Bupropion

Bupropion, formerly called amfebutamone, and sold under the brand name Wellbutrin among others, is an atypical antidepressant that is indicated in the treatment of major depressive disorder and seasonal affective disorder and to support smoking cessation. A norepinephrine–dopamine reuptake inhibitor (NDRI), it is also popular as an add-on medication in the cases of "incomplete response" to the first-line selective serotonin reuptake inhibitor (SSRI) antidepressant. Bupropion has several features that distinguish it from other antidepressants: It does not usually cause sexual dysfunction, it is not associated with weight gain and sleepiness, and it is more effective than SSRIs at improving symptoms of hypersomnia and fatigue. Bupropion, particularly the immediate-release formulation, carries a higher risk of seizure than many other antidepressants; hence, caution is recommended in patients with a history of seizure disorder. The medication is taken by mouth.

Common adverse effects of bupropion with the greatest difference from placebo are dry mouth, nausea, constipation, insomnia, anxiety, tremor, and excessive sweating. Raised blood pressure is notable. Rare but serious side effects include seizures, liver toxicity, psychosis, and risk of overdose. Bupropion use during pregnancy may be associated with increased likelihood of congenital heart defects.

Bupropion acts as a norepinephrine–dopamine reuptake inhibitor (NDRI) and a nicotinic receptor antagonist. However, its effects on dopamine are weak and clinical significance is contentious. Chemically, bupropion is an aminoketone that belongs to the class of substituted cathinones and more generally that of substituted amphetamines and substituted phenethylamines.

Bupropion was invented by Nariman Mehta, who worked at Burroughs Wellcome, in 1969. It was first approved for medical use in the United States in 1985. Bupropion was originally called by the generic name amfebutamone, before being renamed in 2000. In 2023, it was the seventeenth most commonly prescribed medication in the United States and the third most common antidepressant, with more than 30 million prescriptions. It is on the World Health Organization's List of Essential Medicines. In 2022, the US Food and Drug Administration (FDA) approved the combination dextromethorphan/bupropion to serve as a rapid-acting antidepressant in patients with major depressive disorder.

The evidence overall supports the effectiveness of bupropion over placebo for the treatment of depression. Some peer-reviewed studies suggest the quality of evidence is low. Some meta-analyses report that bupropion has an at-most small effect size for depression. One meta-analysis reported a large effect size. However, there were methodological limitations with this meta-analysis, including using a subset of only five trials for the effect size calculation, substantial variability in effect sizes between the selected trials—which led the authors to state that their findings in this area should be interpreted with "extreme caution"—and general lack of inclusion of unpublished trials in the meta-analysis. Unpublished trials are more likely to be negative in findings, and other meta-analyses have included unpublished trials. Evidence suggests that the effectiveness of bupropion for depression is similar to that of other antidepressants.

Over the autumn and winter months, bupropion prevents the development of depression in those who have recurring seasonal affective disorder: 15% of participants on bupropion experienced a major depressive episode vs. 27% of those on placebo. Bupropion also improves depression in bipolar disorder, with the efficacy and risk of an affective switch being similar to other antidepressants.

Bupropion has several features that distinguish it from other antidepressants: for instance, unlike the majority of antidepressants, it does not usually cause sexual dysfunction, and the occurrence of sexual side effects is not different from placebo. Bupropion treatment is not associated with weight gain; on the contrary, the majority of studies observed significant weight loss in bupropion-treated participants. Bupropion treatment also is not associated with the sleepiness that may be produced by other antidepressants. Bupropion is more effective than selective serotonin reuptake inhibitors (SSRIs) at improving symptoms of hypersomnia and fatigue in depressed patients. Bupropion is effective in the treatment of anxious depression and, contrary to common belief, does not exacerbate anxiety in this context. The effectiveness of bupropion for anxious depression is equivalent to that of SSRIs in the case of depression with low or moderate anxiety, whereas SSRIs show a modest effectiveness advantage in terms of response rates for depression with high anxiety.

The addition of bupropion to a prescribed SSRI is a common strategy when people do not respond to the SSRI, and it is supported by clinical trials. However, it appears to be inferior to the addition of atypical antipsychotic aripiprazole.^{[further explanation needed]}