Varenicline

Primer

Varenicline (Tradename: Champix) is a partial nicotine receptor agonist and antagonist, used for smoking cessation.

Mechanism of Action

  • Varenicline is a partial agonist and antagonist at the alpha-4 beta-2 nicotinic receptor (α4β2 or a4b2) nicotinic acetylcholine receptor (nAChR)[1]
  • Plays a significant role in the nicotine reward pathway[2]

Indications

  • Varenicline is safe, tolerable, and efficacious for tobacco cessation in individuals with alcohol use disorder, and might have secondary benefits in reducing alcohol use.[3]

Dosing

  • Start 1 week before quitting
  • 0.5mg PO qAM x 3 days
  • Increase to 0.5mg PO BID x 4 days
  • Then 1mg PO BID x 3 months
    • Up to 6 months

Side Effects

  • For those with gastrointestinal upset, consider taking medication after eating or with a large glass of water
  • For those with insomnia, consider taking medication earlier in the day.
  • For those who experience side effects, consider reduced dosage (0.5 mg BID)
  • Reports of increased rates of depressed mood, agitation, changes in behaviour, suicidal thoughts and behaviour exist with use of varenicline
  • Clinicians should elicit a psychiatric history prior to using this medication and monitor any changes in mood and behaviour during use
  • From the information available to date, it is not possible to determine whether varenicline increases the risk of heart or stroke events in people who have cardiovascular disease

Adverse Events

  • Varenicline was previously thought to increase the risk for neuropsychiatric symptoms, and the FDA applied a black box warning on the medication for this. However, a subsequent 2016 randomized control trial found no significant differences in outcomes between varenicline and placebo, and the warning was removed in 2016.[4][5]
    • Subsequent secondary analyses of the EAGLES trial found that the use of smoking cessation medications, including varenicline, in individuals with stable psychiatric conditions did not pose increased risk of neuropsychiatric side effects across treatments.
    • Caution is advised in unstable psychiatric inpatients due to the potential for clinical confounding, and closer monitoring for worsening psychiatric symptoms is wise.[6]

References

1) Rollema, H., Chambers, L. K., Coe, J. W., Glowa, J., Hurst, R. S., Lebel, L. A., ... & Sands, S. B. (2007). Pharmacological profile of the α 4 β 2 nicotinic acetylcholine receptor partial agonist varenicline, an effective smoking cessation aid. Neuropharmacology, 52(3), 985-994.
2) De Biasi, M., & Dani, J. A. (2011). Reward, addiction, withdrawal to nicotine. Annual review of neuroscience, 34, 105-130
3) Hurt, R. T., Ebbert, J. O., Croghan, I. T., Schroeder, D. R., Hurt, R. D., & Hays, J. T. (2018). Varenicline for tobacco-dependence treatment in alcohol-dependent smokers: A randomized controlled trial. Drug and alcohol dependence.
4) Anthenelli, R. M., Benowitz, N. L., West, R., St Aubin, L., McRae, T., Lawrence, D., ... & Evins, A. E. (2016). Neuropsychiatric safety and efficacy of varenicline, bupropion, and nicotine patch in smokers with and without psychiatric disorders (EAGLES): a double-blind, randomised, placebo-controlled clinical trial. The Lancet, 387(10037), 2507-2520.
5) US Food and Drug Administration. (2016). FDA Drug Safety Communication: FDA revises description of mental health side effects of the stop-smoking medicines Chantix (varenicline) and Zyban (bupropion) to reflect clinical trial findings. Accessed January, 31, 2019.
6) Correa, J. B., Lawrence, D., McKenna, B. S., Gaznick, N., Saccone, P. A., Dubrava, S., ... & Anthenelli, R. M. (2021). Psychiatric comorbidity and multimorbidity in the EAGLES trial: descriptive correlates and associations with neuropsychiatric adverse events, treatment adherence, and smoking cessation. Nicotine and Tobacco Research, 23(10), 1646-1655.