Bupropion: A Leading Antidepressant for Depression and Smoking Cessation
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Bupropion is a widely prescribed antidepressant medication belonging to the class of aminoketones, distinct from commonly used SSRIs and SNRIs. It functions primarily as a norepinephrine–dopamine reuptake inhibitor (NDRI), offering a unique mechanism of action that avoids serotonin-related side effects such as sexual dysfunction or significant weight gain. Approved by the FDA for the treatment of major depressive disorder (MDD) and as an aid to smoking cessation, bupropion is valued for its favorable side effect profile and dual therapeutic benefits. Its efficacy, tolerability, and versatility make it a cornerstone in psychiatric and primary care practice.
Features
- Chemical class: Aminoketone
- Mechanism: Norepinephrine–dopamine reuptake inhibitor (NDRI)
- Available formulations: Immediate-release (IR), sustained-release (SR), extended-release (XL)
- Common brand names: Wellbutrin, Zyban, Aplenzin
- Half-life: Approximately 21 hours (XL formulation)
- Metabolism: Hepatic, primarily via CYP2B6
- Excretion: Renal (87%) and fecal (10%)
Benefits
- Effective relief from symptoms of major depressive disorder, including low mood, anhedonia, and fatigue.
- Supports smoking cessation by reducing nicotine cravings and withdrawal symptoms.
- Lower incidence of sexual dysfunction and weight gain compared to SSRIs.
- May improve focus and energy levels, beneficial for patients with comorbid ADHD or lethargy.
- Non-addictive profile with no associated abuse potential in clinical populations.
- Flexible dosing options (IR, SR, XL) to accommodate individual patient needs and tolerability.
Common use
Bupropion is primarily indicated for the treatment of major depressive disorder in adults. It is also FDA-approved as an aid to smoking cessation treatment. Off-label uses include attention-deficit/hyperactivity disorder (ADHD), seasonal affective disorder (SAD), and bipolar depression (with caution due to seizure risk). It is sometimes used adjunctively with other antidepressants to counteract sexual side effects or augment therapeutic response.
Dosage and direction
For major depressive disorder, the initial dose is typically 100 mg twice daily (IR), 150 mg once daily (SR), or 150 mg once daily (XL), with titration to a maximum of 450 mg per day (400 mg for SR) based on clinical response and tolerability. For smoking cessation, dosing usually begins at 150 mg once daily for 3 days, then increases to 150 mg twice daily (SR formulation), with treatment duration of 7–12 weeks. Administration should occur in the morning to minimize insomnia; doses should be swallowed whole and not crushed, chewed, or divided. Always follow prescribing clinician instructions.
Precautions
Patients should be monitored for emergence of anxiety, agitation, or insomnia. There is an increased risk of seizure, particularly in those with a history of seizure disorder, eating disorders, or abrupt alcohol/sedative withdrawal. Use caution in patients with hepatic or renal impairment; dose adjustment may be necessary. May elevate blood pressure; periodic monitoring recommended. Not recommended during pregnancy unless potential benefits outweigh risks. Avoid use in patients with uncontrolled hypertension or active brain tumors.
Contraindications
Bupropion is contraindicated in patients with a seizure disorder or history of seizures. It must not be used in individuals with a current or prior diagnosis of bulimia or anorexia nervosa due to elevated seizure risk. Concomitant use with monoamine oxidase inhibitors (MAOIs) is contraindicated; a 14-day washout period is required before initiation. Hypersensitivity to bupropion or any component of the formulation is also a contraindication.
Possible side effect
Common side effects include dry mouth, nausea, headache, insomnia, and tremor. Less frequently, patients may experience anxiety, dizziness, sweating, or tinnitus. Serious but rare adverse effects include seizures, hypertension, allergic reactions, angle-closure glaucoma, and hepatotoxicity. Any unusual mood changes, suicidal thoughts, or severe skin reactions should be reported immediately to a healthcare provider.
Drug interaction
Bupropion is a substrate of CYP2B6 and may interact with inhibitors (e.g., ticlopidine, clopidogrel) or inducers (e.g., ritonavir, carbamazepine) of this enzyme. Concomitant use with other dopaminergic or noradrenergic agents may increase the risk of hypertension or CNS stimulation. Avoid use with MAOIs. Caution is advised with drugs that lower seizure threshold (e.g., antipsychotics, antidepressants, tramadol). May increase levels of certain CYP2D6 substrates (e.g., venlafaxine, metoprolol).
Missed dose
If a dose is missed, it should be taken as soon as remembered unless it is close to the time of the next scheduled dose. In that case, skip the missed dose and resume the regular dosing schedule. Do not double the dose to make up for a missed one. Consistent daily administration is important for maintaining steady-state plasma concentrations.
Overdose
Symptoms of overdose may include seizures, hallucinations, tachycardia, and loss of consciousness. Fatal outcomes have been reported, often involving multiple drug ingestion. Management is supportive and may include airway protection, ECG monitoring, and benzodiazepines for seizure control. Gastric lavage or activated charcoal may be considered if presented early. Contact a poison control center or emergency department immediately.
Storage
Store at room temperature (20–25°C or 68–77°F) in a tightly closed container, away from light, moisture, and heat. Keep out of reach of children and pets. Do not use beyond the expiration date printed on the packaging.
Disclaimer
This information is intended for educational purposes only and is not a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or other qualified health provider with any questions you may have regarding a medical condition or medication. Do not disregard professional medical advice or delay in seeking it because of something you have read here.
Reviews
Clinical studies and meta-analyses consistently demonstrate bupropion’s efficacy in reducing depressive symptoms and aiding smoking cessation. Patient reports often highlight improved energy and mood with minimal sexual side effects. However, individual experiences vary; some report initial anxiety or sleep disturbances. Overall, it remains a well-regarded option within its indications.