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Journal of Clinical Medicine Sep 2021The aim of this review was to assess the quality of international treatment guidelines for post-traumatic stress disorder (PTSD), and identify differences between... (Review)
Review
BACKGROUND
The aim of this review was to assess the quality of international treatment guidelines for post-traumatic stress disorder (PTSD), and identify differences between guideline recommendations, with a focus on the treatment of nightmares.
METHODS
Guidelines were identified through electronic searches of MEDLINE, CINAHL, PubMed, Embase and Science Direct, as well as web-based searches of international guideline repositories, websites of psychiatric organisations and targeted web-searches for guidelines from the three most populous English-speaking countries in each continent. Data in relation to recommendations were extracted and the AGREE II criteria were applied to assess for quality.
RESULTS
Fourteen guidelines, published between 2004-2020, were identified for inclusion in this review. Only five were less than 5 years old. Three guidelines scored highly across all AGREE II domains, while others varied between domains. Most guidelines consider both psychological and pharmacological therapies as first-line in PTSD. All but one guideline recommended cognitive behavioural therapy (CBT) as first-line psychological treatment, and selective serotonin reuptake inhibitors (SSRIs) as first-line pharmacological treatment. Most guidelines do not mention the targeted treatment of nightmares as a symptom of PTSD. Prazosin is discussed in several guidelines for the treatment of nightmares, but recommendations vary widely. Most PTSD guidelines were deemed to be of good quality; however, many could be considered out of date. Recommendations for core PTSD symptoms do not differ greatly between guidelines. However, despite the availability of targeted treatments for nightmares, most guidelines do not adequately address this.
CONCLUSIONS
Guidelines need to be kept current to maintain clinical utility. Improvements are most needed in the AGREE II key domains of 'applicability', 'rigour of development' and 'stakeholder involvement'. Due to the treatment-resistant nature of nightmares, guideline development groups should consider producing more detailed recommendations for their targeted treatment. More high-quality trials are also required to provide a solid foundation for making these clinical recommendations for the management of nightmares in PTSD.
PubMed: 34575284
DOI: 10.3390/jcm10184175 -
PLoS Medicine Aug 2020Complex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse, and domestic violence are increasingly prevalent. People exposed... (Meta-Analysis)
Meta-Analysis
Psychological and pharmacological interventions for posttraumatic stress disorder and comorbid mental health problems following complex traumatic events: Systematic review and component network meta-analysis.
BACKGROUND
Complex traumatic events associated with armed conflict, forcible displacement, childhood sexual abuse, and domestic violence are increasingly prevalent. People exposed to complex traumatic events are at risk of not only posttraumatic stress disorder (PTSD) but also other mental health comorbidities. Whereas evidence-based psychological and pharmacological treatments are effective for single-event PTSD, it is not known if people who have experienced complex traumatic events can benefit and tolerate these commonly available treatments. Furthermore, it is not known which components of psychological interventions are most effective for managing PTSD in this population. We performed a systematic review and component network meta-analysis to assess the effectiveness of psychological and pharmacological interventions for managing mental health problems in people exposed to complex traumatic events.
METHODS AND FINDINGS
We searched CINAHL, Cochrane Central Register of Controlled Trials, EMBASE, International Pharmaceutical Abstracts, MEDLINE, Published International Literature on Traumatic Stress, PsycINFO, and Science Citation Index for randomised controlled trials (RCTs) and non-RCTs of psychological and pharmacological treatments for PTSD symptoms in people exposed to complex traumatic events, published up to 25 October 2019. We adopted a nondiagnostic approach and included studies of adults who have experienced complex trauma. Complex-trauma subgroups included veterans; childhood sexual abuse; war-affected; refugees; and domestic violence. The primary outcome was reduction in PTSD symptoms. Secondary outcomes were depressive and anxiety symptoms, quality of life, sleep quality, and positive and negative affect. We included 116 studies, of which 50 were conducted in hospital settings, 24 were delivered in community settings, seven were delivered in military clinics for veterans or active military personnel, five were conducted in refugee camps, four used remote delivery via web-based or telephone platforms, four were conducted in specialist trauma clinics, two were delivered in home settings, and two were delivered in primary care clinics; clinical setting was not reported in 17 studies. Ninety-four RCTs, for a total of 6,158 participants, were included in meta-analyses across the primary and secondary outcomes; 18 RCTs for