SRIs Overwhelming evidence from multiple randomized, double-blind, placebo-controlled studies support the efficacy of SRIs. In adults, well-designed and controlled trials have demonstrated the relative efficacy of clomipramine, fluoxetine, sertraline, paroxetine, and fluvoxamine vs. placebo.
SRIs also have been shown to be significantly more effective than tricyclic antidepressants (TCAs) in both placebo-controlled and non-placebo-controlled studies.
Despite initial reports that clomipramine may be more effective than SSRIs, a growing number of studies and a recent comprehensive literature review suggest that the SRIs all have comparable efficacy.16 Because clomipramine has significantly more anticholinergic- and antiadrenergic-mediated side effects than the SSRIs, however, many clinicians choose SSRIs as the initial agent.
When using SRIs, remember that response is typically delayed; an adequate trial requires at least 10 weeks. Indeed, a meaningful proportion of responders continue to emerge past the 8-week mark. Experts suggest that optimal dosages of SRIs for OCD may exceed those typically used for major depression. Guidelines for SRI dosage ranges for OCD appear in (Table 1).
Data regarding treatment duration also suggest that discontinuation of SRIs results in a high relapse rate, though the use of lower maintenance dosages of SRIs is still debated.
Table 2
Ratings of SRI-augmenting agents for OCD treatment
| Likely effective ♦♦ | Possibly effective (insufficient data for adequate assessment of efficacy) ♦ |
|---|---|
| Neuroleptics | Clonidine |
| Busipirone | Fenfluramine |
| Clonazepam | Nortriptyline |
| Lithium | Pindolol |
| Trazodone | |
| Tryptophan | |
| Dosage for these agents has not been adequately studied for augmentation of SRIs. Clinical trial length should be for 2 to 8 weeks. | |
Augmentation of SRIs When first-line interventions fail, second-line pharmacological approaches include augmentation of SRIs with additional medications (Table 2). Numerous agents have been tried for patients who were unresponsive or only partially responsive to SRIs alone.17 Few controlled trials of such strategies have been conducted, however. The most impressive data document the benefits of adding low doses of dopamine antagonists (both conventional and atypical neuroleptics).
Table 3
Using alternative monotherapies
| Drug | Dosage | Duration | Comments |
|---|---|---|---|
| Clonazepam | 0.5-5 mg/d | ≥ 4 weeks | extrapolated from experience with benzodiazepines for other anxiety disorders and a few reports in OCD |
| MAO inhibitor | 60-90 mg/d | ≥ 10 weeks | extrapolated from clinical practice with MAO inhibitors for major depression, panic disorder; tyramine diet must be adhered to; adequate washout of most antidepressants is required before initiating |
| Buspirone | up to 60 mg/d | ≥ 6 weeks | reflecting protocols adopted in clinical trials for OCD |
Recent uncontrolled studies of augmentation with atypical neuroleptics have yielded encouraging preliminary results, as has one controlled trial of augmentation of an SRI with risperidone. Other data suggest that lithium, buspirone, and clonazepam may also be effective.
Numerous other agents have been tried in combination with SRIs, including clonidine, tryptophan, fenfluramine, pindolol, trazodone, nortriptyline, and other antidepressants. The small number of subjects, lack of sufficient controls, and mixed results preclude drawing even preliminary conclusions as to the potential efficacy of such strategies.
Alternative Monotherapies For patients who do not respond satisfactorily to trials of SRIs alone or to augmentation strategies, consider alternative monotherapies in place of SRIs (Table 3). In addition to uncontrolled data, positive controlled studies lend some support for trials of clonazepam, monoamine oxidase (MAO) inhibitors, and buspirone.
Pertinent negative findings are worthy of mention. In contrast to promising results with risperidone as an augmenter, an open trial of the atypical antipsychotic clozapine suggests inefficacy as a monotherapy. Several case reports suggest that clozapine can actually precipitate obsessive-compulsive symptoms in patients with psychotic disorders.18 Controlled trials have not demonstrated the efficacy of trazodone, clonidine, and diphenhydramine as monotherapies.
Pharmacotherapy + or vs. behavioral therapy
Only a few studies directly comparing behavior therapy vs. medication have been reported. In practice, the two are routinely used in concert. Experts have long recommended this treatment approach. Two recent studies19,20 have demonstrated that the combination is more effective than either treatment alone.
In another study, behavior therapy significantly outperformed clomipramine; no significant incremental benefit was seen from the two treatments in combination.21 However, the dosages of clomipramine were relatively low (mean=164 mg/d and maximum=225 mg/d) and of inadequate duration (6 weeks). Still another older head-to-head comparison of behavior therapy and clomipramine showed that medication was better for reducing obsessional doubt, whereas behavior therapy more effectively reduced compulsive rituals.
Third-line treatments may include the unproven augmentation therapies described above, or intravenous clomipramine if available.22
Treatments of last resort
Finally, other nonpharmacologic treatments, including neurosurgery and electroconvulsive therapy (ECT), have remained controversial and are reserved for particular clinical situations or as treatments of last resort.
Despite a large body of uncontrolled data reporting antiobsessional benefits from a variety of neurosurgical procedures, ethical considerations and technical limitations have precluded the performance of sham-controlled studies to definitively establish the efficacy of these strategies.