Wellbutrin: Effective Depression Relief with Low Sexual Side Effects
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Wellbutrin (bupropion hydrochloride) is a unique norepinephrine-dopamine reuptake inhibitor (NDRI) antidepressant medication approved for the treatment of major depressive disorder (MDD) and seasonal affective disorder (SAD). Unlike many conventional antidepressants that primarily target serotonin, Wellbutrin’s distinct mechanism offers a differentiated clinical profile, particularly noted for its minimal impact on sexual function and potential benefits for energy and motivation. This comprehensive product card provides detailed information for healthcare professionals regarding its appropriate use, dosing, safety profile, and clinical considerations.
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)
- Standard dosage strengths: 75 mg, 100 mg (IR); 100 mg, 150 mg, 200 mg (SR); 150 mg, 300 mg (XL)
Benefits
- Demonstrates efficacy comparable to SSRIs in treating major depressive disorder with a different side effect profile
- Associated with minimal sexual dysfunction compared to serotonin-based antidepressants
- May provide beneficial effects on energy, motivation, and concentration
- Does not typically cause weight gain and may be associated with modest weight loss
- Lower incidence of sedation compared to many other antidepressant classes
- Approved for both depression and smoking cessation, offering potential dual benefits
Common use
Wellbutrin is primarily prescribed for the management of major depressive disorder in adults. Its unique pharmacological profile makes it particularly suitable for patients who experience significant sexual side effects, weight gain, or fatigue with other antidepressants. It is also commonly used as an augmentation strategy when patients have had partial response to SSRIs or SNRIs. The extended-release formulation (XL) is additionally approved for the prevention of seasonal affective disorder. Off-label uses may include attention-deficit/hyperactivity disorder (ADHD) and bipolar depression, though these require careful clinical consideration and monitoring.
Dosage and direction
Dosing must be individualized based on patient response and tolerance. The recommended starting dose for Wellbutrin XL is 150 mg once daily in the morning. After at least 3 days, the dose may be increased to 300 mg once daily, which is the maximum recommended dose for most patients. The sustained-release formulation (SR) is typically initiated at 150 mg once daily, with possible increase to 150 mg twice daily after at least 3 days, with at least 8 hours between doses. Immediate-release tablets are usually administered three times daily, with at least 6 hours between doses. All formulations should be swallowed whole and not crushed, divided, or chewed. Dose escalation should be gradual to minimize the risk of seizure.
Precautions
Wellbutrin carries a boxed warning regarding the increased risk of suicidal thoughts and behaviors in children, adolescents, and young adults, particularly during initial treatment or dosage adjustments. Patients should be closely monitored for clinical worsening, suicidality, or unusual changes in behavior. The medication is associated with a dose-dependent risk of seizure (approximately 0.1% at 300 mg/day and 0.4% at 400 mg/day), which necessitates careful patient selection and adherence to recommended dosing guidelines. Caution is advised in patients with hepatic or renal impairment, requiring dosage adjustment. Blood pressure monitoring is recommended as hypertension has been reported. Abrupt discontinuation should generally be avoided.
Contraindications
Wellbutrin is contraindicated in patients with a seizure disorder or history of seizures. It should 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, and a 14-day washout period must be observed when switching between these medications. Hypersensitivity to bupropion or any component of the formulation prohibits use. The medication is not recommended for patients undergoing abrupt discontinuation of alcohol or sedatives.
Possible side effect
Common adverse reactions (≥5% and at least twice the rate of placebo) include dry mouth, nausea, insomnia, headache, dizziness, and constipation. Less frequently, patients may experience anxiety, agitation, tremor, sweating, tinnitus, and taste perception changes. The incidence of sexual dysfunction is notably lower than with SSRIs. Serious but rare side effects include seizures, allergic reactions, angle-closure glaucoma, and severe skin reactions. Psychiatric side effects such as anxiety, agitation, and rarely, psychosis or mania may occur, particularly in susceptible individuals.
Drug interaction
Wellbutrin is primarily metabolized by CYP2B6 and inhibits CYP2D6. Significant interactions may occur with MAOIs (contraindicated), other antidepressants, antipsychotics, beta-blockers, antiarrhythmics, and tamoxifen. Concomitant use with drugs that lower seizure threshold (other antidepressants, antipsychotics, corticosteroids, theophylline, etc.) requires caution. Alcohol consumption should be minimized due to increased seizure risk. Dose adjustment may be necessary when coadministered with strong CYP2B6 inhibitors (e.g., ticlopidine, clopidogrel) or inducters.
Missed dose
If a dose is missed, patients should take it as soon as they remember, 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 the twice-daily formulation (SR), if a dose is missed and remembered within a few hours of the scheduled time, it may be taken, but subsequent doses should maintain the minimum 8-hour interval. For the once-daily formulation (XL), the dose should be taken in the morning regardless of when remembered, but not if close to the next day’s dose.
Overdose
Wellbutrin overdose is characterized by seizures, sinus tachycardia, ECG changes (prolonged QRS, QTc), hallucinations, loss of consciousness, and cardiac arrest. Fatal outcomes have been reported, particularly with large overdoses. Management requires immediate medical attention with supportive care, including ECG monitoring for at least 48 hours. Seizures should be treated with benzodiazepines; barbiturates or phenytoin may be considered if seizures persist. Activated charcoal may be administered if presentation is early. There is no specific antidote; hemodialysis is not likely to be beneficial due to large volume of distribution.
Storage
Wellbutrin tablets should be stored at room temperature (20-25°C or 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. All antidepressants should be stored securely out of reach of children and pets to prevent accidental ingestion. Unused medication should be disposed of properly through medication take-back programs when available.
Disclaimer
This information is intended for healthcare professionals and should not replace clinical judgment. Prescribing decisions must be based on individual patient assessment, including consideration of contraindications, warnings, precautions, and potential adverse effects. Full prescribing information should be consulted before initiating therapy. Patients should be advised to read the medication guide provided with their prescription and to discuss any questions with their healthcare provider.
Reviews
Clinical studies demonstrate Wellbutrin’s efficacy in major depressive disorder with response rates comparable to SSRIs. Systematic reviews highlight its favorable sexual side effect profile and lower incidence of weight gain. Many clinicians report positive experiences using Wellbutrin either as monotherapy or as an augmentation strategy, particularly for patients experiencing SSRI-induced sexual dysfunction or fatigue. Patient-reported outcomes often note improvements in energy, motivation, and concentration. However, some patients report increased anxiety or insomnia, particularly during dose titration. The smoking cessation benefits are well-documented in the literature, with sustained abstinence rates approximately double that of placebo at one year.