Adjunctive zonisamide for treatment refractory anxiety

The aim of the study was to assess the use of a novel anticonvulsant, zonisamide, in patients with treatment refractory anxiety. Pilot and open study of a cohort of patients with anxiety (n = 10), who were deemed partial or non-responders to anxiolytic therapy, and received adjunctive zonisamide in a naturalistic fashion. The primary outcome measures were the Hamilton Anxiety Scale (HAM-A), the Clinical Global Impression of Severity (CGI-S) and the Clinical Global Impression of Improvement (CGI-I). Patients included were markedly ill with a mean number of previous medication trials of 4.9 +/- 1.9, a baseline HAM-A score of 27.9 +/- 3.8, and a baseline CGI-S score of 5.7 +/- 0.5. Patients improved significantly with an end-point HAM-A score of 12.6 +/- 7.4 (p < 0.001), CGI-S score of 3.6 +/- 1.3 (p < 0.002) and CGI-I score of 2.5 +/- 1.3. Zonisamide at a mean +/- SD dose of 160 +/- 70 mg/day for 9.2 +/- 4.5 weeks was generally well tolerated. Adverse events were generally mild, and no patients discontinued zonisamide because of side effects. Six patients (60%) met responder criteria at end-point (CGI-I <= 2). Results from this pilot and open naturalistic study suggest that zonisamide may effectively augment response to anxiolytic medications in patients with treatment refractory anxiety. Larger and controlled studies are warranted to confirm these preliminary findings.