Effects of the Opioid Receptor Antagonist Naltrexone on Smoking and Related Behaviors in Smokers Preparing to Quit: A Randomized Controlled Trial.
King A, Cao D, Zhang L, Rueger SY.
Addiction. 2013 May 28
Background: Studies done looking at naltrexone for smoking have had mixed results, both positive and negative. Limitations of prior studies include single dose naltrexone, inclusion of non treatment seekers and lack of long term follow-up (some studies looked at effects just hours after naltrexone). Currently, the Cochran database states there is not enough evidence to make a recommendation either way.
Patient selection: Patients had to be 18-65 years of age, smoke 12-40 cigarettes per day x2 years and had to report a desire to quit. Study was also limited to patients with BMI between 19-38 and their liver function tests had to be < 2.5 times normal. They could not be taking any opiate or other psychotropic medications, and could not have in the past year any major medical or psychiatric disorder. They could not have any diagnosis of opiate abuse or dependence in their lifetime. The study also declined patients who were pregnant or nursing. Of the 707 individuals screened, 315 underwent randomization with a mean age of 42 years and 57% white.
Study design and methods: The study was a double blind, placebo controlled, randomized study with randomization either to naltrexone or placebo. There was a pre-quit phase, one week before the quit date, where patients randomized to naltrexone were given 12.5 mg on day 1, 25 mg on days 2 and 3, then 50 mg on day 4-7 (day 7 being the quit date). After the quit date, both groups received weekly counseling sessions and nicotine patches (open label) for 1 month (post quit phase). After the initial month, naltrexone or placebo was the only therapy. Compliance was measured by urine, saliva and pill counts. Participants filled out short questionnaires each night assessing number of cigarettes smoked, urge to smoke, smoking pleasure/taste, alcoholic drinks consumed, food/sweets consumption and caffeine intake (control). Follow up was done as far out as 12 weeks (though this study is focused on correlation of pre-quit phase findings and post-quit results, not the results of naltrexone on tobacco cessation at 12 weeks.)
Results: There was a 6% drop out rate, slightly higher in the placebo group, with "smoking related" causes being the most common. Otherwise, naltrexone participants reported a higher incidence of nausea, dizziness and sedation (45% versus 22%) but this was rated as mild. In the pre-quit phase, those with naltrexone had a 26% reduction in smoking (versus 17%, or, in terms of number smoked 4.21 fewer cigarettes per day versus 2.93 ), along with reduced smoking urge, cigarette taste and alcoholic consumption. Other measures, when results were adjusted for demographics and nausea, were not significant (i.e. sweets consumption, food consumption/taste, smoking pleasure/taste). When measured at one month, the naltrexone group continued to show reductions in cigarette number, reduced urge to smoke and alcohol consumption. At 12 weeks, alcohol consumption remained reduced.
Moral of the story: Naltrexone taken one week before a patient's quit date appears to reduce cigarette smoking, urge and alcohol consumption.
Thoughts: Although the study included follow up at 12 weeks, the results of the 12 week follow up is detailed in a different study. This study focused on whether data collected in the pre-quit phase could predict post-quit phase results.
Review by Jacqueline Wong, MD.
