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Benefits of Topiramate Treatment in a Dual-Diagnosis Patient

TO THE EDITOR: Individuals with psychiatric illness are at greater risk for substance use disorders. One-third (37%) of individuals with an alcohol-related disorder and about one-half (53%) of individuals with a drug-related disorder had a lifetime incidence of comorbidity of another psychiatric diagnosis. Individuals with dual diagnosis also tend to utilize more psychiatric services and other costly services such as emergency room visits and inpatient hospitalizations.¹ Therefore, treatments that are useful in the dual-diagnosis population are of great value to clinicians treating this complicated group.

Topiramate is currently FDA-approved for the treatment of seizures and for the prophylactic treatment of migraine headaches. However, it also has been reported to be useful in the treatment of alcohol use disorders² and for weight loss in obesity.³ Clozapine is an effective treatment for psychotic symptoms in individuals with schizophrenia;⁴ however, it is associated with significant weight gain and increased risk for diabetes and dyslipidemia.

Case Report

"Mr. M" is a 34-year-old man with a complex history of a traumatic brain injury (TBI) at the age of 16 as a result of a motor vehicle accident, which affected his bilateral frontal brain region. He displayed frontal signs of immaturity and excessive speech, as well as poor attention and memory. Two years after the accident, Mr. M developed auditory hallucinations and paranoia.

Within 2 years of the onset of psychotic symptoms (i.e., at the age of 20 years), the patient developed comorbid alcohol dependence. Over the past 13 years, his use of alcohol increased to a level of 24 servings (12 ounces) of beer per day. His parents reported that they frequently find him blacked out, and he has had legal problems as a result of alcohol use and has required numerous hospitalizations for his psychotic symptoms and his alcohol dependence. He had previously attended Alcoholics Anonymous and received outpatient counseling but relapsed quickly after each attempt at intervention.

Mr. M’s psychotic symptoms required clozapine for adequate management. He gained 54 pounds over the ensuing 5-year period. The patient developed diabetes, requiring insulin to maintain good glycemic control. Because of the severity of his untreated psychosis, the decision was made to maintain clozapine therapy despite the weight gain and diabetes.

Mr. M was started on topiramate 1 year ago in an effort to reduce his body weight. At the time topiramate was started, its effects on alcohol use were not discussed with the patient, and no additional counseling or treatment of alcohol-dependence was implemented or in force. The patient was titrated to a dose of 200 mg over an 8-week period. He then spontaneously reported that it was now easier to abstain from alcohol use. Within 6 weeks of reaching the 200-mg dose, the patient had achieved complete abstinence from alcohol, and he has remained abstinent for 8 months at the time of this writing. A recent GGT test was normal, thus verifying alcohol abstinence reports. The patient also was successful in his weight-loss efforts. Although he denies dieting in any formal fashion, he finds that he no longer overeats, and he has lost 33 pounds over the course of 10 months of topiramate treatment.

Discussion

Dual-diagnosis patients bear a worse prognosis than those without concomitant substance use disorders. Individuals with schizophrenia and other psychotic disorders also have difficulty navigating the non–medication-based treatments frequently used to treat alcohol dependence.⁵ Therefore, medication treatments for dual diagnosis should be particularly useful for this population, as is illustrated by the case of Mr. M. The patient reported both a reduced desire for alcohol and for overeating. Improvements in drinking behavior are thought to be due to reduced reinforcing effects of alcohol through facilitation of gamma-aminobutyric acid function and inhibition of glutaminergic pathways in the cortico-mesolimbic system.² Given the commonalities between drug and food reinforcement,⁶ it is likely that these same mechanisms may be involved in weight control.

Although one cannot draw definite conclusions from a single case, this report suggests that topiramate may be a useful treatment for dual-diagnosis patients treated with clozapine. This patient has had a prolonged period of abstinence from alcohol use with minimal intervention other than the medication use. In a population that may have difficulty utilizing counseling treatment options for alcohol use disorders, topiramate, or perhaps other medication interventions, may prove beneficial.

REFERENCES

1. Bartels SJ, Teague GB, Drake RE, et al: Substance abuse in schizophrenia: service utilization and costs. J Nerv Ment Dis 1993; 181:227–232[CrossRef][Medline]
2. Johnson BA, Rosenthal N, Capece JA, et al: Topiramate for treating alcohol dependence: a randomized, controlled trial. JAMA 2007; 298:1641–1651[Abstract/Free Full Text]
3. 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]
4. Wahlbeck K, Cheine MV, Essali A: Clozapine versus typical neuroleptic medications for schizophrenia. Cochrane Database of Systematic Reviews, 1999. Issue 4, Article No: CD000059. DOI: 10.1002/14651858.CD000059
5. Cleary M, Hunt G, Matheson S, et al: Psychosocial interventions for people with both severe mental illness and substance misuse. Cochrane Database Systematic Reviews, 2008. Jan 23:(1):CD001088
6. Carrelli RM: The nucleus accumbens and reward: neurophysiological investigations in behaving animals. Behav Cogn Neurosci Rev 2002; 1:281–296[Abstract/Free Full Text]

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