Usage
Bupropion is prescribed for:
- Major Depressive Disorder (MDD)
- Seasonal Affective Disorder (SAD)
- Smoking Cessation (as an aid)
- Off-label uses include Attention-Deficit/Hyperactivity Disorder (ADHD) and sometimes in combination with mood stabilizers in patients with both ADHD and Bipolar Disorder.
Pharmacological Classification: Aminoketone antidepressant, atypical antidepressant.
Mechanism of Action: Bupropion’s exact mechanism is not fully understood, but it is believed to work primarily through the inhibition of dopamine and norepinephrine reuptake, increasing their levels in the synaptic cleft. It also has some weak effect on serotonin reuptake inhibition and nicotinic acetylcholine receptor antagonism.
Alternate Names
International and Regional Variations: Amfebutamone (previous name)
Brand Names: Wellbutrin, Wellbutrin SR, Wellbutrin XL, Aplenzin, Zyban, Buproban, Forfivo XL
How It Works
Pharmacodynamics: Bupropion’s primary effect is to increase the levels of dopamine and norepinephrine, thereby improving mood, motivation, and energy levels. It also exhibits some nicotinic acetylcholine receptor antagonism, which may play a role in its effectiveness for smoking cessation.
Pharmacokinetics:
- Absorption: Well-absorbed orally, but the extent of absorption can be affected by food.
- Metabolism: Extensively metabolized in the liver, primarily by CYP2B6, to three active metabolites: hydroxybupropion, threohydrobupropion, and erythrohydrobupropion. These metabolites have longer half-lives than the parent drug and contribute to its clinical effects.
- Elimination: Primarily excreted in the urine, with small amounts eliminated in the feces.
- Half-life: Bupropion’s half-life is approximately 10-20 hours, depending on the formulation and metabolism. However, its active metabolites have significantly longer half-lives.
Mode of Action: Bupropion inhibits the dopamine transporter (DAT) and the norepinephrine transporter (NET), preventing their reuptake into the presynaptic neuron. This increases the concentration of these neurotransmitters in the synaptic cleft, leading to enhanced postsynaptic signaling. Bupropion also appears to be a non-competitive antagonist of nicotinic acetylcholine receptors, reducing cravings and withdrawal symptoms associated with nicotine dependence.
Receptor Binding/Enzyme Inhibition/Neurotransmitter Modulation: Primarily DAT and NET inhibition, with some weak nicotinic acetylcholine receptor antagonism. Weak effects on the serotonin transporter (SERT). Metabolism involves CYP2B6.
Dosage
Standard Dosage
Adults:
- Immediate-release (IR): Initial: 100 mg twice daily. Increase after 3 days to 100 mg three times daily. Maximum dose: 450 mg/day (single doses not to exceed 150 mg).
- Sustained-release (SR): Initial: 150 mg once daily. Increase after 3 days to 150 mg twice daily. Maximum dose: 400 mg/day (single doses not to exceed 200 mg).
- Extended-release (XL): Initial: 150 mg once daily. Increase after 4 days to 300 mg once daily. Maximum dose: 450 mg/day. A 450 mg XL formulation is available for patients already titrated to 300 mg/day of another formulation.
- Aplenzin (hydrobromide): Initial: 174 mg once daily. Increase after 7 days to 348 mg once daily. Maximum dose: 522 mg/day.
Children (off-label use for ADHD): Initial: 3 mg/kg/day in divided doses. Titrate gradually to a maximum of 6 mg/kg/day or 300 mg/day (whichever is less). Single doses should not exceed 150 mg. Monitor closely for side effects.
Special Cases:
- Elderly Patients: Start with a lower dose and titrate more slowly due to potential age-related changes in drug clearance.
- Patients with Renal Impairment: Reduce dose and/or frequency. 450 mg XL is not recommended.
- Patients with Hepatic Dysfunction: Reduce dose and/or frequency depending on severity. Consult product information for specific recommendations based on Child-Pugh score and formulation.
- Patients with Comorbid Conditions: Use with caution in patients with a history of seizures, eating disorders, or those undergoing abrupt discontinuation of alcohol or other CNS depressants.
Clinical Use Cases
Bupropion is not typically used in clinical settings like intubation, surgical procedures, mechanical ventilation, or the ICU. It is primarily used for the outpatient treatment of depression, SAD, and smoking cessation.
Dosage Adjustments
Dosage adjustments may be necessary based on individual patient factors such as:
- Renal or hepatic impairment
- Age
- Concomitant medications (especially CYP2B6 inhibitors/inducers)
- Tolerance and side effects
- Therapeutic response
Side Effects
Common Side Effects
- Dry mouth
- Insomnia
- Headache
- Nausea
- Constipation
- Dizziness
- Tremor
- Sweating
- Agitation
Rare but Serious Side Effects
- Seizures
- Suicidal thoughts and behaviors (especially in young adults)
- Allergic reactions (e.g., skin rash, itching, swelling)
- Hallucinations
- Delusions
- Mania
- Hypertension
- Arrhythmias
- Serotonin syndrome (if combined with serotonergic medications)
- Angle-closure glaucoma
Long-Term Effects
Long-term side effects are generally similar to the common side effects. There is a potential for weight changes (either gain or loss) with prolonged use.
