Unexpected Improvement of Obsessive-Compulsive Disorder Symptoms Following the Mistaken Prescription of Clomiphene: A Novel Perspective on Hormonal Influences in OCD.

BACKGROUND

Obsessive-compulsive disorder (OCD) is a chronic psychiatric disorder commonly treated with selective serotonin reuptake inhibitors (SSRIs) and, in more severe or resistant cases, clomipramine. Clomiphene citrate, a selective estrogen receptor (ER) modulator primarily used for infertility, is not indicated for psychiatric disorders but may influence neuroendocrine and serotonergic pathways. This case describes an unexpected improvement in OCD symptoms following the accidental prescription of clomiphene instead of clomipramine.

CASE PRESENTATION: A 50-year-old woman with a longstanding history of anxiety and recurrent major depressive disorder (MDD) developed OCD symptoms after childbirth during her second pregnancy. Her symptoms previously responded well to sertraline, clonazepam, and clomipramine. After ~15 years of relative stability, clomipramine was discontinued because of anticholinergic side effects, resulting in relapse of obsessive-compulsive symptoms. A 3-month trial of sertraline 200 mg/day was ineffective. When clomipramine was intended to be restarted, a prescribing error led to clomiphene 25 mg/day being dispensed instead. The patient took clomiphene together with sertraline 100 mg/day and clonazepam 2 mg/night for 12 weeks. During this period, she experienced a dramatic and complete remission of her obsessive-compulsive symptoms, with an estimated reduction in Yale-Brown Obsessive Compulsive Scale (Y-BOCS) score from 23 to ~7. No adverse effects were identified. After the error was recognized, clomiphene was discontinued, the incident was reported, and clomipramine was reintroduced, although the same degree of improvement was not reproduced.

CONCLUSION

This case raises a speculative but clinically important hypothesis regarding the possible role of hormonal modulation in a subgroup of hormonally sensitive patients with OCD. However, causality cannot be established because hormonal measurements were unavailable and alternative explanations, including placebo effects, spontaneous symptom fluctuation, and concomitant medication effects, remain possible. Future studies should longitudinally assess OCD symptom changes during hormonally sensitive periods, ideally in conjunction with standardized clinical measures and hormonal biomarkers. The case also underscores the ethical and patient-safety importance of preventing medication errors.