(FDA approved in bold)

• Partial-onset seizures (adjunctive in adults)
  
• Partial-onset seizures (adjunctive in pediatric patients)
  
• Primary generalized tonic-clonic seizures (adjunctive; adults and pediatric patients age 2–16)
  
• Myoclonic epilepsy, Lennox-Gastaut syndrome
  
• Infantile spasms (West syndrome)
  
• Migraine prophylaxis
  
• Obesity
  
• Bipolar disorder
  
• Binge-eating disorder/bulimia
  
• Neuropathic pain
  
• Parkinson’s disease

Unknown but there are multiple mechanisms of action that may be important

• Sodium channel antagonist
  
• Modulates T-type calcium channels
  
• Binds to GABA receptors
  
• Weak carbonic anhydrase inhibitor
  
• MAO-B inhibition
  
• May help facilitate dopamine and serotonin neurotransmission

• Seizures – by 2–3 weeks
  
• Migraines – can take up to 3 months on a stable dose to see full effect

• Seizures – goal is the remission of seizures. Continue as long as effective and well-tolerated. Consider tapering and slowly stopping after 2 years seizure-free, depending on the type of epilepsy
  
• Migraine – goal is a 50% or greater reduction in migraine frequency or severity. Consider tapering or stopping if headaches remit for more than 6 months or if patient considering pregnancy

• Increase to highest tolerated dose
  
• Epilepsy: consider changing to another agent, adding a second agent or referral for epilepsy surgery evaluation
  
• Migraine: address other issues such as medication-overuse, other coexisting medical disorders, such as anxiety, and consider changing to another agent or adding a second agent

• For some patients with epilepsy or migraine, low-dose polytherapy with 2 or more drugs may be better tolerated and more effective than high-dose monotherapy
  
• Epilepsy: keep in mind drug interactions and their effect on levels
  
• Migraine: consider beta-blockers, antidepressants, natural products, other AEDs, and non-medication treatments, such as biofeedback, to improve headache control

• Mild to moderate decreases in bicarbonate can occur with zonisamide, but are uncommon reasons for discontinuation. Routine screening for metabolic acidosis is not recommended