Med. 2019;7(6):S184. doi:org/10.21037/atm.2019.07.65

31. Mathew SJ, Yudofsky SC, McCullough LB et al. Attitudes toward neurosurgical procedures for Parkinson’s disease and obsessive-compulsive disorder. J Neuropsychiatry Clin Neurosci. 1999;11:259-267. doi:org/10.1176/jnp.11.2.259

This article originally appeared on Psychiatry Advisor