What are the dosage and potential side effects of Wellbutrin (bupropion)?

Wellbutrin (Bupropion) Dosing and Side Effects

Dosing Guidelines

For major depressive disorder, start bupropion SR at 150 mg once daily for 3 days, then increase to 150 mg twice daily (300 mg total daily), with a maximum dose of 400 mg/day for SR formulation or 450 mg/day for XL formulation. 1

Standard Dosing by Formulation

Bupropion SR (Sustained Release):

• Initial dose: 100-150 mg once daily 2, 1
• Maintenance dose: 150 mg twice daily (300 mg total) 2, 1
• Maximum dose: 400 mg per day 1
• Critical timing: Take the second dose before 3 PM to minimize insomnia risk 1, 3

Bupropion XL (Extended Release):

• Initial dose: 150 mg once daily in the morning 2, 1
• Maintenance dose: 150-300 mg once daily 2, 1
• Maximum dose: 450 mg per day 2, 1, 4
• Doses should be at least 24 hours apart 4

Smoking Cessation Dosing

Begin bupropion 1-2 weeks before the target quit date at 150 mg twice daily (300 mg total) for 7-12 weeks. 1

• This allows therapeutic drug levels to be established before cessation attempts 1
• Efficacy should be assessed after 7-12 weeks of treatment 1
• Particularly beneficial for patients with comorbid depression 1

Special Population Adjustments

Hepatic Impairment:

• Moderate to severe impairment (Child-Pugh 7-15): Maximum 150 mg every other day 4
• Mild impairment (Child-Pugh 5-6): Consider dose/frequency reduction 4
• Total daily dose should not exceed 150 mg 2, 3

Renal Impairment:

• Moderate to severe impairment (GFR <90 mL/min): Reduce total daily dose by half 2, 1, 3
• Bupropion and metabolites are cleared renally and may accumulate 1

Older Adults:

• Start with 37.5 mg every morning 1
• Increase gradually by 37.5 mg every 3 days as tolerated 1
• Maximum dose: 150 mg twice daily (300 mg total) 1
• Second dose must be before 3 PM to prevent sleep disturbances 1

Side Effects and Safety Concerns

Most Common Side Effects

The most common side effects include trouble sleeping, anxiety, stuffy nose, nausea, dry mouth, constipation, dizziness, and joint aches. 4

• Dry mouth is the most frequently reported side effect 5
• Insomnia can be minimized by avoiding late-day dosing 4
• Nervousness and agitation are common activating effects 6

Serious Safety Concerns

Seizure Risk (Most Critical):

• Seizure is the predominant concern with bupropion, occurring in approximately one-third of overdose cases 4
• Therapeutic dose seizure rate: 0.06-0.10% at doses up to 300 mg/day 7
• Maximum dose of 450 mg/day must not be exceeded to minimize seizure risk 1, 3, 4
• Doses of 2.7g and upward can lead to seizures, encephalopathy, and cardiovascular effects 8
• Seizure rate is comparable to other antidepressants when dosing guidelines are followed 7, 5, 9

Cardiovascular Effects:

• Elevated heart rate and blood pressure 2, 3
• 10 to 100 times less likely to cause cardiac conduction problems than tricyclic antidepressants 5
• Orthostatic hypotension is rare 5
• In overdose: sinus tachycardia, ECG changes, arrhythmias, bradycardia, cardiac failure 4

Neuropsychiatric Effects:

• Black box warning: Risk of suicidal thoughts/behaviors in patients under 24 years old 2, 3
• Agitation and excitement (most common reason for discontinuation at 9.1%) 9
• In overdose: hallucinations, loss of consciousness, mental status changes, clonus, myoclonus, hyperreflexia 4

Overdose Manifestations:

• Seizures, fever, muscle rigidity, rhabdomyolysis, hypotension, stupor, coma, respiratory failure 4
• Deaths have been reported with large overdoses 4
• No known antidotes; treatment is supportive care 4

Advantages Over Other Antidepressants

Bupropion has significantly lower rates of sexual adverse events compared to SSRIs like fluoxetine or sertraline. 3

• Minimal anticholinergic effects make it generally well tolerated 5
• May have lower cardiovascular event risk compared to venlafaxine 3
• Less likely to provoke mania than serotonergic antidepressants 6

Critical Contraindications

Absolute Contraindications:

• Seizure disorders or conditions that lower seizure threshold 2, 1, 3
• Eating disorders (bulimia, anorexia nervosa) due to increased seizure risk 1
• Current MAOI use or within 14 days of discontinuing MAOIs 2, 1, 3
• Uncontrolled hypertension 2, 1
• Concurrent use with tamoxifen 1

Administration Pearls

Critical Administration Rules:

• Swallow tablets whole; never chew, cut, or crush 4
• Crushing releases medication too quickly and increases seizure risk 4
• Can be taken with or without food 4
• If a dose is missed, skip it and take the next dose at the regular time—never double up 4
• The insoluble XL shell may appear intact in stool; this is normal 4

Monitoring Requirements:

• Monitor for neuropsychiatric adverse effects, especially in patients under 24 years 1
• Monitor blood pressure regularly 1
• Assess efficacy after 6-8 weeks at adequate dose 1
• Close monitoring required in renal/hepatic impairment for adverse reactions 1

Drug Interactions and Precautions

• Inhibits CYP2D6, raising concern for clinically relevant drug interactions 6
• Limit or avoid alcohol; sudden alcohol cessation may increase seizure risk 4
• May cause false-positive amphetamine result on urine drug screening 4
• Do not use with other bupropion-containing products (e.g., Zyban) 4

Pregnancy and Breastfeeding

• Does not appear associated with major congenital malformations, though data are limited 2
• Small absolute increase in left ventricular outflow tract obstruction and ventricular septal defects reported, but confounding by indication cannot be ruled out 2
• Present in breast milk at very low levels; two case reports of seizures in breastfed infants 2
• Overall recommendation: Caution is advised during breastfeeding 2