Levetiracetam for Treatment-Refractory Posttraumatic Stress Disorder

Kinrys, Gustavo; Wygant, Lisa E; Pardo, Tamara B.; Melo, Maria do Carmo Barros de

doi:10.4088/jcp.v67n0206

Cited by 47 publications

(21 citation statements)

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“…A retrospective, naturalistic study examining levetiracetam (mean dose = 1967 mg/d) for an average of 10 weeks in 23 patients with treatment-resistant PTSD showed a 56% response rate and a 26% remission rate by PTSD Checklist-Civilian Version and CGI-Severity of Illness scale scores [39].…”

Section: Levetiracetammentioning

confidence: 99%

Glutamate and anxiety disorders

Amiel

Mathew²

2007

Curr Psychiatry Rep

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Anxiety disorders are among the most prevalent psychiatric disorders, but they represent a particular challenge for treatment. The standard first-line treatments, including antidepressants, benzodiazepines, and buspirone, result in significant response rates for a majority of patients; however, unfavorable side effect profiles or risk for dependency for particular agents might limit their use by anxious patients, who often have low thresholds for medication discontinuation. Novel pharmacologic agents that modulate particular receptors, ion channels, or transporters relevant to glutamatergic neurotransmission may represent a new approach to the treatment of anxiety disorders, with generally more favorable side effect profiles. Although the role of glutamate in the pathophysiology of anxiety disorders is still being elucidated, the use of these agents in treatment of anxiety disorders and commonly comorbid conditions such as substance abuse and mood disorders will continue to increase.

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Section: Levetiracetammentioning

confidence: 99%

Glutamate and anxiety disorders

Amiel

Mathew²

2007

Curr Psychiatry Rep

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“…Levetiracetam is a Food and Drug Administration-approved treatment for epilepsy (reviewed in Ref. 11) that also shows promise in the treatment of anxiety disorders (27,28,47), pain (12,13,36), dyskinesias (7,32,40,43,48), and posttraumatic stress disorder (28). Thus SV2 represents a vesicle protein whose action is likely to play an important (and targetable) regulatory action at synapses.…”

mentioning

confidence: 99%

SV2 regulates neurotransmitter release via multiple mechanisms

Nowack¹,

Yao²,

Custer

et al. 2010

American Journal of Physiology-Cell Physiology

115

116

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Nowack A, Yao J, Custer KL, Bajjalieh SM. SV2 regulates neurotransmitter release via multiple mechanisms. Am J Physiol Cell Physiol 299: C960 -C967, 2010. First published August 11, 2010 doi:10.1152/ajpcell.00259.2010.-Among the proteins that mediate calcium-stimulated transmitter release, the synaptic vesicle protein 2 (SV2) stands out as a unique modulator specific to the neurons and endocrine cells of vertebrates. In synapses, SV2 regulates the expression and trafficking of the calcium sensor protein synaptotagmin, an action consistent with the reduced calcium-mediated exocytosis observed in neurons lacking SV2. Yet SV2 contains amino acid motifs consistent with it performing other actions that could regulate presynaptic functioning and that might underlie the mechanism of drug action. To test the role of these functional motifs, we performed a mutagenic analysis of SV2A and assessed the ability of mutant SV2A proteins to restore normal synaptic transmission in neurons from SV2A/B knockout mice. We report that SV2A-R231Q, harboring a mutation in a canonical transporter motif, restored normal synaptic depression (a measure of release probability and signature deficit of neurons lacking SV2). In contrast, normal synaptic depression was not restored by SV2A-W300A and SV2A-W666A, harboring mutations of conserved tryptophans in the 5th and 10th transmembrane domains. Although they did not rescue normal neurotransmission, SV2A-W300A and SV2A-W666A did restore normal levels of synaptotagmin expression and internalization. This indicates that tryptophans 300 and 666 support an essential action of SV2 that is unrelated to its role in synaptotagmin expression or trafficking. These results indicate that SV2 performs at least two actions at the synapse that contribute to neurotransmitter release. synapse; neurotransmission; exocytosis THE CALCIUM-REGULATED SECRETION of neurotransmitters is a specialized form of membrane fusion that requires regulatory proteins that are unique to transmitter-containing vesicles. One of these is synaptic vesicle protein 2 (SV2), a membrane glycoprotein expressed exclusively in neurons and endocrine cells. SV2 is the binding site of a class of drugs typified by levetiracetam (5,17,26,29,31). Levetiracetam is a Food and Drug Administration-approved treatment for epilepsy (reviewed in Ref. 11) that also shows promise in the treatment of anxiety disorders (27, 28, 47), pain (12, 13, 36), dyskinesias (7,32,40,43,48), and posttraumatic stress disorder (28). Thus SV2 represents a vesicle protein whose action is likely to play an important (and targetable) regulatory action at synapses.SV2 is essential for normal neurotransmission. Neurons lacking SV2A and SV2B demonstrate reduced neurotransmission and reduced synaptic depression (8 -10, 22, 41, 44). These phenotypes reflect reduced release probability due to impaired ability of vesicles to fuse in response to elevated cytoplasmic calcium. This effect occurs after vesicle docking (10) and before formation of the SNARE (soluble N-ethylmaleimidese...

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“…Animal models show that levetiracetam may reduce the anxiety induced by withdrawal from benzodiazepines (Kinrys, Wygant, Pardo, & Melo, 2006). In a retrospective study, Kinrys et al (2006) treated non-responding PTSD patients with levetiracetam in an adjunctive therapy fashion. A mean dose of 1967 ± 650 mg/day was given to patients for an average of 9.7 ± 3.7 weeks.…”

Section: Levetiracetammentioning

confidence: 99%