nicotine

General Information

Nicotine replacement therapy (NRT) provides controlled nicotine delivery (patch, gum, lozenge, inhaler, nasal spray) to reduce nicotine withdrawal symptoms and cravings during smoking cessation (review/guideline).

Evidence syntheses show NRT improves quit rates compared with placebo/no pharmacotherapy, particularly when paired with behavioral support and structured follow-up (review/guideline).

In psychiatric care, smoking cessation itself can change medication levels because tobacco smoke induces CYP1A2; stopping smoke exposure can increase exposure to CYP1A2 substrates such as clozapine and olanzapine. This effect is driven by quitting smoking (not by nicotine) and applies when switching to NRT as well (clinical).

The EAGLES trial supports neuropsychiatric safety of nicotine patch in smokers with and without psychiatric disorders, with no significant increase in moderate-to-severe neuropsychiatric adverse events versus placebo (trial).

The compare view, nicotine evidence feed, and nicotine print page support shared decision-making when smoking cessation intersects with anxiety, sleep disruption, and medication-level monitoring.

Often used as a first-line smoking cessation pharmacotherapy, alone or in combination (patch + short-acting). Practical counseling often focuses on withdrawal symptom expectations, sleep effects, and monitoring of CYP1A2 substrate medications when smoking status changes (review/clinical).

Mechanism of Action

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

Nicotine is an agonist at nicotinic acetylcholine receptors. In NRT, controlled delivery reduces withdrawal symptoms and cravings while avoiding exposure to tobacco smoke toxins (review).

Nicotine is not the driver of tobacco-smoke CYP1A2 induction; switching from cigarettes to NRT still removes smoke exposure and can increase levels of CYP1A2 substrates (clinical).

• Nicotinic acetylcholine receptor agonism (review).

Metabolism and Pharmacokinetics

• Nicotine is primarily metabolized via CYP2A6 to cotinine and other metabolites; elimination is largely via urinary metabolites (review).
• Nicotine’s elimination half-life is on the order of ~2 hours, while cotinine persists longer and is commonly used as a biomarker of nicotine exposure (review).
• Transdermal delivery provides steadier nicotine exposure than cigarette smoking and can reduce peak/trough withdrawal swings (clinical/review).

Dosing and Administration

• Patch dosing is commonly step-down based on baseline cigarette use. For Nicoderm CQ, one labeled schedule is: >10 cigarettes/day: Step 1 (21 mg) weeks 1–6, Step 2 (14 mg) weeks 7–8, Step 3 (7 mg) weeks 9–10 (label).
• For ≤10 cigarettes/day, the label starts at Step 2 (14 mg) for 6 weeks, then Step 3 (7 mg) for 2 weeks (label).
• Patches are generally applied once daily and may be worn 16 or 24 hours depending on cravings and sleep tolerability (label/clinical).
• Short-acting NRT forms (gum/lozenge) are often used for breakthrough cravings; combination NRT (patch + short-acting) is commonly considered when cravings persist despite a patch alone (review/clinical).

Monitoring & Labs

• Track smoking status and withdrawal symptoms; ensure counseling support and troubleshoot adherence (clinical).
• Monitor sleep disturbance and adjust patch wear time (16h vs 24h) when insomnia or vivid dreams are problematic (label/clinical).
• If the patient takes CYP1A2 substrates (e.g., clozapine or olanzapine), plan follow-up for potential level increases after quitting smoking (clinical).

Many quit attempts require multiple cycles; documenting prior response and tolerability helps tailor future strategies (clinical).

Adverse Effects

Interactions

• Stopping tobacco smoke exposure (not nicotine) can increase exposure to CYP1A2 substrates such as clozapine and olanzapine; monitoring plans often start when smoking status changes (clinical).
• When combined with other cessation pharmacotherapies, regimen review often focuses on overlapping adverse effects (sleep disturbance, anxiety, nausea) and adherence (clinical).

Other Useful Information

• Cochrane evidence supports NRT effectiveness, and guidelines generally recommend combining pharmacotherapy with behavioral counseling for best outcomes (review/guideline).
• In psychiatric populations, careful follow-up can help distinguish withdrawal-related mood changes from adverse effects and supports safe monitoring of CYP1A2-substrate medications during quit attempts (clinical).

References

1. NICODERM CQ (nicotine) patch, extended release drug facts label — DailyMed (2025)
2. Nicotine replacement therapy versus control for smoking cessation — Cochrane Database of Systematic Reviews (2018)
3. Interventions for Tobacco Smoking Cessation in Adults, Including Pregnant Persons: US Preventive Services Task Force Recommendation Statement — JAMA (2021)
4. 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)
5. Nicotine chemistry, metabolism, kinetics and biomarkers — Handbook of Experimental Pharmacology (2009)