Topiramate-Induced Psychosis in an Individual With Alcohol Dependent

Abstract

Sir: Topiramate, an antiepileptic drug, has been shown to reduce alcohol craving and heavy drinking and to improve abstinence among alcohol-dependent individuals.1 By potentiating the inhibitory effects of γ-aminobutyric acid (GABA)2 and depressing the excitatory action of kainate on α-amino-3-hy-droxy-5-methylisoxazole-4-propionic acid (AMPA) glutamate receptors,3 topiramate reduces mesocorticolimbic dopamine activity, which is a crucial pathway by which alcohol exerts its rewarding effects.4–6 Doses of up to 300 mg per day have been effective in reducing craving in alcoholdependent patients. The drug is started at a low dose and increased slowly to avoid adverse effects. Psychiatric side effects occur in up to 23.9% of patients with epilepsy7 and are related to a personal or family history of psychiatric illness and rapid dose escalation. These psychiatric side effects include depression, anxiety, aggression, cognitive slowing, and psychosis. Topiramate has also been reported to precipitate psychosis in patients with schizophrenia8 and mood disorder.9 Case report. Mr. A, a 42-year-old man, was admitted to our Deaddiction Centre in January 2005 with a diagnosis of alcohol dependence syndrome (according to ICD-10 criteria) and presented with delirium tremens. The patient had a history of alcohol consumption for the last 15 years and had developed features of salience, tolerance, craving, and loss of control over drinking over the last 8 years. He presented with tremors; irritability; insomnia; loss of appetite; auditory, visual, and tactile hallucinations; disorientation; and clouding of consciousness, all of which began after 24 hours of abstinence. He had a history of possible withdrawal seizures in the past. There was no history of psychosis. There was a family history of alcohol dependence in his father and 2 male siblings. There was no family history of psychosis or mood disorder. Laboratory findings were within normal limits. The patient was started on a detoxification regimen with lorazepam, 16 mg per day PO in tapering doses, and vitamin supplementation. His withdrawal symptoms subsided within 48 hours, with hallucinations subsiding within 24 hours. After detoxification for 10 days, the patient was started on topiramate 25 mg per day as long-term medication for alcohol dependence. On the third day after starting topiramate, the patient suddenly awoke at around 1:00 a.m., looked anxious, and reported that he could hear “voices calling out to him from hell” and discussing his death. He continued to hear these voices even after he was fully awake. He remained anxious, apprehensive, and distressed for the next 30 minutes and was sedated with intravenous haloperidol 10 mg and lorazepam 4 mg, both of which had to be repeated after 2 hours. During this episode, there was no disorientation, clouding of consciousness, or tremulousness. After topiramate was stopped, these psychotic symptoms remitted completely within 48 hours and did not recur. Topiramate has been hypothesized to induce psychosis as a result of its antiglutamatergic properties in the nucleus accumbens and prefrontal cortex.8 Brief psychosis was the most common presentation in a series of patients with epilepsy.7 As patients with alcohol dependence syndrome show changes in glutamate receptors, especially during withdrawal,6 they may be more sensitive to the effects of topiramate. To the best of our knowledge, this is the first report of topiramate precipitating psychosis in a patient with alcohol dependence. It is possible that patients presenting with alcohol withdrawal are more susceptible to this particular adverse effect.