The Sinclair Method defined: Targeted Pharmacological Extinction
The Sinclair Method definitive statement (click for complete statement)
"The Sinclair Method (TSM) uses the nervous system’s own mechanism, called “extinction”, for gradually removing the interest in alcohol and the behaviors involved in alcohol drinking. Therefore, the technical term for TSM is “pharmacological extinction.”
Sinclair, J.D. Method for Treating Alcohol‑Drinking Response. USA patent 4,882,335 Nov. 21, 1989. (Full Text)
"Instead of counteracting the drive for alcohol or temporarily satisfying it, a successful treatment for alcoholics should permanently weaken the alcohol-drinking response. Fortunately, there is a well-established method for weakening a learned response: 'extinction'. Extinction consists of having the response emitted repeatedly in the absence of positive reinforcement."
How Opioid Antagonists Reduce the Craving for Alcohol, by David Sinclair, Roy Eskapa and Michael Sinclair (Full Text)
"The results suggest that the primary influence of the antagonists on craving and drinking is not directly from the medicine itself but instead is produced by repeated extinction sessions in which alcohol is drunk while reinforcement is blocked by an opioid antagonist."
Peer Reviewed Support for Targeted Naltrexone
Kranzler, H. R., Tennen, H., Armeli, S., Chan, G., Covault, J., Arias, A., & Oncken, C. (2009). Targeted naltrexone for problem drinkers. Journal of Clinical Psychopharmacology, 29(4), 350–357. http://doi.org/10.1097/JCP.0b013e3181ac5213
"The targeted naltrexone group drank less than the daily naltrexone group with the opposite pattern in evidence for the targeted and daily placebo."
"data show that detoxification is not required and that targeted medication taken only when craving occurs is effective in maintaining the reduction in heavy drinking."
Naltrexone for the reduction of heavy drinking
Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for Adults With Alcohol Use Disorders in Outpatient Settings: A Systematic Review and Meta-analysis. JAMA. 2014;311(18):1889-1900. doi:10.1001/jama.2014.3628. (Full Text)
This meta-analysis included 122 RCTs and a cohort study with a total of 22,803 participants. Authors determined the NNT for oral naltrexone to prevent any drinking (abstinence) was 20, with the NNT dropping to 12 for reduction of heavy drinking (moderation); while injectable naltrexone was found to have no association with return to drinking or heavy drinking but was associated with a reduction in heavy drinking days.
Alcohol Deprivation Effect
"Depriving rats of alcohol, following a prolonged period of access to the solution, produced a much higher alcohol preference than did continual access. This “alcohol deprivation effect” is seen as possibly demonstrating a “need” for alcohol."
"Both strains demonstrated an "alcohol deprivation effect" (ADE), temporarily drinking significantly more of the alcohol solution on the 2 days after the period without alcohol than on the 2 days immediately before it (p < .01)."
Naltrexone for the reduction of heavy drinking
Jonas DE, Amick HR, Feltner C, et al. Pharmacotherapy for Adults With Alcohol Use Disorders in Outpatient Settings: A Systematic Review and Meta-analysis. JAMA. 2014;311(18):1889-1900. doi:10.1001/jama.2014.3628. (Full Text)
This meta-analysis included 122 RCTs and a cohort study with a total of 22,803 participants. Authors determined the NNT for oral naltrexone to prevent any drinking (abstinence) was 20, with the NNT dropping to 12 for reduction of heavy drinking; while injectable naltrexone was found to have no association with return to drinking or heavy drinking but was associated with a reduction in heavy drinking days.
Additional research on naltrexone and nalmefene for alcohol use disorder
Sinclair, J.D. Rats learning to work for alcohol. Nature 249: 590‑592, 1974.
Sinclair, J.D. Drugs to decrease alcohol drinking. Annals of Medicine 22: 357‑362, 1990.
Concurrent Naltrexone and Prolonged Exposure Therapy for Patients With Comorbid Alcohol Dependence and PTSDA Randomized Clinical Trial JAMA. 2013;310(5):488-495. doi:10.1001/jama.2013.8268 (Full Text)