Wellbutrin (bupropion) causes side effects in most people during the first few weeks, with dry mouth, insomnia, nausea, and headache being the most common. Most of these are mild and fade as your body adjusts, typically within a few days to a few weeks. But some effects are more serious and worth understanding before you start or while you’re taking it.
The Most Common Side Effects
In clinical trials of the sustained-release formulation at 300 mg per day, the side effects that showed up most often were headache (26%), dry mouth (17%), nausea (13%), and insomnia (11%). At 400 mg per day, those numbers climbed: dry mouth hit 24%, nausea 18%, and insomnia 16%. For context, people taking a placebo reported headache at 23%, so the headache risk is only slightly above baseline. Dry mouth and insomnia, on the other hand, occur at roughly two to three times the rate seen with placebo.
These side effects tend to be temporary, lasting anywhere from a few days to a few weeks as your body adjusts to the medication. Dry mouth often responds to staying hydrated or chewing sugar-free gum. Insomnia can sometimes be managed by taking your dose earlier in the day rather than in the afternoon or evening.
Anxiety and Restlessness in Early Weeks
Wellbutrin works differently from SSRIs. Instead of targeting serotonin, it increases the activity of dopamine and norepinephrine in the brain. That stimulating quality is part of why it helps with fatigue and low motivation, but it also means a substantial proportion of people experience increased restlessness, agitation, anxiety, or insomnia shortly after starting treatment. The drug’s manufacturer acknowledges this “activation” effect directly.
If you already deal with anxiety alongside depression, this is worth discussing with your prescriber before starting. For some people the agitation settles within the first couple of weeks. For others, it persists and signals that bupropion isn’t the right fit.
Lower Risk of Sexual Side Effects
One of the main reasons doctors prescribe Wellbutrin over other antidepressants is its sexual side effect profile. SSRIs like sertraline, escitalopram, and paroxetine are the most likely antidepressants to cause problems with desire, arousal, and orgasm, because they increase serotonin activity. Wellbutrin, which doesn’t significantly affect serotonin, consistently ranks among the antidepressants least likely to cause sexual dysfunction. For people who’ve experienced these issues on an SSRI, switching to or adding Wellbutrin is a common strategy.
Seizure Risk and Dose Limits
Seizures are the most well-known serious risk of Wellbutrin, and the risk is directly tied to dose. At 300 mg per day, the chance of a seizure in someone with no seizure history is roughly 1 in 1,000. At 450 mg per day (the maximum recommended dose), that jumps to about 1 in 250. This is why doctors rarely prescribe above 450 mg and why single doses are kept below a certain threshold.
Several conditions lower the seizure threshold further, making Wellbutrin more dangerous. The medication is strictly contraindicated if you have a seizure disorder, a current or past diagnosis of bulimia or anorexia nervosa (eating disorders significantly raise seizure risk with this drug), or if you’re going through abrupt withdrawal from alcohol, benzodiazepines, or barbiturates. These aren’t just cautions. They’re hard rules on the FDA label.
Blood Pressure Changes
Wellbutrin can raise blood pressure, sometimes enough to cause or worsen hypertension. The FDA label recommends checking blood pressure before starting treatment and monitoring it periodically while you’re on the medication. The risk increases if you’re also using nicotine replacement therapy (patches, gum, or lozenges), which is relevant since bupropion is also prescribed for smoking cessation under a different brand name.
In a small clinical trial of people with stable heart failure, 2 out of 36 patients had their existing high blood pressure worsen enough to require stopping the drug. If you already have high blood pressure or heart disease, regular monitoring matters more.
Suicidal Thoughts in Young Adults
Wellbutrin carries the same FDA boxed warning as all antidepressants regarding suicidal thoughts and behavior. This risk is highest in children, adolescents, and young adults ages 18 to 24. Pooled data from clinical trials shows 14 additional cases of suicidal thinking per 1,000 patients treated among those under 18, and 5 additional cases per 1,000 among those ages 18 to 24.
Beyond age 24, clinical trials have not shown an increased risk compared to placebo. In adults 65 and older, antidepressants were actually associated with a reduced risk. The critical period is the first few weeks after starting or after a dose change, which is when close monitoring by family, caregivers, or the prescriber is most important.
Who Should Not Take Wellbutrin
Beyond seizure disorders and eating disorders, Wellbutrin is contraindicated in a few other situations. You should not take it if you’ve used an MAOI (a specific older class of antidepressant) within the past 14 days, as the combination can cause dangerous spikes in blood pressure. It’s also contraindicated if you have a known allergy to bupropion or any inactive ingredient in the formulation.
The restriction around alcohol and sedative withdrawal is especially important to understand. If you drink heavily and plan to stop, or if you’re tapering off benzodiazepines, the withdrawal process itself lowers your seizure threshold. Adding Wellbutrin on top of that creates a compounding risk. Timing matters: this doesn’t mean you can never take Wellbutrin if you’ve had alcohol issues, but starting it during active withdrawal is dangerous.