Naproxen adjunct to fluoxetine for moderate‐to‐severe obsessive‐compulsive disorder: A randomized, double‐blind, placebo‐controlled trial

Aim Current treatments for obsessive‐compulsive disorder (OCD) encounter resistance and limiting adverse events, necessitating novel therapeutic strategies. This study aimed to investigate the benefits of naproxen, a medication with effects on inflammation and neuronal function, on OCD. Methods One hundred and four OCD outpatients with a Yale‐Brown Obsessive‐Compulsive Scale (Y‐BOCS) score of >21 were equally assigned to receive fluoxetine plus either naproxen 250 mg or matched placebo q12hr. Patients were assessed using the Y‐BOCS by recording the subscale scores at baseline and weeks 5 and 10 to evaluate efficacy. They were also assessed in terms of tolerability. Results Data from 96 patients were analyzed. The baseline characteristics were comparable between the groups. There were significant time‐treatment interaction effects on the obsession subscale ( = 0.055) and total ( = 0.043) scores of Y‐BOCS. Reductions in the obsession subscale and total scores of Y‐BOCS were significantly greater in the fluoxetine plus naproxen group until the endpoint (Cohen's d = 0.560 and Cohen's d = 0.477, respectively). However, the difference in compulsion subscale score changes between the groups was not significant. Respondents with a reduction of ≥35% in Y‐BOCS total scores were significantly more in the fluoxetine plus naproxen group (80.0% versus 47.8%). The side effect frequencies were comparable between the groups. Conclusion Naproxen, adjunct to fluoxetine, outperformed adjunctive placebo in treating obsession and total symptoms of OCD patients in a safe and tolerable manner. Clinical trial registration The study protocol was registered and published in the Iranian Registry of Clinical Trials (http://www.irct.ir; registration number IRCT20090117001556N139).