The treatments described below are listed approximately in the recommended sequence. The Figure outlines the stepwise approach suggested for treatment-resistant OCD. Although some evidence exists for the following strategies, relatively few have been validated in controlled trials.
Augmentation Strategies
Atypical antipsychotics. Within the last decade, it has become increasingly evident that medications with both D2 receptor and 5-HT2 receptor antagonism can be effective for treatment-resistant OCD (Jenike and Rauch, 1994). Typical antipsychotics have been demonstrated to be particularly efficacious with comorbid tic disorders (McDougle et al., 1994). More recently, atypical antipsychotics have been demonstrated to have efficacy for augmentation in OCD, with lower risks for extrapyramidal side effects and tardive dyskinesia.
Risperidone (Risperdal) has shown to be effective in open trials and in case series (Saxena et al., 1996). A randomized, controlled trial conducted on 36 patients with SRI-refractory OCD demonstrated that 50% of those taking risperidone, but none of those taking placebo, were "much" or "very much" improved on the Clinical Global Impression (CGI) scale (Hollander et al., 2003a; McDougle et al., 2000).
Two open trials have been conducted using olanzapine (Zyprexa) in patients showing partial response to an SRI (Bogetto et al., 2000; Weiss et al., 1999).
Quetiapine (Seroquel) has also been studied in two open-label trials, one showing a 70% response rate, compared to only 25% in the other study (Denys et al., 2002; Sevincok and Topuz, 2003). In a single-blind, placebo-controlled study, nine of 14 patients showed a 60% or greater improvement on the YBOCS (and one with a 30% improvement), while none in the placebo group responded (Atmaca et al., 2002). Another double-blind, placebo-controlled study showed that 40% of 20 patients were responders versus 10% with placebo, with an average of 31% decrease in YBOCS scores (Denys et al., 2004).
Atypical antipsychotics in combination with an SRI are often efficacious in the management of nonresponders to SRI treatment. In addition, the combination is generally well tolerated. The response tends to occur at lower doses (Bogetto et al., 2000; Hollander et al., 2003a), and a four-week therapeutic trial at the maximum tolerated dose is considered sufficient.
Clomipramine. Clomipramine may be added to an SRI as augmentation. This was demonstrated in a study in which the combination of clomipramine with citalopram (Celexa) was more effective than citalopram alone in treatment-resistant OCD (Pallanti et al., 1999). This strategy should be used with caution, as there is potential for drug-drug interactions (although with cytochrome P450 3A4 inhibitors such as fluvoxamine [Luvox], this may be advantageous in order to increase the parent-to-metabolite ratio).
