Is Zonisamide (Zonegran) suitable as a first-line treatment for agitation in the elderly?

Zonisamide is Not Recommended as First-Line Treatment for Agitation in the Elderly

Zonisamide should not be used as a first-line treatment for agitation in elderly patients due to lack of evidence for this indication and potential for significant adverse effects.

Evidence-Based Approach to Agitation in the Elderly

First-Line Approaches

1. Non-pharmacological interventions should always be attempted first 1:

   • Creating a dementia-friendly environment
   • Providing predictable daily routines
   • Identifying and addressing triggers using ABC (antecedent-behavior-consequences) charting
   • Caregiver education and support

2. If pharmacological treatment is necessary for severe agitation where the patient is threatening harm to self or others:

   • Antipsychotics may be considered at the lowest effective dose for the shortest possible duration 1
   • Atypical antipsychotics like quetiapine are preferred over typical antipsychotics 2
   • Recent evidence suggests quetiapine may have a lower frequency of adverse events compared to haloperidol 3

Why Not Zonisamide?

1. Lack of evidence for agitation:

   • No evidence is available for zonisamide's efficacy in treating agitation in the elderly 1
   • It is primarily indicated for seizure disorders 4

2. Significant adverse effects:

   • Zonisamide can cause psychosis (incidence of 2%) 5
   • Case reports document zonisamide-induced hallucinations and altered mental status 5
   • Common side effects include somnolence, dizziness, and anorexia/weight loss 4
   • Overdose can cause central nervous system depression, metabolic acidosis, and polyuria 6

3. Particular concerns in elderly patients:

   • Side effects like somnolence, dizziness, and mental clouding are especially problematic in older adults 1
   • These effects could potentially worsen agitation and confusion

Alternative Pharmacological Options

If non-pharmacological approaches fail and medication is necessary for severe agitation:

1. For mood stabilization (if indicated):

   • Divalproex sodium (initial dose 125mg twice daily) 2
   • Carbamazepine as an alternative (initial dose 100mg twice daily) 2

2. For severe agitation with risk of harm:

   • Atypical antipsychotics at lowest effective dose for shortest duration 1, 2
   • Quetiapine may have a better safety profile in the elderly 3

3. Medications to avoid:

   • Benzodiazepines (except for alcohol/benzodiazepine withdrawal) due to risk of worsening delirium 1
   • Typical antipsychotics due to severe side effects 2
   • Medications with high risk for precipitating delirium 1

Monitoring and Reassessment

• Regular monitoring for effectiveness and side effects is essential 2
• Use quantitative measures like the Neuropsychiatric Inventory Questionnaire (NPI-Q) 2
• Reassess at least every 6 months 2
• Document triggers and patterns to refine non-pharmacological approaches 2

Conclusion

When managing agitation in the elderly, prioritize non-pharmacological interventions first. If medication becomes necessary, zonisamide should not be considered as a first-line option due to lack of evidence for this indication and potential for significant adverse effects including psychosis and hallucinations. Instead, consider evidence-based alternatives like atypical antipsychotics at the lowest effective dose for the shortest duration when patients are severely agitated and at risk of harm.