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

BACKGROUND

Several 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.

OBJECTIVE

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

STUDY DESIGN

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

STUDY SETTING

The 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.

INTERVENTIONS

Participants 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 MEASURE

Patients 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.

RESULTS

Of 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.

CONCLUSION

Granisetron 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.