The sleep effects of tiagabine on the first night of treatment predict post-traumatic stress disorder response at three weeks.

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2014-05

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Abstract

INTRODUCTION: We sought to test the hypothesis that improvements in sleep might mediate treatment-related improvements in daytime symptoms of post-traumatic stress disorder (PTSD). We evaluated whether changes in sleep occurring on the first night of tiagabine (a gamma-amino butyric acid (GABA) reuptake inhibitor) administration predicted subsequent PTSD response. METHODS: This was an open-label three-week polysomnographic (PSG) study of nightly treatment with tiagabine dosing from 2-12 mg including 20 adults with PTSD with ≥30 min of self-reported and PSG wake time after sleep onset (WASO). RESULTS: A treatment night 1 decrease in self-reported and PSG WASO and an increase in slow-wave sleep (SWS) accounted for 94% of the variance in week 3 Short PTSD Rating Interview (SPRINT) score, the primary outcome measure (p<0.001). Increased night 1 SWS also accounted for 91% of the variance in Work/School Impairment and 45% of the variance in Social Life Impairment as measured with the Sheehan Disability Scale (p<0.001). These relationships were much stronger correlates of three-week outcome than three-week sleep effects. CONCLUSIONS: The initial sleep response to tiagabine may mediate or be an indicator of the subsequent PTSD response. The findings highlight the importance of sleep maintenance and SWS in the treatment of PTSD and also suggest a potential relationship between SWS and daytime function.

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Sleep, post-traumatic stress disorder, tiagabine, Adult, Female, Humans, Male, Neurotransmitter Uptake Inhibitors, Nipecotic Acids, Polysomnography, Sleep, Stress Disorders, Post-Traumatic

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Published Version (Please cite this version)

10.1177/0269881113509903

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Krystal, Andrew D, Wei Zhang, Jonathan RT Davidson and Kathryn M Connor (2014). The sleep effects of tiagabine on the first night of treatment predict post-traumatic stress disorder response at three weeks. J Psychopharmacol, 28(5). pp. 457–465. 10.1177/0269881113509903 Retrieved from https://hdl.handle.net/10161/13045.

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Scholars@Duke

Krystal

Andrew Darrell Krystal

Professor Emeritus of Psychiatry and Behavioral Sciences

My research is focused on better understanding the pathophysiology of sleep disorders and mood disorders and developing improved treatments for these conditions. My primary research tools are: electroencepahlography (EEG), polysomnography (PSG), computer signal analysis and modeling, functional magnetic resonance imaging (fMRI), and positron emission tomograophy (PET). Nearly all of my projects have been carried out with humans, however, projects are ongoing with gene knock-out models in mice, and lemurs in collaboration with the Duke Primate Center. A few representative current studies are: 1) Defining physiologic (EEG, PSG, PET, fMRI) correlates of sleep complaints and subtyping insomnia on the basis of the associated pathophysiology, 2) Studying the relationship of EEG data recorded during non-REM sleep, daytime function, and insomnia treatment response, 3) Developing new pharmacologic and non-pharmacologic treatments for insomnia, 4) Studying the relationship of natural sleep and hibernation-like phenomena (torpor), 5) Predicting depression treatment response on the basis of pre-treatment EEG and structural MRI data.

Jonathan R.T. Davidson

Professor Emeritus of Psychiatry and Behavioral Sciences

Currently, my research focuses upon the theoretical aspects of homeopathy and its clinical utilization, as well as the broader field of alternative (complementary) medicine. this is a field which has traditionally been overlooked as a legitimate scientific discipline. Other areas of activity are as in the past, i.e., clinical treatment, epidemiology, risk factors, pathogenesis of posttraumatic stress, social phobia, other anxiety status, and depression. These are illustrated by recent publications on treatment, epidemiology, health service utilization and quality of life in social phobia and PTSD, drug treatment of panic disorder. Magnetic resonance studies of social phobia have been completed and further studies are planned.


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