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In the COMBINE study (Anton et al., 2006), acamprosate failed to reduce alcohol consumption either alone or when combined with naltrexone. Topiramate. Topiramate affects multiple enzyme and neurotransmitter systems. First approved as an anticonvulsant in 1996, it was subsequently approved to prevent migraine and, in combination with phentermine, for weight loss. Three RCTs have shown topiramate to be efficacious in reducing alcohol consumption. In both single-site and multi-site trials, Johnson et al. (2003, 2007) found that topiramate 300 mg/day resulted in large, significant reductions in both self-reported drinking and GGT concentration. Miranda et al. (2008) compared the effects of topiramate 200 mg/day, topiramate 300 mg/day, and placebo in heavy drinkers. Olaparib chemical structure In this study, topiramate was titrated to the target dosage over a 32-day period, where it was maintained for 1 week. During the titration period, the frequency of heavy drinking was significantly lower in both topiramate groups than in the placebo group, with no significant difference between the topiramate groups. Together bepotastine with its effects to reduce drinking, topiramate produces a variety of adverse effects that limit its clinical utility. The most common adverse effects include paresthesia, anorexia (with weight loss), difficulties with memory or concentration, and mild-to-moderate taste disturbances (Markind, 1998). Rarely, topiramate causes serious ophthalmologic effects. Baclofen. Because of its activity as a GABAB agonist, the antispasmodic baclofen has generated interest as a treatment for alcohol dependence. In a 30-day RCT of 39 patients with alcohol dependence, 70% of baclofen-treated patients remained abstinent compared with 21% of those in the placebo group (Addolorato et al., 2002). A subsequent 12-week study of 84 patients with hepatic cirrhosis (Addolorato et al., 2007) yielded a similar advantage for baclofen over placebo. However, Garbutt and colleagues (2005) found no effect of baclofen on drinking outcomes in an RCT of 80 subjects with alcohol dependence. Selleckchem Y 27632 Muzyk et al. (2012) concluded that, although the evidence did not support the use of baclofen as a first-line agent, it could be of value in patients with cirrhosis. Pharmacogenetic approaches Based on advances in human genetics, in the past decade there have been a number of studies examining genetic variants as potential moderators of the effects of medications to treat alcohol dependence, which have led to the identification of specific genotypes associated with treatment response. In some naltrexone studies, for example, carriers of a variant (118G or Asp40) allele in OPRM1, the gene encoding the ?-opioid receptor, had a better clinical response to naltrexone than 118A (or Asn40) allele homozygotes (Anton et al., 2008; Oslin et al. 2003).