Effects of levetiracetam on tardive dyskinesia: a randomized, double-blind, placebo-controlled study.
OBJECTIVE
The goal of this study was to evaluate the efficacy and safety of levetiracetam versus placebo for tardive dyskinesia (TD).


METHODS
This double-blind, placebo-controlled, randomized study was conducted at the Connecticut Mental Health Center between September 2004 and April 2006. Antipsychotic-treated patients meeting Glazer-Morgenstern criteria for TD were assigned at random to receive levetiracetam 500 mg/day to 3000 mg/day or placebo for 12 weeks. After completion of 12 weeks, patients were permitted to receive open-label levetiracetam for a further 12 weeks. The principal efficacy outcome measure was improvement in the Abnormal Involuntary Movement Scale (AIMS) total score. Safety was assessed with an adverse event scale, psychiatric symptom rating scales, weight, and hematologic tests.


RESULTS
A total of 50 patients were randomly assigned to treatment. AIMS total scores were moderate in severity at baseline. Mixed regression models revealed that AIMS total scores declined 43.5% from baseline in the levetiracetam group compared to 18.7% for placebo (p = .022). Patients continuing levetiracetam in the open-label phase continued to improve, and patients crossed over to open-label levetiracetam improved to a similar degree as those initially assigned. Levetiracetam was well tolerated.


CONCLUSIONS
Levetiracetam appeared effective for TD in this study. The mechanisms of its therapeutic effect are unclear but may involve reducing neuronal hypersynchrony in basal ganglia. Future studies should attempt to replicate the current results.


BACKGROUND
clinicaltrials.gov Identifier: NCT00291213.
Woods
Scott W
SW
Department of Psychiatry, Yale University, Connecticut Mental Health Center, New Haven 06519, USA. scott.woods@yale.edu
Saksa
John R
JR
Baker
C Bruce
CB
Cohen
Shuki J
SJ
Tek
Cenk
C
D000465:Algorithms; D039721:Diagnostic and Statistical Manual of Mental Disorders; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004409:Dyskinesia, Drug-Induced / Q000175:diagnosis / Q000188:drug therapy*; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D008875:Middle Aged; D018697:Nootropic Agents / Q000627:therapeutic use*; D010889:Piracetam / Q000031:analogs & derivatives* / Q000627:therapeutic use; D016896:Treatment Outcome
D018697:Nootropic Agents; D000077287:Levetiracetam; D010889:Piracetam