What are the next steps for a patient with anhedonia who experienced temporary relief with bupropion (Wellbutrin) but developed significant leg shaking as a side effect?

Bupropion-Induced Movement Disorder: Clinical Management

Immediate Recommendation

Discontinue bupropion immediately and do not restart it—the leg shaking you experienced represents a drug-induced movement disorder (likely myoclonus or akathisia), and the loss of therapeutic effect after the first day indicates rapid tolerance, making this medication unsuitable for your anhedonia. 1, 2

Understanding What Happened

The Movement Disorder (Leg Shaking)

• Your leg shaking was likely bupropion-induced myoclonus or akathisia, a recognized adverse effect that typically appears within days of starting or increasing the dose 2, 3
• The American Academy of Sleep Medicine specifically recommends against using bupropion for restless legs syndrome, indicating this medication can worsen or cause involuntary leg movements 1
• Case reports document that bupropion-induced movement disorders typically resolve within 24-48 hours after discontinuation 2, 3

The Brief Anhedonia Relief

• The half-hour improvement in anhedonia followed by loss of effect suggests acute dopamine release with rapid tolerance development, which is not a sustainable therapeutic response 4
• Bupropion works by inhibiting dopamine and norepinephrine reuptake, and your experience of immediate but unsustained benefit indicates your brain may have quickly adapted to this mechanism 4
• Research shows bupropion is particularly effective for motivational anhedonia (lack of drive to pursue rewards) rather than consummatory anhedonia (inability to enjoy rewards once obtained) 4

Why You Should Not Continue Bupropion

Safety Concerns

• Movement disorders like yours can progress to more severe neurological symptoms including tremor, ataxia, confusion, and delirium if bupropion is continued, especially at higher doses 3
• The FDA warns that bupropion carries significant risks including seizures (0.1-0.4% incidence), with risk increasing dose-dependently above 300 mg daily 5
• Your experience of side effects on day one suggests you may be particularly sensitive to bupropion's neurological effects 2, 3

Lack of Sustained Efficacy

• Therapeutic response to antidepressants requires 6-8 weeks at adequate doses to properly assess efficacy—a half-hour of improvement is not a therapeutic response 6
• The rapid loss of effect after the first day indicates tolerance development, which is not typical of effective antidepressant treatment 4

Next Steps for Treating Your Anhedonia

First-Line Alternatives

The American College of Physicians recommends either cognitive behavioral therapy (CBT) or second-generation antidepressants (SSRIs/SNRIs) as first-line treatment for depression with anhedonia 1

For medication options:

• SSRIs (like sertraline, fluoxetine, or escitalopram) are the preferred first-line pharmacological treatment, with equivalent efficacy to bupropion but better tolerability profiles for most patients 1, 4
• Evidence from Huntington's disease research (which shares anhedonia as a core feature) shows SSRIs outperform SNRIs for depression with motivational anhedonia 4
• If sexual dysfunction is a concern with SSRIs, this would have been bupropion's main advantage, but given your adverse reaction, this is no longer an option 1, 6

Combination Strategies (If Monotherapy Fails)

• If an SSRI alone provides partial response after 6-8 weeks, augmentation with a different mechanism may be considered, though bupropion is contraindicated for you 6
• Low-quality evidence suggests augmenting SSRIs with bupropion is more effective than augmentation with buspirone, but again, this is not an option given your reaction 6

Non-Pharmacological Approaches

• Cognitive behavioral therapy should be strongly considered as either monotherapy or in combination with medication, as it has equivalent efficacy to antidepressants with lower relapse rates 1
• CBT specifically targets motivational anhedonia through behavioral activation techniques 1

Critical Safety Points

Do Not Restart Bupropion

• The American Academy of Sleep Medicine explicitly recommends against bupropion use for movement disorders 1
• Your movement disorder is a clear contraindication to future bupropion use 2, 3
• Even if you were tempted to try a lower dose, the FDA warns that neurological adverse effects can occur at any dose and may worsen with continued exposure 5

Monitor for Persistent Symptoms

• Most bupropion-induced movement disorders resolve within 24-48 hours of discontinuation 2
• If leg shaking persists beyond 2-3 days after stopping bupropion, seek immediate medical evaluation 2, 3
• In rare cases, symptoms may require treatment with clonazepam or other agents 2

What to Tell Your Prescriber

Inform your doctor that:

1. You experienced drug-induced movement disorder (leg shaking/myoclonus) with bupropion 2
2. The therapeutic effect lasted only 30 minutes on day one, indicating rapid tolerance 4
3. You need an alternative approach—preferably an SSRI or CBT—for your anhedonia 1, 4
4. Bupropion should be documented as contraindicated in your medical record due to movement disorder 1, 2