Bupropion (Wellbutrin)

What it treats

Bupropion is approved by the U.S. Food and Drug Administration to treat major depressive disorder and, in the extended-release form, to prevent seasonal affective disorder, a depression that follows the seasons and tends to return in the darker months. Under the brand name Zyban, it's also approved to help people stop smoking.

Prescribers also use it in ways the label doesn't formally list, which is called an off-label use, meaning a purpose evidence and practice support even though the label doesn't name it. The most common one is adding bupropion to an SSRI to counter sexual side effects or low energy. It's also sometimes used to help with attention.

How it works

Bupropion is not an SSRI. It's a norepinephrine-dopamine reuptake inhibitor, usually shortened to NDRI. Nerve cells in the brain pass messages using chemical messengers, and norepinephrine and dopamine are two of them. After a cell releases a messenger, it normally reabsorbs much of it, a process called reuptake. Bupropion slows the reuptake of norepinephrine and dopamine, so more of each stays available between cells.

Because it acts on different messengers than SSRIs do, its side-effect profile is different too. How that change eases depression isn't fully understood, and it's worth being honest about that. What is clear is that the early shift in signaling sets off slower adjustments in the brain over the following weeks. Those slower changes are thought to do the real work, which is part of why the medication takes time rather than working the day you start it.

What to expect

Common side effects, and which ones fade

Most people get some side effects. The common ones include:

• Dry mouth.
• Trouble sleeping.
• Headache.
• Nausea.
• Feeling jittery or restless, and anxiety.
• Tremor.
• Constipation.
• Increased sweating.
• Reduced appetite.

Bupropion tends to be activating rather than sedating, so wakefulness and restlessness are more common than drowsiness. Many of these early effects ease within a couple of weeks. If a side effect is severe, or it isn't improving after a few weeks, that's a conversation to have with the prescriber rather than a reason to stop on your own.

Serious side effects and warnings

Serious problems are uncommon, but a few are worth knowing.

Boxed warning. Like all antidepressants, bupropion carries an FDA boxed warning that it can increase suicidal thoughts and behaviors in children, teenagers, and young adults under 25, especially in the first weeks of treatment or after a dose change. This does not mean the medication harms most people. It means the early period deserves close attention, and that any worsening of mood, agitation, or new thoughts of self-harm should prompt contact with the prescriber promptly.

An earlier boxed warning about serious neuropsychiatric events, which applied when bupropion was used for smoking cessation, was removed by the FDA in 2016 after additional data, and the antidepressant warning above still applies.

• Seizure risk. This is the most important caution. Bupropion lowers the seizure threshold in a dose-related way, so the risk rises at higher doses and with rapid dose increases. It should not be used, meaning it's contraindicated, in people with a seizure disorder, in people with a current or past diagnosis of anorexia or bulimia, or in people stopping alcohol or sedatives abruptly. Daily-dose and single-dose limits exist specifically to keep this risk low.
• Increased blood pressure. Bupropion can raise blood pressure, and a prescriber may check it, especially if a nicotine patch is also being used.
• Worsened anxiety or insomnia. Because bupropion is activating, it can make anxiety or trouble sleeping worse.
• Allergic reactions. These are rare, but they need urgent care.

Sexual side effects

This is one area where bupropion has good news. Unlike SSRIs, it rarely causes sexual side effects. That's one reason it's sometimes chosen in the first place.

It's also why prescribers sometimes add bupropion alongside an SSRI, specifically to counter the sexual side effects the SSRI is causing. No medication is free of trade-offs, but on this measure bupropion is usually an easier one.

Weight, appetite, and sleep

Bupropion is usually weight-neutral or linked with mild weight loss rather than weight gain, and it can reduce appetite. That sets it apart from several other antidepressants.

It is activating, so it commonly causes trouble sleeping. For that reason it's taken earlier in the day, and the once-daily extended-release form is taken in the morning. Taking it late can disturb sleep.

