Psychosomatics 47:529-530, December 2006
doi: 10.1176/appi.psy.47.6.529
© 2006 Academy of Psychosomatic Medicine
Hyperthyroidism Associated With Topiramate Treatment
Jessica L. Gören, Pharm.D., BCPP
Received January 18, 2006; accepted January 27, 2006. From the Univ. of Rhode Island, Cambridge Health Alliance, and Harvard Medical School, Somerville, MA. Send correspondence and reprint requests to Dr. Gören, Cambridge Health Alliance, Somerville, MA. e-mail: jgoren{at}challiance.org
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INTRODUCTION
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Topiramate is an anticonvulsant that causes significant weight loss in patients.1 Weight loss reported has ranged from 0.5 kg to 13.5 kg, depending on the population studied.1–16 Most studies report approximately a 6-kg weight loss.2–16 The mechanism of topiramate-induced weight loss is unknown, and pre-marketing studies did not show weight loss to be associated with topiramate-induced hyperthyroidism.1
A case of a patient referred to an outpatient clinic is reported here. Referral was made after the initiation and subsequent discontinuation of topiramate, where the patient experienced clinical signs and laboratory abnormalities consistent with hyperthyroidism.
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Case Report
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An 18-year-old man presented to the clinic for a second opinion concerning his current treatment. The patient had a several-year history of early-onset psychotic affective illness, probably bipolar or schizoaffective disorder. He lived in a group home, and his medication administration was monitored by staff. He was doing reasonably well on a combination of 500 mg daily of clozapine (serum levels around 600 ng/ml) and 1 gm daily of divalproex (serum levels around 110 mcg/ml). Other medications prescribed included citalopram 20 mg, omeprazole 20 mg, and doxycycline 100 mg. He had discontinued lithium therapy at least 4 months earlier because of acne. Further details on this lithium trial are not known.
During the early fall of 1999, he was somewhat depressed and concerned about his weight gain (he weighed 120 lbs at 4 ft 11 in). His divalproex was lowered to 750 mg daily, and topiramate therapy was added and titrated to 200 mg daily to limit his weight gain. Once topiramate was at 100 mg daily, the patient’s thyroid-stimulating hormone (TSH) levels increased to 6.4 uU/mL. No other thyroid laboratory values were available. Aside from weight gain and depression, no other clinical signs of hypothyroidism were present, and previous thyroid function tests were not available.
By early October, on this regimen, the patient began experiencing an increase in symptoms. He was sleeping less, was energetic, and was experiencing more psychotic thinking and violent fantasies. His clozapine level at that time was 477 ng/ml, and his complete blood count (CBC) was within normal limits. A valproate level was not drawn at that time.
During the month of October, the patient’s white blood cell count (WBC) dropped to 5,600, with 1,800 neutrophils, and transaminases and alkaline phosphatase were elevated (serum glutamate pyruvate transaminase [SGPT]: 199). His TSH fell to nearly undetectable levels (<0.06), and his thyroxine (T4) level was elevated (18 ug/dL). The patient’s pulse was noted to be consistently elevated at that time. Topiramate was discontinued, and an endocrinologist was consulted.
Methimazole was started at 10 mg tid, and propranolol was added (up to 80 mg daily). Despite treatment, his pulse remained elevated in sinus tachycardia (about 124/min.), and an electrocardiogram (ECG) showed delayed QTc (520 msec.).
By the end of October, the patient’s WBC was 5,500, with <1,500 neutrophils, and he had a hematocrit of 37%, hemoglobin of 13, and 315,000 platelets. Transaminases began to fall (SGPT: 158). Clozapine serum levels were as low as 179 ng/ml, despite an increased dose of 700 mg daily. Another dose increase of clozapine, to 750 mg daily, resulted in a clozapine level of 242 ng/ml. By the end of the month, a topiramate taper was completed. In early November, the patient’s WBC was 6,800 (2,448 neutrophils), and serum levels of clozapine were continuing to rise. Thyroid function tests were normalized by the end of November, and the patient was clinically euthyroid. Per the outpatient clinician, a retrial of topiramate caused a similar reaction.
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Discussion
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This is the first case report of topiramate-induced hyperthyroidism. Although a case report is not conclusive evidence, the On–Off–On nature of the reaction indicates that the hyperthyroidism was most likely associated with the topiramate therapy.
The patient experienced many of the classic signs of hyperthyroidism. Use of the Naranjo Adverse Drug Reaction (ADR) probability scale indicated that this was a probable topiramate-induced adverse event.17
Although routine monitoring of thyroid functioning is important in many psychiatric disorders, routine monitoring of thyroid function simply because topiramate has been added to a treatment regimen is not recommended. However, in patients experiencing unexplained changes in blood levels of other medications or re-emergence of symptoms after the addition of topiramate to a medication regimen, it is reasonable to test thyroid functioning.
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REFERENCES
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- Ortho-McNeil: Prescribing Information for Topiramate. Raritan, NJ, December, 2003
- Ben-Menachem E, Axelsen M, Johanson EH, et al: Predictors of weight loss in adults with topiramate-treated epilepsy. Obes Res 2003; 11:556–562[Medline]
- Bray GA, Hollander P, Klein S, et al: A 6-month, randomized, placebo-controlled, dose-ranging trial of topiramate for weight loss in obesity. Obes Res 2003; 11:722–733[Medline]
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- Chengappa KN, Chalasani L, Braar JS, et al: Changes in body weight and body mass index among psychiatric patients receiving lithium, valproate, or topiramate: an open-label, non-randomized chart review. Clin Ther 2002; 24:1576–1584[CrossRef][Medline]
- Chengappa KN, Rathore D, Levine J, et al: Topiramate as add-on treatment for patients with bipolar mania. Bipolar Disord 1999; 1:42–53[CrossRef][Medline]
- Calabrese JR, Keck PE Jr, McElroy SL, et al: A pilot study of topiramate in the treatment of acute mania. J Clin Psychopharmacol 2001; 21:340–342[CrossRef][Medline]
- Ghaemi SN, Manwani SG, Katzow JJ, et al: Topiramate treatment of bipolar disorders: a retrospective chart review. Ann Clin Psychiatry 2001; 13:185–189[CrossRef][Medline]
- McIntyre RS, Mancini DA, McCann S, et al: Topiramate versus bupropion SR when added to mood-stabilizer therapy for the depressive phase of bipolar disorder: a preliminary, single-blind study. Bipolar Disord 2002; 207-213
- Li Z, Maglione M, Tu W, et al: Meta-analysis: pharmacologic treatment of obesity. Ann Intern Med 2005; 142:532–546[Abstract/Free Full Text]
- Naranjo CA, Busto U, Sellers EM, et al: A method for estimating the probability of adverse drug reactions. Clin Pharmacol Ther 1981; 30:239–245[Medline]
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INTRODUCTION
Case Report
