Can a patient with Parkinson’s disease who is taking levodopa/carbidopa, dopamine agonists (e.g., ropinirole, pramipexole) and MAO‑B inhibitors (e.g., selegiline, rasagiline) safely start buspirone (BuSpar) for anxiety, and what dosing and monitoring are recommended?

Buspirone Use in Parkinson's Disease Patients on Levodopa/Carbidopa and Dopamine Agonists

Buspirone can be used cautiously in Parkinson's disease patients taking levodopa/carbidopa and dopamine agonists, but should be started at 5 mg twice daily with slow titration and close monitoring for motor worsening, as doses above 40 mg/day may exacerbate parkinsonian symptoms. 1, 2

Safety Profile and Drug Interactions

No Contraindications with Standard PD Medications

• There are no documented pharmacologic interactions between buspirone and levodopa/carbidopa, dopamine agonists (ropinirole, pramipexole), or MAO-B inhibitors (selegiline, rasagiline). 3
• Buspirone does not displace tightly bound drugs like phenytoin or propranolol from serum proteins, suggesting minimal interaction risk with most PD medications. 3

Critical MAO-B Inhibitor Consideration

• While buspirone is not contraindicated with MAO-B inhibitors used in PD (selegiline, rasagiline), avoid combining buspirone with non-selective MAOIs (phenelzine, isocarboxazid) due to severe serotonin syndrome risk. 1
• Monitor for serotonin syndrome symptoms (confusion, agitation, tremors, hyperreflexia, autonomic instability) within 24-48 hours of starting buspirone, especially if the patient is on other serotonergic agents. 1

Dosing Algorithm

Initial Dosing

• Start buspirone at 5 mg twice daily (lower than the standard 7.5 mg twice daily used in non-PD populations). 1, 2
• This conservative approach is supported by clinical trial data showing 41% of PD patients failed to complete treatment at standard doses, with 53% experiencing motor worsening. 2

Titration Strategy

• Increase by 5 mg increments every 5-7 days based on anxiety response and motor tolerability. 1
• Target dose: 10-20 mg twice daily (maximum 40 mg/day for anxiolytic effect). 1, 4, 5
• The median tolerated dose in PD patients was only 7.5 mg twice daily in recent trials. 2

Dose Ceiling

• Do not exceed 40 mg/day in PD patients. Doses of 100 mg/day caused significant worsening of disability ratings and increased anxiety in controlled studies. 4
• At high doses (≥100 mg/day), buspirone produces noradrenergic stimulation in the locus ceruleus that adversely affects parkinsonian symptoms. 4

Monitoring Requirements

Motor Function Assessment

• Evaluate motor symptoms at baseline, week 2, week 4, and week 8 using standardized scales (e.g., UPDRS motor scores). 2, 4
• Watch specifically for:
  • Worsening bradykinesia, rigidity, or tremor 4, 5
  • Changes in dyskinesia severity (buspirone may actually reduce dyskinesias at 20 mg/day) 6
  • Increased "off" time duration 2

Anxiety Response

• Assess anxiety severity at 4 weeks using validated scales (Hamilton Anxiety Rating Scale or Parkinson Anxiety Scale). 2
• Buspirone requires 2-4 weeks to become effective for anxiety. 1
• If no response after 8 weeks at 20 mg twice daily, consider switching to an SSRI (sertraline or escitalopram preferred). 7

Timing with Levodopa

• Administer buspirone without regard to levodopa timing, as there is no absorption interaction. 3
• Continue taking levodopa/carbidopa at least 30 minutes before meals to maximize its absorption. 1, 8, 9

Common Pitfalls and Caveats

Concomitant Anxiolytic Use

• If the patient is already on benzodiazepines or SSRIs, consider tapering these before starting buspirone to better assess tolerability. 2
• The 2020 trial showed that 88% of participants were on concomitant antidepressants/anxiolytics, which may have contributed to the high discontinuation rate. 2

CYP3A4 Interactions

• If the patient takes strong CYP3A4 inhibitors (ketoconazole, itraconazole, erythromycin, grapefruit juice), start buspirone at 2.5 mg twice daily due to 13-19 fold increases in buspirone levels. 3
• Conversely, CYP3A4 inducers like carbamazepine may require higher buspirone doses to maintain anxiolytic effect. 3

Paradoxical Motor Effects

• At conventional anxiolytic doses (10-40 mg/day), buspirone is generally well tolerated without worsening parkinsonism. 4, 5
• However, individual sensitivity varies—approximately 40% of PD patients may not tolerate even low doses. 2

Alternative if Buspirone Fails

• SSRIs (sertraline 50-150 mg/day or escitalopram 10-20 mg/day) are preferred first-line agents for anxiety in PD if buspirone is not tolerated or ineffective. 7
• SSRIs have minimal CYP450 interactions with PD medications and do not worsen motor symptoms. 1, 7

Efficacy Signal

• Despite tolerability concerns, buspirone showed a mean improvement of 3.9 points on the Hamilton Anxiety Rating Scale and 7.1 points on the Parkinson Anxiety Scale at 12 weeks. 2
• Buspirone at 20 mg/day significantly reduced levodopa-induced dyskinesias in 5 of 7 patients in one small trial, suggesting potential dual benefit. 6