Wellbutrin

Wellbutrin SR (bupropion hydrochloride) is a prescription antidepressant medication belonging to the aminoketone class, distinct from commonly prescribed SSRIs. It is specifically formulated with a sustained-release mechanism to provide consistent therapeutic levels of the active ingredient over a 12-hour period, supporting stable mood management. This medication is indicated for the treatment of major depressive disorder (MDD) and has also received approval for seasonal affective disorder (SAD). Its unique neurochemical profile, primarily acting as a norepinephrine-dopamine reuptake inhibitor (NDRI), offers a valuable alternative for patients who may not tolerate or respond adequately to serotonergic agents.

Features

• Active ingredient: Bupropion hydrochloride (150 mg per tablet)
• Formulation: Sustained-release (SR) oral tablets
• Pharmacologic class: Aminoketone antidepressant, norepinephrine-dopamine reuptake inhibitor (NDRI)
• Dosing frequency: Typically twice daily, approximately 8 hours apart
• Bioavailability: Approximately 87% under fasting conditions
• Half-life: Average elimination half-life of 21 hours (± 9 hours)
• Metabolism: Hepatic, primarily via CYP2B6 isoenzyme
• Excretion: Renal (87%) and fecal (10%) as metabolites

Benefits

• Provides sustained, steady-state plasma concentrations for consistent antidepressant effect throughout the day
• Lower incidence of sexual dysfunction and weight gain compared to many SSRI antidepressants
• May improve energy levels, focus, and motivation in addition to mood elevation
• Does not typically cause sedation, making it suitable for daytime use
• May be particularly effective for patients with atypical depression featuring hypersomnia and fatigue
• Can be used as augmentation therapy in partial responders to other antidepressants

Common use

Wellbutrin SR is primarily indicated for the treatment of major depressive disorder (MDD) in adults. It is also FDA-approved for the prevention of seasonal affective disorder (SAD). Clinicians may sometimes prescribe it off-label for attention deficit hyperactivity disorder (ADHD), particularly when comorbid with depression, and as an aid for smoking cessation (though the XL formulation is specifically approved for this indication). The sustained-release formulation is particularly valuable for patients who require twice-daily dosing to maintain stable therapeutic levels while minimizing peak-trough fluctuations that can occur with immediate-release formulations.

Dosage and direction

The initial recommended dosage for Wellbutrin SR is 150 mg administered once daily in the morning. After at least 3 days, based on clinical response and tolerability, the dose may be increased to the target dose of 150 mg twice daily, with doses separated by at least 8 hours. The maximum recommended dose is 400 mg per day, given as 200 mg twice daily. Doses should be swallowed whole and not crushed, chewed, or divided, as this would compromise the sustained-release properties. Administration with food may decrease the incidence of gastrointestinal side effects. Dosage adjustments are necessary in patients with hepatic impairment, and the drug is not recommended in patients with severe hepatic cirrhosis.

Precautions

Patients should be monitored for emerging anxiety, agitation, panic attacks, insomnia, irritability, hostility, aggressiveness, impulsivity, akathisia, hypomania, and mania. Clinical worsening and suicide risk should be monitored, especially at the beginning of treatment and during dosage adjustments. Use cautiously in patients with a history of seizure disorder, cranial trauma, or other predisposition to seizures, as bupropion lowers the seizure threshold. Blood pressure monitoring is recommended, as hypertension has been reported. Hepatic and renal function should be assessed before initiation. Abrupt discontinuation should be avoided; gradual dose reduction is recommended.

Contraindications

Wellbutrin SR is contraindicated in patients with a seizure disorder or history of seizures. It must not be used in patients with a current or prior diagnosis of bulimia or anorexia nervosa due to increased seizure risk. Concomitant use with monoamine oxidase inhibitors (MAOIs) is contraindicated; at least 14 days should elapse between discontinuing an MAOI and initiating Wellbutrin SR. Hypersensitivity to bupropion or any component of the formulation prohibits use. The medication is also contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives (including benzodiazepines).

Possible side effect

Common adverse reactions (≥5% and at least twice the rate of placebo) include dry mouth, nausea, insomnia, dizziness, pharyngitis, constipation, agitation, anxiety, tremor, palpitations, sweating, tinnitus, and taste perception changes. Less frequently, patients may experience weight loss, blurred vision, urinary frequency, rash, and hypertension. Serious but rare side effects include seizures (approximately 0.1% at 300 mg/day and 0.4% at 400 mg/day), allergic reactions, angle-closure glaucoma, and severe skin reactions. Neuropsychiatric events and suicidal ideation have been reported, particularly in children and young adults.

Drug interaction

Wellbutrin SR exhibits significant interactions with drugs metabolized by CYP2D6 (e.g., antidepressants, antipsychotics, beta-blockers, type 1C antiarrhythmics). Concomitant use with other drugs that lower seizure threshold (e.g., antipsychotics, antidepressants, systemic corticosteroids) requires caution. MAOIs are absolutely contraindicated. Dopaminergic drugs may have synergistic effects. Alcohol consumption should be minimized or avoided. Caution is advised with levodopa and amantadine. Drugs that induce CYP2B6 (e.g., carbamazepine, phenobarbital, phenytoin) may decrease bupropion levels, while inhibitors (e.g., ticlopidine, clopidogrel) may increase them.

Missed dose

If a dose is missed, it should be taken as soon as remembered. However, if it is close to the time of the next scheduled dose, the missed dose should be skipped and the regular dosing schedule resumed. Patients should never take a double dose to make up for a missed one, as this significantly increases the risk of adverse effects, including seizures. Maintaining consistent dosing intervals of approximately 8 hours between the two daily doses is important for maintaining stable plasma concentrations and therapeutic effect.

Overdose

Bupropion overdose presents a medical emergency characterized by seizures, hallucinations, loss of consciousness, sinus tachycardia, and ECG changes (e.g., QRS prolongation). Fatal outcomes have been reported, particularly with large overdoses (over 10 grams) and in combination with other drugs. Management includes securing airway, cardiac monitoring, and ECG for at least 48 hours. Gastrointestinal decontamination may be considered if presentation is early. Seizures should be managed with benzodiazepines; barbiturates or phenytoin may be needed for refractory cases. There is no specific antidote; treatment is supportive and symptomatic.

Storage

Wellbutrin SR tablets should be stored at controlled room temperature, 20°-25°C (68°-77°F), with excursions permitted between 15°-30°C (59°-86°F). The medication must be kept in its original container, tightly closed, and protected from light and moisture. It should be stored out of reach of children and pets. Unused or expired medication should be disposed of properly through medication take-back programs or according to FDA-recommended disposal methods (mixing with unpalatable substance in sealed container), never flushed down the toilet unless specifically instructed.

Disclaimer

This information is for educational purposes only and does not constitute medical advice. Wellbutrin SR is available by prescription only and should be used under appropriate medical supervision. Individual patient responses may vary. Only a qualified healthcare provider can determine the appropriate treatment based on individual medical history, current condition, and complete evaluation. Patients should not initiate, adjust, or discontinue medication without consulting their prescribing physician.

Reviews

Clinical studies demonstrate Wellbutrin SR’s efficacy in major depressive disorder, with response rates significantly superior to placebo. Many patients report particular satisfaction with the lack of weight gain and sexual side effects compared to other antidepressants. Some note initial side effects such as insomnia or agitation that often diminish with continued use. The twice-daily dosing is generally well-accepted, though some patients prefer once-daily formulations for convenience. Overall, Wellbutrin SR represents an important therapeutic option in the antidepressant arsenal, particularly for patients who cannot tolerate or have not responded to SSRIs/SNRIs.