varenicline

General Information

Varenicline (brand Chantix; generics) is a smoking-cessation medication and a partial agonist at nicotinic acetylcholine receptors (α4β2) (label).

Evidence syntheses show varenicline improves quit rates compared with placebo and is among the most effective single-agent cessation pharmacotherapies (review).

In psychiatric care, a key practical point is that smoking cessation itself can change medication levels. Tobacco smoke induces CYP1A2, so stopping smoking can increase exposure to CYP1A2 substrates such as clozapine and olanzapine (clinical).

A large trial in smokers with and without psychiatric disorders found no significant increase in moderate-to-severe neuropsychiatric adverse events with varenicline compared with placebo, nicotine patch, or bupropion, while varenicline remained effective for cessation (trial).

The compare view, varenicline evidence feed, and varenicline print page support shared decision-making when quit attempts overlap with mood, sleep, and medication-level monitoring.

Often selected as a first-line cessation medication because of strong efficacy. Counseling frequently addresses nausea, sleep effects, and the need to monitor CYP1A2-substrate medications when smoking status changes.

Mechanism of Action

Refer to the Glossary entry on Neurotransmitters for background on receptor systems involved in serious mental illness.

Partial agonist at α4β2 nicotinic acetylcholine receptors. Partial agonism can reduce cravings/withdrawal while also blunting the reinforcing effects of nicotine from cigarettes (label/review).

Behavioral support improves outcomes and is commonly paired with pharmacotherapy (guideline/clinical).

• α4β2 nicotinic acetylcholine receptor partial agonism.

Metabolism and Pharmacokinetics

• Minimal metabolism; primarily excreted unchanged in urine (label).
• Dose adjustment is recommended in severe renal impairment (label).
• Not a significant CYP inducer or inhibitor; most “interaction” issues in psychiatric practice relate to smoking cessation itself (clinical).

Dosing and Administration

• Label dosing is typically started before the target quit date with a short titration to reduce nausea, then continued for a defined course (often 12 weeks) with behavioral support (label/guideline).
• Treatment duration can be extended in selected patients based on response and relapse risk (label/clinical).
• Dose adjustment is recommended in severe renal impairment (label).

Monitoring & Labs

• Track smoking status and document quit attempts, because medication doses for CYP1A2 substrates may need reassessment when smoking stops (clinical).
• Monitor nausea and sleep effects early; adjust the plan based on tolerability and functional impact (label/clinical).
• Monitor mood symptoms during cessation attempts, especially in people with active depression/anxiety or unstable psychiatric illness (clinical).
• Renal function assessment is commonly used when comorbidity is present or when severe impairment is suspected (label/clinical).

Distinguishing nicotine-withdrawal symptoms from medication effects can prevent unnecessary discontinuation of effective cessation therapy.

Adverse Effects

Interactions

• Few CYP-mediated interactions because varenicline has minimal metabolism; regimen review typically focuses on renal dosing and symptom overlap (label/clinical).
• Smoking cessation increases exposure to CYP1A2 substrates (for example, clozapine and olanzapine) due to reduced tobacco-smoke induction; this is driven by quitting rather than by varenicline itself (clinical).

Other Useful Information

• Cochrane reviews consistently rank varenicline among the most effective single-agent cessation pharmacotherapies (review).
• The EAGLES trial provides neuropsychiatric safety data in smokers with and without psychiatric disorders and supports use with appropriate clinical monitoring (trial).
• Combination strategies (for example, pairing cessation medications with behavioral counseling or, in selected cases, combining pharmacotherapies) can be considered when single-agent approaches are insufficient (guideline/clinical).
• In psychiatric practice, documenting cigarette use (and changes) helps avoid inadvertent toxicity from CYP1A2-substrate medication level increases after quitting (clinical).

References

1. Varenicline tablets prescribing information — DailyMed (2025)
2. Nicotine receptor partial agonists for smoking cessation — Cochrane Database of Systematic Reviews (2016)
3. 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 (2016)
4. Treating Tobacco Use and Dependence: 2008 Update — U.S. Department of Health and Human Services (2008)