Wellbutrin: A Clinically Proven Antidepressant for Major Depressive Disorder
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Wellbutrin (bupropion hydrochloride) is a norepinephrine-dopamine reuptake inhibitor (NDRI) antidepressant medication with a distinct pharmacological profile from SSRIs. Approved by the FDA for the treatment of major depressive disorder (MDD) and seasonal affective disorder (SAD), it offers a valuable therapeutic option particularly for patients experiencing SSRI-associated sexual dysfunction or weight gain. Its mechanism of action involves the inhibition of neuronal reuptake of dopamine and norepinephrine, with minimal effect on serotonin reuptake, resulting in a unique side effect and efficacy profile. This makes it a first-line option for many clinicians and a commonly used agent in augmentation strategies.
Features
- Active ingredient: Bupropion hydrochloride
- Available formulations: Immediate-release (IR), sustained-release (SR), and extended-release (XL) tablets
- Standard dosage strengths: 75 mg, 100 mg, 150 mg, 200 mg, 300 mg
- Pregnancy category: C
- Half-life: Approximately 21 hours for Wellbutrin XL
- Excretion: Primarily renal
Benefits
- Effective reduction of depressive symptoms in major depressive disorder
- Lower incidence of sexual dysfunction compared to SSRI antidepressants
- Generally weight-neutral or associated with modest weight loss rather than gain
- May improve energy levels, focus, and motivation in some patients
- Approved for prevention of seasonal affective disorder (SAD)
- Used off-label for attention-deficit/hyperactivity disorder (ADHD) and smoking cessation
Common use
Wellbutrin is primarily prescribed for the treatment of major depressive disorder (MDD) in adults. It is also FDA-approved for the prevention of seasonal affective disorder (SAD). Off-label uses include augmentation in treatment-resistant depression, management of ADHD symptoms in adults, and as an aid in smoking cessation treatment (under the brand name Zyban). Its distinct mechanism of action makes it particularly useful for patients who cannot tolerate SSRI side effects, especially those related to sexual function and weight changes.
Dosage and direction
Dosing must be individualized based on clinical response and tolerance. The usual starting dose for Wellbutrin XL is 150 mg once daily in the morning. After at least 3 days, the dose may be increased to the maximum recommended dose of 300 mg once daily. For Wellbutrin SR, the initial dose is 150 mg once daily, with increase to 150 mg twice daily after at least 3 days, with at least 8 hours between doses. Maximum dose for SR formulation is 200 mg twice daily. Tablets should be swallowed whole and not crushed, divided, or chewed. Doses should be taken at the same time each day to maintain steady plasma concentrations.
Precautions
Patients should be monitored for worsening depression, suicidality, or unusual changes in behavior, particularly during initial treatment or dose adjustments. Use with caution in patients with hepatic or renal impairment, dose adjustment may be necessary. May lower seizure threshold; use with caution in patients with history of seizure, head trauma, or eating disorders. May cause hypertension; periodic blood pressure monitoring recommended. Use caution when driving or operating machinery until response is known. Avoid alcohol consumption during treatment. Not recommended for patients with bipolar disorder unless accompanied by mood stabilizer due to risk of inducing manic episodes.
Contraindications
Wellbutrin is contraindicated in patients with seizure disorder or history of seizures. Contraindicated in patients with current or prior diagnosis of bulimia or anorexia nervosa due to increased seizure risk. Should not be used concomitantly with monoamine oxidase inhibitors (MAOIs) or within 14 days of discontinuing MAOI treatment. Contraindicated in patients undergoing abrupt discontinuation of alcohol or sedatives. Not recommended for patients with known hypersensitivity to bupropion or any component of the formulation.
Possible side effects
Common side effects (≥1%) include dry mouth, nausea, insomnia, headache, dizziness, constipation, anxiety, and tremor. Less frequently, patients may experience sweating, rash, tinnitus, blurred vision, tachycardia, or weight changes. Serious side effects requiring immediate medical attention include seizures (risk approximately 0.4% at 300 mg/day), allergic reactions, hypertension, angle-closure glaucoma, and psychiatric symptoms such as hallucinations or paranoia. The incidence of sexual dysfunction is notably lower than with SSRIs.
Drug interaction
Significant interactions occur with MAOIs (risk of hypertensive crisis); minimum 14-day washout period required. May interact with drugs that lower seizure threshold (antipsychotics, antidepressants, tramadol, etc.). CYP2B6 inhibitors (e.g., ticlopidine, clopidogrel) may increase bupropion levels. Bupropion inhibits CYP2D6 and may increase levels of drugs metabolized by this enzyme (beta-blockers, antipsychotics, some antidepressants, etc.). Use caution with levodopa and amantadine. May potentiate effects of alcohol and sedatives.
Missed dose
If a dose is missed, take it as soon as remembered unless it is close to the next scheduled dose. Do not double the dose to make up for a missed dose. For twice-daily formulations (SR), if missed and remembered within 4 hours of next dose, skip missed dose. For once-daily formulations (XL), if remembered within 12 hours of next dose, skip missed dose. Maintaining regular dosing schedule is important for therapeutic effect.
Overdose
Overdose may lead to seizures, hallucinations, loss of consciousness, sinus tachycardia, and ECG changes including QRS prolongation. Fatal outcomes have been reported, particularly with mixed overdoses involving multiple drugs. Management includes gastric lavage if presented early, activated charcoal, and supportive care with continuous ECG monitoring. Seizures should be treated with benzodiazepines; status epilepticus may require additional anticonvulsants. There is no specific antidote for bupropion overdose.
Storage
Store at room temperature (20-25°C or 68-77°F), with excursions permitted between 15-30°C (59-86°F). Keep in original container, tightly closed, and protect from light and moisture. Keep out of reach of children and pets. Do not store in bathroom or other areas with high humidity. Properly dispose of expired or unused medication through medication take-back programs.
Disclaimer
This information is for educational purposes only and does not constitute medical advice. Wellbutrin is a prescription medication that should be used only under the supervision of a qualified healthcare provider. Individual response to medication may vary. Patients should not make changes to their treatment regimen without consulting their physician. The complete prescribing information should be consulted before initiating therapy.
Reviews
Clinical studies demonstrate Wellbutrin’s efficacy in major depressive disorder with response rates comparable to other antidepressants. In a 8-week randomized controlled trial, 150-300 mg/day of bupropion SR showed significant improvement in HAM-D scores compared to placebo. Patient reviews often highlight improved energy levels and minimal sexual side effects compared to other antidepressants. However, some reports note initial anxiety or insomnia during dose titration. Overall satisfaction rates are generally high, particularly among patients who previously experienced SSRI-related side effects.