Stop taking varenicline or bupropion and contact your prescriber immediately if you notice new agitation, hostility, aggressive behavior, depressed mood, or thoughts of suicide. Call 911 or go to the nearest emergency room for thoughts of self-harm that feel urgent. If you have a seizure while taking bupropion, do not take another dose, and tell your prescriber right away.
How Varenicline and Bupropion Help People Quit
Varenicline and bupropion are two prescription pills approved by the FDA to help adults quit smoking. Neither contains nicotine. Instead, each works on the brain in a different way to ease cravings and withdrawal, and a prescriber decides which one, if either, fits a person’s health history.
These are two of seven FDA-approved quit-smoking medicines. The other five are nicotine replacement products like the patch, gum, and lozenge. This article focuses on the two pill options and how they work in the body.
How Bupropion Works
Bupropion affects chemicals in the brain, and researchers have not fully mapped out exactly how it reduces the urge to smoke. What is established is its effect: it lowers cravings and eases some nicotine withdrawal symptoms. Bupropion was originally developed and is still used as an antidepressant, so a prescriber will ask about mental health history and any seizure history before prescribing it.
People usually start bupropion before their quit date, and a prescriber sets the exact schedule and timing. Only a licensed clinician should decide when to start, adjust, or stop this medicine.
How Varenicline Works
Varenicline works in two ways. First, it attaches to some of the same brain receptors that nicotine attaches to, which can ease withdrawal symptoms and the urge to smoke. Second, because varenicline is already occupying those receptors, nicotine from a cigarette has less room to attach and produce its usual effect. This can make smoking feel less rewarding, which may make it easier to stay quit.
As with bupropion, a prescriber sets the starting date and schedule for varenicline based on a person’s individual quit plan and health history.
Varenicline vs. Bupropion: Key Differences
Both medications are prescription-only, non-nicotine pills. Here is how they generally compare:
- Varenicline: Works directly on nicotine receptors in the brain; research reviews have found it somewhat more effective than bupropion for helping people stay smoke-free; a prescriber may watch kidney function more closely, since it can affect dosing.
- Bupropion: Works through broader brain chemistry effects tied to its antidepressant history; not recommended for people with a seizure history or certain eating disorder histories, since it can raise seizure risk; may be considered when a person also has symptoms of depression, under a clinician’s judgment.
- Shared ground: Both are typically started before the quit date on a schedule set by a prescriber, both can cause sleep-related side effects, and both carry a patient Medication Guide that explains risks in detail.
A prescriber is the right person to weigh these differences against an individual’s health history. If a prescribing platform is being used instead of an in-person visit, our Telehealth for Smoking Cessation guide explains what to check before signing up, including who is actually writing the prescription.
What Clinical Trials Show About Quit Rates
Research reviews, including analyses published by the Cochrane Library, have found that people taking varenicline are more likely to stay smoke-free at six months to a year compared with people taking a placebo, and that varenicline has outperformed bupropion in head-to-head comparisons in several trials. Bupropion has also been shown to work better than placebo, though the size of that effect is generally smaller than what has been reported for varenicline.
The FDA has also reviewed a large clinical trial confirming that stopping smoking with either medicine offers real health benefits that outweigh the medicines’ risks for most adults, which is part of why the agency removed its strongest warning label from both drugs in 2016.
Common Side Effects
Every medicine carries some risk of side effects, and a prescriber can explain how likely these are for a specific person.
- Nausea
- Trouble sleeping or unusual, vivid dreams
- Dry mouth or constipation
- Headache
- Changes in mood, behavior, or thinking (see the warning signs above)
Report any side effect that feels severe or unusual to a healthcare provider rather than waiting it out.
Groups That Need Extra Caution
A prescriber will weigh these factors carefully, and none of them automatically rule a medicine in or out:
- People currently being treated for depression, anxiety disorders, schizophrenia, or another mental illness, or with a past history of one
- People with a history of seizures or certain eating disorders (relevant mainly to bupropion)
- People with existing cardiovascular disease, since research has linked varenicline to a small increase in certain cardiovascular events in this group, alongside a clear quitting benefit
- People with significant kidney problems, which can affect how varenicline is dosed
- People who drink alcohol regularly, since varenicline may lower alcohol tolerance in some people
- People who are pregnant or breastfeeding
Readers managing a diagnosed lung condition alongside a quit attempt may also want to read our COPD & Respiratory Wellness guide for general context on how reduced lung function factors into a quit plan.
Questions to Ask Your Prescriber
- Which medicine, if either, fits my health history and current medications?
- When should I start it relative to my quit date?
- What side effects should prompt a call to your office versus emergency care?
- How long will I likely stay on this medicine?
- Can this be combined with nicotine replacement therapy or counseling support?
- What should I do if I miss a dose or want to stop early?
What the Evidence Doesn’t Tell Us
Research on these medicines is strongest for adults using them as studied in clinical trials, generally alongside behavioral counseling. Evidence is thinner for repeated courses after a medicine has failed once, for use far beyond the studied treatment length, and for some specific populations that were underrepresented in the major trials. This is general educational information, not personalized medical advice, and it does not diagnose any condition or recommend a specific treatment for any individual.
Frequently Asked Questions
Are varenicline and bupropion the same thing?
No. They are two different prescription medicines that work through different mechanisms in the brain, though both are non-nicotine pills used to support quitting smoking.
Do I need a prescription for these medicines?
Yes. Both varenicline and bupropion require a prescription from a licensed healthcare provider, unlike nicotine patches, gum, and lozenges, which are available over the counter.
Can I use one of these medicines with nicotine replacement therapy?
Some people combine a quit-smoking pill with nicotine replacement products, but this should only be done under a prescriber’s guidance based on an individual’s situation.
Is one of these medicines more effective than the other?
Research reviews have generally found varenicline somewhat more effective than bupropion for helping people stay smoke-free, but individual results vary, and a prescriber may still recommend bupropion based on a person’s health history.
Educational Disclaimer
This article provides general educational information about smoking cessation medications. It is not medical advice, does not diagnose or treat any condition, and is not a substitute for care from a licensed healthcare provider. Only a qualified clinician can decide whether varenicline or bupropion is appropriate, and how to start, adjust, or stop either medicine. See our full Medical Disclaimer for more detail, and our How We Review page for how we verify the sources behind articles like this one. If you are experiencing a mental health crisis or thoughts of suicide, call or text 988 in the United States for the Suicide & Crisis Lifeline.