Zonisamide, topiramate, and levetiracetam: efficacy and neuropsychological effects in alcohol use disorders.

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.

Concealment and fabrication by experienced research subjects.

BACKGROUND: Subjects who enroll in multiple studies have been found to use deception at times to overcome restrictive screening criteria. Deception undermines subject safety as well as study integrity. Little is known about the extent to which experienced research subjects use deception and what type of information is concealed, withheld, or distorted. PURPOSE: This study examined the prevalence of deception and types of deception used by subjects enrolling in multiple studies. METHODS: Self-report of deceptive behavior used to gain entry into clinical trials was measured among a sample of 100 subjects who had participated in at least two studies in the past year. RESULTS: Three quarters of subjects reported concealing some health information from researchers in their lifetime to avoid exclusion from enrollment in a study. Health problems were concealed by 32% of the sample, use of prescribed medications by 28%, and recreational drug use by 20% of the sample. One quarter of subjects reported exaggerating symptoms in order to qualify for a study and 14% reported pretending to have a health condition in order to qualify. LIMITATIONS: Although this study finds high rates of lifetime deceptive behavior, the frequency and context of this behavior is unknown. Understanding the context and frequency of deception will inform the extent to which it jeopardizes study integrity and safety. CONCLUSION: The use of deception threatens both participant safety and the integrity of research findings. Deception may be fueled in part by undue inducements, overly restrictive criteria for entry, and increased demand for healthy controls. Screening measures designed to detect deception among study subjects would aid in both protecting subjects and ensuring the quality of research findings.

The anticonvulsant zonisamide reduces ethanol self-administration by risky drinkers.

OBJECTIVE: The purpose of this study is to examine the effects of zonisamide on ethanol self-administration and subjective effects in risky drinkers using a human laboratory paradigm. METHOD: We conducted a double-blind, placebo-controlled study of the effects of zonisamide 100 mg on ethanol self-administration and urge to drink in risky drinkers (N = 10) ( [1] ). RESULT: During the second hour of a 2-hour self-administration session ethanol consumption was 50% lower in the zonisamide group as compared to the placebo group. Urge to drink was also significantly lower under the zonisamide condition. CONCLUSION: These results indicate that a single dose of zonisamide reduces urge to drink and the quantity of ethanol self-administered by risky drinkers during their second hour of access to alcohol. SCIENTIFIC SIGNIFICANCE: Zonisamide may help individuals drinking at risky levels reduce their intake of alcohol.

The effects of levetiracetam on alcohol consumption in alcohol-dependent subjects: an open label study.

The aim of this open-label pilot study was to assess the efficacy and safety of the novel anticonvulsant agent, levetiracetam, for the treatment of alcohol dependence. A maximal dose of 2000 mg was administered daily for 10 weeks to alcohol dependent subjects (n = 20). Mean reported ethanol intake declined significantly from 5.3 to 1.7 standard drinks per day. Levetiracetam was well tolerated by most subjects.