From the Guidelines
Wellbutrin (bupropion) works by primarily affecting dopamine and norepinephrine rather than serotonin, making it a unique antidepressant medication. The mechanism of action of Wellbutrin is distinct from most other antidepressants, which mainly target serotonin. According to the most recent and highest quality study available, 1, bupropion's efficacy as a cessation aid is also apparent, and it acts as an inhibitor of nicotinic acetylcholingeric receptors.
Key Points
- Wellbutrin is typically prescribed at starting doses of 150 mg once daily for 3-4 days, then increased to 150 mg twice daily if tolerated, with a maximum recommended dose of 450 mg daily, divided into multiple doses 2.
- Common side effects include insomnia, headache, dry mouth, nausea, and agitation, but unlike many antidepressants, Wellbutrin is less likely to cause sexual dysfunction or weight gain, making it a good option for patients concerned about these side effects 3.
- Wellbutrin should be avoided in patients with seizure disorders, eating disorders, or those undergoing abrupt alcohol or sedative withdrawal, as it can lower the seizure threshold, with a reported seizure risk of 0.1% among those receiving the drug for smoking cessation 4.
- The medication comes in immediate-release (taken three times daily), sustained-release (SR, taken twice daily), and extended-release (XL, taken once daily) formulations, and is also used for smoking cessation (under the brand name Zyban) and sometimes as an adjunct treatment for ADHD 1.
Important Considerations
- Bupropion may be particularly beneficial as a smoking cessation agent for persons with depression, and longer duration of bupropion treatment may help prevent relapse in those who have successfully quit 1.
- Recent systematic reviews of the data have found that serious neuropsychiatric adverse events were rarely associated with bupropion prescribed for smoking cessation, including studies of bupropion in patients with mental illness 1.
- A 2014 meta-analysis of 12 trials examining the combination of bupropion and NRT revealed a nonsignificant trend in improved cessation with the addition of NRT to bupropion 5.
Recommendation
Based on the most recent and highest quality evidence, Wellbutrin (bupropion) is a recommended treatment option for patients with depression, smoking cessation, and ADHD, due to its unique mechanism of action and relatively favorable side effect profile. However, it is essential to carefully consider the potential risks and benefits, particularly in patients with a history of seizure disorders or other comorbid conditions, and to closely monitor patients for adverse effects, as recommended by the American College of Physicians 2.
From the FDA Drug Label
The mechanism of action of bupropion is unknown, as is the case with other antidepressants. However, it is presumed that this action is mediated by noradrenergic and/or dopaminergic mechanisms. Bupropion is a relatively weak inhibitor of the neuronal uptake of norepinephrine and dopamine and does not inhibit monoamine oxidase or the reuptake of serotonin.
The mechanism of action of Wellbutrin (Bupropion) is unknown, but it is presumed to be mediated by noradrenergic and/or dopaminergic mechanisms. Key points about its mechanism include:
- Inhibition of norepinephrine and dopamine uptake: Bupropion is a relatively weak inhibitor of the neuronal uptake of these neurotransmitters.
- No inhibition of monoamine oxidase or serotonin reuptake: Bupropion does not affect these enzymes or the reuptake of serotonin 6.
From the Research
Mechanism of Action of Wellbutrin (Bupropion)
- The main mechanism of action of bupropion is believed to be via dopamine and noradrenalin reuptake inhibition 7.
- Bupropion acts as a selective norepinephrine and dopamine reuptake inhibitor (NDRI) 8.
- This mechanism of action is different from most antidepressants, which makes bupropion a valuable treatment option for major depressive disorder (MDD) 9.
Clinical Efficacy and Tolerability
- Bupropion has demonstrated efficacy in the treatment of MDD, seasonal affective disorder, and smoking cessation 7, 9.
- It has a favorable acceptability and tolerability profile, with minimal effects on sexual function and lower rates of somnolence, weight gain, and sedation compared to other antidepressants 9.
- Common side effects of bupropion include nausea, headache, tremor, and insomnia, while rare side effects may include delayed allergic reactions, such as urticaria and angioedema 10, 8.
Pharmacological Properties
- Bupropion is available in immediate-release (IR), sustained-release (SR), and extended-release (XL) formulations 8.
- It is a cytochrome P450 2D6 inhibitor, and care must be taken when coprescribing with drugs cleared by this enzyme or with drugs that lower seizure threshold 7.
- Bupropion overdose can lead to serious neurological and cardiovascular adverse effects, including seizures, encephalopathy, and cardiovascular effects 11.