Is Naltrexone (opioid receptor antagonist) effective for smoking cessation?

Naltrexone for Smoking Cessation

Naltrexone alone is not recommended as a primary treatment for smoking cessation, but may be considered as part of combination therapy with bupropion in patients who need both smoking cessation support and weight management. 1

Efficacy of Naltrexone for Smoking Cessation

• Studies examining naltrexone alone for smoking cessation have shown mixed and generally insufficient evidence to support its use as monotherapy 2
• A randomized trial found no significant effect of naltrexone on smoking abstinence rates compared to placebo (22% vs 19%) 2
• When combined with nicotine patches, naltrexone showed no additional benefit over nicotine patches alone in achieving smoking cessation 2

Naltrexone-Bupropion Combination

• The combination of naltrexone and bupropion (available as naltrexone-bupropion ER) has shown more promising results for smoking cessation than naltrexone alone 1
• Limited data on smoking cessation with the combination of sustained-release bupropion and naltrexone at doses used for obesity showed a reduction of nicotine use and mitigation of associated weight gain 1
• A study investigating the addition of naltrexone to bupropion demonstrated superior efficacy with the combination therapy at 7 weeks of treatment, though equivalent relapse rates were seen at 6 months after treatment termination 1

Sex Differences in Response

• Women may benefit more from naltrexone for smoking cessation than men 3
• In one study, women in the placebo group had significantly lower quit rates than men (39% vs 67%), but with naltrexone, women achieved quit rates comparable to men (58% vs 62%) 3
• Naltrexone reduced cessation-related weight gain in both sexes and selectively reduced women's urge to smoke to relieve negative affect and withdrawal 3

Clinical Considerations for Naltrexone Use

• Naltrexone is an opioid antagonist that should not be used in patients requiring short-term or long-term opioid therapy 1
• It must be discontinued before procedures requiring opioid analgesia to prevent reduced analgesic efficacy or precipitated withdrawal 1
• The standard dose for naltrexone is 50 mg daily, though some protocols start with 25 mg daily for the first few days 3
• Liver function tests should be monitored at baseline and every three to six months due to potential hepatic injury at supratherapeutic doses 1

Naltrexone-Bupropion ER for Dual Purpose Treatment

• For patients with both obesity and tobacco use disorder, naltrexone-bupropion ER may be considered as it addresses both conditions 1
• The American Gastroenterological Association (AGA) suggests using naltrexone-bupropion ER with lifestyle modifications for weight management in patients attempting smoking cessation 1
• The combination may be particularly beneficial for patients who experience weight gain during smoking cessation attempts 1, 4

Limitations and Monitoring

• Blood pressure and heart rate should be monitored periodically while taking naltrexone-bupropion ER, especially in the first 12 weeks of treatment 1
• Naltrexone-bupropion ER should be avoided in patients with seizure disorders and used with caution in patients at risk of seizures 1
• Long-term cardiovascular safety of naltrexone-bupropion ER remains unclear as cardiovascular outcome trials were terminated early 1

Alternative First-Line Smoking Cessation Options

• Varenicline has shown superior efficacy for smoking cessation compared to the combination of varenicline and naltrexone in heavy-drinking smokers 5
• Bupropion alone is FDA-approved for smoking cessation and may be considered before adding naltrexone 1
• Nicotine replacement therapy remains a first-line treatment option with established efficacy 2