Bupropion (Wellbutrin, Zyban)

Class

Norepinephrine-Dopamine Reuptake Inhibitor (NDRI)

Mechanism

Inhibits norepinephrine and dopamine reuptake and acts as a noncompetitive antagonist at nicotinic acetylcholine receptors, enhancing catecholaminergic neurotransmission and aiding smoking cessation.

FDA-Approved Use

Major depressive disorder (MDD), seasonal affective disorder (SAD), smoking cessation (nicotine dependence)

Off-Label Use

Neuropathic pain, weight loss, attention deficit hyperactivity disorder (ADHD), migraine prophylaxis, methamphetamine dependence, selective serotonin reuptake inhibitor (SSRI)-associated sexual dysfunction, cognitive enhancement and fatigue in multiple sclerosis (MS), post-stroke apathy

Formulation

Immediate-release (IR), sustained-release (SR), extended-release (XL) tablets (75 mg, 100 mg, 150 mg, 200 mg)

Titration

150 mg p.o. daily (SR or XL), titrating as clinically appropriate

Dose Range

150–400 mg/day depending on formulation

Kinetics

Half-life ~21 hours; metabolized primarily via CYP2B6; steady state in ~8 days

Common AEs

Insomnia, headache, dry mouth, nausea, anxiety, tremor, weight loss

Serious/Rare AEs

Seizures (dose-dependent risk), hypertensive episodes, hypersensitivity reactions

Monitoring

Monitor for seizure risk factors, blood pressure, mood changes, and suicidality

Black Box Warning

Increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults with MDD and other psychiatric disorders

Considerations

Bupropion lowers the seizure threshold, particularly at higher doses, and is contraindicated in patients with seizure disorders or eating disorders such as bulimia nervosa and anorexia nervosa. It is generally activating and may benefit patients with fatigue or hypersomnia. It may enhance motivation and reduce fatigue in traumatic brain injury (TBI) or multiple sclerosis (MS) when seizure risk is low. In Parkinson’s disease (PD), bupropion can improve depressive symptoms but should be used cautiously due to potential interactions with dopaminergic medications. Elderly patients may require dose adjustments due to increased sensitivity to side effects such as insomnia or agitation.