Levetiracetam for treatment-refractory posttraumatic stress disorder.
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.
- SourceAvailable from: Jia Yao
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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 ."
ABSTRACT: Synaptic vesicles are specialized cycling endosomes that contain a unique constellation of membrane proteins. Proteins are sorted to vesicles by short amino acid sequences that serve as binding sites for clathrin adaptor proteins. Here we show that a tyrosine-based endocytosis motif in the vesicle protein SV2 is required for trafficking to synaptic vesicles of both SV2 and the calcium sensor protein synaptotagmin. Aberrant neurotransmission in cultured hippocampal neurons lacking SV2 was rescued by expression of wild-type SV2A, but not by SV2A-Y46A, a mutant containing a disrupted endocytosis motif in SV2A's cytoplasmic N terminus. Neurons expressing SV2A-Y46A had significantly more SV2 on the plasma membrane, indicating reduced internalization. A screen for proteins that preferentially bound wild-type SV2A identified multiple endocytosis-related proteins, and in vitro binding studies confirmed binding to the clathrin adaptors AP2, EPS15, and amphiphysin 2/Bin1. Neurons lacking SV2 contained less synaptotagmin and had a higher proportion of synaptotagmin on the plasma membrane. Expression of either wild-type SV2A or SV2A-Y46A restored synaptotagmin expression levels; however, only wild-type SV2A restored a normal proportion of synaptotagmin on the plasma membrane. These findings indicate that SV2 influences the expression and trafficking of synaptotagmin via separate mechanisms. Synaptic vesicles immunoisolated from SV2A/B double knock-out mice had significantly less synaptotagmin than vesicles isolated from wild-type mice. Our results indicate that SV2 plays a major role in regulating the amount of synaptotagmin in synaptic vesicles and provide an explanation for the observation that synapses lacking SV2 have fewer vesicles competent for calcium-induced fusion.The Journal of Neuroscience : The Official Journal of the Society for Neuroscience 04/2010; 30(16):5569-78. DOI:10.1523/JNEUROSCI.4781-09.2010 · 6.75 Impact Factor
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- "As such, anticonvulsant medications, with their putative anti-kindling effects, have been investigated for PTSD. Although the bulk of the evidence for use of these agents (which include carbamazepine, valproic acid, lamotrigine, gabapentin, oxcarbazepine, vigabatrin, tiagabine, pregabalin, and levetiracetam) stems from case series and open trials (Berlant and van Kammen, 2002; Berlant, 2004; Clark et al., 1999; Fesler, 1991; Kinrys et al., 2006; Otte et al., 2004), a limited number of controlled trials have also been conducted. "
ABSTRACT: Post-traumatic stress disorder (PTSD) is a prevalent anxiety disorder that results in multiple disabling symptoms. Research into the underlying neurobiology has implicated dysregulation in multiple neurotransmitter systems including norepinephrine, serotonin, and glutamate as well as the hypothalamic-pituitary axis. Understanding how these biological systems interact with each other and how they may affect key neural structures, such as the amygdala, hippocampus, and prefrontal cortex, to produce post-traumatic symptoms is critical for the development of effective pharmacological treatments. We briefly discuss the proposed biological dysfunctions underlying PTSD and how agents that target these dysfunctions may be utilized in PTSD. We then provide a review of the different pharmacological agents that have been investigated in PTSD. These drugs include: antidepressants, anti-adrenergic agents, anticonvulsants, benzodiazepines, atypical antipsychotics, and novel agents.Brain research 04/2009; 1293:24-39. DOI:10.1016/j.brainres.2009.03.037 · 2.83 Impact Factor
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- "In a retrospective naturalistic study with 35 civilian patients with chronic refractory PTSD, Kinrys et al. (2006) showed that adding levitiracetam (1,000–3,000 mg/day, mean: 1,967 mg/day), a novel anticonvulsant, to antidepressants for 4– 20 weeks led to a significant decrease in the scores of the PCL-C. "
ABSTRACT: The selective serotonin reuptake inhibitors (SSRIs) are considered the first-line pharmacological treatment for PTSD. However, even when treated with this class of drugs, response rates rarely exceed 60% and less than 20-30% of the patients achieve full remission. The aim of this study was to address this limitation by systematically reviewing the options left for the treatment of PTSD when patients do not respond satisfactorily to or tolerate SSRIs. A systematic review covering all original articles, letters and brief reports published in any language until October 2008 was conducted through searches in the ISI/Web of Science, PubMed and PILOTS databases. The search terms included the pharmacological class of each agent or its generic name plus "PTSD" or "stress disorder" in the title, in the abstract or as a keyword. Sixty-three articles were selected, covering the following categories: antipsychotics, anticonvulsants, adrenergic-inhibiting agents, opioid antagonists, benzodiazepines and other agents. None of the identified agents reached the level A of scientific evidence, 5 reached level B, 7 level C and 13 level D. The non-antidepressant agent with the strongest scientific evidence supporting its use in PTSD is risperidone, which can be envisaged as an effective add-on therapy when patients did not fully benefit from previous treatment with SSRIs. Prazosin, an adrenergic-inhibiting agent, is a promising alternative for cases of PTSD where nightmares and insomnia are prominent symptoms. So far, there is no consistent empirical support for using benzodiazepines in the prevention or in the treatment of PTSD, although these drugs could alleviate some associated non-specific symptoms, such as insomnia or anxiety. Further controlled clinical trials and meta-analysis are needed to guide clinicians in their search of effective pharmacological alternatives to antidepressants in PTSD.Progress in Neuro-Psychopharmacology and Biological Psychiatry 03/2009; 33(2):169-80. DOI:10.1016/j.pnpbp.2008.12.004 · 4.03 Impact Factor