levetiracetam and Alcohol-Related-Disorders

Placebo-controlled pharmacotherapy trials for alcohol use disorder (AUD) require an active behavioral platform to avoid putting participants at risk for untreated AUD and to better assess the effectiveness of the medication. Therapist-delivered platforms (TDP) can be costly and present a risk to study design because of the variability in therapist fidelity. Take Control is a novel computer-delivered behavioral platform developed for use in pharmacotherapy trials sponsored by the National Institute on Alcohol Abuse and Alcoholism Clinical Investigations Group (NCIG). This behavioral platform was developed with the goal of reducing trial implementation costs and limiting potential bias introduced by therapists providing TDP. This exploratory study is the first to compare Take Control with TDP on measures related to placebo response rate, medication adherence, and participant retention. Data were drawn from the placebo arms of four multisite, double-blind, randomized controlled trials (RCT) for AUD conducted by NCIG from 2007 to 2015. Data were compared from subjects receiving TDP (n=156) in two RCTs and Take Control (n=155) in another two RCTs. Placebo response rate, as represented by weekly percentage of heavy drinking days, was similar between groups. Subjects who received Take Control had a higher rate of medication adherence than those who received TDP. Subject retention was not significantly different between groups. The findings suggest that Take Control is comparable to TDP on measures of retention, medication adherence, and placebo response. Additional research is needed to evaluate Take Control directly against TDPs in a randomized trial.

Topics: Adult; Alcohol-Related Disorders; Antidiuretic Hormone Receptor Antagonists; Behavior Therapy; Combined Modality Therapy; Double-Blind Method; Female; Humans; Levetiracetam; Male; Medication Adherence; Middle Aged; Piracetam; Placebos; Quetiapine Fumarate; Research Design; Software; Varenicline

The anticonvulsant topiramate not only decreases ethanol consumption in alcohol dependence (AD) but also may produce several adverse events including cognitive impairment. Zonisamide is a structurally related anticonvulsant that is a promising agent for the treatment of AD and may have greater tolerability than topiramate. This study evaluated the effects of zonisamide (400 mg/d) on alcohol consumption and its neurotoxic effects in subjects with AD. A double-blind placebo-controlled clinical trial was conducted using 2 comparator anticonvulsant drugs, topiramate (300 mg/d) and levetiracetam (2000 mg/d), which does not impair cognition. Study medications were administered for 14 weeks, including a 2-week taper period. Medication adherence was facilitated using Brief Behavioral Compliance Enhancement Treatment. The neurotoxicity of the study drugs was assessed using neuropsychological tests and the AB-Neurotoxicity Scale. Compared with placebo, both zonisamide and topiramate produced significant reductions in the drinks consumed per day, percent days drinking, and percent days heavy drinking. Only the percent days heavy drinking was significantly decreased in the levetiracetam group. The topiramate cell was the only group that had a significant increase on the mental slowing subscale of the Neurotoxicity Scale compared with placebo at study weeks 11 and 12. Topiramate and zonisamide both produced modest reductions in verbal fluency and working memory. These findings indicate that zonisamide may have efficacy in the treatment of AD, with effect sizes similar to topiramate. Both of these drugs produced similar patterns of cognitive impairment, although only the topiramate group reported significant increases in mental slowing.

Topics: Adult; Aged; Alcohol Drinking; Alcohol-Related Disorders; Anticonvulsants; Cognition Disorders; Double-Blind Method; Female; Fructose; Humans; Isoxazoles; Levetiracetam; Male; Middle Aged; Neuropsychological Tests; Piracetam; Topiramate; Treatment Outcome; Young Adult; Zonisamide