Bupropion is the only medication with both antidepressant properties and strong evidence for helping people quit smoking, and it remains a first-line prescription option alongside varenicline and nicotine replacement. Dedicated anti-anxiety drugs, by contrast, have mostly failed to prove themselves as quit aids in clinical trials. The relationship between anxiety and tobacco is more tangled than it first appears, though, and understanding which medications actually help, which sound promising but fall short, and what happens to your anxiety after you quit can reshape how you approach the process.
Bupropion and Why It Works
Bupropion (sold as Zyban for smoking cessation and Wellbutrin for depression) is one of two non-nicotine prescription drugs with robust trial evidence for helping people stop smoking. It works through a few different pathways: it weakly blocks the reuptake of dopamine and norepinephrine, and it also acts as an antagonist at nicotinic acetylcholine receptors, meaning it partially blocks the receptors that nicotine normally binds to.1PubMed. How does bupropion work as a smoking cessation aid? That combination means it both eases some of the mood disruption of withdrawal and makes cigarettes less satisfying if you do slip up.
Bupropion is not classified as an anxiolytic, and it was not designed to treat anxiety. But by stabilizing dopamine and norepinephrine levels during the withdrawal period, it can take the edge off the restlessness, irritability, and tension that drive many people back to cigarettes. Its dual identity as an antidepressant and a cessation aid is why it appears in nearly every clinical guideline for quitting. It is typically started a week or two before your quit date and continued for several months.
Why SSRIs Do Not Help You Quit
If bupropion works, you might reasonably expect other antidepressants to help too, especially the SSRIs that millions of people already take for anxiety and depression. Fluoxetine, sertraline, paroxetine, and their relatives are the backbone of modern anxiety treatment, so they seem like natural candidates. The evidence, however, is clear: SSRIs do not meaningfully improve quit rates. A Cochrane review covering the available trial data concluded that SSRIs offer no worthwhile increase in smoking cessation rates compared with existing treatments.2Cochrane Database of Systematic Reviews. Antidepressants for smoking cessation
This is a genuinely surprising result that tells you something about how nicotine withdrawal works. The anxiety and distress of quitting are not garden-variety anxiety that responds to serotonin modulation. They are driven more by the sudden absence of dopamine and norepinephrine signaling that nicotine previously propped up, along with the rebound activity at nicotinic receptors. SSRIs simply do not address those mechanisms. If you are already taking an SSRI for a diagnosed anxiety or depressive disorder, it is worth continuing during your quit attempt, but it will not substitute for a cessation-specific medication.
Nortriptyline as a Second-Line Option
Nortriptyline, an older tricyclic antidepressant, has shown real promise in smoking cessation trials. In a randomized trial, the nortriptyline group had a six-month sustained abstinence rate meaningfully higher than the placebo group. Perhaps more relevant for anxiety, the drug significantly reduced feelings of being anxious and tense within the first week after quitting, along with irritability, difficulty concentrating, restlessness, and insomnia.3JAMA Internal Medicine. A Randomized Trial of Nortriptyline for Smoking Cessation
The catch is side effects. In that same trial, adverse events were significantly higher in the nortriptyline group, leading about one in eleven participants to discontinue the drug. Reported problems included constipation, elevated heart rate, trouble urinating, and in one case a fainting episode that led to a broken bone. Because of this side-effect profile, nortriptyline is generally considered a second-line treatment, meaning clinicians reach for it when bupropion, varenicline, or nicotine replacement have not worked or are not suitable.4PubMed. Nortriptyline for smoking cessation: a review Still, for someone whose primary barrier to quitting is overwhelming withdrawal anxiety, it may be worth the tradeoff.
Buspirone, Benzodiazepines, and Other Anxiolytics
Given that anxiety is one of the most commonly reported withdrawal symptoms, it seems obvious to test actual anti-anxiety medications as quit aids. Researchers have done exactly that, and the results have been mostly disappointing. A Cochrane review looked at trials of the anxiolytics buspirone, diazepam, meprobamate, metoprolol, and oxprenolol. None showed strong evidence of helping smokers quit, though the confidence intervals were wide enough that an effect could not be completely ruled out either.5PubMed Central. Anxiolytics for smoking cessation
Buspirone, the non-benzodiazepine anxiolytic most often prescribed for generalized anxiety disorder, had an intriguing result in one trial: among participants with high baseline anxiety, it significantly boosted quit rates by the end of drug therapy. But a second trial failed to replicate that benefit.6Cochrane Database of Systematic Reviews. Anxiolytics for smoking cessation That pattern, a promising signal in one small study followed by a failure to reproduce, is common in cessation research and is a warning against reading too much into any single trial. Buspirone might help a specific subset of highly anxious smokers, but the data is too thin to recommend it broadly.
As for benzodiazepines like diazepam, they come with the obvious problem of dependence risk. Using one habit-forming substance to quit another is rarely the approach clinicians want to take, and the trial data does not even support it working. If you are already prescribed a benzodiazepine for an anxiety disorder, your doctor can help you weigh the risks and benefits of continuing it during a quit attempt, but no one should be starting a benzodiazepine specifically to stop smoking.
