What is the recommended timing for taking zonisamide as a replacement for amantadine in an adult patient with Parkinson's disease?

Timing for Taking Zonisamide as Replacement for Amantadine in Parkinson's Disease

Zonisamide should be initiated at 25 mg once daily in the morning, taken with or without food, and can be started immediately after discontinuing amantadine without requiring a washout period or gradual cross-titration. 1, 2

Discontinuation of Amantadine

• Amantadine can be stopped abruptly without requiring a taper in most patients, as it does not cause withdrawal symptoms when discontinued 3
• However, if the patient is elderly (≥65 years) or has been on amantadine for an extended period, consider a brief 3-5 day taper by reducing to 100 mg daily (if on higher doses) before complete discontinuation to avoid sudden loss of symptomatic benefit 3, 4
• Monitor for return of parkinsonian symptoms during the transition period, particularly tremor and rigidity, which amantadine may have been controlling 5, 6

Initiation of Zonisamide

• Start zonisamide at 25 mg once daily, which is the recommended therapeutic dose that demonstrated significant efficacy in clinical trials 1, 2
• Administer in the morning to minimize potential sleep disturbances, as zonisamide can occasionally cause insomnia 1
• Zonisamide can be taken with or without food, though taking with food may reduce gastrointestinal side effects 2
• No dose titration is required - the 25 mg once daily dose is both the starting and maintenance dose for most patients 2

Timing Strategy for the Transition

• Day 1 approach: Stop amantadine and start zonisamide 25 mg the same day, as there are no known drug interactions requiring separation 1, 2
• Continue all other Parkinson's medications (levodopa, dopamine agonists) at their current doses during the transition 1
• The full therapeutic effect of zonisamide typically develops over 4-12 weeks, so temporary worsening of symptoms during the first 2-4 weeks is expected 1

Monitoring During Transition

• Assess motor function at 2 weeks using UPDRS Part III or clinical observation to determine if additional symptomatic therapy is needed during the transition period 1
• Watch specifically for increased "off" time, as zonisamide's primary benefit is reducing off-time duration, which may take 4-8 weeks to manifest 1, 7
• Monitor for somnolence (increased probability with zonisamide) and reduced appetite, which are the most common adverse effects requiring dose adjustment 7

Special Considerations for Elderly Patients

• If the patient is ≥65 years old, the same 25 mg once daily dose applies, but monitor more closely for somnolence and cognitive effects during the first month 7
• Elderly patients previously on amantadine may have been receiving reduced doses (100 mg/day maximum) due to renal function decline, so the transition to zonisamide may actually provide better symptom control without CNS toxicity risk 3, 4
• Verify renal function before starting zonisamide, though dose adjustment is not typically required for mild-moderate renal impairment 1

Dose Escalation (If Needed)

• If 25 mg once daily provides insufficient benefit after 4-6 weeks, increase to 50 mg once daily 1
• The 100 mg once daily dose showed higher adverse event rates without proportionally greater efficacy, so reserve this dose only for patients with inadequate response to 50 mg 1
• Each dose increase should be maintained for at least 4 weeks before further escalation to allow full therapeutic effect 1

Common Pitfalls to Avoid

• Do not attempt gradual cross-titration (overlapping amantadine taper with zonisamide uptitration), as this unnecessarily prolongs the transition and provides no clinical benefit 1, 2
• Do not start zonisamide at doses higher than 25 mg in an attempt to prevent symptom worsening, as this significantly increases adverse event risk without faster onset of benefit 1
• Do not discontinue levodopa or reduce its dose during the transition, as zonisamide is adjunctive therapy and not a levodopa replacement 1, 2