Results suggest these medications could play an important role to reduce alcohol use and smoking at the same time. Unexpectedly, nicotine replacement therapy performed as well as the prescription drugs varenicline and cytisine.
The study, published Aug. 5 in JAMA Network Open, involved 400 people living with HIV in Russia and was designed by researchers from Vanderbilt University Medical Center (VUMC), Boston University School of Medicine, Boston Medical Center and First Pavlov State Medical University of St. Petersburg, Russia.
The investigators, who included addiction specialists and HIV researchers, recruited volunteers who self-identified as engaging in risky drinking and daily smoking. Participants were followed up to 12 months after enrollment in the clinical trial. Medications were placebo-controlled, so participants and investigators did not know who was assigned to which medication.
The study showed that after three months, alcohol consumption decreased regardless of whether participants were given nicotine replacement therapy, varenicline or cytisine. The main outcome was number of heavy drinking days in the past month at three months, and secondary outcomes included abstinence from alcohol at three months, and abstinence from smoking at six months.
“A single medication to treat both risky drinking and smoking could improve health efficiently and significantly. Risky drinking and smoking frequently co-occur, and they both threaten health by increasing risk of cardiovascular disease, cancer and other important health outcomes,” said the study’s lead author, Hilary Tindle, MD, MPH, the William Anderson Spickard, Jr., MD, Professor of Medicine, and associate professor of Medicine at VUMC. “
“It was gratifying to see high-risk research participants being included in NIH-funded research,” said. Matthew Freiberg, MD, MSc, a study principal investigator, Dorothy and Laurence Grossman Chair in Cardiology and professor of Medicine at VUMC.
Freiberg noted that when investigators had designed the study, they envisioned the nicotine replacement as the “control” arm for alcohol consumption. Nicotine replacement therapy has been available in the United States to treat tobacco addiction since the early 1980s and is not used for reduction of alcohol consumption.
The study enrolled participants who engaged in five or more heavy drinking days in the past month (defined as five or more drinks in one day for a man or four or more drinks in one day for a woman) and who smoked five or more cigarettes a day.
“Another important observation in our post-hoc analysis was that rates of alcohol consumption were lower, and rates of alcohol abstinence were higher, among the people who quit smoking as compared to those who continued to smoke. These results need further study to understand if findings were due to the medications directly, quitting smoking or both,” said Samet, the senior author on the study.
Tindle added that there is much to be learned about how the study drugs—termed nicotinic acetylcholine receptor agonists—may work to reduce voluntary alcohol intake. Studies in animal models show that stimulation of a very specific receptor type containing the alpha four subunit is required. Importantly, all three of the study medications target these very receptors.
The investigators concluded that the results of the study, which was conducted from July 2017 to December 2020, extends prior work in several ways. Notably, this is the largest trial to study nicotinic acetylcholine receptor partial agonists to target alcohol consumption and the first to examine cytisine to treat both alcohol and tobacco.
Cytisine is not yet approved by the U.S. Food and Drug Administration to treat tobacco use but it has been used widely in Eastern Europe for decades and is under active study globally.
here is a now a wealth of evidence on which to recommend that smokers making a quit attempt should be offered varenicline as a first-line treatment, in combination with behavioral counseling, consistent with the US Surgeon General’s recommendations103.
Varenicline has proven to be more effective than placebo, bupropion and NRT in the general population11,12,33 and in populations with comorbid conditions, such as those with psychiatric disease33,44,45,104, CVD39,40 and COPD37. In addition, efficacy results have been replicated in numerous geographical areas28–31,33.
Data suggest that in addition to the standard administration of varenicline, several alternative treatment paradigms/quit approaches may prove beneficial. Those that have already received regulatory approval include extended varenicline treatment as maintenance therapy in people who have succeeded in quitting47,48, lower daily doses, and reduce-to-quit or flexible quit date approaches in those unwilling or unable to quit abruptly52,53. While currently not included in the prescribing information, varenicline pre-loading50,51,105 has demonstrated improved efficacy, particularly in highly dependent smokers. These additions to the practitioner’s arsenal may be considered depending on the history and preference of the individual, and present opportunities to use varenicline more flexibly, to thereby maximize its efficacy, and to extend its clinical reach.
Varenicline has an acceptable safety/tolerability profile. The most frequently reported AE is nausea; varenicline treatment has also been associated with sleep disturbance and abnormal dreams. Most AEs are transient and mild in severity. Despite earlier case reports, there is now a large body of evidence that does not support the notion of increased risk of serious neuropsychiatric AEs33,44,45 with varenicline in comparison with smokers quitting with placebo or the other approved medications. The rate of serious neuropsychiatric AEs is higher in smokers attempting to quit who have a psychiatric history compared to those without such a history, but this is observed across all treatments including placebo. Consequently, varenicline may be offered to smokers with psychiatric conditions who seek help with stopping smoking. Likewise, there is no evidence that use of varenicline is associated with increased risk of CV events80.
There are a number of areas in which future research could broaden the application of varenicline. As discussed in the current article, studies that further investigate varenicline pre-loading and combination therapy with NRT or bupropion could confirm the potential benefits of these approaches. Additional research on the combination of varenicline specifically with short-acting NRT forms (gum and lozenges) or e-cigarettes also warrants further investigation. In addition, other research questions may be important that were beyond the scope of the current article. Varenicline may be a promising treatment for post-smoking cessation nicotine use in individuals who continue to use nicotine replacement products for years106. Finally, varenicline has shown some potential for indications beyond smoking cessation, including for alcohol use disorder and addiction treatment for other drugs such as cocaine107–109. Additional research could also confirm these uses.
reference link : https://www.tandfonline.com/doi/full/10.1080/03007995.2020.1729708
More information: Effectiveness of Varenicline and Cytisine for Alcohol Use Reduction Among People With HIV and Substance Use, JAMA Network Open (2022).
