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Treatment terms

Bupropion

Shariq Refai, MD, MBA, board-certified psychiatrist and the reviewer of this article.

Reviewed by Shariq Refai, MD, MBA·Updated March 15, 2026·About 3 minutes

About this term

Quick definition
An atypical antidepressant that affects dopamine and norepinephrine signaling. Used for depression, and separately for smoking cessation and prevention of seasonal depressive episodes.
Full clinical definition
Bupropion inhibits the reuptake of norepinephrine and dopamine. It does not act significantly on serotonin. It is FDA approved for major depressive disorder, prevention of seasonal major depressive episodes (sustained-release and extended-release formulations), and, under separate brand and indication, smoking cessation. Available as immediate-release, sustained-release (SR), and extended-release (XL) formulations.
Epidemiology
Bupropion is among the most prescribed antidepressants in the United States. It is one of the most common second-line choices when an SSRI does not produce remission, and it is a frequent augmentation choice in the STAR*D trial sequence (Trivedi et al., 2006).
What it can feel like
For people who respond, energy and motivation often improve before mood. Many describe a clearer head and an easier start to the day within the first three to four weeks. Some people notice early activation that feels like jitteriness or insomnia, especially if the dose is started high or taken late in the day.
Why it is chosen
It is often chosen when low motivation, fatigue, and anhedonia dominate, or when sexual side effects from SSRIs or SNRIs are a concern. It is also a common choice when weight gain is a concern with other antidepressants. It does not generally cause sexual side effects and is weight-neutral or weight-reducing for many patients.
How clinicians assess response
PHQ-9 over six to eight weeks. Sleep, appetite, energy, and motivation are tracked alongside mood. Blood pressure is checked periodically because bupropion can produce small increases in some patients.
Common side effects
Insomnia, dry mouth, headache, agitation, decreased appetite, and tremor. Bupropion lowers the seizure threshold and is generally avoided in people with a history of seizures, eating disorders (anorexia nervosa or bulimia), or active heavy alcohol use. Risk of seizure is dose-related and is one reason maximum doses are firm.
Treatment implications
Bupropion is a first-line option in current APA guidelines, alone or as an augmenting agent. It is the most common first-line choice for prevention of winter-pattern seasonal depression and is started in early fall, before symptoms typically begin.
Related terms
Antidepressant. SSRI. SNRI. Seasonal depression. Medication management.
Related articles
Treatment. Antidepressant comparison. Seasonal depression (Types).

Sources

  • American Psychiatric Association. Practice Guideline for the Treatment of Patients with Major Depressive Disorder.
  • Trivedi MH, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D. Am J Psychiatry. 2006.
  • Modell JG, et al. Seasonal affective disorder and its prevention by anticipatory treatment with bupropion XL. Biol Psychiatry. 2005.

Frequently asked questions

What is bupropion?
Bupropion (Wellbutrin) is an antidepressant that acts on dopamine and norepinephrine rather than serotonin. It is FDA-approved for major depressive disorder, seasonal affective disorder, and (under the brand name Zyban) smoking cessation. It is often used when anhedonia, low motivation, or fatigue are prominent.
How is bupropion different from SSRIs?
Bupropion does not act on serotonin, so it tends not to cause the sexual side effects, weight gain, or emotional blunting that some patients have on SSRIs. It can be activating, which makes it useful for low energy but less suitable for patients with prominent anxiety or insomnia.
What are the most common bupropion side effects?
Common side effects include dry mouth, insomnia, headache, nausea, and a small rise in blood pressure. Anxiety or jitteriness can occur, especially early on. Bupropion is associated with a small dose-dependent increase in seizure risk, which is why it is avoided in patients with active eating disorders or a history of seizures.
Does bupropion cause weight gain?
No. Bupropion is one of the few antidepressants associated with weight loss rather than weight gain in clinical trials, particularly at the higher dose range. This is one reason it is sometimes preferred when weight is a concern.
Is bupropion safe with other antidepressants?
Bupropion is commonly added to an SSRI or SNRI when the first medication is not enough on its own (a strategy known as combination therapy). The combination is generally well tolerated, and bupropion can offset the sexual side effects of SSRIs. Combinations should be supervised by a prescriber.

Last reviewed March 15, 2026.

Every clinical page on DepressionResource.org is written in plain language, dated, and reviewed by a board-certified psychiatrist against current clinical guidelines. See our editorial standards and medical review process.