Issues In The Pharmacological Treatment of Obsessive-Compulsive Disorder

S. B. Math; Y. C. Janardhan Reddy


Int J Clin Pract. 2007;61(7):1170-1180. 

In This Article

First-Line Treatment Options for OCD

Obsessive-compulsive disorder responds preferentially to a class of antidepressant drugs called serotonin reuptake inhibitors (SRIs).[20,21,22] Therefore, SRIs are first-line agents in the treatment of OCD.[23,24,25,26,27] They are effective in about 40-60% of patients.[24,27] The US Food and Drug Administration have approved clomipramine, fluvoxamine, fluoxetine, sertraline and paroxetine for the treatment of OCD. There is, however, some evidence to suggest that citalopram,[28,29] mirtazapine[30] and venlafaxine[31] are also possibly efficacious in treating OCD, but additional data from controlled studies is necessary. It is obvious that one has to make a choice from a class of drugs with a similar pharmacological property because all the SRIs are somewhat equally effective in treating OCD.[32] Before we discuss how to choose a SRI to treat OCD, we highlight some of the unique characteristics of treatment response in OCD that pertain to the medication dose and onset of response.

Obsessive-compulsive disorder is usually treated with much higher doses of SRIs than that used in depression and other anxiety disorders. There is modest research evidence to suggest that response is better at higher doses. Studies have shown positive dose-response relationship for fluoxetine,[33] paroxetine[34] and sertraline[35] but not for clomipramine, fluvoxamine and citalopram.[24] However, considering the mixed nature of evidence in support of higher doses and the recommendations of expert consensus guidelines in favour of higher doses,[36] it is widely accepted now that OCD has to be treated with higher than usual doses of antidepressants.[37] Table 1 provides the usual dosages to treat OCD.

Response to SRIs in OCD occurs slowly over a period of 8-12 weeks unlike in depression, where maximum improvement occurs within 4-6 weeks. Initial response to the medications starts around 6-8 weeks and maximum benefit occurs only at 10-12 weeks.[24,37] As improvement occurs over several weeks, it is recommended that modest but optimum range of dose be maintained at least for about 10 weeks before dose escalation is considered. However, once the highest dose is reached it is best to continue treatment for at least 3 months and sometimes even longer. Responders may continue to benefit for several months with long-term continuation of medication.[37] Therefore, sensitising the patients in advance to the delay in the onset of response and the need for a somewhat prolonged trial helps in dealing with unrealistic expectations from the patients and the resultant pressure on the clinicians to escalate or change the drug prematurely.

Meta-analyses, but not head-to-head comparison studies have shown that clomipramine is probably somewhat superior to other SRIs in its efficacy but has a less favourable side effect profile.[21,23,26,27,38] Clomipramine is associated with prominent sedation, anticholinergic effects and decreased seizure threshold at higher doses. Therefore, the other SRIs are the first-line drugs to treat OCD because of their established efficacy, better acceptability and tolerability. The issue is how to select among the other SRIs as all of them are almost equally efficacious in treating OCD. Largely, the choice of SRI is based upon the side effect profile of a particular SRI and the presence of particular comorbid conditions in the given patient.[39] Table 2 provides details about unique side effect profile of various SRIs that help in the choice of the drug. For example, fluoxetine is associated with agitation and insomnia, paroxetine with anticholinergic side effects, and sertraline with gastrointestinal effects. Apart from these minor variations in the side effect profile of various SRIs, there are no clear advantages for one over the other. The choice may to an extent depend upon drug interactions. Paroxetine, fluoxetine are potent inhibitors of CYP2D6, thereby raising the plasma levels of most antipsychotics, beta-blockers and certain anti-arrhythmic drugs.[24,40] Fluvoxamine inhibits CYP1A2 isoenzyme, thereby increasing the level of olanzapine and clozapine.[41] Sertraline, citalopram and escitalopram have somewhat less drug-drug interactions and are preferred in subjects who are on other medications for comorbid medical and psychiatric illnesses.[39]


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