Gender Differences in Response to Sertraline Pharmacotherapy in Type A Alcohol Dependence
Drexel University, Filadelfia, Pennsylvania, United States American Journal on Addictions
(Impact Factor: 1.74).
05/2004; 13(3):236-47. DOI: 10.1080/10550490490459906
We previously established that Babor Type A "lower-risk/severity" alcoholics (n = 55) had better treatment response to fourteen weeks of sertraline (200 mg/day) than placebo, a finding not present for Type B "higher-risk/severity" alcoholics (n = 45). This exploratory study extended these results by examining the original sample for gender differences in response to sertraline pharmacotherapy. Type A alcoholic men, but not Type A alcoholic women, had consistently better outcomes with sertraline compared to placebo on several common drinking measures: time to relapse, days drinking, days drinking heavily, drinks per drinking day, and number of those continually abstinent. There were no significant differences in drinking with sertraline compared to placebo in Type B alcoholic men or women.
Available from: Miles D. Thompson
- "There are strong and consistent differences in sex and stress hormones that effect drinking (Mendelson and Mello, 1988). Consistent with these observations are the gender-specific responses to treatment such as those reported for sertraline in AD women (Pettinati et al., 2004) that are particularly evident in those with specific polymorphisms (Roache, 2012). "
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ABSTRACT: SLC6A4, the gene encoding the serotonin transporter protein (5-HTT), has been extensively examined as a risk factor for alcohol dependence (AD). More recently, variability in the transporter gene was identified to be a potential moderator of treatment response to serotonergic medications such as ondansetron and sertraline. There is an insertion-deletion polymorphism in the promoter region (5-HTTLPR) of the SLC6A4, with the most common alleles being a 14-repeat short (S) allele and a 16-repeat long (L) allele. The S allele has often been associated with AD. By contrast, the L allele has been associated with pharmacological responsiveness in some individuals with AD. Differences in clinical phenotype may determine the utility of the 5-HTTLPR polymorphism as a moderator of pharmacological interventions for AD. We review the AD typology and disease onset in the context of pharmacogenetic and genomic studies that examine the utility of 5-HTTLPR in improving treatment outcomes.
© The Author 2015. Medical Council on Alcohol and Oxford University Press. All rights reserved.
Available from: Peter Clapp
- "Its effectiveness as an adjunct to naltrexone is not clear. Trials that evaluated sertraline as adjunctive therapy to naltrexone used 100 mg,78,79 compared to other trials where 200 mg was used when sertraline was tested as monotherapy in AUD.75–77 "
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ABSTRACT: Alcohol use disorders (AUD) continue to be a concerning health issue worldwide. Harmful alcohol use leads to 2.5 million deaths annually worldwide. Multiple options exist for the management of dependence on alcohol, not all of which are approved by drug-regulating agencies. Current practice in treating AUD does not reflect the diversity of pharmacologic options that have potential to provide benefit, and guidance for clinicians is limited. Few medications are approved for treatment of AUD, and these have exhibited small and/or inconsistent effects in broad patient populations with diverse drinking patterns. The need for continued research into the treatment of this disease is evident in order to provide patients with more specific and effective options. This review describes the neurobiological mechanisms of AUD that are amenable to treatment and drug therapies that target pathophysiological conditions of AUD to reduce drinking. In addition, current literature on pharmacologic (both approved and non-approved) treatment options for AUD offered in the United States and elsewhere are reviewed. The aim is to inform clinicians regarding the options for alcohol abuse treatment, keeping in mind that not all treatments are completely successful in reducing craving or heavy drinking or increasing abstinence.
Available from: Colin A Hodgkinson
- "Future analyses will explore these hypotheses. Because our study sample included many individuals with early onset of alcoholism, different results may have been obtained in patients with lower risk and severity, characteristics that have predicted positive response to monotherapy with sertraline (Brady et al., 2005; Pettinati et al., 2003, 2004a). "
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ABSTRACT: Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians.
Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence.
Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response.
Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism.
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