a total of 933 participants were included in the component network meta-analysis. The mean age of participants in the included RCTs was 42.6 ± 9.3 years, and 42% were male. Nine non-RCTs were included. The mean age of participants in the non-RCTs was 40.6 ± 9.4 years, and 47% were male. The average length of follow-up across all included studies at posttreatment for the primary outcome was 11.5 weeks. The pairwise meta-analysis showed that psychological interventions reduce PTSD symptoms more than inactive control (k = 46; n = 3,389; standardised mean difference [SMD] = -0.82, 95% confidence interval [CI] -1.02 to -0.63) and active control (k-9; n = 662; SMD = -0.35, 95% CI -0.56 to -0.14) at posttreatment and also compared with inactive control at 6-month follow-up (k = 10; n = 738; SMD = -0.45, 95% CI -0.82 to -0.08). Psychological interventions reduced depressive symptoms (k = 31; n = 2,075; SMD = -0.87, 95% CI -1.11 to -0.63; I2 = 82.7%, p = 0.000) and anxiety (k = 15; n = 1,395; SMD = -1.03, 95% CI -1.44 to -0.61; p = 0.000) at posttreatment compared with inactive control. Sleep quality was significantly improved at posttreatment by psychological interventions compared with inactive control (k = 3; n = 111; SMD = -1.00, 95% CI -1.49 to -0.51; p = 0.245). There were no significant differences between psychological interventions and inactive control group at posttreatment for quality of life (k = 6; n = 401; SMD = 0.33, 95% CI -0.01 to 0.66; p = 0.021). Antipsychotic medicine (k = 5; n = 364; SMD = -0.45; -0.85 to -0.05; p = 0.085) and prazosin (k = 3; n = 110; SMD = -0.52; -1.03 to -0.02; p = 0.182) were effective in reducing PTSD symptoms. Phase-based psychological interventions that included skills-based strategies along with trauma-focused strategies were the most promising interventions for emotional dysregulation and interpersonal problems. Compared with pharmacological interventions, we observed that psychological interventions were associated with greater reductions in PTSD and depression symptoms and improved sleep quality. Sensitivity analysis showed that psychological interventions were acceptable with lower dropout, even in studies rated at low risk of attrition bias. Trauma-focused psychological interventions were superior to non-trauma-focused interventions across trauma subgroups for PTSD symptoms, but effects among veterans and war-affected populations were significantly reduced. The network meta-analysis showed that multicomponent interventions that included cognitive restructuring and imaginal exposure were the most effective for reducing PTSD symptoms (k = 17; n = 1,077; mean difference = -37.95, 95% CI -60.84 to -15.16). Our use of a non-diagnostic inclusion strategy may have overlooked certain complex-trauma populations with severe and enduring mental health comorbidities. Additionally, the relative contribution of skills-based intervention components was not feasibly evaluated in the network meta-analysis.
CONCLUSIONS
In this systematic review and meta-analysis, we observed that trauma-focused psychological interventions are effective for managing mental health problems and comorbidities in people exposed to complex trauma. Multicomponent interventions, which can include phase-based approaches, were the most effective treatment package for managing PTSD in complex trauma. Establishing optimal ways to deliver multicomponent psychological interventions for people exposed to complex traumatic events is a research and clinical priority.
Topics: Antipsychotic Agents; Cognitive Behavioral Therapy; Comorbidity; Humans; Mental Disorders; Mental Health; Network Meta-Analysis; Psychotherapy; Randomized Controlled Trials as Topic; Stress Disorders, Post-Traumatic
PubMed: 32813696
DOI: 10.1371/journal.pmed.1003262 -
Psychiatry Research Jan 2021Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present... (Meta-Analysis)
Meta-Analysis
Geriatric patients with dementia frequently present with agitation, aggression, psychosis, and other behavioral and psychological symptoms of dementia (BPSD). We present an update of our previously published algorithms for the use of psychopharmacologic agents in these patients taking into account more recent studies and findings in meta-analyses, reviews, and other published algorithms. We propose three algorithms: BPSD in an emergent, urgent, and non-urgent setting. In the emergent setting when intramuscular (IM) administration is necessary, the first-line recommendation is for olanzapine (since IM aripiprazole, previously favored, is no longer available) and haloperidol injection is the second choice, followed by possible consideration of an IM benzodiazepine. In the urgent setting, the first line would be oral second-generation antipsychotics (SGAs) aripiprazole and risperidone. Perhaps next could be then prazosin, and lastly electroconvulsive therapy is a consideration. There are risks associated with these agents, and adverse effects can be severe. Dosing strategies, discontinuation considerations, and side effects are discussed. In the non-emergent setting, medications are proposed for use in the following order: trazodone, donepezil and memantine, antidepressants such as escitalopram and sertraline, SGAs, prazosin, and carbamazepine. Other options with less support but potential future promise are discussed.
