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]

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.