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Annals of Internal Medicine Mar 2024The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of...
The Management of Posttraumatic Stress Disorder and Acute Stress Disorder: Synopsis of the 2023 U.S. Department of Veterans Affairs and U.S. Department of Defense Clinical Practice Guideline.
DESCRIPTION
The U.S. Department of Veterans Affairs (VA) and Department of Defense (DoD) worked together to revise the 2017 VA/DoD Clinical Practice Guideline for the Management of Posttraumatic Stress Disorder and Acute Stress Disorder. This article summarizes the 2023 clinical practice guideline (CPG) and its development process, focusing on assessments and treatments for which evidence was sufficient to support a recommendation for or against.
METHODS
Subject experts from both departments developed 12 key questions and reviewed the published literature after a systematic search using the PICOTS (population, intervention, comparator, outcomes, timing of outcomes measurement, and setting) method. The evidence was then evaluated using the GRADE (Grading of Recommendations Assessment, Development and Evaluation) method. Recommendations were made after consensus was reached; they were based on quality and strength of evidence and informed by other factors, including feasibility and patient perspectives. Once the draft was peer reviewed by an external group of experts and their inputs were incorporated, the final document was completed.
RECOMMENDATIONS
The revised CPG includes 34 recommendations in the following 5 topic areas: assessment and diagnosis, prevention, treatment, treatment of nightmares, and treatment of posttraumatic stress disorder (PTSD) with co-occurring conditions. Six recommendations on PTSD treatment were rated as strong. The CPG recommends use of specific manualized psychotherapies over pharmacotherapy; prolonged exposure, cognitive processing therapy, or eye movement desensitization and reprocessing psychotherapy; paroxetine, sertraline, or venlafaxine; and secure video teleconferencing to deliver recommended psychotherapy when that therapy has been validated for use with video teleconferencing or when other options are unavailable. The CPG also recommends against use of benzodiazepines, cannabis, or cannabis-derived products. Providers are encouraged to use this guideline to support evidence-based, patient-centered care and shared decision making to optimize individuals' health outcomes and quality of life.
Topics: Humans; United States; Stress Disorders, Post-Traumatic; Stress Disorders, Traumatic, Acute; Veterans; Quality of Life; Psychotherapy; United States Department of Veterans Affairs
PubMed: 38408360
DOI: 10.7326/M23-2757 -
International Journal of Molecular... Dec 2023Pathological cardiac remodeling is associated with cardiovascular disease and can lead to heart failure. Nuclear factor-kappa B (NF-κB) is upregulated in the...
Cardioprotective Effects of the GRK2 Inhibitor Paroxetine on Isoproterenol-Induced Cardiac Remodeling by Modulating NF-κB Mediated Prohypertrophic and Profibrotic Gene Expression.
Pathological cardiac remodeling is associated with cardiovascular disease and can lead to heart failure. Nuclear factor-kappa B (NF-κB) is upregulated in the hypertrophic heart. Moreover, the expression of the G-protein-coupled receptor kinase 2 (GRK2) is increased and linked to the progression of heart failure. The inhibitory effects of paroxetine on GRK2 have been established. However, its protective effect on IκBα/NFκB signaling has not been elucidated. This study investigated the cardioprotective effect of paroxetine in an animal model of cardiac hypertrophy (CH), focusing on its effect on GRK2-mediated NF-κB-regulated expression of prohypertrophic and profibrotic genes. Wistar albino rats were administered normal saline, paroxetine, or fluoxetine, followed by isoproterenol to induce CH. The cardioprotective effects of the treatments were determined by assessing cardiac injury, inflammatory biomarker levels, histopathological changes, and hypertrophic and fibrotic genes in cardiomyocytes. Paroxetine pre-treatment significantly decreased the HW/BW ratio ( < 0.001), and the expression of prohypertrophic and profibrotic genes Troponin-I ( < 0.001), BNP ( < 0.01), ( < 0.001), hydroxyproline ( < 0.05), ( < 0.05), and ( < 0.01) as well as inflammatory markers. It also markedly decreased pIκBα, NFκB(p105) subunit expression ( < 0.05) and phosphorylation. The findings suggest that paroxetine prevents pathological cardiac remodeling by inhibiting the GRK2-mediated IκBα/NF-κB signaling pathway.
