Can Combination NRT (Gum, Patch, and Lozenges) Cause Anxiety?
Combination nicotine replacement therapy does not cause anxiety and actually reduces anxiety symptoms during smoking cessation, particularly in highly dependent smokers. 1
Evidence for Anxiety Reduction with NRT
The relationship between NRT and anxiety is counterintuitive but well-established:
Nicotine lozenges significantly reduce anxiety symptoms in high-dependence smokers through the first 4 weeks of treatment, with the 4-mg dose showing consistent reductions versus placebo (P = 0.002-P = 0.049). 2
Oral nicotine forms have high-strength evidence for reducing total withdrawal discomfort, irritability, and anxiety during smoking cessation, based on systematic review of quality studies. 3
Anxiety decreases after smoking cessation, not increases—studies of lapse-free abstinent smokers show significant reduction in anxiety starting from the first week of abstinence, suggesting nicotine itself is an anxiogenic agent. 4
Mechanism: Withdrawal vs. Nicotine Effects
The key distinction is understanding what causes anxiety during quit attempts:
Nicotine withdrawal causes anxiety, not nicotine replacement. The withdrawal syndrome includes increased anxiety as a symptom, which peaks within 1-2 weeks of quitting. 5
Adequate NRT dosing prevents withdrawal-related anxiety by maintaining sufficient nicotine levels to suppress withdrawal symptoms. Blood nicotine levels from combination NRT remain significantly lower than from smoking, making toxicity rare. 5
Combination therapy (patch + short-acting NRT) is specifically designed to provide steady baseline nicotine levels (from patch) plus breakthrough relief for cravings and acute withdrawal symptoms (from gum/lozenges). 5
Clinical Application for Anxiety-Prone Patients
For patients with pre-existing anxiety disorders or concerns about anxiety:
Use combination NRT confidently—the 4-mg nicotine lozenge reduces all affective withdrawal symptoms including anxiety, irritability, difficulty concentrating, restlessness, and depressed mood through week 4 in high-dependence smokers. 2
Ensure adequate dosing: For smokers of ≥10 cigarettes/day, start with 21 mg/24-hour patch combined with 4 mg gum or lozenges (for those smoking within 30 minutes of waking) or 2 mg forms (for those smoking >30 minutes after waking). 5
Maintain therapy for minimum 12 weeks, as longer duration (>14 weeks) shows superior results and anxiety reduction is sustained through this period. 5
Important Caveats
Inadequate dosing is the primary pitfall—underdosing allows breakthrough withdrawal symptoms including anxiety. Ensure patients use sufficient nicotine doses to control withdrawal symptoms. 5
Premature discontinuation undermines anxiety benefits—encourage continued therapy even through brief slips, as the anxiety-reducing effects build over weeks. 5
Smoking itself causes anxiety long-term—while smokers may perceive cigarettes as anxiety-relieving, nicotine is actually an anxiogenic agent, and giving up smoking is rapidly followed by anxiety reduction. 4
Safety Profile
Combination NRT is completely safe with no increased cardiovascular or neuropsychiatric risk compared to single-form NRT or placebo. 1
No evidence of increased anxiety risk was found in large trials including patients with psychiatric disorders (n=4,116 in EAGLES trial), where varenicline and NRT showed no significant increase in neuropsychiatric events versus placebo. 1
Common side effects of NRT include local skin reactions, nausea, and sleep disturbances—but not anxiety or worsening of anxiety disorders. 5