Substantial evidence from controlled studies demonstrate efficacy for clomipramine and SSRIs in the acute treatment of OCD across the lifespan. There have been fewer studies of long-term treatment and it remains less conclusively understood as to how well treatments that have been shown to be effective in short-term studies maintain their efficacy over the longer term, though placebo-referenced trials suggest efficacy for clomipramine, fluoxetine and sertraline up to twelve months. Most relapse prevention studies in acute responders revealed a significant advantage for remaining on active treatment (paroxetine, sertraline and fluoxetine at higher doses). For some of these studies methodological problems impaired their ability to discriminate active from placebo treatment on the chosen relapse criterion.

In a double-blind dose-finding study, 458 OCD patients were randomized to escitalopram (fixed at 10mg or 20mg), or 40mg paroxetine or placebo. At week 12 - the primary efficacy endpoint - 20 mg escitalopram showed a significant improvement in the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) compared to placebo (p<0.005). At week 24, escitalopram 10mg (p<0.05) and 20mg (p<0.005) showed significantly greater improvements in Y-BOCS total scores than placebo - as did paroxetine 40 mg (p<0.005). In a relapse prevention study, 320 patients (ITT) who had responded following 16 weeks of open treatment with escitalopram, were randomized to placebo or escitalopram for a further 24 weeks of double-blind treatment. The primary analysis (time to relapse) showed a significant advantage for escitalopram (Log-rank test p<0.001), and the risk of relapsing was 2.7 times higher for placebo compared to escitalopram. These results suggest that escitalopram is effective for acute and long-term treatment and relapse-prevention in OCD.