Topics: Rats; Animals; NF-kappa B; Paroxetine; NF-KappaB Inhibitor alpha; Isoproterenol; G-Protein-Coupled Receptor Kinase 2; Ventricular Remodeling; Myocytes, Cardiac; Cardiomegaly; Heart Failure; Rats, Wistar; Gene Expression
PubMed: 38139099
DOI: 10.3390/ijms242417270 -
Journal of Pharmacy Practice Dec 2023This brief report describes the case of a 16-year-old girl who was commenced on sertraline for anxiety and depression, and subsequently developed severe and debilitating... (Review)
Review
This brief report describes the case of a 16-year-old girl who was commenced on sertraline for anxiety and depression, and subsequently developed severe and debilitating motor tics. Cessation of sertraline was associated with the resolution of tics; after this, paroxetine was trialled and well tolerated with good response of targeted symptoms and without re-emergence of tics. A narrative literature review yielded a retrospective observational study and eight single case reports on selective serotonin receptor inhibitor-induced motor tics (three in adolescents and five in adults). Tics are not commonly considered as a side-effect of SSRIs. This case report is novel is several aspects: the tics emergence was immediate whereas previous cases were delayed; the tics symptoms were measured and quantified by a validated scale; a dose-response relationship was observed; to our knowledge, our case was the first adolescent female reported; and finally, paroxetine was well-tolerated as a substitute, although it is unclear whether the observed tics-sparing effect is co-incidental, ideocratic or can be replicated.
Topics: Adolescent; Female; Humans; Anxiety; Observational Studies as Topic; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sertraline; Tics; Adult
PubMed: 35943957
DOI: 10.1177/08971900221118015 -
Psychopharmacology Nov 2023Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these...
RATIONALE
Non-invasive home cage monitoring is emerging as a valuable tool to assess the effects of experimental interventions on mouse behaviour. A field in which these techniques may prove useful is the study of repeated selective serotonin reuptake inhibitor (SSRI) treatment and discontinuation. SSRI discontinuation syndrome is an under-researched condition that includes the emergence of sleep disturbances following treatment cessation.
OBJECTIVES
We used passive infrared (PIR) monitoring to investigate changes in activity, sleep, and circadian rhythms during repeated treatment with the SSRI paroxetine and its discontinuation in mice.
METHODS
Male mice received paroxetine (10 mg/kg/day, s.c.) for 12 days, then were swapped to saline injections for a 13 day discontinuation period and compared to mice that received saline injections throughout. Mice were continuously tracked using the Continuous Open Mouse Phenotyping of Activity and Sleep Status (COMPASS) system.
RESULTS
Repeated paroxetine treatment reduced activity and increased behaviourally-defined sleep in the dark phase. These effects recovered to saline-control levels within 24 h of paroxetine cessation, yet there was also evidence of a lengthening of sleep bouts in the dark phase for up to a week following discontinuation.
CONCLUSIONS
This study provides the first example of how continuous non-invasive home cage monitoring can be used to detect objective behavioural changes in activity and sleep during and after drug treatment in mice. These data suggest that effects of paroxetine administration reversed soon after its discontinuation but identified an emergent change in sleep bout duration, which could be used as a biomarker in future preclinical studies to prevent or minimise SSRI discontinuation symptoms.
Topics: Male; Animals; Mice; Paroxetine; Selective Serotonin Reuptake Inhibitors; Sleep; Circadian Rhythm
PubMed: 37584734
DOI: 10.1007/s00213-023-06442-3 -
Expert Review of Neurotherapeutics Jul 2024Despite its milder severity, the chronic nature of dysthymia leads to significant impairments and functional limitations. The treatment of dysthymia has received... (Review)
Review
INTRODUCTION
Despite its milder severity, the chronic nature of dysthymia leads to significant impairments and functional limitations. The treatment of dysthymia has received considerably less research attention compared to major depressive disorder (MDD).
