Can Wellbutrin (bupropion) cause muscle spasm in an adult who is beginning or titrating the medication?

Can Wellbutrin Cause Muscle Spasm?

Yes, muscle spasm (reported as "twitch" and "tremor") is a recognized adverse effect of bupropion (Wellbutrin), occurring in 1–6% of patients depending on dose and formulation.

Documented Incidence from FDA Drug Label

The FDA-approved prescribing information for bupropion documents musculoskeletal and neurological adverse effects that include muscle-related symptoms 1:

• Tremor occurs in 1–6% of patients across different bupropion formulations, with higher rates at 400 mg/day sustained-release dosing (6%) compared to 300 mg/day (1%) 1
• Twitch (muscle twitching) is reported in 1–2% of patients taking bupropion 1
• Myalgia (muscle pain) occurs in 2–6% of patients, which may accompany or be confused with muscle spasm 1

Postmarketing Reports

Beyond controlled trial data, the FDA label documents additional musculoskeletal and neurological effects reported after market approval 1:

• Muscle weakness has been reported in postmarketing surveillance 1
• Dystonia (sustained muscle contractions causing twisting movements) is documented as a postmarketing adverse reaction 1
• Hypertonia (increased muscle tone/rigidity) has been reported 1

Mechanism and Clinical Context

Bupropion's noradrenergic and dopaminergic activity likely underlies these motor symptoms 2, 3:

• The drug inhibits reuptake of norepinephrine and dopamine without significant serotonergic effects, which can increase sympathetic nervous system activity and affect motor pathways 2, 3
• Tremor and muscle twitching represent dose-related effects that are more common at higher doses (≥400 mg/day) 1

Distinguishing from Serious Neurological Events

While muscle spasm/twitch is generally benign, clinicians must differentiate it from more serious neurological adverse effects 4, 1:

• Seizures are the most serious neurological risk with bupropion, occurring at approximately 0.1% (1 in 1,000) at doses ≤300 mg/day for smoking cessation, but muscle spasm is not a seizure warning sign 5, 4
• Extrapyramidal syndrome and dystonia are rare but serious postmarketing reports that require immediate evaluation if sustained muscle contractions or movement abnormalities develop 1

Monitoring Recommendations

For patients experiencing muscle spasm or tremor on bupropion 5, 4:

• Assess whether the symptom is dose-related by reviewing current dosing—tremor incidence increases from 1% at 300 mg/day to 6% at 400 mg/day 1
• Rule out seizure risk factors (prior seizure history, structural brain lesions, eating disorders, alcohol withdrawal, concomitant medications lowering seizure threshold) 5, 4
• Monitor blood pressure and heart rate, as bupropion's sympathomimetic effects can contribute to tremor 5, 4
• Consider dose reduction if tremor or muscle twitching is bothersome, as these symptoms are dose-dependent 1

Common Pitfalls

• Do not dismiss tremor as insignificant—while usually benign, it may indicate excessive noradrenergic stimulation and can be distressing to patients 1
• Do not confuse benign tremor with seizure activity—seizures present with loss of consciousness, convulsions, and postictal confusion, not isolated tremor 4
• Do not exceed maximum doses (450 mg/day for XL, 400 mg/day for SR) as seizure risk and motor side effects increase substantially above these thresholds 5, 4