Wellbutrin: Effective Depression Relief with Low Sexual Side Effects
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Wellbutrin (bupropion hydrochloride) is a norepinephrine-dopamine reuptake inhibitor (NDRI) antidepressant medication approved by the FDA for the treatment of major depressive disorder (MDD) and seasonal affective disorder (SAD). Unlike many conventional antidepressants that primarily target serotonin systems, Wellbutrin works through a unique mechanism that modulates norepinephrine and dopamine pathways, offering a distinct therapeutic profile. This makes it particularly valuable for patients who experience undesirable side effects with other antidepressant classes, especially those concerning sexual function, weight gain, or sedation. Clinicians frequently prescribe Wellbutrin both as monotherapy and as an augmentation strategy in treatment-resistant depression.
Features
- Active ingredient: Bupropion hydrochloride
- Available formulations: Immediate-release (IR), sustained-release (SR), and extended-release (XL) tablets
- Mechanism of action: Norepinephrine-dopamine reuptake inhibitor (NDRI)
- FDA-approved indications: Major depressive disorder (MDD), seasonal affective disorder (SAD), and smoking cessation (as Zyban)
- Non-serotonergic pharmacological profile
- Multiple strength options: 75 mg, 100 mg, 150 mg, 200 mg, 300 mg
Benefits
- Demonstrates efficacy comparable to SSRIs in treating major depressive disorder with a different side effect profile
- Minimal impact on sexual function compared to serotonergic antidepressants
- Generally weight-neutral or associated with modest weight loss rather than gain
- Lower incidence of sedation and somnolence, potentially improving daytime alertness
- Approved for smoking cessation support when marketed as Zyban
- May improve energy, motivation, and concentration in some patients
Common use
Wellbutrin is primarily prescribed for the management of major depressive disorder in adults. Its unique mechanism of action makes it particularly useful for patients who have not responded adequately to selective serotonin reuptake inhibitors (SSRIs) or serotonin-norepinephrine reuptake inhibitors (SNRIs). Clinicians often utilize Wellbutrin as an augmentation agent when partial response to first-line antidepressants occurs. The extended-release formulation (XL) is also approved for preventing seasonal affective disorder when initiated prior to the symptomatic season. Off-label uses include attention-deficit/hyperactivity disorder (ADHD), bipolar depression (with mood stabilizer), and sexual dysfunction induced by other antidepressants.
Dosage and direction
Dosing must be individualized based on clinical response and tolerability. For major depressive disorder, the initial recommended dose is 200 mg per day administered as 100 mg twice daily using the immediate-release formulation. After three days, this may be increased to 100 mg three times daily with at least 6 hours between doses. For the sustained-release formulation, the initial dose is 150 mg once daily in the morning, potentially increasing to 150 mg twice daily after at least three days, with doses separated by at least 8 hours. The extended-release formulation is typically initiated at 150 mg once daily in the morning, which may be increased to 300 mg once daily after several days if needed. The maximum recommended dose is 450 mg per day for immediate-release and 400 mg per day for sustained-release formulations. Tablets should be swallowed whole and not crushed, chewed, or divided.
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 during initial treatment and dose adjustments. Use with caution in patients with hepatic impairment, renal impairment, or substantial alcohol use. Abrupt discontinuation should be avoided; taper dose when discontinuing treatment. May lower seizure threshold; use caution in patients with history of seizure, head trauma, or concomitant medications that lower seizure threshold. May cause hypertension; monitor blood pressure regularly. Angle-closure glaucoma has been reported with antidepressant use.
Contraindications
Wellbutrin is contraindicated in patients with seizure disorder or history of seizures. It is contraindicated in patients with current or prior diagnosis of bulimia or anorexia nervosa due to increased seizure risk. Concurrent administration with monoamine oxidase inhibitors (MAOIs) is contraindicated; at least 14 days should elapse between discontinuation of an MAOI and initiation of Wellbutrin. Hypersensitivity to bupropion or any component of the formulation is a contraindication. Should not be used in patients undergoing abrupt discontinuation of alcohol or sedatives.
Possible side effect
Common side effects (≥10%) include dry mouth, nausea, insomnia, dizziness, and headache. Less common side effects (1-10%) include constipation, anxiety, agitation, tremor, sweating, blurred vision, tachycardia, rash, and weight loss. Serious side effects requiring medical attention include seizures (dose-dependent risk), hypertension, allergic reactions, angle-closure glaucoma, hepatotoxicity, and neuropsychiatric symptoms including suicidal ideation. Sexual side effects are less common than with SSRIs but may include changes in libido.
Drug interaction
MAOIs: Contraindicated due to risk of hypertensive crisis. Medications that lower seizure threshold: Concurrent use with antipsychotics, antidepressants, tramadol, systemic corticosteroids, theophylline, or quinolones may increase seizure risk. CYP2B6 inhibitors: Drugs like ticlopidine and clopidogrel may increase bupropion exposure. CYP2D6 substrates: Bupropion may increase levels of drugs metabolized by CYP2D6 including antidepressants, antipsychotics, beta-blockers, and type 1C antiarrhythmics. Dopaminergic drugs: May have additive effects with levodopa and amantadine. Alcohol: May increase risk of neuropsychiatric events.
Missed dose
If a dose is missed, it should be taken as soon as remembered unless it is close to the time for the next scheduled dose. In that case, the missed dose should be skipped and the regular dosing schedule resumed. Patients should not take double or extra doses to make up for a missed dose. For twice-daily formulations, if remembered within 4 hours of the next dose, skip the missed dose. For once-daily formulations, if remembered within 8 hours of the next dose, skip the missed dose.
Overdose
Wellbutrin overdose may be associated with seizures, hallucinations, loss of consciousness, sinus tachycardia, and ECG changes including QTc prolongation. Fatal outcomes have been reported, particularly with large overdoses and in combination with other drugs. Multiple seizures occur in approximately one-third of overdose cases. Symptoms generally emerge within 4-8 hours of ingestion. Management includes cardiac monitoring for at least 48 hours, ECG monitoring, and supportive care. Activated charcoal may be considered if presented early. Seizures should be treated with benzodiazepines; status epilepticus may require additional anticonvulsants.
Storage
Store at room temperature (20-25°C or 68-77°F); excursions permitted to 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 humid areas. 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 only be used under the supervision of a qualified healthcare provider. Individual results may vary. Patients should not make changes to their medication regimen without consulting their prescribing 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 SSRIs. In a 8-week randomized controlled trial, Wellbutrin SR 150-400 mg/day demonstrated significant improvement in Hamilton Depression Rating Scale scores compared to placebo. Patient-reported outcomes often highlight improved energy levels and minimal sexual side effects compared to other antidepressants. Many reviews note particular benefit for patients who experienced weight gain or sexual dysfunction with SSRIs. Some patients report initial side effects including insomnia and anxiety that often diminish with continued treatment. Overall satisfaction rates are generally high, particularly among patients who value the activating properties and weight-neutral profile of this medication.