Wellbutrin SR (bupropion hydrochloride sustained-release) is a widely prescribed antidepressant belonging to the aminoketone class, 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 weight gain or sexual dysfunction. Clinically, it is indicated for the treatment of major depressive disorder (MDD) and seasonal affective disorder (SAD), and is also utilized as an aid to smoking cessation. Its sustained-release formulation ensures stable plasma concentrations, supporting consistent therapeutic effect with twice-daily dosing. This profile provides a comprehensive overview of its medical use, pharmacological properties, and essential safety information.

Features

• Active ingredient: Bupropion hydrochloride (150 mg or 100 mg per tablet)
• Pharmacologic class: Aminoketone; norepinephrine–dopamine reuptake inhibitor (NDRI)
• Formulation: Sustained-release (SR) oral tablets
• Dosing frequency: Twice daily (approximately 8 hours apart)
• Available strengths: 100 mg and 150 mg
• Half-life: Approximately 21 hours (± 9 hours)
• Bioavailability: Approximately 87% relative to immediate-release formulation
• Metabolism: Hepatic, primarily via CYP2B6
• Excretion: Renal (87%) and fecal (10%)

Benefits

• Reduces symptoms of major depressive disorder, including low mood, anhedonia, and fatigue, through dual enhancement of norepinephrine and dopamine activity.
• Avoids serotonin-mediated adverse effects such as weight gain and sexual dysfunction, offering a favorable side effect profile for many patients.
• Supports smoking cessation by reducing nicotine cravings and withdrawal symptoms.
• Sustained-release technology maintains consistent drug levels, improving adherence and minimizing peak-trough fluctuations.
• May improve energy, focus, and motivation in certain individuals due to its dopaminergic activity.
• Not associated with significant sedation, making it suitable for daytime use.

Common use

Wellbutrin SR is primarily indicated for the treatment of major depressive disorder (MDD) in adults. It is also approved for the prevention of seasonal affective disorder (SAD) and as an aid to smoking cessation treatment. Off-label uses may include attention-deficit/hyperactivity disorder (ADHD), bipolar depression (with caution due to seizure risk), and augmentation in treatment-resistant depression. It is not indicated for generalized anxiety disorder and may exacerbate anxiety in some individuals.

Dosage and direction

The recommended starting dose for Wellbutrin SR in the treatment of MDD is 150 mg once daily in the morning. After at least 3 days, the dose may be increased to 150 mg twice daily, with at least 8 hours between doses. The maximum recommended dose is 400 mg per day, given as 200 mg twice daily. For smoking cessation, dosing begins with 150 mg once daily for 3 days, then increases to 150 mg twice daily. Doses should be swallowed whole and not crushed, chewed, or divided. Administration with food may reduce gastrointestinal irritation.

Precautions

Patients should be monitored for emergence of anxiety, agitation, panic attacks, insomnia, irritability, hostility, impulsivity, akathisia, hypomania, and mania. Clinical worsening and suicide risk should be assessed, especially at treatment initiation and during dosage adjustments. Use with caution in patients with a history of seizure disorder, cranial trauma, or conditions that lower seizure threshold (e.g., eating disorders, alcohol withdrawal). May cause elevated blood pressure; periodic monitoring is advised. Hepatic or renal impairment requires dosage adjustment. Avoid use in patients with angle-closure glaucoma. Not recommended during pregnancy unless potential benefit justifies potential risk.

Contraindications

Wellbutrin SR is contraindicated in patients with a seizure disorder; current or prior diagnosis of bulimia or anorexia nervosa; use of monoamine oxidase inhibitors (MAOIs) within the preceding 14 days; known hypersensitivity to bupropion or any component of the formulation; and patients undergoing abrupt discontinuation of alcohol or sedatives. Concomitant use with other bupropion-containing products is also contraindicated.

Possible side effect

Common adverse reactions (≥1%) include dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, tremor, agitation, anxiety, sweating, tinnitus, and taste disturbance. Less frequently, tachycardia, hypertension, rash, pruritus, urticaria, and weight loss may occur. Serious side effects include seizures (dose-dependent), angioedema, Stevens-Johnson syndrome, hallucinations, psychosis, confusion, and severe hypertension. Any unusual behavioral changes or suicidal ideation should be reported immediately.

Drug interaction

Wellbutrin SR interacts significantly with drugs metabolized by CYP2D6 (e.g., antidepressants, antipsychotics, beta-blockers, type 1C antiarrhythmics), potentially increasing their plasma levels. Concomitant use with MAOIs is contraindicated due to risk of hypertensive crisis. May lower seizure threshold when used with other agents that predispose to seizures (e.g., antipsychotics, antidepressants, systemic corticosteroids). Caution is advised with levodopa and amantadine. Alcohol consumption should be minimized due to increased risk of neuropsychiatric events.

Missed dose

If a dose is missed, it should be taken as soon as remembered unless it is nearly time for the next dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Doubling doses is not recommended due to increased risk of adverse effects, including seizure.

Overdose

Overdose may lead to seizures, hallucinations, loss of consciousness, sinus tachycardia, ECG changes (e.g., QRS prolongation), and hyperthermia. Fatal outcomes have been reported, often involving multiple drug ingestion. Management includes ECG monitoring, supportive care, and seizure control with benzodiazepines. Activated charcoal may be useful if administered early. Hemodialysis is not likely to be effective.

Storage

Store at 20°–25°C (68°–77°F); excursions permitted to 15°–30°C (59°–86°F). Keep in a tightly closed container, protected from light and moisture. Keep out of reach of children and pets. Dispose of unused medication via a drug take-back program or according to local regulations.

Disclaimer

This information is intended for educational purposes and does not replace professional medical advice, diagnosis, or treatment. Always consult a qualified healthcare provider before starting, changing, or discontinuing any medication. Individual response to therapy may vary. Not all uses or risks are discussed here.

Reviews

Clinical studies and post-marketing surveillance indicate that Wellbutrin SR is effective in reducing depressive symptoms with a side effect profile distinct from SSRIs. Many patients report improved energy and minimal weight gain. However, some experience insomnia, agitation, or dry mouth. Efficacy in smoking cessation is well-documented. Overall, it is considered a valuable option for MDD, particularly when serotonin-related side effects are a concern.