Long-Term Side Effects of Wellbutrin (Bupropion)
Bupropion is generally well-tolerated for long-term use with minimal chronic adverse effects, though patients require ongoing monitoring for seizure risk, blood pressure elevation, and neuropsychiatric symptoms. 1
Common Long-Term Side Effects
The most frequently reported side effects that may persist with chronic bupropion use include:
- Insomnia and sleep disturbances - This is the most common persistent side effect, though it often resolves or diminishes over time 2, 3
- Dry mouth - Occurs significantly more frequently than placebo and may persist long-term 2, 3
- Headache - Common but typically transient 3
- Constipation - May persist with chronic use 3
- Dizziness - Generally mild and often resolves 3
These common side effects are typically mild and often resolve without intervention, though dose reduction can be considered if they persist 2.
Serious Long-Term Risks Requiring Monitoring
Seizure Risk
The seizure risk remains approximately 0.1% (1 in 1,000) when the maximum dose of 450 mg/day is not exceeded and patients are appropriately screened. 4, 1, 5 This risk does not appear to increase with duration of treatment when dosing guidelines are followed 5, 6. The seizure threshold concern is dose-dependent, with risk increasing at doses above 450 mg/day 1, 5.
Cardiovascular Effects
- Hypertension - Blood pressure elevation can occur and may be severe, particularly when combined with nicotine replacement therapy 1
- Blood pressure should be monitored periodically throughout treatment, especially during the first 12 weeks 4
- Bupropion causes minimal cardiac conduction problems compared to tricyclic antidepressants and rarely causes orthostatic hypotension 5
Neuropsychiatric Effects
The FDA black box warning highlights increased risk of suicidal thoughts and behavior, particularly in patients under 24 years of age, which requires close monitoring especially during the first few months but also throughout treatment. 4, 1
Long-term neuropsychiatric monitoring should include:
- Changes in mood, behavior, or thinking 1
- Agitation, hostility, or aggression 1
- Worsening depression or anxiety 1
- Manic episodes in patients with bipolar disorder risk 1
These symptoms can emerge at any point during treatment, not just at initiation 1.
Favorable Long-Term Profile
Bupropion has several advantages for long-term use compared to other antidepressants:
- Minimal sexual dysfunction - Among the lowest rates of any antidepressant 7, 3
- Minimal weight gain - Unlike many antidepressants, weight gain is not a significant concern 3
- Low somnolence - Does not typically cause sedation or fatigue 3
- Minimal anticholinergic effects - Well-tolerated with fewer anticholinergic side effects than tricyclics 5
Special Populations and Long-Term Considerations
Hepatic and Renal Impairment
- Patients with moderate to severe hepatic impairment should not exceed 150 mg daily long-term 4, 8
- Those with moderate to severe renal impairment require a 50% dose reduction for chronic use 4, 8
Pregnancy and Breastfeeding
- Limited data suggest no major congenital malformations with long-term use, though small increases in specific cardiovascular defects have been reported 9
- Bupropion is present in breast milk at low levels; two case reports of seizures in breastfed infants warrant caution 9
Critical Safety Monitoring for Long-Term Use
Patients on chronic bupropion therapy require:
- Periodic blood pressure and heart rate monitoring 4
- Ongoing assessment for mood changes and suicidal ideation 1
- Avoidance of alcohol or careful monitoring if alcohol use changes, as abrupt alcohol cessation increases seizure risk 1
- Awareness that the maximum daily dose of 450 mg should never be exceeded 4, 1
Drug Interactions Relevant to Long-Term Use
- Never combine with MAOIs or use within 14 days of MAOI discontinuation 4, 8
- Bupropion inhibits CYP2D6, raising concern for drug interactions with chronic co-administration of other medications 7
- Avoid in patients taking tamoxifen due to potential interaction 4
Discontinuation Considerations
Patients should never stop bupropion abruptly without consulting their healthcare provider, as this can cause withdrawal symptoms. 1 However, bupropion has a relatively favorable discontinuation profile compared to SSRIs 7.