Topiramate may induce obsessive‐compulsive disorder

Topiramate is an anti-epileptic drug approved for partial and generalized epilepsy syndromes and for migraine. It may induce psychiatric adverse events such as depression, nervousness, behavioral disorders and mood lability.1 We present a case of obsessive-compulsive disorder (OCD) probably induced by topiramate. Mrs X is a 57-year-old woman with a history of secondary progressive multiple sclerosis (MS) according to the Poser diagnostic criteria.2 She was treated with interferon-β-1A for 8 months, and had recurrent major depressive disorder in remission for 6 years under milnacipran, and migraine. Despite pharmacotherapy strategies including beta-blockers, non-steroidal anti-inflammatory drugs, benzodiazepine, dihydroergotamine and other analgesics, migraine remained unimproved. Topiramate was therefore started at a dose of 15 mg/day for 1 week and gradually increased to 50 mg/day within 1 month. She then began to feel anxious and irritable, and abruptly presented intrusive and repetitive thoughts of violence such as harming herself or her husband. She was afraid that she would jump from the window or assault her husband with a knife. She felt driven to check the absence of harmful objects such as a knife in her handbag. She also manifested self-harming skin picking behaviors that were aimed at preventing dreaded behaviors such as harming other people. All these symptoms were present nearly all the time. She unambiguously acknowledged these intrusive thoughts and repetitive behaviors as inappropriate and clearly stated that she was not suicidal and still loved her husband. Her attempts to suppress her obsessions and compulsions were, however, completely ineffective. After 2 months she was hospitalized due to extreme distress and topiramate was discontinued. Physical examination was unchanged and ancillary blood tests were unremarkable. All obsessions and compulsions dramatically improved and stopped within 4 days as shown by the Yale–Brown Obsessive Compulsive Scale, which dropped from 28 (obsession subscale: 18, compulsion subscale: 10) at admission to 0. The rest of the treatment was kept unchanged. Brain magnetic resonance imaging (MRI) showed no sign of an acute inflammatory phase of MS compared with previous MRI. She was discharged after 1 week and OCD had not re-occurred by 3-month follow up. Although OCD has previously been described in patients with MS,3 there was no evidence of an acute phase of MS in the present patient. The age of the patient, poorly consistent with an idiopathic OCD; the co-occurrence of OCD and topiramate treatment; and the dramatic improvement after the discontinuation of topiramate support the causal role of topiramate. This is consistent with previous reports of a high prevalence of psychiatric adverse events with topiramate, particularly in patients with a psychiatric history.4 One case of OCD associated with topiramate has been reported in a 19-year-old patient, an age that is also consistent with an idiopathic OCD.5 The OCD improved partially after topiramate discontinuation and the prescription of citalopram. The mechanisms involved remain unknown. Clinicians should, however, be alerted about the risk of psychiatric adverse events including OCD when prescribing topiramate, even in low dosages, especially for patients with a psychiatric history.