Beta-Blockers Are Not the Answer
Beta-blockers like propranolol are sometimes used off-label for performance anxiety and situational nerves, so they occasionally come up in conversations about managing withdrawal. A placebo-controlled trial tested propranolol in smokers trying to quit: out of 73 participants, only six managed to stop by the end of eight weeks, split evenly between the propranolol and placebo groups. There was no evidence of any helpful effect.7British Journal of Diseases of the Chest. Propranolol and giving up smoking Beta-blockers blunt the physical symptoms of anxiety, like a racing heart, but they do not address the neurochemical disruption that makes quitting so difficult.
Safety for People Who Already Have Anxiety Disorders
One of the most important questions for smokers with a diagnosed anxiety disorder is whether cessation medications are safe for them. For years, there were concerns that both varenicline and bupropion might worsen psychiatric symptoms, including anxiety, agitation, and suicidal thinking. The EAGLES trial, a large randomized study designed specifically to test this, provided reassuring answers.
Among participants with anxiety disorders, neither varenicline nor bupropion was associated with a significant increase in neuropsychiatric adverse events compared with nicotine patches or placebo.8PubMed Central. Neuropsychiatric Safety and Efficacy of Varenicline, Bupropion, and Nicotine Patch in Smokers With Psychotic, Anxiety, and Mood Disorders in the EAGLES Trial The same held true across subgroups with psychotic and mood disorders. In an analysis focused specifically on anxiety disorder subtypes, there were no significant differences in moderate-to-severe neuropsychiatric side effects by treatment group. Smokers with panic disorder were somewhat more likely to experience these events overall compared with non-psychiatric participants, but that elevated risk applied equally regardless of which treatment they were taking.9PubMed Central. Efficacy and safety of pharmacotherapies for smoking cessation in anxiety disorders: Subgroup analysis of the randomized active- and placebo-controlled EAGLES trial
The practical takeaway is that having an anxiety disorder should not disqualify you from using first-line cessation medications. The earlier FDA black-box warnings on varenicline, which frightened many clinicians away from prescribing it to psychiatric patients, were eventually removed after the EAGLES data came in. If your doctor is hesitant to prescribe cessation medications because of your anxiety history, pointing to this evidence can be useful.
The Self-Medication Trap
Many smokers with anxiety believe that cigarettes are managing their symptoms, and this belief is one of the biggest obstacles to quitting. The logic feels airtight: smoking calms you down, so losing cigarettes will make your anxiety worse. Research on self-medication tells a more complicated story. A longitudinal study found that people with anxiety disorders who used substances (including tobacco) to self-medicate had significantly higher odds of developing new substance use disorders, with adjusted odds ratios ranging from about 2.5 to nearly 5.10JAMA Psychiatry. Role of Self-medication in the Development of Comorbid Anxiety and Substance Use Disorders: A Longitudinal Investigation In other words, the “treatment” tends to deepen the problem rather than resolve it.
What nicotine actually does is create a cycle where each cigarette briefly relieves the withdrawal anxiety caused by the last one wearing off. The calming sensation is real, but it is solving a problem that nicotine itself created. This distinction matters because it means the anxiety you are afraid of experiencing after quitting is largely an artifact of dependence, not an unmasking of some underlying condition that smoking was keeping in check.
What Actually Happens to Anxiety After You Quit
Here is where the evidence gets genuinely encouraging. A study following smokers through four weeks of abstinence found no increase in anxiety after quitting. Instead, there was a significant decrease in anxiety starting in the first week of abstinence.11PubMed. What happens to anxiety levels on giving up smoking? And this is not an isolated finding. A systematic review and meta-analysis pooling data across multiple studies found that people who quit smoking experienced meaningful reductions in anxiety, depression, and stress compared with people who kept smoking.12BMJ. Change in mental health after smoking cessation: systematic review and meta-analysis
The size of the anxiety reduction was comparable to the effect you would expect from an anxiety treatment. That is a remarkable finding: quitting smoking, all by itself, functions as an anxiety intervention. The first few days can be rough, no question. But the trajectory is downward after that, and people who push through the initial withdrawal period typically report feeling less anxious than they did while smoking. This information alone can change the calculus for someone who has avoided quitting out of fear that their anxiety will spiral.
Anxiety Sensitivity and Tailored Approaches
Not all smokers experience anxiety the same way, and one of the most useful concepts in this area is anxiety sensitivity, the tendency to fear the sensations of anxiety themselves. Someone with high anxiety sensitivity does not just feel anxious; they feel anxious about feeling anxious. A racing heart makes them think something is medically wrong, shortness of breath triggers panic, and the general discomfort of withdrawal feels unbearable rather than merely unpleasant.
