A drug once used to treat high blood pressure can help alcoholics with withdrawal symptoms reduce or eliminate their drinking, Yale University researchers reported in the American Journal of Psychiatry.
In a double-blind study, researchers gave the drug prazosin or a placebo to 100 people entering outpatient treatment after being diagnosed with alcohol use disorder. All of the patients had experienced varying degrees of withdrawal symptoms prior to entering treatment, wrote Bill Hathaway in a YaleNews article published on 19 November 2020.
According to the researchers, subjects with more severe symptoms – including shakes, heightened cravings and anxiety, and difficulty sleeping – who received prazosin significantly reduced the number of heavy drinking episodes and days they drank compared to those who received a placebo.
The drug had little effect on those with few or no withdrawal symptoms.
"There has been no treatment readily available for people who experience severe withdrawal symptoms and these are the people at highest risk of relapse and are most likely to end up in hospital emergency rooms," said corresponding author Rajita Sinha, Foundations Fund Professor of Psychiatry, a professor of neuroscience, and director of the Yale Stress Center.
Prazosin was originally developed to treat high blood pressure and is still used to treat prostate problems in men, among other conditions. Previous studies conducted at Yale have shown that the drug works on stress centers in the brain and helps to improve working memory and curb anxiety and craving.
Sinha's lab has shown that stress centers of the brain are severely disrupted early in recovery, especially for those with withdrawal symptoms and high cravings, but that the disruption decreases the longer the person maintains sobriety.
Prazosin could help bridge that gap by moderating cravings and withdrawal symptoms earlier in recovery and increasing the chances that patients refrain from drinking, she said.
One drawback is that in its current form prazosin needs to be administered three times daily to be effective, Sinha noted.
The study was conducted at the Yale Stress Center and the Connecticut Mental Health Center's Clinical Neuroscience Research Unit. It was supported by the National Institute of Alcoholism and Alcohol Abuse at the National Institutes of Health and the Connecticut State Department of Mental Health and Addiction Services.
Moderation of Prazosin’s Efficacy by Alcohol Withdrawal Symptoms
The American Journal of Psychiatry. Published on 19 November 2020.
Authors
Rajita Sinha, Stephanie Wemm, Nia Fogelman, Verica Milivojevic, Peter M Morgan, Gustavo A Angarita, Gretchen Hermes and Helen C Fox
Abstract
Alcohol use disorder (AUD) is a leading cause of global disease burden. Chronic, heavy use increases the likelihood of alcohol withdrawal symptoms and associated secondary outcomes of alcohol craving and mood, anxiety, and sleep disturbances, which are predictive of poor treatment outcomes.
The authors examined whether alcohol withdrawal symptoms moderate the efficacy of prazosin in reducing alcohol intake and associated secondary outcomes.
Methods
A 12-week, double-blind, randomised, controlled proof-of-concept trial of prazosin (16 mg/day, with a 2-week titration) was conducted in community-recruited adults with current alcohol dependence (N=100) with varying levels of alcohol withdrawal symptoms assessed at treatment entry.
Primary outcomes were daily self-reported drinking days and heavy drinking days, and secondary outcomes were average drinks/day and mood, anxiety, craving, and sleep quality ratings.
Results
Modified intent-to-treat analyses indicated a significant interaction of alcohol withdrawal symptom score by treatment by full-dose treatment period (weeks 3–12) for drinking days, heavy drinking days, and average drinks/day.
By week 12, participants with high alcohol withdrawal symptoms on prazosin reported 7.07% heavy drinking days and 27.46% drinking days, while those on placebo had 35.58% heavy drinking days and 58.47% drinking days (heavy drinking days: odds ratio=0.14, 95% CI=0.058, 0.333; drinking days: odds ratio=0.265, 95% CI=0.146, 0.481). No such benefit of prazosin was observed in those reporting low or no alcohol withdrawal symptoms.
Individuals with high alcohol withdrawal symptoms on prazosin compared with placebo also showed significantly improved anxiety, depression, and alcohol craving over the course of the trial.
Conclusions
The findings indicate that alcohol withdrawal symptoms are a significant moderator of prazosin treatment response for alcohol use outcomes and for associated symptoms of alcohol craving, anxiety, and mood symptoms.
These data support further evaluation of alcohol withdrawal symptoms as a prognostic indicator of prazosin’s efficacy in the treatment of AUD.
[link url="https://news.yale.edu/2020/11/19/drug-eases-recovery-those-severe-alcohol-withdrawal"]YaleNews story – Drug eases recovery for those with severe alcohol withdrawal[/link]
[link url="https://ajp.psychiatryonline.org/doi/10.1176/appi.ajp.2020.20050609"]American Journal of Psychiatry article – Moderation of Prazosin’s Efficacy by Alcohol Withdrawal Symptoms[/link]