Elsevier

Addictive Behaviors

Volume 30, Issue 9, October 2005, Pages 1630-1637
Addictive Behaviors

Reductions in and relations between “craving” and drinking in a prospective, open-label trial of ondansetron in adolescents with alcohol dependence

https://doi.org/10.1016/j.addbeh.2005.07.004Get rights and content

Abstract

Recently, we reported that ondansetron (a 5-HT3 antagonist) as an adjunct to cognitive behavioral therapy (CBT) produced significant within-group decreases (improvement) in drinking in adolescents with alcohol dependence. We previously have hypothesized that the mechanism of ondansetron treatment response in adolescents with alcohol dependence should be similar to early onset adult alcoholics, wherein blockade of serotonin-3 receptors may decrease dopamine release and subsequent alcohol consumption and craving. We now suggest that one mechanism by which ondansetron diminishes drinking in adolescents with alcohol dependence is through a reduction in “craving” as measured by the Adolescent Obsessive–Compulsive Drinking Scale (A-OCDS). We conducted an 8-week, prospective, open-label study of ondansetron (4 μg/kg b.i.d.) in 12 adolescents (age 14–20 years) who had alcohol dependence. Results showed that “irresistibility” and total scores as measured by the A-OCDS were correlated significantly with drinking indices (drinks / day, percent days abstinent) at the end of treatment, and that “irresistibility” and total A-OCDS scores decreased significantly by the end of treatment. These preliminary results suggest that the A-OCDS can be useful as an outcome measure in clinical studies of adolescents with alcohol dependence.

Introduction

Recent prospective findings have shown that untreated alcohol problems in adolescence often lead to alcohol and other drug dependencies by young adulthood (Fleming et al., 1982, Tubman et al., 1990). Unfortunately, most current treatments for adolescent alcohol dependence have been limited to psychosocial therapies (Deas & Thomas, 2001). Although many alcohol-dependent adolescents do not benefit from psychosocial treatments alone (Brown & D'Amico, 2003), few open-label or placebo-controlled medication studies have been conducted in this population (Dawes & Johnson, 2004). Although well-designed studies are near completion, no adequately powered, double-blind, placebo-controlled medication studies for adolescents with alcohol use disorders have been published. Controlled clinical trials of medications as adjunctive treatments to psychosocial interventions are clearly warranted (Dawes & Johnson, 2004). The lack of treatment studies using medications as adjuncts to psychosocial treatments is unfortunate, since studies in adults suggest this combined approach holds the promise of greater efficacy compared to psychosocial treatment alone (Johnson, 2004a, Johnson, 2004b, Johnson & Ait-Daoud, 2000).

Ondansetron, a serotonin-3 antagonist, is of particular interest in early onset alcohol dependence (EOA; i.e., alcohol dependence that onsets before age 25 years). Ondansetron has been shown to be efficacious in the treatment of EOA adults (Johnson et al., 2000, Johnson & Ait-Daoud, 2000, Kranzler et al., 2003). In a recent prospective, open-label study, Dawes, Johnson, Ait-Daoud, Ma, and Cornelius (2005) showed that ondansetron along with cognitive behavioral therapy (CBT) produced significant within-group decreases (improvement) in drinks / drinking day and drinks / day and increases in percent days abstinence in adolescents with alcohol dependence.

Adolescents with alcohol dependence may share some of the phenomenology seen with their adult counterparts, including alcohol cue reactivity and intrusive thoughts and urges to drinking (Thomas, Drobes, & Deas, 2005). Intrusive thoughts and urges to drink, often described as components of “craving”(Anton et al., 1995, Modell et al., 1992) have been hypothesized to be associated with maintenance of drinking, alcohol withdrawal, and relapse (Ludwig & Wikler, 1974, Rankin et al., 1979). Reduction in the urge to drink may be one process by which ondansetron diminishes the rewarding effects of alcohol in dependent adolescents.

To quantify the craving phenomena, standardized multidimensional measures are used commonly in adult alcoholics. In the adult alcoholism literature, the Obsessive–Compulsive Drinking Scale (OCDS) (Anton et al., 1995) is one such measure that is validated, reliable, and sensitive to measuring change following treatment. An adolescent version of the OCDS, the Adolescent Obsessive–Compulsive Drinking Scale (A-OCDS), has been developed recently (Deas, Roberts, Randall, & Anton, 2001). The A-OCDS yields a total score and two subscales, “irresistibility” and “interference.” The A-OCDS has been shown to be specific and sensitive to identify problematic drinking in adolescents and young adults who were college students (Deas, Roberts, Randall, & Anton, 2002) or were admitted to a dual-diagnosis inpatient unit (Deas, Thomas, Randall, & Anton, 2002). In both of these studies, threshold scores were used to indicate the presence of problem drinking, though none of the participants had been diagnosed with an alcohol use disorder. The utility of the A-OCDS as a quantitative measure of the severity of craving in adolescent alcoholics is the topic of an article in this issue of Addictive Behaviors (Thomas & Deas, 2005). The A-OCDS has yet to be used to examine changes in drinking and craving in adolescents over the course of treatment for alcohol use disorders, which is the focus of the present study.

The hypothesis of the present study is that the A-OCDS and drinking reduction are correlated significantly and the A-OCDS total and subscale scores decrease significantly, in a prospective, open-label treatment study using ondansetron with cognitive behavioral therapy in treating adolescents with alcohol dependence.

Section snippets

Participants

This study was conducted at the South Texas Addiction Research and Technology (START) Center in San Antonio, Texas. Participants were treatment-seeking adolescents with alcohol dependence who were recruited primarily by health practitioners working in the community. Before study entry the potential risks and benefits of participation were explained to participants, and, when applicable, to their parents. Participants who were 18 to 20 years old gave their written informed consent. For 14 to 17

Sample characteristics

The mean age was 18.0 years (range 14–20 years). Eight of 12 adolescent participants had a disruptive behavior disorder, and 3 participants had a mood disorder. All participants had DSM-IV-TR alcohol dependence, and 10 of 12 subjects also met DSM-IV-R criteria for cannabis dependence.

A-OCDS and drinking outcomes

For the analyses of A-OCDS factors and drinking outcomes, we used the corrected irresistibility scale with the drinking items 7 and 8 removed. At baseline assessment, 2 items from the baseline corrected

Discussion

To our knowledge, this is the first prospective, open-label treatment study to report on the use of the Adolescent Obsessive–Compulsive Drinking Scale (A-OCDS) as a clinical outcome measure in adolescent alcohol-dependent outpatients. The results showed that irresistibility and total A-OCDS scores decreased significantly during treatment. The results also revealed that these measures were significantly positively correlated with drinks / day and significantly negatively correlated with percent

Acknowledgements

This work was supported in part by a donation from a private foundation that wishes to remain anonymous, and by grants to Dr. Johnson from the National Institute on Alcohol Abuse and Alcoholism (R01 AA010522 and R01 AA012964-03).

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    Disclosure: The lead author currently receives no research funding from pharmaceutical companies.

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