Predicting response to opiate antagonists and placebo in the treatment of pathological gambling

Department of Psychiatry, University of Minnesota School of Medicine, 2450 Riverside Avenue, Minneapolis, MN 55454, USA.
Psychopharmacology (Impact Factor: 3.88). 06/2008; 200(4):521-7. DOI: 10.1007/s00213-008-1235-3
Source: PubMed


Although opiate antagonists have shown promise in the treatment of pathological gambling (PG), individual responses vary. No studies have systematically examined predictors of medication treatment outcome in PG. Understanding clinical variables related to treatment outcome should help generate treatment algorithms for PG.
We sought to identify clinical variables associated with treatment outcome in PG subjects receiving opiate antagonists.
Two hundred eighty-four subjects [137 (48.2%) women] with DSM-IV PG were treated in one of two double-blind placebo-controlled trials (16 weeks of nalmefene or 18 weeks of naltrexone). Gambling severity was assessed with the Yale Brown Obsessive Compulsive Scale Modified for Pathological Gambling (PG-YBOCS) with positive response defined as > or =35% reduction in PG-YBOCS score for at least 1 month by study endpoint. Depression, anxiety, and psychosocial functioning were included in stepwise logistic regression analyses designed to identify clinical factors independently associated with treatment response.
The clinical variable most strongly associated with a positive response to an opiate antagonist was a positive family history of alcoholism (p = 0.006). Among individuals receiving higher doses of opiate antagonists (i.e., nalmefene 50 or 100 mg/day or naltrexone 100 or 150 mg/day), intensity of gambling urges (PG-YBOCS urge subscale) was associated with a positive response on a trend level (p = 0.036). Among individuals receiving placebo, younger age was associated, on a trend level, with positive treatment outcome (p = 0.012).
A family history of alcoholism appears to predict response to an opiate antagonist in PG. Future research is needed to identify specific factors (e.g., genetic) mediating favorable responses.

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    • "). This case study reported successful treatment with naltrexone, which has also proven effective in the treatment of other impulse control disorders, such as pathological gambling and kleptomania (Grant et al. 2008, 2009). The patient in this study was a 31-year-old male with compulsive cybersexual behavior (chatting online, masturbating for hours, and occasionally, sex with Internet contacts ). "

    Internet Addiction. Neuroscientific Approaches and Therapeutical Interventions, 1^ edited by Christian Montag, Martin Reuter, 02/2015: chapter 10: pages 151-165; Springer International Publishing., ISBN: 978-3-319-07241-8
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    • "For example, opiates are known to increase DA release in the reward pathway, and the opiate antagonists naltrexone and nalmefene, which are known to decrease DA release, have been found to reduce reward sensitivity and probably increase punishment sensitivity as well (Petrovic et al., 2008). Moreover, treatment with opiate antagonists has been shown to be effective in PG and to diminish gambling urges (Kim and Grant, 2001; Kim et al., 2001; Modesto-Lowe and Van Kirk, 2002; Grant et al., 2008a, b, 2010b). "
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    ABSTRACT: In problem gamblers, diminished cognitive control and increased impulsivity is present compared to healthy controls. Moreover, impulsivity has been found to be a vulnerability marker for the development of pathological gambling (PG) and problem gambling (PrG) and to be a predictor of relapse. In this review, the most recent findings on functioning of the brain circuitry relating to impulsivity and cognitive control in PG and PrG are discussed. Diminished functioning of several prefrontal areas and of the anterior cingulate cortex (ACC) indicate that cognitive-control related brain circuitry functions are diminished in PG and PrG compared to healthy controls. From the available cue reactivity studies on PG and PrG, increased responsiveness towards gambling stimuli in fronto-striatal reward circuitry and brain areas related to attentional processing is present compared to healthy controls. At this point it is unresolved whether PG is associated with hyper- or hypo-activity in the reward circuitry in response to monetary cues. More research is needed to elucidate the complex interactions for reward responsivity in different stages of gambling and across different types of reward. Conflicting findings from basic neuroscience studies are integrated in the context of recent neurobiological addiction models. Neuroscience studies on the interface between cognitive control and motivational processing are discussed in light of current addiction theories. Clinical implications: We suggest that innovation in PG therapy should focus on improvement of dysfunctional cognitive control and/or motivational functions. The implementation of novel treatment methods like neuromodulation, cognitive training and pharmacological interventions as add-on therapies to standard treatment in PG and PrG, in combination with the study of their effects on brain-behavior mechanisms could prove an important clinical step forward towards personalizing and improving treatment results in PG.
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    • "Fluvoxamine (SSRI) mean dose 195 mg/day Double-blind cross-over placebo-controlled 15 patients for 16 weeks Fluvoxamine is superior to placebo Blanco et al. 2002 [20] Fluvoxamine (SSRI) mean dose 200 mg/day Double-blind placebo-controlled 32 patients for 6 months Fluvoxamine is not significantly superior to placebo Kim et al. 2002 [12] Paroxetine (SSRI) 20–60 mg/day Double-blind placebo-controlled 45 patients for 8 weeks Paroxetine is superior to placebo Grant and Potenza 2003 [23] Paroxetine (SSRI) 10–60 mg/day Double-blind placebo-controlled 76 patients for 16 weeks Paroxetine is not significantly superior to placebo Saiz-Ruiz et al. 2005 [14] Sertraline (SSRI) 50–150 mg/day Double-blind placebo-controlled 60 patients for 6 months Sertraline is not significantly superior to placebo Grant et al. 2006 [13] Escitalopram (SSRI) mean dose 25 mg/day Open-label for 12 weeks Double-blind placebo-controlled for 8 weeks 13 patients with comorbid anxiety for 20 weeks Escitalopram is superior to placebo Black et al. 2007 [26] Bupropion (NDRI) mean dose 325 mg/day Double-blind placebo-controlled 39 patients for 12 weeks Bupropion is not significantly superior to placebo opioid antagonists in the treatment of the disorder, showing a reduction of urges to engage in the addictive behaviour and longer periods of abstinence [15] [16] [28] "
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