Topics: Academic Medical Centers; Aged; Algorithms; Antidepressive Agents; Antipsychotic Agents; Aripiprazole; Benzodiazepines; Citalopram; Dementia; Electroconvulsive Therapy; Haloperidol; Humans; Olanzapine; Psychopharmacology; Risperidone
PubMed: 33340800
DOI: 10.1016/j.psychres.2020.113641 -
European Journal of Psychotraumatology 2021: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all... (Meta-Analysis)
Meta-Analysis
: Pharmacological approaches are widely used for post-traumatic stress disorder (PTSD) despite uncertainty over efficacy. : To determine the efficacy of all pharmacological approaches, including monotherapy, augmentation and head-to-head approaches (drug versus drug, drug versus psychotherapy), in reducing PTSD symptom severity. : A systematic review and meta-analysis of randomised controlled trials were undertaken; 115 studies were included. : Selective serotonin reuptake inhibitors (SSRIs) were found to be statistically superior to placebo in reduction of PTSD symptoms but the effect size was small (standardised mean difference -0.28, 95% CI -0.39 to -0.17). For individual monotherapy agents compared to placebo in two or more studies, we found small statistically significant evidence for the antidepressants fluoxetine, paroxetine, sertraline, venlafaxine and the antipsychotic quetiapine. For pharmacological augmentation, we found small statistically significant evidence for prazosin and risperidone. : Some medications have a small positive effect on reducing PTSD symptom severity and can be considered as potential monotherapy treatments; these include fluoxetine, paroxetine, sertraline, venlafaxine and quetiapine. Two medications, prazosin and risperidone, also have a small positive effect when used to augment pharmacological monotherapy. There was no evidence of superiority for one intervention over another in the small number of head-to-head comparison studies.
Topics: Adrenergic alpha-1 Receptor Antagonists; Antipsychotic Agents; Drug Synergism; Drug Therapy, Combination; Humans; Selective Serotonin Reuptake Inhibitors; Stress Disorders, Post-Traumatic
PubMed: 34992738
DOI: 10.1080/20008198.2020.1802920 -
International Journal of Environmental... Dec 2022Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and... (Meta-Analysis)
Meta-Analysis Review
Nightmares are highly prevalent and distressing for the sufferer, which underlines the need for well-documented treatments. A comprehensive literature review and meta-analysis of the effects of different pharmacological placebo-controlled randomized clinical trials, covering the period up to 1 December 2022, was performed. Searches were conducted in PubMed, Embase, Web of Science, PsychInfo, Cinahl, and Google Scholar, resulting in the identification of 1762 articles, of which 14 met the inclusion criteria: pharmacological intervention of nightmares, based on a placebo-controlled randomized trial published in a European language, reporting outcomes either/or in terms of nightmare frequency, nightmare distress, or nightmare intensity, and reporting sufficient information enabling calculation of effect sizes. Most studies involved the effect of the α-adrenergic antagonist prazosin in samples of veterans or soldiers suffering from posttraumatic stress disorder. Other medications used were hydroxyzine, clonazepam, cyproheptadine, nabilone, and doxazosin. The vast majority of studies were conducted in the USA. The studies comprised a total of 830 participants. The Clinician-Administered PTSD Scale was the most frequently used outcome measure. The results showed an overall effect size of Hedges' = 0.50 (0.42 after adjustment for publication bias). The synthetic cannabinoid nabilone (one study) showed the highest effect size ( = 1.86), followed by the histamine H-antagonist hydroxyzine (one study), and prazosin (10 studies), with effect sizes of = 1.17 and = 0.54, respectively. Findings and limitations are discussed, and recommendations for future studies are provided.
Topics: Humans; Dreams; Randomized Controlled Trials as Topic; Prazosin; Adrenergic alpha-1 Receptor Antagonists; Stress Disorders, Post-Traumatic; Hydroxyzine
PubMed: 36613097
DOI: 10.3390/ijerph20010777 -
Neuroscience and Biobehavioral Reviews Aug 2022This network meta-analysis compares the efficacy and acceptability of all published psychotherapeutic and pharmacological interventions for trauma-related nightmares... (Meta-Analysis)
Meta-Analysis Review
This network meta-analysis compares the efficacy and acceptability of all published psychotherapeutic and pharmacological interventions for trauma-related nightmares (TRN) in adults. The analysis included data from 29 randomized clinical trials involving 14 psychotherapeutic and pharmacological interventions and involved 2214 trauma survivors. Prazosin and image rehearsal therapy (IRT) were found to be the two effective interventions for TRN. Other interventions such as risperidone, paroxetine, cognitive behavioral therapy for insomnia (CBT-I), CBT-I+IRT, prolonged exposure (PE), and IRT+PE, did not show significantly greater efficacy compared with control conditions. The rates of all-cause discontinuations were comparable among majority of the interventions and did not show significant differences compared with control conditions. Prazosin and IRT should be considered as the initial choice of pharmacological and psychotherapeutic interventions for TRN. The efficacy of other pharmacological and psychotherapeutic interventions remains to be demonstrated. Future guidelines and daily clinical decision making on the choice of interventions for TRN should consider these findings.
Topics: Adult; Dreams; Humans; Implosive Therapy; Network Meta-Analysis; Prazosin; Psychotropic Drugs; Stress Disorders, Post-Traumatic
PubMed: 35661755
DOI: 10.1016/j.neubiorev.2022.104717 -
The Primary Care Companion For CNS... Jul 2016To consolidate the evidence from the literature to evaluate the role of prazosin in the treatment of posttraumatic stress disorder (PTSD). (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To consolidate the evidence from the literature to evaluate the role of prazosin in the treatment of posttraumatic stress disorder (PTSD).
DATA SOURCES
Major databases, including PubMed, Ovid EMBASE, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Ovid PsycINFO, and Scopus, were searched through August 2015 for studies reporting the role of prazosin in the treatment of PTSD with no language constraints. Keywords included (PTSD OR posttraumatic stress OR posttraumatic stress OR nightmares) AND prazosin.
STUDY SELECTION
Of 402 screened articles, 6 studies were included in the systematic review and meta-analysis.
DATA EXTRACTION
Two reviewers independently extracted relevant data (study characteristics, type of intervention, outcome measures, and follow-up) from the included studies using a standardized data extraction form. Only randomized controlled trials comparing prazosin to a placebo or control group in patients with PTSD were included.
RESULTS
The patients with PTSD receiving prazosin showed significant improvement in nightmares (standardized mean difference [SMD] = 1.01; 95% CI, 0.72-1.30), overall PTSD symptoms (SMD = 0.77; 95% CI, 0.48-1.06), and clinical global improvement (SMD = 0.94; 95%, CI 0.6-1.29) compared to the placebo/control group. Prazosin improved sleep quality (SMD = 0.87; 95% CI, 0.55-1.19), hyperarousal symptoms (SMD = 1.04; 95% CI, 0.23-1.84), dream content (SMD = 1.33; 95% CI, 0.69-1.97), and total sleep time (60.98 minutes; 95% CI, 18.69-103.26). Prazosin was fairly well tolerated. Minor side effects were reported, which were similar between the prazosin and placebo groups.
CONCLUSIONS
This study suggests that prazosin improves nightmares and overall PTSD symptoms including hyperarousal, sleep disturbances, total sleep time, and sleep quality.
Topics: Adult; Dreams; Female; Humans; Male; Middle Aged; Prazosin; Randomized Controlled Trials as Topic; Sleep Wake Disorders; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 27828694
DOI: 10.4088/PCC.16r01943 -
Journal of the Royal Army Medical Corps Jul 2018In 2015, the Australian Army commissioned a systematic review to assess the evidence on effectiveness and safety of pharmacological and biotechnological products for... (Review)
Review
INTRODUCTION
In 2015, the Australian Army commissioned a systematic review to assess the evidence on effectiveness and safety of pharmacological and biotechnological products for cognitive enhancement specifically in Army personnel.
METHODS
Searches for studies examining biotechnological and pharmacological products in Army populations were conducted in December 2015. Cochrane CENTRAL, MEDLINE, EMBASE, CINAHL and PsycINFO were searched without date or language restrictions. WHO's International Clinical Trials Registry Platform and ClinicalTrials.gov were searched to identify ongoing trials. Studies meeting inclusion criteria were evaluated for risk of bias using Cochrane's Risk of Bias tool. Due to heterogeneity of findings, meta-analysis could not be conducted. Findings were synthesised narratively and by vote-counting method.
RESULTS
Sixteen pharmacological enhancement products were evaluated in 22 randomised controlled trials (RCTs), involving 1284 personnel. Only three of the studies were published since 2010. The interventions evaluated were varied, including supplements (eg, carbohydrate), stimulants (eg, caffeine) and hormones (eg, melatonin). Generally, caffeine provided an improvement in performance compared with placebo on 5/7 reported cognitive outcomes, followed by levothyroxine (four cognitive outcomes) and prazosin (three cognitive outcomes). Performance results were mixed (finding an improvement and no effect in comparison to placebo) for caffeine and melatonin on two outcomes. No evidence was found pertaining to biotechnological products. Studies rarely reported safety outcomes (eg, adverse events and addiction).
CONCLUSION
Findings from this review need to be interpreted with considerable caution. Future studies should include outcomes such as acute and long-term adverse events, and should evaluate cognitive performance using cognitive tests that are specific to the Army population.
Topics: Biotechnology; Cognition; Evidence-Based Medicine; Humans; Military Medicine; Performance-Enhancing Substances
PubMed: 28835510
DOI: 10.1136/jramc-2016-000752 -
Journal of Clinical Psychopharmacology Feb 2017The aim of this systematic review was to identify published articles that evaluated the use of prazosin for treating nightmares in children and adolescents who have... (Review)
Review
BACKGROUND
The aim of this systematic review was to identify published articles that evaluated the use of prazosin for treating nightmares in children and adolescents who have posttraumatic stress disorder (PTSD).
PROCEDURES
A literature search was conducted of PubMed, MEDLINE, EMBASE, Cochrane Collaboration, and PsycINFO databases for published articles in any language that evaluated the use of prazosin for treating nightmares in the context of PTSD in children and adolescents using the following key words: PTSD, nightmares, prazosin, children, adolescents, trauma, and sleep.
RESULTS
A total of 9 published articles related to the use of prazosin for treatment of nightmares in PTSD in children and adolescents were identified. Six of the 9 articles that met our inclusion criteria were case reports. All of these 6 case reports showed marked improvement in nightmares when prazosin was used, although at a generally lower dose when compared with its use in adults, with dosing ranging from 1 to 4 mg/d.
CONCLUSIONS
Prazosin has shown promising outcomes in treating nightmares associated with PTSD in children and adolescents, although this has not been well studied. Future placebo-controlled trials are needed to assess the efficacy and safety of prazosin in treating PTSD-related nightmares in children and adolescents.
Topics: Adolescent; Adrenergic alpha-1 Receptor Antagonists; Child; Dreams; Humans; Prazosin; Sleep Wake Disorders; Stress Disorders, Post-Traumatic
PubMed: 27930498
DOI: 10.1097/JCP.0000000000000638 -
CNS Spectrums Aug 2021Prazosin has been an accepted treatment for patients with post-traumatic stress disorder (PTSD) who experience sleep disturbances, including nightmares. Results of a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Prazosin has been an accepted treatment for patients with post-traumatic stress disorder (PTSD) who experience sleep disturbances, including nightmares. Results of a recent large randomized control trial did not find benefit of prazosin vs placebo in improving such outcomes. A meta-analysis that includes this most recent trial was conducted to examine the pooled effect of prazosin vs placebo on sleep disturbances and overall PTSD symptoms in patients with PTSD.
METHODS
A systematic review of the published literature on trials comparing prazosin vs placebo for improvement of overall PTSD scores, nightmares, and sleep quality was conducted. Hedges' g standardized mean differences (SMD) between prazosin and placebo were calculated for each outcome across studies.
RESULTS
Six randomized placebo-controlled studies representing 429 patients were included in the analysis, including two studies with a crossover design. Results showed prazosin significantly improved overall PTSD scores (SMD = -0.31; 95% confidence intervals [CI]: -0.62, -0.01), nightmares (SMD = -0.75; 95% CI: -1.24, -0.27), and sleep quality (SMD = -0.57; 95% CI: -1.02, -0.13). In the largest trial, prazosin showed a reduction in clinical outcome measures similar to past studies, but a relatively large placebo effect size, particularly for nightmares, contributed to no treatment differences.
CONCLUSIONS
Despite the results of a recent, large randomized study, pooled effect estimates show that prazosin has a statistically significant benefit on PTSD symptoms and sleep disturbances. Limitations that should be considered include heterogeneity of study design and study populations as well as the small number of studies conducted and included in this meta-analysis.
Topics: Adrenergic alpha-1 Receptor Antagonists; Humans; Prazosin; Stress Disorders, Post-Traumatic; Treatment Outcome
PubMed: 32362287
DOI: 10.1017/S1092852920001121