Adverse Drug Reactions (ADR)
Serious ADRs include seizures, suicidal thoughts/behaviors, severe allergic reactions, serotonin syndrome, and neuropsychiatric symptoms.
Contraindications
- Seizure disorder
- Current or prior diagnosis of bulimia or anorexia nervosa
- Abrupt discontinuation of alcohol or sedatives (e.g., benzodiazepines, barbiturates)
- Concomitant use of Monoamine Oxidase Inhibitors (MAOIs)
Drug Interactions
- MAOIs: Risk of hypertensive crisis and other serious interactions.
- CYP2B6 inhibitors: Increased bupropion levels. Examples include ticlopidine, clopidogrel, and certain HIV protease inhibitors.
- CYP2B6 inducers: Decreased bupropion levels. Examples include carbamazepine, phenytoin, and rifampin.
- Other antidepressants (especially serotonergic): Increased risk of serotonin syndrome.
- Alcohol: Increased risk of seizures and other adverse effects.
- Levodopa and amantadine: Increased risk of adverse effects.
- Nicotine replacement therapy: May increase blood pressure.
Pregnancy and Breastfeeding
- Pregnancy Safety Category: C (according to older FDA classification). Limited data available, potential risks should be weighed against the benefits of treatment.
- Fetal Risks: Some studies have suggested a slightly increased risk of congenital heart defects, but further research is needed.
- Breastfeeding: Bupropion is excreted in breast milk. The risks to the infant should be considered.
Drug Profile Summary
- Mechanism of Action: Dopamine and norepinephrine reuptake inhibitor, nicotinic acetylcholine receptor antagonist.
- Side Effects: Common: Dry mouth, insomnia, headache, nausea. Serious: Seizures, suicidal thoughts, allergic reactions.
- Contraindications: Seizure disorder, bulimia/anorexia, abrupt discontinuation of alcohol/sedatives, MAOI use.
- Drug Interactions: MAOIs, CYP2B6 inhibitors/inducers, other antidepressants, alcohol, nicotine replacement.
- Pregnancy & Breastfeeding: Category C, potential fetal risks, excreted in breast milk.
- Dosage: See detailed dosage section above.
- Monitoring Parameters: Monitor for mood changes, suicidal ideation, blood pressure, heart rate, and signs of seizures. Periodic liver function tests may be considered.
Popular Combinations
Bupropion is sometimes combined with naltrexone (Contrave) for weight management or with dextromethorphan (Auvelity) for treatment resistant depression. Always consult updated therapeutic guidelines and the latest research for appropriate combinations.
Precautions
- General Precautions: Screen patients for history of seizures, eating disorders, bipolar disorder, and suicidal ideation. Monitor blood pressure and heart rate.
- Pregnant Women: Carefully assess risks and benefits.
- Breastfeeding Mothers: Monitor infant for side effects.
- Children & Elderly: Use with caution and adjust dose accordingly.
- Lifestyle Considerations: Advise patients to limit alcohol intake and avoid driving or operating machinery until they know how bupropion affects them.
FAQs (Frequently Asked Questions)
Q1: What is the recommended dosage for Bupropion?
A: Dosage varies depending on the formulation (IR, SR, XL, Aplenzin) and the indication. See the detailed dosage section above for specific recommendations.
Q2: What are the most common side effects of Bupropion?
A: Common side effects include dry mouth, insomnia, headache, nausea, constipation, dizziness, tremor, sweating, and agitation.
A: Seizures, suicidal thoughts/behaviors, severe allergic reactions (e.g., anaphylaxis), neuropsychiatric symptoms (e.g., hallucinations, delusions), serotonin syndrome (if combined with serotonergic medications).
Q4: Can Bupropion be used in patients with epilepsy?
A: No, bupropion is contraindicated in patients with a seizure disorder because it can lower the seizure threshold.
Q5: Can Bupropion be used during pregnancy?
A: Bupropion is Pregnancy Category C. Use only if the potential benefits outweigh the risks. Consult with a specialist and discuss alternative treatment options.
Q6: How does Bupropion interact with alcohol?
A: Concurrent alcohol use can increase the risk of seizures and other adverse effects. Patients should be advised to limit or avoid alcohol consumption while taking bupropion.
Q7: Can Bupropion be used with other antidepressants?
A: Combining bupropion with other antidepressants, especially serotonergic agents (e.g., SSRIs, SNRIs), can increase the risk of serotonin syndrome. Caution is advised, and careful monitoring is necessary if such combinations are used.
Q8: Does Bupropion cause weight gain?
A: Bupropion is less likely to cause weight gain than some other antidepressants. In some cases, it can even lead to weight loss. However, weight changes can vary among individuals.
Q9: How should Bupropion be discontinued?
A: Generally, it is recommended to gradually taper the dose of bupropion rather than abruptly discontinuing it, especially after prolonged use. This can help minimize potential withdrawal symptoms. A specific tapering schedule should be individualized based on patient factors and clinical judgement.
Q10: What should I monitor in patients taking Bupropion?
A: Monitor for mood changes, suicidal ideation, seizures, blood pressure, heart rate, and any signs of adverse effects. Periodic liver function tests may be appropriate in certain cases. Close monitoring is especially important during dose adjustments and in patients with pre-existing medical conditions.
