Granisetron adjunct to fluvoxamine for moderate to severe obsessive-compulsive disorder: a randomized, double-blind, placebo-controlled trial.

backgroundSeveral small studies have shown beneficial effects of ondansetron, a serotonin 5-HT(3) receptor antagonist, in the treatment of obsessive-compulsive disorder (OCD). The efficacy of other 5-HT(3) receptor antagonists in patients with OCD is still unclear. Granisetron does not alter cytochrome P450 activity and might have a lower risk of drug interactions, a longer duration of action and a better tolerability profile than other 5-HT(3) receptor antagonists.

objectiveThe objective of this study was to assess the efficacy and tolerability of granisetron augmentation of fluvoxamine in patients with OCD. STUDY

designThis was a two-centre, randomized, double-blind, placebo-controlled, parallel-group study conducted from November 2011 to March 2012. STUDY

settingThe study setting was outpatient clinics of two large referral centres. PATIENTS: Study participants were men and women, aged 18-60 years, who met the diagnostic criteria of OCD based on the DSM-IV-TR and who had a Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score of at least 21.

interventionsParticipants were randomly assigned to granisetron (Kytril(®); SmithKline Beecham, Philadelphia, PA, USA) 1 mg every 12 hours or placebo every 12 hours in addition to fluvoxamine for 8 weeks.

main outcome measurePatients were assessed using the Y-BOCS at baseline, second, fourth, sixth and eighth weeks. The primary outcome measure was the difference in the score change of Y-BOCS total score from baseline to week 8 between the two groups. We also compared changes in the obsession and compulsion subscales of the Y-BOCS, and frequencies of partial response (≥25% reduction in Y-BOCS score), complete response (≥35% reduction in Y-BOCS score) and remission (Y-BOCS score ≤16) between the two groups.

resultsOf the 42 included patients, 39 (20 in the placebo group, 19 in the granisetron group) completed the study. Significant time X treatment interaction was observed for total Y-BOCS (F [2.097, 79.678] = 4.941, p = 0.009), obsession (F [2.337, 88.799] = 4.938, p = 0.006) and compulsion (F [2.050, 77.899] = 4.674, p = 0.012) subscales. By week 8, complete response and remission were achieved by 20 (100%) and 18 (90%) patients in the granisetron group and by 7 (35%) patients in the placebo group (p-value of Fisher's exact test <0.001, risk ratio (RR) [95% CI] = 3.857 [2.039, 7.297]). There was no significant difference in the tolerability between the two regimens.

conclusionGranisetron is an efficacious adjunct for the short-term treatment of patients with moderate to severe OCD and is well tolerated. CLINICAL TRIAL REGISTRATION NUMBER: IRCT201202041556N32.