Somnolence zonisamide

Zonisamide Modulate sodium and calcium channels Loading dose Not recommended due to excessive adverse effects Maintenance dose 1 00-600 mg/day start at 100 mg/day and titrate upward as indicated by response Half-life 63 hours Apparent volume of distribution 1.45 L/kg Protein binding 40% Primary elimination route Hepatic Not established Dizziness, somnolence Metabolic acidosis, oligohidrosis, paresthesias, renal calculi... 

Cognitive/Neuropsychiatric adverse events Use of zonisamide was frequently associated with the following CNS-related adverse events 1) Psychiatric symptoms, including depression and psychosis 2) psychomotor slowing, difficulty with concentration, and speech or language problems, in particular, word-finding difficulties and 3) somnolence or fatigue. 

The most commonly observed adverse events associated with the use of zonisamide were agitation/irritability, anorexia, dizziness, headache, nausea, and somnolence. 

In a double-bUnd, placebo-controUed, add-on, randomized trial of zonisamide 400 mg/day in 203 patients over 14 years of age with refractory partial-onset seizures, the response rate was 42% (3). The most common treatment-emergent adverse events were somnolence, anorexia, rhinitis, dizziness, nausea or vomiting, ataxia, fatigue, and headache. With zonisamide, 22% of the patients lost over 2.3 kg compared with 10% on placebo. 

TOXICITY Zonisamide is well tolerated. Adverse effects include somnolence, ataxia, anorexia, nervousness, and fatigue. Approximately 1% of individuals develop renal calculi during treatment with zonisamide, probably related to its ability to inhibit carbonic anhydrase. 

Zonisamide 50-68h 100-400 mg Somnolence, ataxia, agitation bradycardia, hypotension, respiratory depression. 

In 317 patients with refractory partial epilepsy who had completed a fixed-dose, randomized, double-blind, add-on trial with zonisamide, and were recruited into an open extension study, retention rates at 1, 2, and 3 years were 65%, 45%, and 29% respectively [440 ]. Adverse effects were reported by 89% of patients, the most commonly reported being dizziness (12%), somnolence (12%), and weight loss (11%). Serious adverse effects were reported in 52 patients (16%) and convulsions were the most common. The overall withdrawal rate due to adverse effects was 22%. 

Zonisamide versus CBZ Zonisamide and CBZ were compared in patients newly diagnosed with focal epilepsy. The most frequent adverse effects reported in both groups were headache, somnolence, dizziness, decreased appetite and weight loss. Dizziness was more frequent in the CBZ group whereas decreased appetite and weight loss were more frequent in the zonisamide group [28 ]. 

Observational studies The safety and efficacy of zonisamide for intractable focal epilepsy were investigated in 121 Korean patients taking a dose of 200 mg/day. The most common adverse events were dizziness (28.1%), somnolence (24.0%), anorexia (18.2%), headache (14%), nausea (13.2%), and weight loss (10.7%) [203 ]. 

Placebo-controlled studies A study of zonisamide for weight loss randomized participants to receive zonisamide 200 mg/day, 400 mg/day, or placebo [204 ]. Altered taste, constipation, diarrhea, dry mouth, headache, fatigue, nausea/vomiting, somnolence, language and speech problems, impaired attention or concentration, memory problems, anxiety, and depression were more common with one or both of the zonisamide doses when compared to placebo. 

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