Clinical Guidance: Gabapentin Combined With Naltrexone for Treatment of Alcohol Dependence 

Gabapentin and naltrexone have both been proposed as treatments to diminish relapse in recently abstinent patients with alcoholism. In a 16-week trial of naltrexone (50 mg/day), naltrexone combined with gabapentin (up to 1,200 mg/day) for the first 6 weeks, or double placebo, the combined treatment outperformed both naltrexone alone and placebo, but the effect did not persist beyond 6 weeks. The 6-week period was chosen because Anton et al. (CME, p. 709) believed that initial co-treatment with gabapentin would help by diminishing the insomnia and mood instability experienced by patients in their first 6 weeks of abstinence. O'Brien points out in an editorial (p. 670) that the combination is safe and that the study is a good example of the rigorous evaluation of a rational combination designed to address the range of symptoms and difficulties presented by patients with alcoholism who seek to maintain abstinence.

Clinical Guidance: Effectiveness and Safety of Continued Polypharmacy Versus Switch to Monotherapy in Schizophrenia 

In a 12-month study, Essock et al. (p. 702) switched patients who had been treated with two antipsychotic drugs to monotherapy. Compared to a control group who stayed on their pharmacy, significantly more of the patients switched to monotherapy required further intervention, generally a resumption of the previous polypharmacy. However, a substantial minority could be maintained on a single drug without loss of treatment effectiveness. These monotherapy patients also experienced a 2% weight loss, compared to 1% weight gain for the polypharmacy patients. Goff (p. 667) notes in an editorial that clozapine remains the only intervention with proven effectiveness for patients who fail to respond to monotherapy.

Clinical Guidance: Effectiveness and Safety of Combining Antidepressants 

Rush et al. (p. 689) compared two combination therapies, 300 mg/day of extended-release venlafaxine plus 45 mg/day of mirtazapine and 20 mg/day of escitalopram plus 400 mg/day of sustained-release bupropion, to escitalopram alone in a 12-week trial in chronically depressed patients. Remission rates (38%) and response rates (52%) did not differ among the three treatment arms. Patients who received venlafaxine plus mirtazapine experienced more side effects. In an editorial, Coryell (p. 664) points out that the difference between these results and the more encouraging results of an earlier study by Blier et al. (Am J Psychiatry 2010; 167:281—288) are not clear.