Starting and dosing basics

This section is general background, not a dosing instruction for any individual. The right form and dose are a decision for a prescriber.

Bupropion comes in three forms: immediate-release, sustained-release taken twice a day, and extended-release taken once a day. The extended-release form is often started at 150 mg each morning and increased toward a target of 300 mg a day, with 450 mg the usual maximum. Doses are spaced out and capped specifically to keep seizure risk low, and bupropion isn't taken late in the day because it can disturb sleep.

Missed doses and interactions

If you miss a dose, the general guidance is to take it when you remember, unless it is almost time for the next dose. In that case, skip the missed dose and carry on. Never take two doses close together. That matters here in particular, because a single large dose raises seizure risk.

Several interactions matter. Bupropion must not be combined with MAOI antidepressants, and a gap is needed when switching between them. Other medicines or conditions that lower the seizure threshold add to the seizure risk. Bupropion also changes how the body processes some other medications, because it blocks a liver enzyme, which can raise the levels of certain drugs. For that reason the prescriber and pharmacist need a complete list of your medications and supplements, including over-the-counter ones.

Alcohol is best limited or avoided. Importantly, suddenly stopping heavy alcohol or sedative use while on bupropion raises seizure risk, and that's a situation where bupropion should not be used at all.

Stopping and tapering

Because bupropion doesn't act on serotonin, the classic SSRI discontinuation syndrome, the "brain zaps" and flu-like feelings many people describe, is much less of an issue. Stopping is generally easier than with an SSRI.

Even so, it's best done with a prescriber, and a gradual reduction is reasonable. Deciding to stop because you feel better is understandable, and sometimes it is the right call, but it is still worth doing with guidance.

Pregnancy and breastfeeding

This is an area where individual circumstances matter and the decision belongs with a clinician. Untreated depression carries its own risks during pregnancy. Bupropion passes into breast milk. The safety data are somewhat more limited than for some SSRIs, which is one factor a clinician weighs. None of that adds up to one answer that fits everyone. Anyone who is pregnant, planning a pregnancy, or breastfeeding should talk it through with their prescriber so the specific risks and benefits can be weighed for their situation.

Cost and generic availability

Bupropion has been available as a generic for many years and is inexpensive. The brand name Wellbutrin and generic bupropion contain the same active medication and work the same way. Most insurance plans cover it, and for people paying out of pocket, generic bupropion is among the lower-cost antidepressants.

Common questions

How long until bupropion works? Some early effects on energy can show within the first couple of weeks. The fuller effect on mood usually takes four to six weeks, sometimes up to eight.

Is bupropion addictive? No, not in the usual sense. It doesn't cause cravings or compulsive use. In fact, bupropion is also used to help people stop smoking.

Can I drink alcohol while taking it? Alcohol is best limited or avoided. And bupropion should not be used while abruptly stopping heavy drinking, because that raises seizure risk.

Will it cause weight gain? Usually not. Bupropion is often weight-neutral or linked with slight weight loss, which sets it apart from several other antidepressants.

Does it cause sexual side effects? Usually not. Bupropion rarely affects sexual function, which is one reason it's sometimes prescribed.

Should I take it in the morning or at night? The morning, because bupropion is activating and taking it late can disturb sleep.

Questions to ask your prescriber

• What are we hoping this treats, and how will we know it's working?
• Which side effects should I expect early, and which ones should I call about?
• How long should I plan to take it?
• What's the plan if it doesn't help enough?
• If we decide to stop it later, how would we do that safely?

Sources

This guide draws on current prescribing information and public health references. It is reviewed for clinical accuracy and updated as guidance changes.

• U.S. Food and Drug Administration. Bupropion hydrochloride (Wellbutrin) prescribing information.
• MedlinePlus, U.S. National Library of Medicine. Bupropion.
• National Institute of Mental Health. Mental health medications.
• American Psychiatric Association. Practice guideline for the treatment of patients with major depressive disorder.