Evidence-Based Reviews

Treatment-resistant OCD: Options beyond first-line medications

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Cognitive-behavioral therapy (CBT) has been shown to be effective for OCD as monotherapy and augmentation to pharmacotherapy. CBT consists of cognitive and behavioral components, typically involving some form of cognitive restructuring and exposure response prevention. Although these 2 types of interventions arise from independent traditions, in CBT they are frequently intertwined, particularly when the focus of OCD patients’ anxiety is ego-dystonic thoughts.

One benefit of CBT over pharmacotherapy is that effects persist after treatment is terminated. A recent prospective study found CBT was effective for treatment-refractory OCD, with 74% of patients demonstrating clinical response after 20 to 25 sessions over 2 months and 61% maintaining clinical response 1 year after treatment.40 CBT administered remotely via teleconference, also known as “teletherapy,” has shown efficacy for OCD.41

Alternative medicine

Despite widespread use of herbal remedies for OCD, no trials have shown a strong positive effect. Both Hypericum perforatum (St. John’s wort) and Silybum marianum (milk thistle) have been used to treat obsessive and compulsive symptoms; however, placebo-controlled trials did not find any significant differences in symptoms or side effects between treatment groups.42,43 Lower-quality studies have reported modest effects for mindfulness meditation, yoga, and acupuncture.44

Because many patients continue to use complementary and alternative medicine therapies despite the lack of data on efficacy, it is important to monitor for potential interactions with prescription medications. St. John’s wort interacts with many medications because of induction of the cytochrome P450 (CYP) isoenzymes 3A4 and 2C9. This interaction may lower blood levels of alprazolam and clonazepam (3A4). Combining St. John’s wort with SSRIs increases the risk of serotonin syndrome. Milk thistle inhibits CYP450 isoenzyme 3A4, and may increase serum levels of other medications metabolized by this pathway.

Invasive therapies

Invasive options may be considered after several pharmacotherapeutic and psychotherapeutic approaches have not been effective or when significant functional impairment remains (Table 2). These therapies typically are reserved for patients whose treatment resistance is strongest.

Electroconvulsive therapy (ECT). Although ECT is an effective tool for treatment-resistant mood disorders or treatment-resistant anxiety complicated by severe depression, studies have not found ECT to be effective for OCD. One uncontrolled case series reported considerable improvements in OCD patients the year after ECT, although improvement was correlated with improved depression scores.45

Vagal nerve stimulation (VNS). In an open-label study of 7 OCD patients who received VNS, 3 were acute responders—characterized by a ≥25% improvement on the Y-BOCS—and 2 received continued benefits at 4-year follow up (2 patients dropped out).46

Repetitive transcranial magnetic stimulation (rTMS). A meta-analysis of 3 RCTs of rTMS for patients with OCD did not yield a large or statistically significant effect.47 Limitations of these trials included asymmetric stimulation sites (eg, left vs right only), limited stimulation sites (dorsolateral prefrontal cortex), different stimulation frequencies between studies, and a lack of sham stimulation conditions. A more recent RCT and subsequent review described moderate efficacy (defined by ≥25% decrease in Y-BOCS scores) compared with sham stimulations in OCD patients at 4 weeks, using the supplementary motor area as a stimulation site.48,49

The main limitation of rTMS is the inability to penetrate deeper brain structures implicated in OCD (eg, caudate nucleus, thalamus, anterior capsule fiber tracts), as well as a lack of specificity in stimulation site.

Surgical approaches. Cingulotomy is the most commonly employed surgical procedure for OCD in North America, likely because of a combination of clinical efficacy and low morbidity and mortality rates.50 Of the >1,000 cingulotomies that have been performed at Massachusetts General Hospital, no deaths or postoperative infections have been reported and 2 subdural hematomas have occurred.50 Common postsurgical side effects include transient headache, nausea, or difficulty urinating. The most serious common side effect—postoperative seizures—has been reported in 1% to 9% of cases.

Outcomes for these procedures cannot be fully assessed until at least 6 months to 2 years after the procedure, which suggests postoperative neural reorganization plays an important role in recovery. Direct comparisons of each lesion approach within studies are extremely rare. Overall, long-term outcomes of these approaches have demonstrated significant therapeutic effects of each of these procedures. Reported response rates vary between 30% to 70%, when applied to remission, response (≥35% Y-BOCS reduction), and functional improvements in quality of life.50

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