AREAS COVERED
The authors have conducted a comprehensive review on the treatment of dysthymia. Their primary objective was to identify therapeutic options that have demonstrated genuine efficacy. To do this, they searched the PubMed database, without any time restrictions, to retrieve original studies. The samples were exclusively comprised individuals diagnosed with dysthymia according to the diagnostic criteria outlined in DSM-III, DSM-III-R, DSM-IV, or DSM-IV-TR.
EXPERT OPINION
Within the realm of dysthymia treatment, several antidepressants, including imipramine, sertraline, paroxetine, minaprine, moclobemide, and amineptine, in addition to the antipsychotic agent amisulpride, have demonstrated superiority over placebo. In certain studies, psychotherapeutic interventions did not distinguish themselves significantly from pharmacological treatments and failed to exhibit greater efficacy than a placebo. However, these findings remain inconclusive due to the limited number of studies and substantial methodological limitations prevalent in a significant proportion of them. Limitations include factors like small sample sizes, the absence of placebo comparisons, and a lack of study blinding.
Topics: Humans; Dysthymic Disorder; Antidepressive Agents; Antipsychotic Agents; Psychotherapy
PubMed: 38805342
DOI: 10.1080/14737175.2024.2360671 -
Sleep Medicine Jul 2024Sleep disturbances are an important symptom dimension of post-traumatic-stress-disorder (PTSD). There is no meta-analytic evidence examining the effects of all types of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Sleep disturbances are an important symptom dimension of post-traumatic-stress-disorder (PTSD). There is no meta-analytic evidence examining the effects of all types of pharmacotherapy on sleep outcomes among patients with PTSD.
METHODS
Medline/Embase/PsychInfo/CENTRAL/clinicaltrials.gov/ICTRP, reference lists of published reviews and all included studies were searched for Randomised Controlled Trials (RCTs) examining any pharmacotherapy vs. placebo or any other drug among patients with PTSD.
PRIMARY OUTCOMES
total sleep time, nightmares, sleep quality.
SECONDARY OUTCOMES
sleep onset latency, number of nocturnal awakenings, time spent awake following sleep onset, dropouts due to sleep-related adverse-effects, insomnia/somnolence/vivid-dreams as adverse-effects. Pairwise and network meta-analyses were performed.
RESULTS
99 RCTs with 10,481 participants were included. Prazosin may be the most effective treatment for insomnia (SMD = -0.88, 95%CI = [-1.22;-0.54], nightmares (SMD = -0.44, 95%CI = [-0.84;-0.04]) and poor sleep quality (SMD = -0.55, 95%CI = [-1.01;-0.10]). Evidence is scarce and indicates lack of efficacy for SSRIs, Mirtazapine, z-drugs and benzodiazepines, which are widely used in daily practice. Risperidone and Quetiapine carry a high risk of causing somnolence without having a clear therapeutic benefit. Hydroxyzine, Trazodone, Nabilone, Paroxetine and MDMA-assisted psychotherapy may be promising options, but more research is needed.
CONCLUSIONS
Underpowered individual comparisons and very-low to moderate confidence in effect estimates hinder the generalisability of the results. More RCTs, specifically reporting on sleep-related outcomes, are urgently needed.
Topics: Humans; Stress Disorders, Post-Traumatic; Network Meta-Analysis; Sleep Wake Disorders; Prazosin; Randomized Controlled Trials as Topic; Dreams; Sleep Initiation and Maintenance Disorders
PubMed: 38795401
DOI: 10.1016/j.sleep.2024.05.032 -
CNS Drugs Apr 2024Compulsive sexual behavior disorder (CSBD) has recently been recognized as a psychiatric disorder. Pharmacological treatments for CSBD have received little study and... (Review)
Review
Compulsive sexual behavior disorder (CSBD) has recently been recognized as a psychiatric disorder. Pharmacological treatments for CSBD have received little study and thus have limited empirical support. The main objective of the present work is to review existing literature on the efficacy of different drugs on the symptomatology of CSBD, including the subtype of problematic pornography use (PPU). The main pharmacological approaches to treating CSBD have included opioid antagonists (naltrexone and nalmefene), selective serotonin reuptake inhibitors (paroxetine, citalopram, fluoxetine, and sertraline), mood stabilizers (topiramate), tricyclic antidepressants (clomipramine), serotonin antagonist and reuptake inhibitors (nefazodone), and N-acetylcysteine. Since people with CSBD may experience different co-occurring disorders, these should be considered when choosing the best pharmacological treatment. Pharmacological therapy for CSBD/PPU has been suggested as an adjunct to psychological therapies, which, for the moment, have the most empirical evidence. However, to evaluate the efficacy of most of the drugs presented in this narrative review, data to date have only been available from case studies. Thus, empirical support is scant and generalizability of results is limited, highlighting the need for more research in this area.
