Introduction
Bupropion is an atypical antidepressant medication belonging to the aminoketone class, chemically distinct from selective serotonin reuptake inhibitors (SSRIs), tricyclic antidepressants, and monoamine oxidase inhibitors. Initially approved by the FDA in 1985, it has since gained additional indications and remains widely used in clinical practice due to its unique pharmacological profile and favorable side effect characteristics.
Mechanism of Action
Bupropion functions primarily as a norepinephrine-dopamine reuptake inhibitor (NDRI). It weakly inhibits the reuptake of norepinephrine and dopamine without significantly affecting serotonin reuptake. The drug has minimal affinity for histaminergic, muscarinic, or adrenergic receptors, which accounts for its favorable side effect profile compared to many other antidepressants. Its antidepressant effects are believed to stem from enhanced dopaminergic and noradrenergic neurotransmission in key brain regions involved in mood regulation.
Indications
- Major depressive disorder (MDD)
- Seasonal affective disorder (SAD)
- Smoking cessation aid (as bupropion hydrochloride)
- Off-label uses: Attention-deficit/hyperactivity disorder (ADHD), bipolar depression (with caution), and sexual dysfunction associated with SSRIs
Dosage and Administration
Immediate-release (IR): 100 mg twice daily initially, increased to 100 mg three times daily after several days (maximum 450 mg/day) Sustained-release (SR): 150 mg once daily initially, increased to 150 mg twice daily after several days (maximum 400 mg/day) Extended-release (XL): 150 mg once daily initially, increased to 300 mg once daily after several days (maximum 450 mg/day) Special Populations:- Hepatic impairment: Reduce dose in patients with moderate to severe cirrhosis
- Renal impairment: Use with caution in patients with renal impairment
- Geriatric patients: Consider lower initial doses
- Pediatric patients: Not approved for depression treatment in children
Pharmacokinetics
Absorption: Well-absorbed orally but undergoes extensive first-pass metabolism Distribution: Volume of distribution approximately 20 L/kg; 84% protein-bound Metabolism: Extensive hepatic metabolism via CYP2B6 to active metabolites (hydroxybupropion, threohydrobupropion, erythrohydrobupropion) Elimination: Half-life of parent drug 10-14 hours (longer for XL formulation); primarily renal excretion (87%) with minor fecal eliminationContraindications
- Seizure disorder or history of seizures
- Current or prior diagnosis of bulimia or anorexia nervosa
- Abrupt discontinuation of alcohol or sedatives
- Use of monoamine oxidase inhibitors (MAOIs) within preceding 14 days
- Known hypersensitivity to bupropion or any component of the formulation
Warnings and Precautions
Boxed Warning: Increased risk of suicidal thinking and behavior in children, adolescents, and young adults with major depressive disorder and other psychiatric disorders Additional Warnings:- Seizure risk: Dose-dependent (0.1% at 300 mg/day, 0.4% at 400 mg/day)
- Hypertension: Monitor blood pressure regularly
- Psychiatric symptoms: May precipitate manic episodes in bipolar disorder
- Angle-closure glaucoma: Has been reported
- Hepatic impairment: Use with caution and consider dose reduction
Drug Interactions
Significant Interactions:- MAOIs: Risk of hypertensive crisis (contraindicated)
- CYP2B6 inhibitors (e.g., ticlopidine, clopidogrel): Increased bupropion levels
- CYP2B6 inducers: Decreased bupropion levels
- Drugs that lower seizure threshold: Additive risk
- Nicotine replacement therapy: Increased hypertension risk
- Antidepressants metabolized by CYP2D6: Bupropion may increase their levels
Adverse Effects
Common (≥10%): Dry mouth, nausea, insomnia, headache, constipation, dizziness Less Common (1-10%): Anxiety, agitation, tremor, sweating, tinnitus, taste disturbances Serious (<1%): Seizures, allergic reactions, hallucinations, suicidal ideation, hepatic dysfunction, hypertensionMonitoring Parameters
- Mental status and suicidal ideation (especially during initiation)
- Seizure activity
- Blood pressure (baseline and periodically during treatment)
- Hepatic and renal function (baseline and as clinically indicated)
- Therapeutic response and adverse effects
- Weight changes (may cause weight loss)
Patient Education
- Take exactly as prescribed; do not crush or chew extended-release formulations
- Avoid alcohol consumption during treatment
- Report any seizures, unusual behaviors, or suicidal thoughts immediately
- May cause insomnia; take morning doses early in the day
- Inform all healthcare providers about bupropion use before starting new medications
- Do not discontinue abruptly without medical supervision
- Smoking cessation: Continue counseling support alongside medication
- May affect ability to drive or operate machinery until response is known
References
1. FDA Prescribing Information: Wellbutrin (bupropion hydrochloride) 2. Stahl SM. Essential Psychopharmacology: Neuroscientific Basis and Practical Applications. 4th ed. Cambridge University Press; 2013. 3. Fava M, Rush AJ, Thase ME, et al. 15 years of clinical experience with bupropion HCl: from bupropion to bupropion SR to bupropion XL. Prim Care Companion J Clin Psychiatry. 2005;7(3):106-113. 4. Hughes JR, Stead LF, Hartmann-Boyce J, et al. Antidepressants for smoking cessation. Cochrane Database Syst Rev. 2014;(1):CD000031. 5. Jefferson JW, Pradko JF, Muir KT. Bupropion for major depressive disorder: Pharmacokinetic and formulation considerations. Clin Ther. 2005;27(11):1685-1695. 6. Wimbiscus M, Kostenko O, Malone D. Bupropion: chemistry, mechanism of action, and clinical characteristics. Expert Opin Drug Metab Toxicol. 2010;6(9):1139-1149.