Topiramate induced pruritus in a patient with alcohol dependence.

Topiramate is an antiepileptic medication frequently used for the management of alcohol dependence and in other psychiatric disorders. Though cutaneous side effects are known to occur with it, isolated pure pruritus is rarely reported with topiramate in the literature. We wish to report a case of pruritus associated with topiramate use in a male with alcohol dependence syndrome.

Introduction

Topiramate is an anticonvulsant medication that has been approved by Food and Drug Administration (FDA) for the various types of seizure disorder and for prophylaxis of migraine headache. It is, however, also used for a variety of other indications, including alcohol dependence to reduce craving, obesity, bipolar disorder and other psychiatric disorders.[12] Chemically, topiramate is a sulfamate-substituted monosaccharide, related to fructose. Pruritus is an unpleasant sensation that leads to intensive scratching. Though benign, it is a very troublesome side effect and often leads to drug discontinuation. Though a variety of cutaneous adverse effects have been reported with topiramate, pruritus as an isolated side effect has only been rarely reported. We hereby report a case of a male of alcohol dependence, who developed pruritus while taking topiramate.

Case Report

A 44-year-old male was diagnosed as a case of alcohol dependence syndrome as per ICD 10 criteria. There was no other psychiatric or medical comorbidity. All his blood investigations were normal except for mild elevation of transaminases (elevated around three times the normal range). Ultrasonography liver revealed fatty liver. He was initially detoxified with chlordiazepoxide which was started at a dose of 70 mg/day and was gradually tapered over a period of 2 weeks. He was also prescribed multivitamin injectables on alternate day for a total period of 10 days. He was followed up after a period of 1 month, wherein he was abstinent from alcohol and was now taking only multivitamin in capsule form. Motivational counselling sessions were started. He was followed up after 2 weeks. He reported craving for taking alcohol. His repeat liver function tests were within normal limits. He was started on Topiramate 25 mg/day increased to 50 mg after 1 week. Multivitamin capsules were continued. After 2 days of 50 mg topiramate, the patient reported itching all over the body. He thought it to be drug related and consequently stopped medications on his own. Itching improved in 3 days duration without any treatment. He then again took alcohol on one occasion. Consequently, he again started topiramate 50 mg/day on his own. He again developed itching after about 2 days of taking topiramate. He was brought to the outpatient department. Dermatology consultation did not reveal any abnormality. He had no known drug allergies. Other than topiramate, the patient was taking multivitamin capsule which he had continued without any adverse effect.

All his investigations, including liver function tests, bile pigments and other tests, were normal. There was no other systemic illness. Drug-induced pruritus was considered and topiramate was stopped. Cetrizine, 5 mg during bed time, was prescribed for a few days. The patient improved in 2 days time without any recurrence of itch. He is currently maintaining well on disulfiram therapy without any relapse of alcohol consumption or any other problem.

Discussion

Our case was diagnosed as topiramate induced pruritus. Because of temporal correlation, the side effect occurred twice while the drug was re-started and subsided with drug discontinuation. There was no other cause to suggest any other etiology for the pruritus. The use of Naranjo Adverse drug probability scale revealed a score of 9 suggestive of definitive relationship between pruritus and topiramate.[3]

Side effects frequently caused by topiramate include cognitive impairment, word-finding difficulties, and bodyweight loss, and less commonly renal calculi, hepatotoxicity, and ocular pathology such as glaucoma.[4]

Regarding cutaneous side effects, topiramate can cause acneiform eruptions, alopecia, drug-induced pigmentation, exanthematous reaction, hyperhidrosis, hypertrichosis, hair texture change, lichenoid eruption, photosensitivity, and fixed drug eruptions.[5] Hypohidrosis related to the administration of topiramate to children has been reported.[6]

Pruritus as a side effect has been reported commonly with antimalarials, plasma volume expanders, opioids, penicillin ACE inhibitors and others.[7] However, it is reported to be a rare side effect of antiepileptic drugs. We could find only one report wherein four patients with epilepsy developed pruritus after the addition of topiramate to their anticonvulsant regimens.[8] These patients had history of previous drug allergies and this could have had a bearing on pruritus associated with topiramate. The possible mechanisms behind pruritus involve either an allergic reaction or secondary to skin lesions. Possible other hypothesized mechanisms for drug-induced pruritus are cholestatic liver injury, xerosis of the skin, deposits of drugs or their metabolites in the skin, phototoxicity, or neurological alterations. Often, the underlying mechanism is not known.[79]

Our case was that of “pure” drug-induced pruritus as there were no other skin lesions associated with it.

Drug-induced pruritus without associated skin lesions is in itself rare, occurring at a frequency of around 12% of all drug reactions.[10]

Previous reports suggest that toprimate's side effects, especially cutaneous side effects, occur when used with other medications.[811] It is possible that the combinations of topiramate with antipsychotic and anticonvulsant medications further alter neural thresholds in such a fashion as to effect the sensation of itch. The neural effects of topiramate might account for its efficacy in treating psoriasis,[12] a disease in which the importance of neural function continues to be defined.

However, our case was not on any other medication that could have potentiated the action of topiramate.

To conclude, one should be vigilant for such benign side effects as these are very troublesome for the patient. More studies to understand the pathogenesis and to identify the risk factors for cutaneous side effects of topiramate are warranted.