The antidepressant that behaves differently from most others, including helping smokers quit
Bupropion, sold as Wellbutrin, works on norepinephrine and dopamine rather than serotonin. Unlike most antidepressants it usually does not cause sexual side effects, weight gain or drowsiness, and it doubles as a smoking-cessation aid. In 2023 it was the seventeenth most prescribed medicine in the United States.
Nariman Mehta invented the drug at Burroughs Wellcome in 1969, and it won US approval in 1985. Its original generic name, amfebutamone, was dropped in 2000. Chemically it is an aminoketone from the substituted cathinone family, relatives of the amphetamines. It blocks the reuptake of norepinephrine and dopamine and also antagonises nicotinic receptors, though its dopamine effect is weak and how much it matters clinically is disputed. It appears on the World Health Organization's List of Essential Medicines.
Evidence overall favours it over placebo for depression, with effectiveness similar to other antidepressants, though some meta-analyses find a small effect at most and some reviewers rate the evidence as low quality. Its profile is unusual: sexual side effects occur no more often than on placebo, most studies record weight loss rather than gain, and it outperforms SSRIs against the heavy fatigue and oversleeping some depressed patients experience. Contrary to a common belief, it does not worsen anxiety in anxious depression. In one trial for recurring seasonal affective disorder, 15% of people taking it had a major depressive episode over autumn and winter, compared with 27% on placebo.
As a smoking aid it eases nicotine cravings and withdrawal symptoms such as irritability. Courses typically last seven to twelve weeks, with the quit date about ten days in. Six months after treatment it raises the odds of quitting about 1.6-fold versus placebo, matching nicotine replacement but trailing varenicline, and abstinence fades from 37% at three months to 20% after a year. Combined with naltrexone it is approved for obesity, and with dextromethorphan as a faster-acting antidepressant, approved in 2022.
It carries a higher seizure risk than many antidepressants, especially the immediate-release version, and the FDA label rules it out for people with epilepsy or conditions like bulimia that lower the seizure threshold. Common side effects include dry mouth, nausea, insomnia and tremor, and it raises blood pressure. Its use for ADHD, apathy and other conditions rests on limited or low-quality evidence.
Source: Bupropion
