Is varenicline (Chantix) appropriate for a patient with a history of major depressive disorder, anxiety, bipolar disorder, schizophrenia, suicidal thoughts, recent myocardial infarction or unstable angina, uncontrolled hypertension, severe arrhythmias, creatinine clearance <30 mL/min, or who is pregnant or breastfeeding?

Concerns for Starting Varenicline (Chantix)

Varenicline is safe and appropriate for most patients seeking smoking cessation, including those with stable psychiatric illness, but is absolutely contraindicated in patients with brain metastases or active seizure disorders and should be avoided in pregnancy, breastfeeding, and those with a history of serious hypersensitivity reactions to the drug. 1

Absolute Contraindications

• Brain metastases or active seizure disorder: Varenicline carries a rare but significant seizure risk and must be avoided in these patients 2, 1
• Known serious hypersensitivity or skin reactions to varenicline: This is an FDA-labeled contraindication 1
• Pregnancy and breastfeeding: Varenicline is not FDA-approved for use in these populations 3

Psychiatric Illness – Evidence Supports Safety

The landmark EAGLES trial (N=8,144) definitively demonstrated that varenicline does NOT increase neuropsychiatric adverse events compared to placebo or nicotine patch in patients with or without psychiatric disorders. 2

• In over 4,000 patients with diagnosed psychiatric disorders (including depression, anxiety, bipolar disorder, and schizophrenia), varenicline showed no significant increase in neuropsychiatric events relative to nicotine patch or placebo 2
• A 2015 systematic review and meta-analysis of 39 randomized controlled trials found no evidence that varenicline increases risk of suicide attempts, suicidal ideation, depression, or death 2
• A separate analysis of 8,027 patients from 17 placebo-controlled trials confirmed varenicline increased nausea (OR=3.69) but not rates of suicidal events, depression, or aggression/agitation 4
• Varenicline increased smoking cessation rates without exacerbating anxiety and depression symptoms in adults with stably treated current or past depression 2

Critical Monitoring Requirements for All Patients

Despite the reassuring trial data, immediate discontinuation is mandatory if any of the following emerge: worsening depression, suicidal ideation or behavior, agitation, anxiety/panic attacks, hostility, aggression, delusions, hallucinations, or homicidal ideation 1

• Patients and caregivers must be counseled to stop varenicline and contact a healthcare provider immediately if these symptoms occur 1
• Although smoking cessation itself can cause mood changes and nicotine withdrawal symptoms, some postmarketing neuropsychiatric events occurred in patients who continued to smoke while taking varenicline 1
• Ongoing monitoring and supportive care should continue until symptoms resolve, as symptoms may persist even after discontinuation in some cases 1

Cardiovascular Disease – Generally Safe with Caveats

Recent systematic reviews and meta-analyses of randomized controlled trial data have NOT identified a significant link between varenicline and increased risk of serious cardiovascular adverse events. 2

• A 2015 retrospective review of 164,766 individuals receiving smoking cessation pharmacotherapy found that varenicline posed no elevated risk of cardiovascular events compared with nicotine replacement therapy 2
• The NCCN panel considers varenicline to have a favorable risk/benefit ratio for cardiovascular patients, though patients with underlying cardiovascular disease may be at increased risk that must be balanced against the health benefits of smoking cessation 2, 1

Specific Cardiovascular Scenarios

• Recent myocardial infarction or unstable angina: While not an absolute contraindication, comprehensive cardiovascular risk assessment is warranted; the mortality benefit of smoking cessation typically outweighs theoretical medication risks 2, 1
• Uncontrolled hypertension: Not a contraindication; varenicline does not significantly affect blood pressure 2
• Severe arrhythmias: Requires individualized assessment, but no specific contraindication exists in FDA labeling 1

Renal Impairment

• Creatinine clearance <30 mL/min: Dose adjustment is required (specific dosing not detailed in provided evidence, but this is a recognized consideration rather than an absolute contraindication) 1

Alcohol Use – Important Interaction

• Postmarketing reports describe increased intoxicating effects of alcohol with varenicline, including unusual and sometimes aggressive behavior accompanied by amnesia 1
• Patients must be advised to reduce alcohol consumption while taking varenicline until they know whether it affects their alcohol tolerance 1
• Some neuropsychiatric adverse events may have been worsened by concomitant alcohol use 1

Other Safety Considerations

Accidental Injury Risk

• Postmarketing reports include traffic accidents and near-miss incidents attributed to somnolence, dizziness, loss of consciousness, or difficulty concentrating 1
• Patients should use caution when driving, operating machinery, or engaging in potentially hazardous activities until they know how varenicline affects them 1

Common Side Effects (Not Contraindications)

• Nausea occurs in 28-40% of patients, typically peaks in weeks 1-2, and diminishes over time; attributable discontinuation rates range from 0.6% to 7.6% 2, 5
• Insomnia (14%) and abnormal dreams (10-13%) are common but generally mild 2
• The recommended titration schedule (0.5 mg once daily for days 1-3,0.5 mg twice daily for days 4-7, then 1 mg twice daily) is specifically designed to minimize nausea 3

Clinical Decision Algorithm

1. Screen for absolute contraindications: brain metastases, active seizure disorder, serious hypersensitivity to varenicline, pregnancy, breastfeeding 1
2. If any absolute contraindication exists: Do NOT prescribe varenicline; use nicotine replacement therapy or bupropion instead 2
3. Assess psychiatric history: Take a baseline psychiatric and suicide risk assessment, but current evidence does NOT support withholding varenicline based solely on psychiatric history 3
4. Assess cardiovascular status: Weigh cardiovascular risk against the substantial mortality benefit of smoking cessation; varenicline is generally safe 2
5. Counsel on alcohol: Advise reduction in alcohol consumption during treatment 1
6. Educate patient and caregivers: Provide explicit instructions to stop varenicline immediately and contact provider if neuropsychiatric symptoms emerge 1
7. Schedule mandatory follow-up: First visit within 2-3 weeks of starting medication, then at 12 weeks, and every 12 weeks if therapy is extended 3
8. Combine with behavioral counseling: Varenicline must always be paired with at least four counseling sessions during the 12-week treatment period 3

Efficacy Context

Varenicline increases quit odds almost 3-fold compared to placebo (RR 2.24,95% CI 2.06-2.43) and outperforms both bupropion (RR 1.39) and single forms of nicotine replacement therapy (RR 1.25). 3

• Continuous abstinence rates at weeks 9-12 ranged from 43.9% to 65.4% with varenicline versus 17.6% with placebo 3
• At 52 weeks, abstinence rates were 23% with varenicline versus 10.3% with placebo 3
• The substantial efficacy advantage means that for most patients, the benefits of varenicline far outweigh the risks 2, 4