Academic journal article Indian Journal of Psychiatry

Familial Vulnerability to an Unusual Cognitive Adverse Effect of Topiramate: Discussion of Mechanisms

Academic journal article Indian Journal of Psychiatry

Familial Vulnerability to an Unusual Cognitive Adverse Effect of Topiramate: Discussion of Mechanisms

Article excerpt

Byline: Chittaranjan. Andrade, Savita. Bhakta, Praveen. Fernandes

Background: Some patients experience cognitive disturbances with topiramate. Case histories: A 19-year-old bipolar woman and her 46-year-old mother with paranoid personality disorder both used topiramate (25-50 mg/day) off-label for weight loss. Both women suffer from learning disorders, and both are excessively sensitive to the sedative adverse effects of psychotropic medications. Results: Within days of starting topiramate, the women began to exhibit troublesome word- and phrase-repetition and word substitution, both occurring only in their written expression. The symptoms were associated with mild sedation, persisted during two weeks of topiramate treatment, and remitted days after topiramate was withdrawn. Discussion: The presence of the learning disorders and the sensitivity to the sedative adverse effects of drugs may explain why cognitive adverse effects, known to occur with topiramate, developed at the low dose of 25-50 mg/day. The proclivity of topiramate to affect language functions and a possible familial vulnerability herein may explain why the women explained similar, language-specific symptoms. An investigation of topiramate-induced cognitive impairments in family members with epilepsy may throw light on the subject.


Topiramate is a newer antiepileptic drug which has been approved (as monotherapy or as adjunctive therapy) by the USA Food and Drug Administration for the treatment of partial as well as primary generalized seizures in adults as well as in children above the age of two. Topiramate has also received approval for the prophylaxis of migraine. Other indications for which topiramate may be effective include neuropathic pain syndromes, [sup][1] alcoholism but not necessarily smoking, [sup][2],[3],[4],[5],[6],[7] obesity, [sup][8] eating disorders, [sup][9] and drug-induced weight gain. [sup][10],[11] Although efficacy in posttraumatic stress disorder is uncertain, [sup][12] the drug is ineffective in bipolar disorder. [sup][13],[14]

Broad-spectrum cognitive disturbances are prominent among the adverse effects reported with topiramate. [sup][15],[16] For example, Gomer et al [sup][17] described deficits in cognitive speed, verbal fluency, and short-term memory in focal epilepsy patients who received topiramate as compared with those prescribed levetiracetam. Such deficits are dose-dependent, occur in up to 44% of the patients even within a dose range of 50-100 mg/day, and reverse upon discontinuation of the drug. [sup][18] Verbal functions appear particularly sensitive to topiramate. [sup][19] As with adults, children are also affected; [sup][20] in fact, topiramate-induced severe but reversible language regression in children and adolescents has also been described. [sup][21]

The risk of cognitive adverse effects with topiramate is probably smaller when the upward dose titration is slow. [sup][22] However, word-finding difficulty, which occurs in about 7% of epileptic patients treated with the drug, may be independent of the titration schedule and may be related to a specific biological vulnerability in the left temporal lobe. [sup][23]

We herein describe an unusual cognitive adverse effect of topiramate in a mother-daughter pair and consider the possible biological underpinnings thereof.

Case Reports

Ms. N is a 19-year-old female student with a seven-year history of bipolar II disorder. She was receiving bupropion 300 mg/day, escitalopram 20 mg/day, and lamotrigine 300 mg/day. She was much distressed at being overweight (body-mass index=28.2) and requested for assistance with weight loss. Accordingly, she was prescribed topiramate 25 mg/day along with a regimen of diet and exercise; the dose of topiramate was raised to 50 mg/day after a week.

Within days of onset of topiramate treatment, she developed frequent and uncharacteristic word repetition and word substitution. …

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