A 30‑year‑old woman taking bupropion (Wellbutrin) 150 mg daily reports new‑onset excessive sweating; how should this be managed?

Bupropion-Associated Sweating: Management Approach

Excessive sweating is a recognized adverse effect of bupropion that occurs in approximately 5–14% of patients; first-line management is dose reduction to 150 mg once daily or switching to an alternative antidepressant with lower sweating risk, such as mirtazapine or nortriptyline. 1, 2, 3, 4

Understanding the Side Effect

Bupropion commonly causes sweating as a documented adverse reaction, appearing in FDA labeling and clinical trials at rates significantly higher than placebo when used at 300 mg/day. 2 This side effect:

• Occurs in 5–14% of patients taking antidepressants, with bupropion specifically listed among agents causing this reaction 3, 4
• Typically manifests prominently on the scalp (62%), face (95%), neck (48%), and chest (57%) 4
• Usually presents either episodically or with episodic bursts (82% of cases) 4
• Can persist throughout treatment (median duration 63 months in one study) and causes subjective distress and functional impairment 4

Immediate Management Algorithm

Step 1: Dose Reduction

Reduce bupropion from 150 mg daily to 75 mg daily (half the current dose) for 2 weeks and reassess. 3 If sweating improves but depression symptoms worsen, proceed to Step 2. 3

Step 2: Switch Antidepressants

Discontinue bupropion over 10–14 days to limit withdrawal symptoms, then switch to an alternative antidepressant with lower sweating risk. 5, 3

Preferred alternatives based on side-effect profiles:

• Mirtazapine 7.5–30 mg at bedtime: Well tolerated with minimal sweating risk; promotes sleep and may counteract any insomnia from prior bupropion 5
• Nortriptyline 10–40 mg daily: Lower anticholinergic effects than other tricyclics; therapeutic blood level window of 50–150 ng/mL 5
• Desipramine 10–25 mg in morning: Activating properties similar to bupropion but lower sweating incidence 5

Step 3: Pharmacologic Treatment of Sweating (If Switching Is Not Feasible)

If the patient cannot discontinue bupropion due to excellent antidepressant response or prior treatment failures, add terazosin 1 mg at bedtime, titrating up to 6 mg/day as tolerated over 6 weeks. 4

• In the only clinical trial for antidepressant-induced sweating, 22 of 23 patients (96%) responded to terazosin, with median severity scores improving from 5 to 2 on the Clinical Global Impressions scale (P < 0.0001) 4
• Common side effects include dizziness/lightheadedness (39% of patients) and dry mouth (17%), but no patients discontinued due to adverse effects 4
• Monitor sitting and standing blood pressure, as median decreases of 3–5 mm Hg may occur 4

Alternative pharmacologic option: Benztropine 0.5–2 mg daily or cyproheptadine 4–8 mg daily, though these have less robust evidence than terazosin. 3

Critical Safety Considerations

Before making any changes:

• Confirm the patient has no absolute contraindications to continuing bupropion: seizure history, eating disorders, uncontrolled hypertension, concurrent MAOI use, or abrupt alcohol/benzodiazepine discontinuation 6, 1, 2
• Assess for other causes of sweating: hyperthyroidism, menopause, infection, hypoglycemia, or other medications 3
• Monitor for suicidal ideation during any antidepressant transition, especially in patients under 24 years old, with greatest risk in the first 1–2 months 6, 2

Common Pitfalls to Avoid

1. Do not abruptly discontinue bupropion: Taper over 10–14 days to minimize withdrawal symptoms including mood destabilization, irritability, and sleep disturbance 5

2. Do not add SSRIs to address sweating: SSRIs (fluoxetine, paroxetine, sertraline) are themselves common causes of excessive sweating and will likely worsen the problem 5, 3, 4

3. Do not wait for spontaneous resolution: Antidepressant-induced sweating typically persists throughout treatment and rarely resolves without intervention 4

4. Do not overlook blood pressure monitoring with terazosin: Although generally well-tolerated, terazosin can cause orthostatic hypotension, particularly with the first dose 4

Clinical Reasoning

Bupropion's noradrenergic and dopaminergic activity likely contributes to sweating through sympathetic nervous system activation. 2, 7 Unlike SSRIs where sweating may relate to serotonergic effects, bupropion's mechanism suggests that switching to agents with different receptor profiles (mirtazapine's antihistaminic properties or tricyclics' anticholinergic effects) may provide relief. 5, 3 Terazosin, an alpha-1 adrenergic antagonist, directly counteracts the sympathetic overactivity causing sweating. 4

The 150 mg daily dose this patient is taking is at the lower end of the therapeutic range (typical target 300 mg/day for depression), making dose reduction a viable first strategy without significantly compromising antidepressant efficacy. 6, 2