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 or 450 mg/day for XL formulations. 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
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
- Doses should be at least 24 hours apart 3
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
- Standard dose: 150 mg twice daily of SR formulation 1
- Treatment duration: 7-12 weeks with efficacy assessed after this period 1
- This allows therapeutic drug levels to be established before cessation attempts 1
Special Population Adjustments
Older Adults:
- Start at 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 given before 3 PM 1
Hepatic Impairment:
- Moderate to severe (Child-Pugh 7-15): Maximum 150 mg every other day for XL formulation 3
- Moderate to severe: Do not exceed 150 mg daily total 1, 4
- Mild impairment (Child-Pugh 5-6): Consider reducing dose and/or frequency 3
Renal Impairment:
- Moderate to severe (GFR <90 mL/min): Reduce total daily dose by half 1, 4
- Bupropion and metabolites are cleared renally and may accumulate 1
Critical Safety Considerations and Side Effects
Seizure Risk - The Most Important Concern
The maximum dose of 450 mg/day must never be exceeded to minimize seizure risk, which is the most serious adverse effect of bupropion. 1, 3
- Seizure rate at therapeutic doses (≤300 mg/day): 0.06-0.10% 5
- Seizures occur in approximately one-third of overdose cases 3
- Doses of 2.7g and higher can lead to seizures, encephalopathy, and cardiovascular effects 6
Absolute Contraindications for Seizure Risk:
- History of seizures or seizure disorders 1, 4, 7
- Current or prior diagnosis of bulimia or anorexia nervosa (increased seizure risk) 1
- Brain metastases or conditions that lower seizure threshold 4
- Abrupt discontinuation of alcohol, benzodiazepines, barbiturates, or antiepileptic drugs 1
- Concurrent use with MAOIs or within 14 days of stopping MAOIs 1, 4
Common Side Effects
Most common adverse effects include:
- Dry mouth (most frequent) 3, 7
- Insomnia and trouble sleeping 3
- Nervousness and agitation 3
- Nausea 3
- Constipation 3
- Dizziness 3
- Feeling anxious 3
- Stuffy nose 3
- Joint aches 3
Cardiovascular Effects
Monitor blood pressure closely as bupropion can cause elevated heart rate and blood pressure; avoid in patients with uncontrolled hypertension. 2, 4
- Bupropion may have lower cardiovascular event risk compared to venlafaxine, though evidence is weak 4
- In overdose: sinus tachycardia, ECG changes including conduction disturbances or arrhythmias 3
- Severe overdose can lead to bradycardia, cardiac failure, and cardiac arrest 3
Neuropsychiatric Effects
Black box warning: Monitor for suicidal thoughts or behaviors, especially in patients under 24 years of age. 2, 4
- Increased motor activity and agitation/excitement reported 3
- In overdose: hallucinations, loss of consciousness, mental status changes, clonus, myoclonus, hyperreflexia 3
- Severe cases: fever, muscle rigidity, rhabdomyolysis, stupor, coma, respiratory failure 3
Advantages Over Other Antidepressants
Bupropion has significantly lower rates of sexual dysfunction compared to SSRIs, making it an excellent choice for patients concerned about sexual side effects. 4
- Minimal anticholinergic effects 7
- 10 to 100 times less likely to cause cardiac conduction problems than tricyclics 7
- Orthostatic hypotension is rare 7
- May be less likely to provoke mania than serotonergic antidepressants 8
Critical Administration Instructions
Swallow tablets whole - never chew, cut, or crush bupropion extended-release formulations, as this releases the drug too quickly and dramatically increases seizure risk. 3
- May take with or without food 3
- If a dose is missed, do not double up - wait for the next scheduled dose 3
- Allow 6-8 weeks at adequate dose before determining treatment response 1
- Tablets may have an odor - this is normal 3
- The insoluble shell may appear intact in stool 3
Drug Interactions and Contraindications
Absolute contraindications:
- Concurrent MAOI use or within 14 days of discontinuing MAOIs 1, 4
- Patients taking tamoxifen (bupropion may interfere with tamoxifen metabolism) 1
- Uncontrolled hypertension 2
Important interactions:
- Bupropion inhibits CYP2D6, raising concern for drug interactions 8
- Limit or avoid alcohol during treatment 3
- If you usually drink heavily, do not suddenly stop alcohol as this increases seizure risk 3
Overdose Management
In overdose, there is no antidote for bupropion - provide supportive care and contact Poison Control immediately at 1-800-222-1222. 3
- Overdoses up to 30 grams have been reported 3
- Deaths have occurred with large ingestions 3
- Seizures are the predominant concern in overdose 8
- Two cases of seizures in breastfed infants have been reported 2
Special Clinical Considerations
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; generally no adverse events except 2 case reports of seizures in breastfed infants 2
- Overall caution is advised during breastfeeding 2
Formulation Switching: