A Trial of Prazosin for Combat Trauma PTSD With Nightmares in Active-Duty Soldiers Returned From Iraq and Afghanistan
TL;DR: Prazosin was effective for trauma nightmares, sleep quality, global function, CAPS score, and the CAPS hyperarousal symptom cluster in active-duty soldiers, and benefits are clinically meaningful.
Abstract: ObjectiveThe authors conducted a 15-week randomized controlled trial of the alpha-1 adrenoreceptor antagonist prazosin for combat trauma nightmares, sleep quality, global function, and overall symptoms in active-duty soldiers with posttraumatic stress disorder (PTSD) returned from combat deployments to Iraq and Afghanistan.MethodSixty-seven soldiers were randomly assigned to treatment with prazosin or placebo for 15 weeks. Drug was titrated based on nightmare response over 6 weeks to a possible maximum dose of 5 mg midmorning and 20 mg at bedtime for men and 2 mg midmorning and 10 mg at bedtime for women. Mean achieved bedtime doses were 15.6 mg of prazosin (SD=6.0) and 18.8 mg of placebo (SD=3.3) for men and 7.0 mg of prazosin (SD=3.5) and 10.0 mg of placebo (SD=0.0) for women. Mean achieved midmorning doses were 4.0 mg of prazosin (SD=1.4) and 4.8 mg of placebo (SD=0.8) for men and 1.7 mg of prazosin (SD=0.5) and 2.0 mg of placebo (SD=0.0) mg for women. Primary outcome measures were the nightmare item o...
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01 Jan 2014
TL;DR: This 38th edition of Martindale has been completely redesigned to ensure ease of use and greatly improved readability.
Abstract: Martindale: The Complete Drug Reference provides unbiased, evaluated information on drugs and medicines in use around the world. It is updated by an experienced team of pharmacists and life scientists who use their professional expertise to provide an unbiased and evaluated digest of the available literature, selecting the most clinically relevant and appropriate information from reliable published sources. This 38th edition of Martindale has been completely redesigned to ensure ease of use and greatly improved readability. This latest edition contains over 6000 monographs, including 200 new monographs, on drugs and ancillary substances such as herbals, pharmaceutical excipients, and toxins and poisons. There are over 180,000 preparations giving details of preparation name, manufacturer, ingredients, and uses for proprietary preparations and now covering over 40 countries and regions, including China. The content is evidence-based and extensively referenced with links to the published literature.
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TL;DR: It is determined that increased tonic activity of the LC-NE system is necessary and sufficient for stress-induced anxiety and aversion and a potential intervention for preventing stress-related affective disorders.
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Cites background from "A Trial of Prazosin for Combat Trau..."
...However, clinically, we know that neuromodulators, such as norepinephrine and various neuropeptides, play pivotal roles in long-term outcomes following stress exposure (Raskind et al., 2013)....
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...The response of the LC-NE system to stress is particularly important in the context of stress-induced human neuropsychiatric disorders, such as posttraumatic stress disorder (PTSD) (Olson et al., 2011; Raskind et al., 2013)....
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TL;DR: The state of research on cannabis and sleep up to 2014 is summarized and synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas.
Abstract: The current review aims to summarize the state of research on cannabis and sleep up to 2014 and to review in detail the literature on cannabis and specific sleep disorders from 2014 to the time of publication. Preliminary research into cannabis and insomnia suggests that cannabidiol (CBD) may have therapeutic potential for the treatment of insomnia. Delta-9 tetrahydrocannabinol (THC) may decrease sleep latency but could impair sleep quality long-term. Novel studies investigating cannabinoids and obstructive sleep apnea suggest that synthetic cannabinoids such as nabilone and dronabinol may have short-term benefit for sleep apnea due to their modulatory effects on serotonin-mediated apneas. CBD may hold promise for REM sleep behavior disorder and excessive daytime sleepiness, while nabilone may reduce nightmares associated with PTSD and may improve sleep among patients with chronic pain. Research on cannabis and sleep is in its infancy and has yielded mixed results. Additional controlled and longitudinal research is critical to advance our understanding of research and clinical implications.
305 citations
TL;DR: This In Review paper provides a concise review of the evolution of PTSD diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, impact of PTSD in the community, an overview of the established risk factors for developing PTSD, and assessment and treatment.
Abstract: During the last 30 years, there has been a substantial increase in the study of posttraumatic stress disorder (PTSD). Several high-profile traumatic events, such as the wars in Afghanistan and Iraq, and the terrorist attacks of September 11 on the World Trade Center, have led to a greater public interest in the risk and protective factors for PTSD. In this In Review paper, I discuss some of the important advances in PTSD. The paper provides a concise review of the evolution of PTSD diagnosis in the Diagnostic and Statistical Manual of Mental Disorders, impact of PTSD in the community, an overview of the established risk factors for developing PTSD, and assessment and treatment. Throughout the paper, controversies and clinical implications are discussed.
262 citations
References
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TL;DR: The present scale has been devised for use only on patients already diagnosed as suffering from affective disorder of depressive type, used for quantifying the results of an interview, and its value depends entirely on the skill of the interviewer in eliciting the necessary information.
Abstract: Types of Rating Scale The value of this one, and its limitations, can best be considered against its background, so it is useful to consider the limitations of the various rating scales extant. They can be classified into four groups, the first of which has been devised for use on normal subjects. Patients suffering from mental disorders score very highly on some of the variables and these high scores serve as a measure of their illness. Such scales can be very useful, but have two defects: many symptoms are not found in normal persons; and less obviously, but more important, there is a qualitative difference between symptoms of mental illness and normal variations of behaviour. The difference between the two is not a philosophical problem but a biological one. There is always a loss of function in illness, with impaired efficiency. Self-rating scales are popular because they are easy to administer. Aside from the notorious unreliability of self-assessment, such scales are of little use for semiliterate patients and are no use for seriously ill patients who are unable to deal with them. Many rating scales for behaviour have been devised for assessing the social adjustment of patients and their behaviour in the hospital ward. They are very useful for their purpose but give little or no information about symptoms. Finally, a number of scales have been devised specifically for rating symptoms of mental illness. They cover the whole range of symptoms, but such all-inclusiveness has its disadvantages. In the first place, it is extremely difficult to differentiate some symptoms, e.g., apathy, retardation, stupor. These three look alike, but they are quite different and appear in different settings. Other symptoms are difficult to define, except in terms of their settings, e.g., mild agitation and derealization. A more serious difficulty lies in the fallacy of naming. For example, the term "delusions" covers schizophrenic, depressive, hypochrondriacal, and paranoid delusions. They are all quite different and should be clearly distinguished. Another difficulty may be summarized by saying that the weights given to symptoms should not be linear. Thus, in schizophrenia, the amount of anxiety is of no importance, whereas in anxiety states it is fundamental. Again, a schizophrenic patient who has delusions is not necessarily worse than one who has not, but a depressive patient who has, is much worse. Finally, although rating scales are not used for making a diagnosis, they should have some relation to it. Thus the schizophrenic patients should have a high score on schizophrenia and comparatively small scores on other syndromes. In practice, this does not occur. The present scale has been devised for use only on patients already diagnosed as suffering from affective disorder of depressive type. It is used for quantifying the results of an interview, and its value depends entirely on the skill of the interviewer in eliciting the necessary information. The interviewer may, and should, use all information available to help him with his interview and in making the final assessment. The scale has undergone a number of changes since it was first tried out, and although there is room for further improvement, it will be found efficient and simple in use. It has been found to be of great practical value in assessing results of treatment.
29,488 citations
Additional excerpts
...outcome measures were the 17-item CAPS; the three CAPS symptom clusters (reexperiencing, avoidance, and hyperarousal); the Hamilton Depression Rating Scale (HAM-D) (19); the Patient Health Questionnaire–9 (PHQ-9) (20); and the Quality of Life Inventory (21)....
