Is zonisamide (Zonegran) effective for treating idiopathic intracranial hypertension (IIH)?

Zonisamide for Idiopathic Intracranial Hypertension (IIH)

Zonisamide may be an effective alternative treatment for IIH when topiramate has excessive side effects, though it is considered a second-line option after acetazolamide, which remains the first-line pharmacological therapy. 1, 2

Treatment Algorithm for IIH

First-line Treatments

1. Weight loss (for BMI >30 kg/m²)

   • Target 5-15% reduction in body weight
   • Most effective non-pharmacological intervention 2

2. Acetazolamide

   • Starting dose: 250-500mg twice daily
   • Maximum dose: up to 4g daily as tolerated
   • Supported by highest quality evidence as first-line pharmacological therapy 2
   • The IIHTT demonstrated that acetazolamide with weight loss was effective for treating mild vision loss in IIH 3

Second-line Treatments

1. Topiramate

   • Starting dose: 25mg daily with weekly escalation to 50mg twice daily
   • Benefits: helps with weight loss, reduces ICP through carbonic anhydrase inhibition 1, 2
   • Side effects: depression, cognitive slowing, reduced contraceptive efficacy, teratogenic potential 1

2. Zonisamide

   • Indicated when topiramate has excessive side effects 1
   • Mechanism: carbonic anhydrase inhibitor similar to acetazolamide and topiramate 4
   • More lipophilic than acetazolamide, potentially leading to more effective control of increased intracranial pressure 4

Headache Management in IIH

For patients with migrainous headache phenotype (present in 68% of IIH patients with headache) 1:

1. Acute treatment

   • Triptans with NSAID/paracetamol and antiemetic (limit to 2 days/week or max 10 days/month) 1, 2
   • Avoid opioids 2

2. Preventative treatment

   • Candesartan (weight-neutral alternative to beta blockers) 1, 2
   • Venlafaxine (weight-neutral and helps with depression) 1, 2
   • Botulinum toxin A for coexisting chronic migraine 1

Surgical Interventions (for refractory cases)

1. CSF diversion procedures (not recommended for headache alone) 1

   • Ventriculoperitoneal shunt preferred due to lower revision rates 2
   • Consider only after failed medical management or with threatened vision

2. Venous sinus stenting

   • For patients with venous sinus stenosis who have failed medical therapy and weight loss 1, 2
   • Requires demonstration of significant pressure gradient across stenosis 1

Monitoring and Follow-up

• Regular ophthalmologic evaluations to monitor papilledema, visual acuity, visual fields, and OCT 2
• Frequency based on severity of papilledema and visual field status

Caveats and Considerations

• Many medications for IIH are used off-label, including zonisamide 1
• Medication overuse headache is common in IIH patients and should be addressed 1
• When selecting treatments, avoid medications that could increase weight (beta blockers, tricyclic antidepressants, sodium valproate, pizotifen, flunarizine) 1
• Preventative drugs need to be started slowly and increased to therapeutic dose over 3 months 1

While zonisamide shows promise as an alternative carbonic anhydrase inhibitor for IIH treatment, particularly when topiramate is not tolerated, there is limited direct evidence comparing its efficacy to acetazolamide or topiramate. The recommendation for its use is based primarily on its similar mechanism of action and potentially favorable pharmacokinetic profile rather than robust clinical trial data specific to IIH 4.