Research has identified anxiety sensitivity as a genuine risk factor for poor cessation outcomes. A study testing an integrated program that combined standard smoking cessation treatment with techniques specifically targeting anxiety sensitivity found that participants in the integrated program experienced significantly greater reductions in anxiety sensitivity. The reduction in anxiety sensitivity then mediated improvements in early abstinence, suggesting that treating the fear of anxiety symptoms is itself a meaningful lever for quitting.13PubMed Central. Effects of anxiety sensitivity reduction on smoking abstinence: An analysis from a panic prevention program
A related concept, distress tolerance (how well you handle uncomfortable experiences without trying to escape them), also appears to matter. Exploratory analyses have found that smokers with high distress tolerance benefited more from combination nicotine replacement therapy, suggesting that the ability to sit with discomfort amplifies the effectiveness of pharmacological support.14Nicotine & Tobacco Research. Anxiety Sensitivity and Distress Tolerance in Smokers: Relations With Tobacco Dependence, Withdrawal, and Quitting Success If you recognize yourself as someone who catastrophizes physical discomfort, asking your provider about cognitive-behavioral strategies alongside medication may be more productive than looking for a stronger pill.
Combining Medications and Behavioral Therapy
The most effective quit strategies tend to layer treatments rather than relying on any single one. Early trial data found that combining bupropion with a nicotine patch produced higher quit rates than the patch alone.15PubMed. Anxiolytics and antidepressants for smoking cessation More recent work in people with mental health conditions has shown that combining cognitive-behavioral therapy with dual pharmacotherapy, such as a nicotine patch plus bupropion or a patch plus nicotine gum, significantly improved outcomes. Both combinations roughly doubled the odds of success compared with less intensive approaches.16PubMed. Smoking Cessation Treatment for Patients With Mental Disorders Using CBT and Combined Pharmacotherapy
For someone with anxiety, the behavioral component is not optional padding. Cognitive-behavioral therapy can directly address the catastrophic thinking patterns that make withdrawal feel intolerable. It can help you distinguish between genuine anxiety disorder symptoms and normal, temporary withdrawal discomfort. And it can build the distress tolerance that, as noted above, seems to amplify how well medications work. Some treatment programs have started integrating anxiety-focused components directly into cessation counseling, and the early signals suggest this approach is more effective than treating smoking and anxiety as entirely separate problems.
Gender Differences in Response
There are hints that men and women respond differently to cessation medications, and that some non-nicotine drugs may be particularly helpful for women. Research has noted that certain non-nicotine-replacement medications may produce quit rates in women comparable to those in men, partially closing a gap that often appears with nicotine replacement alone. These gender differences appear to be amplified when treatment includes substantial behavioral counseling. However, some of the medications that may specifically benefit women, such as clonidine and naltrexone, carry side effects that limit their widespread use.17SpringerLink / CNS Drugs. Smoking cessation in women. Special considerations. This is an area where the evidence is suggestive rather than definitive, but it underscores the value of discussing your specific profile with a provider rather than assuming one standard approach will work.
Gabapentin and Early-Stage Research
Gabapentin, a medication most commonly prescribed for nerve pain and seizures, has attracted some interest as a possible cessation aid because of its effects on neurotransmitter systems involved in both anxiety and addiction. A preliminary open-label study tested gabapentin at 1,800 milligrams per day for eight weeks in smokers, looking for initial signals that it might help with abstinence.18Nicotine & Tobacco Research. Gabapentin for Smoking Cessation: A Preliminary Investigation of Efficacy A follow-up proof-of-concept study continued to explore the idea.19Nicotine & Tobacco Research. Gabapentin for smoking cessation
These are very early-stage investigations, the kind that establish whether further research is worth doing rather than proving a drug works. Gabapentin is not recommended for smoking cessation by any major guideline, and prescribing it off-label for this purpose would be getting well ahead of the evidence. That said, for smokers who have cycled through first-line options without success and whose withdrawal is dominated by anxiety and sleep disruption, it is the sort of drug a provider might consider on a case-by-case basis. The research pipeline here is thin, and it would be misleading to present gabapentin as an emerging solution rather than what it is: an early hypothesis being explored.
Herbal Anxiolytics and Animal Research
A small body of preclinical research has looked at whether herbal compounds with anxiolytic properties could ease nicotine withdrawal. One study in rats found that an extract of Semen Ziziphi Spinosae, a traditional Chinese medicinal seed, reduced anxiety-like behaviors during nicotine withdrawal and suppressed stress-related signaling in the brain’s amygdala.20Hindawi / PubMed Central. Aqueous Extract of Semen Ziziphi Spinosae Exerts Anxiolytic Effects during Nicotine Withdrawal via Improvement of Amygdaloid CRF/CRF1R Signaling The mechanism involved dampening corticotropin-releasing factor activity, part of the brain’s stress response system.
Results like these are interesting mechanistically but have not been tested in humans. The gap between a rat study showing reduced anxiety-like behavior and a clinically useful treatment for a person trying to quit smoking is enormous. Supplement sellers sometimes cite this kind of preclinical work to market products to smokers, which is premature at best. If you see a “natural anxiety relief for quitting smoking” product backed by references to animal studies, treat it with appropriate skepticism.