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• W1984979941 abstract "The paper by Subbaraman and colleagues 1 is timely, considering that the newest version of the Diagnostic and Statistical Manual, DSM-5, now contains ‘alcohol craving’ as an item in the diagnostic scheme for alcohol use disorders, thus making it more consistent with the ICD-10 classification. Two important clinical issues involving the concept of craving are how it should be defined 2 and perhaps, more importantly, how it might be used to predict treatment response 3. It is the latter that Subbaraman and colleagues attempt to address by a re-analysis of the COMBINE study (Combining Medications and Behavioral Interventions for Alcoholism) 4 data using the Obsessive Compulsive Drinking Scale (OCDS) 5 as the measurement of craving. Participants were treated with naltrexone versus Combined Behavioral Intervention (CBI) or the combination of the two. The authors evaluated whether OCDS scores reported by subjects at weeks 4 and 12 of a 16-week treatment trial predicted the percentage of days abstinent (PDA) during the final 4 weeks of treatment (weeks 13–16). They found that craving level reported at week 4 of treatment mediated abstinence at the end of treatment for the naltrexone-treated individuals but not the CBI-alone treated individuals, whose craving at week 12 was solely predictive of end-of-study abstinence. Conversely, those with higher craving, compared to those with lower craving at week 4, had more abstinence by the end of the study if treated with naltrexone, CBI or a combination of the two. Overall, the authors' analysis suggests that as much as half of the observed treatment effect on abstinence was accounted for by its effect on craving. These results are consistent with other work, where the naltrexone response was predicted (moderated) by craving level prior to treatment 6 and/or by reduction in craving during treatment 7, 8. It is also consistent with data showing that naltrexone reduces craving in experimental settings 9, 10. Similarly, our group reported that for non-treatment-seeking ‘early stage’ alcoholics, naltrexone could blunt alcohol cue-induced activation of the ventral striatum/nucleus accumbens, and it appeared that the anti-craving effect of naltrexone might be mediated partly through this mechanism 11. Because increased mu opiate receptor binding in the ventral striatum is related to craving (OCDS scores) immediately post-detoxification and up to 5 weeks later 12, it makes sense that naltrexone blockage of these receptors might reduce craving, especially in those most sensitive. It would appear from the Subbaraman analysis that CBI took longer to affect craving and mediate response. This also makes sense clinically, as CBI is a therapeutic process that utilizes subject experiences and reports as a guide for behavioral and motivational strategies intended to mitigate internal urges to drink and avoid craving-related situations. It probably requires more time to learn these techniques, apply them in real-life situations, and eventually manage craving-mediated alcohol consumption. Interestingly, their data imply that the combination of naltrexone and CBI had as strong, or stronger, effects on PDA than the two treatments alone once craving was taken into account. This is a little different to the original results from the COMBINE study, where the treatment combination was no more effective in producing abstinence, or reducing relapse to heavy drinking, than either one alone. However, the Subbaraman analysis did not test this issue directly, so it is difficult to distinguish whether both naltrexone and CBI had independent effects on craving (which mediated response), or one was stronger than the other. It is interesting that in some earlier studies, the combination of cognitive behavioral therapy (CBT) (a crucial ingredient of CBI) with naltrexone was reported to be more effective than CBT alone 13-15. Also, our group reported that naltrexone in combination with CBT appeared to affect craving as measured by the OCDS and this predicted future reduction in drinking 8. Perhaps the effectiveness of the CBI and naltrexone combination can be best understood only in the context of high cravers, or perhaps in those whose craving is the most reduced during treatment. The clinician might wonder how this may be used in practice. One might suggest that clinicians adopt a standard way of measuring craving and apply this during follow-up visits. Overall, those reporting higher craving would do best with either naltrexone or CBI. For naltrexone, if a significant reduction in craving is not observed by the fourth week of treatment, then perhaps CBI should be added or a change of medication considered. If CBI is used alone it would appear that more time should elapse to evaluate its effect on craving, but if no significant improvement is obtained by 12 weeks of treatment, perhaps naltrexone should be added or another medication considered. Overall, recent changes related to craving as expressed in DSM-5, and those already existing in ICD-10, suggest that the monitoring of craving will take on a more important aspect for alcohol use disorder treatment in the future. Clinicians should educate themselves on its measurement and utility, while researchers should define more clearly its neuroanatomical and treatment implications. Consultant for Alkermes, Inc.—a company making long-acting injectable naltrexone (not used in the COMBINE study)." @default.
• W1984979941 created "2016-06-24" @default.
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• W1984979941 date "2013-09-13" @default.
• W1984979941 modified "2023-10-17" @default.
• W1984979941 title "Commentary on Subbaraman<i>et al</i>. (2013): Cravings as a mediator and moderator of drinking outcomes in the<scp>COMBINE</scp>Study" @default.
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• W1984979941 doi "https://doi.org/10.1111/add.12328" @default.
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