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IN THIS ISSUE:
March 2008

Topiramate for Alcohol Dependence
Topiramate (Topamax) has been found to be beneficial in treating alcohol dependence.

Early Intervention for Schizophrenia: A Role for Antidepressants?
Antidepressants may reduce the transition from a prodrome of pre-psychosis to schizophrenia in vulnerable individuals.

In Brief
Duloxetine Approved for GAD; Depression in Parkinson’s Disease; Asthma Linked to Psychiatric Disorder

Adjunctive Antipsychotics for MDD
Patients with treatment-resistant major depressive disorder may benefit from the addition of second-generation antipsychotics to an antidepressant medication regimen.

Antipsychotics in Youth with Schizophrenia
Early-onset schizophrenia-spectrum disorder requires long-term antipsychotic treatment, but children and adolescents are sensitive to antipsychotic side effects and should be monitored carefully.

Topiramate for Alcohol Dependence

March 2008



Alcohol dependence is the third leading cause of preventable deaths in the United States, taking about 85,000 lives each year.1 In November 2006, we reviewed recent advances in medications to facilitate alcohol abstinence (BTP 2006;29:49). Disulfiram (Antabuse), available for half a century, causes an adverse reaction when patients taking it drink alcohol. Two newer agents—naltrexone (Depade) and acamprosate (Campral)—supposedly work by decreasing motivation to drink. A recent study tested the anticonvulsant topiramate (Topamax) for alcohol dependence.2

Topiramate has not been found useful as a mood stabilizer but does help reduce weight in psychiatric patients (BTP 2007;30:15–16,33,49). Active at g-aminobutyric acid (GABA) and glutamate receptors, topiramate reduces corticomesolimbic dopamine release, which may decrease the reinforcing effects of alcohol and the urge to drink. When a small trial suggested that topiramate could help combat alcohol dependence, Johnson and coworkers followed up with a multi-center, double-blind, 14-week study.

Investigators enrolled 371 men and women with alcohol dependence who may or may not have achieved abstinence before entry. In addition to a weekly program of compliance enhancement, participants were randomly assigned to receive either placebo or topiramate, beginning at 25 mg/day and slowly titrated up to 300 mg/day.

To statistically significant degrees, topiramate appeared to reduce drinks per day and increase the number of days abstinent compared with placebo. At the end of 14 weeks, the drug-placebo difference was still increasing, suggesting that longer treatment could confer greater benefits. Adverse effects more common with topiramate were paresthesia, "taste perversion," anorexia, and difficulty concentrating.

This encouraging result suggests topiramate might become another treatment option for alcohol dependence, and one that may not require prior abstinence from drinking. Not yet approved by the US Food and Drug Administration for this indication, topiramate can cause a variety of central nervous system side effects, including cognitive dysfunction, which may be attenuated by slow dose titration.

In an accompanying editorial, Willenbring observes that alcohol dependence is a disorder of the young, beginning at an average age of only 21 years!1 It is more likely to be episodic than chronic and unrelenting, and almost three quarters of patients have only a single episode. The average length of the longest episode is 5 years, and episode lengths tend to diminish over time.

Willenbring laments the insufficient training in alcohol dependence received by both primary care physicians and psychiatrists. The National Institute on Alcohol Abuse and Alcoholism (NIAAA) has a clinician's guide, "Helping Patients Who Drink Too Much," available on their website at www.niaaa.nih.gov/guide or by calling 301-443-3860. It offers Continuing Medical Education credits and new patient handouts. With a growing armamentarium of pharmacologic and behavioral treatment options, it behooves us to become more aware of this disorder and intervene early in its course.

1Willenbring ML: Medications to treat alcohol dependence: Adding to the continuum of care. JAMA 2007;298:1691–1692.

2Johnson BA, Rosenthal N, Capece JA, Wiegand F, Mao L, Beyers K, McKay A, Ait-Daoud N, Anton RF, Ciraulo DA, Kranzler HR, Mann K, O'Malley SS, Swift RM, for the Topiramate for Alcoholism Advisory Board and the Topiramate for Alcoholism Study Group: Topiramate for treating alcohol dependence: A randomized controlled trial. JAMA 2007;298:1641–1651.