Evidence-Based Reviews

Treatment-resistant OCD: Options beyond first-line medications

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Deep brain stimulation (DBS). With this approach, small electrodes are inserted under precise stereotactic MRI guidance. The advantage of DBS over ablative surgery is the ability to adjust and customize neurostimulation. Following implantation, modifiable parameters of electrode stimulation include electrode polarity, intensity, frequency, and laterality. A specially trained psychiatrist can conduct parameter optimization during long-term follow-up.

The first trial of DBS for OCD was reported in 1999 (N = 4), with the initial target selected based on the site of anterior capsulotomy. Three patients derived clinically observed benefit, although no validated questionnaires were administered.51 Since then, at least 7 studies with blinded stimulation have been conducted, totaling 62 patients.52

In recent years, structures adjacent to the internal capsule also have been targeted based on the approach employed in ventral capsulotomy. Across all trials, response rates for this approach consistently have been in the 50% range, with average Y-BOCS score reductions ranging from 6.8 to 31 points.53 Some patients have reported rapid improvements in anhedonia, and this approach is being employed in treatment-resistant depression.

Postoperative complications occur more often with DBS than with lesion approaches because of the prosthetic nature of the procedure (eg, increased risk of infection, lead malfunction, etc.). Additionally, batteries must be periodically explanted and replaced. Reported stimulation-related side effects include mood changes (transient sadness, anxiety, euphoria, and hypomania), sensory disturbances (olfactory, gustatory, and motor sensations), and cognitive changes (confusion and forgetfulness). These side effects typically are stimulation-dependent and disappear after altering stimulation parameters.

Table 2

Invasive therapies for treatment-resistant OCD

TherapyQuality of evidence
  Electroconvulsive therapyPoor
  Vagal nerve stimulationPoor
  Repetitive transcranial magnetic stimulationLimited
Irreversible (surgical)
  Anterior capsulotomy. Target: anterior limb of the internal capsuleFair
  Anterior cingulotomy. Target: anterior cingulate and cingulum bundleFair
  Subcaudate tractotomy. Target: substantia innominata, just inferior to the caudate nucleusFair
  Limbic leucotomy. Target: anterior cingulotomy combined with subcaudate tractotomyFair
  Deep brain stimulation. Multiple targetsFair
OCD: obsessive-compulsive disorder

Related Resources

  • American Psychiatric Association. Treatment of patients with obsessive-compulsive disorder. www.psychiatryonline.com/pracGuide/pracGuideTopic_10.aspx.
  • Hyman BM, Pedrick C. The OCD workbook. Your guide to breaking free from obsessive compulsive disorder. 3rd ed. Oakland, CA: New Harbinger Publications Inc; 2010.
  • Baer L. Getting control: overcoming your obsessions and compulsions. Revised ed. New York, NY: Plume; 2000.

Drug Brand Names

  • Alprazolam • Xanax
  • Aripiprazole • Abilify
  • Citalopram • Celexa
  • Clomipramine • Anafranil
  • Clonazepam • Klonopin
  • Dextroamphetamine • Adderall
  • Duloxetine • Cymbalta
  • Fluoxetine • Prozac
  • Fluvoxamine • Luvox
  • Haloperidol • Haldol
  • Ketamine • Ketalar
  • Memantine • Namenda
  • Methylphenidate • Ritalin
  • Morphine • MS Contin
  • Olanzapine • Zyprexa
  • Ondansetron • Zofran
  • Pindolol • Visken
  • Quetiapine • Seroquel
  • Riluzole • Rilutek
  • Risperidone • Risperdal
  • Sertraline • Zoloft
  • Tramadol • Ultram
  • Venlafaxine • Effexor
  • Ziprasidone • Geodon


Drs. Khalsa and Schiffman report no financial relationship with any company whose products are mentioned in this article or with manufacturers of competing products.

Dr. Bystritsky receives grant support from AstraZeneca, Brainways, Takeda, and Transcept and is a founder, stockholder, and consultant for BrainSonix.


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