What is the best treatment for hyperhidrosis (excessive sweating) caused by Wellbutrin (bupropion)?

Treatment of Bupropion-Induced Hyperhidrosis

For excessive sweating caused by Wellbutrin (bupropion), oxybutynin 2.5-7.5 mg daily is the most effective treatment option, with 60% of patients achieving significant improvement in hyperhidrosis symptoms. 1

Initial Management Strategy

Step 1: Verify Bupropion as the Cause

• Confirm that sweating began after bupropion initiation or dose increase 2
• Rule out other secondary causes of hyperhidrosis (thyroid dysfunction, diabetes, infections, malignancy) 3
• Note that sweating is a recognized side effect of bupropion, reported more frequently than with placebo in clinical trials 4

Step 2: Consider Dose Reduction First

• Attempt dose reduction as the initial intervention if clinically appropriate for the underlying psychiatric condition 5, 2
• Higher doses of bupropion are associated with increased side effect burden 6
• This approach is only suitable if the lower dose maintains adequate therapeutic effect for depression or smoking cessation 2

Step 3: Pharmacological Treatment of Sweating

If dose reduction is ineffective or inappropriate:

Primary recommendation: Oxybutynin

• Start oxybutynin at 2.5 mg daily and titrate gradually to 7.5 mg daily based on response and tolerability 1
• This regimen demonstrated 60% response rate (≥1 point improvement on Hyperhidrosis Disease Severity Scale) compared to 27% with placebo 1
• Significant quality of life improvement (mean DLQI improvement of 6.9 points vs 2.3 with placebo) 1
• Effective for both generalized and localized hyperhidrosis patterns 1
• In a sertraline-induced sweating study (applicable to other antidepressants), oxybutynin 5 mg daily significantly reduced subjective sweating over 2 weeks 7

Alternative agents if oxybutynin is contraindicated or ineffective:

• Benztropine (anticholinergic agent) has been reported successful in controlling antidepressant-induced sweating 2
• Cyproheptadine (antihistamine with anticholinergic properties) is another option for refractory cases 2

Expected Side Effects and Monitoring

Oxybutynin tolerability:

• Dry mouth occurs in 43% of patients (vs 11% with placebo) but is generally mild 1
• Other anticholinergic effects are uncommon at low doses 1
• Side effects were minor enough that treatment continuation was feasible in clinical trials 7, 1

Important contraindications to oxybutynin:

• Urinary retention or gastric retention 1
• Uncontrolled narrow-angle glaucoma 1
• Severe ulcerative colitis or toxic megacolon 1

When to Switch Antidepressants

Consider switching from bupropion to an alternative antidepressant if:

• Sweating persists despite oxybutynin at maximum tolerated dose 2
• Patient cannot tolerate anticholinergic medications 2
• Sweating significantly impairs quality of life and other interventions have failed 2

Note that switching antidepressants carries its own risks, as other antidepressants (SSRIs, SNRIs, tricyclics) also commonly cause hyperhidrosis 2. Bupropion actually has a relatively favorable side effect profile compared to many alternatives 5.

Clinical Pearls

• Female patients may report less subjective sweating improvement than male patients on anticholinergic therapy 7
• Gradual titration of oxybutynin minimizes side effects while optimizing efficacy 1
• The sweating may resolve spontaneously over weeks to months if bupropion is discontinued, though this takes 5+ weeks 2
• Do not discontinue bupropion abruptly if used for depression, as this may precipitate mood destabilization 5