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...Secondary 1004 ajp.psychiatryonline.org Am J Psychiatry 170:9, September 2013 outcome measures were the 17-item CAPS; the three CAPS symptom clusters (reexperiencing, avoidance, and hyperarousal); the Hamilton Depression Rating Scale (HAM-D) (19); the Patient Health Questionnaire–9 (PHQ-9) (20); and the Quality of Life Inventory (21)....
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...Differences in the CAPS reexperiencing and avoidance clusters, the HAM-D, and the PHQ–9 depression scale numerically favored prazosin, but the differences did not reach statistical significance (Table 3)....
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TL;DR: In addition to making criteria-based diagnoses of depressive disorders, the PHQ-9 is also a reliable and valid measure of depression severity, which makes it a useful clinical and research tool.
Abstract: OBJECTIVE: While considerable attention has focused on improving the detection of depression, assessment of severity is also important in guiding treatment decisions. Therefore, we examined the validity of a brief, new measure of depression severity.
26,004 citations
TL;DR: The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
Abstract: Despite the prevalence of sleep complaints among psychiatric patients, few questionnaires have been specifically designed to measure sleep quality in clinical populations. The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Nineteen individual items generate seven "component" scores: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction. The sum of scores for these seven components yields one global score. Clinical and clinimetric properties of the PSQI were assessed over an 18-month period with "good" sleepers (healthy subjects, n = 52) and "poor" sleepers (depressed patients, n = 54; sleep-disorder patients, n = 62). Acceptable measures of internal homogeneity, consistency (test-retest reliability), and validity were obtained. A global PSQI score greater than 5 yielded a diagnostic sensitivity of 89.6% and specificity of 86.5% (kappa = 0.75, p less than 0.001) in distinguishing good and poor sleepers. The clinimetric and clinical properties of the PSQI suggest its utility both in psychiatric clinical practice and research activities.
23,155 citations
"A Trial of Prazosin for Combat Trau..." refers methods in this paper
...Primary outcome measures were the nightmare item of the Clinician-Administered PTSD Scale (CAPS), the Pittsburgh Sleep Quality Index, and the change item of the Clinical Global Impressions Scale anchored to functioning....
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...Results were similar for the CAPS nightmare item (p=0.02; 15-week decrease in participants in the prazosin group not receiving an SSRI, mean=3.5 [SE=0.4]; in those receiving an SSRI, mean=1.9 [SE=0.7]) and the Pittsburgh Sleep Quality Index (p=0.01; 15-week decrease in participants in the prazosin group not receiving an SSRI, mean=6.4 [SE=0.8]; in those receiving an SSRI, mean=2.8 [SE=1.5])....
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...The three prospectively designated primary outcome measures were the CAPS nightmare item, the Pittsburgh Sleep Quality Index (17), and the Clinical Global Impressions Scale (CGI) change item (18) operationalized as treatment impact on self-reported ability to function in daily activities....
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...The decrease in score on the Pittsburgh Sleep Quality Index from baseline to endpoint was 5.6 (SE=0.7) in the prazosin group and 2.8 (SE=0.6) in the placebo group (difference in change from baseline, p=0.003; 95% CI=0.9–4.7)....
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Book•
29 Mar 2013
TL;DR: Linear Mixed-Effects and Nonlinear Mixed-effects (NLME) models have been studied in the literature as mentioned in this paper, where the structure of grouped data has been used for fitting LME models.
Abstract: Linear Mixed-Effects * Theory and Computational Methods for LME Models * Structure of Grouped Data * Fitting LME Models * Extending the Basic LME Model * Nonlinear Mixed-Effects * Theory and Computational Methods for NLME Models * Fitting NLME Models
10,715 citations
"A Trial of Prazosin for Combat Trau..." refers methods in this paper
...Differences between treatment groups in 15-week change from baseline were assessed using linear mixed-effects models, which include all participants and allow for missing values (22)....
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