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New Compounds, Novel Applications Evaluated: Page 2 of 2

New Compounds, Novel Applications Evaluated: Page 2 of 2

The relatively benign adverse-effect profile of gabapentin makes it an attractive neurological agent to evaluate for new applications. Barbara Mason, PhD, Scripps Research Institute, La Jolla, Calif, reported on a double-blind, placebo-controlled trial of gabapentin in 50 treatment-seeking patients who met DSM-IV criteria for cannabis dependence. Mason and colleagues sought to determine whether gabapentin might affect disturbances in sleep and mood and the craving following cannabis cessation that can motivate relapse.

Participants were randomized to 12 weeks of treatment with 1200 mg of gabapentin daily or placebo, and efficacy was determined through assessments of mood, sleep, and cannabis use. Mason reported that compared with placebo, those who received gabapentin exhibited significantly less consumption in grams per week, less craving, and greater improvement on the Beck Depression Inventory and on the Pittsburgh Sleep Quality Index.

“A withdrawal syndrome characterized by an aggregate of superficially mild symptoms may be particularly responsive to treatment with a neuromodulating drug like gaba-pentin,” Mason said. “Thus, the development of gabapentin as pharmacotherapy for cannabis dependence may have potential public health benefits.”

Naltrexone, currently used for both opioid and alcohol dependence, was investigated to determine whether this opioid antagonist could interfere with reward mechanisms that might reinforce the compulsion for kleptomania. Jon Grant, MD, JD, MPH, University of Minnesota, described an 8-week study of 25 subjects meeting DSM-IV criteria for kleptomania, randomized to receive either placebo or naltrexone at a daily dose ranging from 50 to 150 mg. Those who received naltrexone exhibited statistically significantly greater improvement in the Yale-Brown Obsessive Compulsive Scale modified for kleptomania on items related to stealing and stealing behavior. In addition, naltrexone was associated with greater improvement in overall kleptomania severity than placebo, as reflected in reduced CGI scores.

The N-methyl d-aspartate (NMDA) antagonist memantine, approved for the treatment of moderate to severe Alzheimer disease, was investigated in a study funded by the manufacturer, Forest Pharmaceuticals, for neurocognitive deficits associated with bipolar disorder. An additional study, self-funded at the Massachusetts General Hospital, assessed the use of memantine in adults with attention deficit disorder.

Michael Ziffra, MD, Northwestern University Feinberg School of Medicine, Chicago, indicated that neuro-cognitive deficits can persist in many patients with bipolar disorder even though they have achieved mood stability. Although little is known about treatment requirements, researchers were hopeful that memantine might be therapeutically effective.

The trial was conducted with 25 adults who were euthymic with conventional treatment of their bipolar illness. They were randomized to receive 12 weeks of either placebo or memantine titrated to 20 mg daily; with an optional additional 12 weeks of open-label memantine. Cognitive functioning was principally assessed by mean total score of the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS).

Although there was no statistically significant difference between groups in improved mean total score at 12 weeks, those who received memantine achieved significantly greater improvement in the RBANS attention index. In those who received 24 weeks of memantine, the advantage in the attention index was maintained, and there was a statistically significantly greater mean total score than in those who received placebo and only 12 weeks of memantine.

“This suggests that acute treatment with memantine has limited cognitive benefit,” Ziffra indicated, “but longer treatment may lead to more global improvement.”

The apparent benefit of memantine for attention items on the RBANS, albeit in a population with bipolar disorder, supports the investigation by Craig Surman, MD, and colleagues at Massachusetts General Hospital in adults with ADHD. Although NMDA receptors have been theorized to contribute to the pathophysiology of ADHD, Surman indicated that this open-label investigation in 27 persons is the first assessment of memantine for this condition.

Memantine was titrated to a dose of 20 mg daily, and a battery of tests were used to assess effects on attention, hyperactivity, and impulsivity. Surman reported significant improvement at weeks 2 through 12, with most adverse effects characterized as mild. Although double-blind investigation will be needed to corroborate the preliminary findings of this open trial, the researchers were encouraged.

“Memantine may be effective for, and well tolerated by, adults with ADHD or ADHD NOS,” Surman indicated, “and may improve working memory in this population.”

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