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Levetiracetam for treatment-refractory posttraumatic stress disorder

Anxiety Disorders Research Program, Cambridge Health Alliance, Cambridge, MA 02139, and the Department of Psychiatry, Harvard Medical School, Boston, MA, USA.
The Journal of Clinical Psychiatry (Impact Factor: 5.14). 02/2006; 67(2):211-4. DOI: 10.4088/JCP.v67n0206
Source: PubMed

ABSTRACT To assess the use of levetiracetam, a novel anticonvulsant agent, in the treatment of refractory posttraumatic stress disorder (PTSD).
Retrospective analysis was conducted of 23 patients with DSM-IV diagnosis of PTSD who, after being deemed partial or nonresponders to antidepressant therapy, received levetiracetam in a naturalistic fashion. The primary outcome measure was the PTSD Checklist-Civilian Version (PCL-C). Secondary outcome measures included the Hamilton Rating Scale for Anxiety (HAM-A), the Hamilton Rating Scale for Depression (HAM-D), Clinical Global Impressions-Severity of Illness scale (CGI-S), and Clinical Global Impressions-Improvement scale (CGI-I).
Levetiracetam at a mean+/-SD dose of 1967+/-650 mg/day for 9.7+/-3.7 weeks was generally well tolerated. Nineteen patients (83%) were taking at least 1 concomitant medication. Patients were severely ill with a mean baseline PCL-C score of 67.2+/-9.4, CGI-S score of 6.0+/-0.7, and HAM-A score of 26.8+/-4.9. Patients improved significantly on all measures (p<.001). Thirteen patients (56%) met responder criteria at endpoint (PCL-C mean change=23.5, CGI-I score<or=2), and 6 (26%) met remission criteria (CGI-S score<or=2). Adverse events were generally mild, and no patients discontinued levetiracetam because of side effects.
These preliminary data suggest that levetiracetam may be an effective treatment in combination with antidepressant therapy for patients with PTSD who remain symptomatic after initial intervention.

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    • "8 A study of levetiracetam, an anticonvulsant agent, reported 83% of study patients taking at least 1 concomitant medication. 9 Other studies of concomitant medication use in epilepsy and Alzheimer's disease have reported rates of concomitant medication use to be in the 70-75% range, 10-12 although one study of donepezil in Alzheimer's disease found 93% of patient taking at least 1 concomitant medication. 13 "
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    • "Levetiracetam ((S)-α-ethyl-2-oxo-pyrrolidine acetamide) represents a new class of drug for the treatment of neurological and psychiatric disorders. Currently marketed as Keppra®, levetiracetam is FDA-approved for the treatment of epilepsy (reviewed in [1]), though it also shows promise in the treatment of anxiety disorders [2], [3], [4], pain [5], [6], [7], dyskinesias [8], [9], [10], [11], [12], and post-traumatic stress disorder [3]. The protein receptor for levetiracetam is Synaptic Vesicle Protein 2A (SV2A) [13], a membrane glycoprotein specific to the secretory vesicles of neurons and endocrine cells in vertebrates [14]. "
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    • "Mice lacking the most widely expressed isoform, SV2A, develop severe seizures and die within three weeks of birth (K. M. Crowder et al., 1999; R. Janz et al., 1999 ). 2005 ; P. Striano et al., 2007; S. W. Woods et al. , 2008 ; S. A . Zivkovic et al . , 2008 ) , and post - traumatic stress disorder ( G . Kinrys et al . , 2006 ). At present SV2 is the only drug target in synaptic vesicles ."
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