Evidence-Based Reviews

Treatment-resistant OCD: There’s more we can do

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Augmentation strategies may help patients who don’t respond to first-line treatments.



Mr. S, age 30, transfers to your practice and shares that he was first diagnosed with obsessive-compulsive disorder (OCD) at age 10. He currently worries about whether he may have offended people by using the wrong words in his emails and he apologizes excessively. He fears that his body odor disturbs other people, and he sprays room freshener every time he exits a room. To measure the severity of his current symptoms, you complete the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Mr. S’s Y-BOCS score is a 32 out of a maximum of 40, indicating severe OCD. Previously, he has received trials of adequate doses of 2 selective serotonin reuptake inhibitors (SSRIs; fluoxetine and sertraline) and currently is taking clomipramine, 100 mg twice daily. However, he still is experiencing substantial obsessions and compulsions that interfere with his relationships with his friends and family members.

Treatment-resistant OCD can be a debilitating condition. Diagnostic clarity is crucial to fully elicit symptoms and identify comorbid conditions in order to develop practical, evidence-based treatment strategies and improve the patient’s and family’s quality of life. In this article, we delineate first-line strategies for treatment-resistant OCD and then review augmentation strategies, with an emphasis on glutamate-modulating agents.

Making the diagnosis

The diagnosis of OCD is made when a patient meets DSM-5 criteria for the presence of obsessions and/or compulsions, which are defined as unwanted, distressing, intrusive, recurrent thoughts or images (obsessions) and repetitive behaviors or mental acts (compulsions).1 OCD is considered a chronic waxing and waning disorder; stress and lack of sleep lead to worsening symptoms. The hidden nature of symptoms and the reinforcement provided by the reduction in anxiety after performing a compulsion contribute to sustained illness. Eliciting symptoms from patients may be challenging due to the shame they may feel. When reviewing symptoms on the Y-BOCS, it is helpful to preface questions with statements such as “Many people report excessive concern or disgust with…” to help the patient feel understood and less anxious, rather than using direct queries, such as “Are you bothered by…?”

Consider comorbid conditions

After making the initial diagnosis of OCD, it is important to assess whether the symptoms are better accounted for by another condition, and whether comorbid conditions are present (Table 1).

Ruling out other diagnoses

In the course of Mr. S’s evaluation, you rule out a psychotic disorder because he has insight that his behaviors may not be necessary to combat his fears. You also rule out a mood disorder with obsessive features. Although Mr. S admits he is frustrated by a lack of relief from medication, he denies experiencing any sustained periods of mania, low mood, or suicidal thoughts. He does endorse excessive guilt for contaminating people’s homes and poor concentration at work because he often is distracted by his fears that he has offended his colleagues.


Initial treatment: CBT

Cognitive-behavioral therapy with exposures and response prevention (from here on referred to as CBT) has been established as a first-line, evidence-based treatment for OCD in both children and adults.2,3 For patients with treatment-resistant OCD, intensive daily CBT in a partial hospitalization or inpatient setting that is a tailor-made, patient-specific program is one of the most effective treatments, with response rates of up to 70%4-8 CBT’s advantages over medication include lower relapse rates and no known adverse effects. Unfortunately, CBT is underused9-11 due in part to a shortage of trained clinicians, and because patients may favor the ease of taking medication over the time, effort, and cost involved in CBT.

First-line pharmacologic options for treating OCD are SSRIs and clomipramine, as supported by multiple randomized controlled trials (RCTs), meta-analyses, expert guidelines, and consensus statements (Table 22,12-14). No significant difference has been found among SSRIs for the treatment of OCD in a review of 17 studies that included more than 3,000 patients.15 Treatment with SSRIs or clomipramine is effective for 50% to 60% of patients.16 Many clinicians view the combination of an SSRI and CBT as the treatment of choice for OCD.2

Continue to: Reluctance to engage in CBT


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