Topics: Humans; Compulsive Sexual Behavior Disorder; Selective Serotonin Reuptake Inhibitors; Paroxetine; Sertraline; Fluoxetine; Compulsive Behavior
PubMed: 38485889
DOI: 10.1007/s40263-024-01075-2 -
Cureus Jan 2024An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset.... (Review)
Review
An average of 60-80% of all menopausal women experience bothersome vasomotor symptoms (VMSs), such as flushing and sweating, within the first seven years of onset. However, despite increasing prevalence, these hot flashes remain hard to treat and have a negative effect on the quality of life. Though hormone replacement therapy is commonly utilized as a standard treatment for VMSs, this therapy is not recommended for all women. Specifically, the oral form of hormone replacement therapy is associated with several contraindications, including a history of thromboembolic disease, migraine headache with aura, liver failure, heart disease, and hormone-dependent cancers. For women with these medical conditions, current literature indicates that nonhormonal therapies such as selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) are suitable alternatives to reduce the frequency and intensity of VMSs. Currently, the only SSRI that is FDA-approved for the treatment of VMSs is paroxetine, but studies show that fluoxetine, citalopram, escitalopram, and sertraline are also proven to provide similar benefits. Similarly, the SNRI venlafaxine has also been well tolerated and has been shown to reduce the frequency and severity of hot flashes. The present investigation reviews the physiology of VMSs and examines the evidence for the use of nonhormonal pharmacologic therapies as treatment for women experiencing hot flashes. These interventions should be considered whenever hormone replacement therapy is contraindicated, with therapy individualized based on the severity of symptoms.
PubMed: 38371081
DOI: 10.7759/cureus.52467 -
The Medical Letter on Drugs and... Mar 2024
Topics: Humans; Hot Flashes; Menopause
PubMed: 38412276
DOI: 10.58347/tml.2024.1697a -
Journal of Sex Research Dec 2023Compulsive sexual behavior disorder (CSBD) is a burgeoning diagnostic construct. No systematic reviews of CSBD pharmacotherapy interventions have been conducted. We... (Review)
Review
Compulsive sexual behavior disorder (CSBD) is a burgeoning diagnostic construct. No systematic reviews of CSBD pharmacotherapy interventions have been conducted. We addressed this gap using a three-aim approach. We reviewed researchers' theoretical arguments for various pharmacotherapies, outcomes from pharmacotherapy trials, and the generalizability of the extant findings. Our review included = 13 studies, with = 141 participants. An opioid model of reward seeking was the most popular framework, though inconsistently specified. A serotonin model was also documented, though with few details. Naltrexone was the most prominently examined pharmacotherapy and the only medication that reliably demonstrated a therapeutic effect for some (but not all) indicators compared to placebo. Paroxetine and citalopram were also documented in placebo-controlled trials, though their incremental benefit compared to placebo is suspect. Several additional pharmacotherapies have been documented in case series contexts. Across studies, only one female participant was identified. All trials were conducted in developed nations, and race was rarely assessed. We conclude that the case for pharmacotherapy for CSBD is limited and should preferably not occur outside of clinical trial contexts. Naltrexone offers the best evidence for a potential research program, though new theoretically informed approaches are welcome. Finally, we call for additional pharmacotherapy research in women and non-White populations.
PubMed: 38047874
DOI: 10.1080/00224499.2023.2282619