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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 -
Journal of Integrative Neuroscience Jul 2023Stress can lead to emotional and mental symptoms such as anxiety, sadness, panic attacks, and depression. Malic acid was chosen due to malic acid has the ability to...
BACKGROUND
Stress can lead to emotional and mental symptoms such as anxiety, sadness, panic attacks, and depression. Malic acid was chosen due to malic acid has the ability to improve antioxidant activity and improves liver damage. This study evaluates malic acid anti-depressant activity in the hypothalamus of stressed rats.
METHODS
Thirty-six male albino rats were divided into 2 equal groups; Normal and chronic mild stress (CMS) rats. Normal rats were divided into 3 equal groups; control, malic acid, and venlafaxine drug groups: normal rats were administered orally with 1 mL of saline solution, 250 mg/kg of malic acid, and 20 mg/kg of venlafaxine drug, respectively. CMS rats were divided into 3 equal groups; CMS, CMS + malic acid, and CMS + venlafaxine drug: CMS rats were administered orally with 1 mL of saline solution, 250 mg/kg of malic acid, and 20 mg/kg of venlafaxine drug, respectively. All the above-mentioned treatments were administered once a day by oral gavage for 6 weeks.
RESULTS
The obtained results revealed that the animal behavioral tests such as forced swimming test, tail suspension test, sucrose preference test, and open-field test (center square entries test, center square duration test, and distance travelled test), norepinephrine, dopamine, serotonin, γ-aminobutyric acid, nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase activity, oxidative index, conjugated dienes, catalase, glutathione peroxidase, superoxide dismutase, malondialdehyde, interleukin-6, tumor necrosis factor-α, interleukin-10, interleukin-1β, sodium/potassium-ATPase activity, and histamine-N-methyl transferase () and tyrosine hydroxylase () enzymes in the hypothalamus of stressed rats, were returned to approaching the normal state in the stressed group after treating with malic acid for 6 weeks.
CONCLUSIONS
Malic acid ameliorated stressed-related symptoms and it inhibited superoxide anion and neuro-inflammation in the hypothalamus of stressed rats.
Topics: Rats; Male; Animals; Venlafaxine Hydrochloride; Saline Solution; Depression; Hypothalamus; Stress, Psychological; Oxidative Stress
PubMed: 37519180
DOI: 10.31083/j.jin2204098 -
Frontiers in Pharmacology 2023Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and...
Non-adherence to antidepressants is associated with worse disease outcomes (morbidity and mortality) and correlates with higher healthcare resource utilization and costs. A population-based registry study was conducted to assess non-adherence and to analyze the economic burden of treatment and from non-adherence to antidepressants in 2021. Non-adherence was measured by the Medication Possession Ratio and those below 80% were classified as non-adherent. In 2021, 246,718 patients (10.60% [95% CI: 10.48-10.72]) received antidepressants at a cost of €29 million. The median antidepressant cost per patient/year was €70.08€, ranging from €7.58 for amitriptyline to €396.66 for agomelatine. Out-of-pocket costs represented 6.09% of total expenditures, with a median copayment of €2.78 per patient. The 19.87% [95% CI 19.52-20.22)] of patients were non-adherent to antidepressants, costing €3.9 million (13.30% of total antidepressant costs). Non-adherence rates exceeded 20% for the tricyclic antidepressants, fluoxetine (23.53%), fluvoxamine (22.42%), and vortioxetine (20.58%). Venlafaxine (14.64%) and citalopram (14.88%) had the lowest non-adherence rates, of less than 15%. The median cost of non-adherent medications per patient/year was €18.96 and ranged from €2.50 (amitriptyline) to €133.42 (agomelatine). Reducing non-adherence to antidepressants is critical to improving clinical and economic outcomes. The implementation of interventions and standardized measures, including early detection indicators, is urgently needed. Antidepressants differ with regard to non-adherence and their cost, and this should be considered when prescribing this medication. The Medication Possession Ratio could be used by the healthcare provider and clinician to identify non-adherent patients for monitoring, and to take necessary corrective actions.
PubMed: 38035007
DOI: 10.3389/fphar.2023.1266034 -
The Science of the Total Environment Dec 2023This study utilizes wastewater-based epidemiology (WBE) to evaluate spatiotemporal changes in the consumption of antidepressants before and during the COVID-19 pandemic...
This study utilizes wastewater-based epidemiology (WBE) to evaluate spatiotemporal changes in the consumption of antidepressants before and during the COVID-19 pandemic in Slovenia. Composite 24-h influent wastewater samples (n = 210) were collected from six wastewater treatment plants between summer 2019 and spring 2021. The samples were extracted using 96-well solid-phase extraction and analysed by liquid chromatography-tandem mass spectrometry. The measured concentrations of target antidepressant biomarkers were then converted to population-normalised mass loads (PNMLs), taking into account flow rate and catchment population. Ten biomarkers, including amitriptyline, bupropion, bupropion-OH, citalopram, norcitalopram, normirtazapine, venlafaxine, O-desmethylvenlafaxine, trazodone, and moclobemide, were above the lower limit of quantification and were included in the spatiotemporal temporal assessment. The highest PNMLs were detected for O-desmethylvenlafaxine (mean ± SD: 82.1 ± 21.2 mg/day/1000 inhabitants) and venlafaxine (38.0 ± 10.6 mg/day/1000 inhabitants), followed by citalopram (27.0 ± 10.7 mg/day/1000 inhabitants). In addition, the mean metabolite/parent compound ratios were comparable with other WBE studies indicating consumption rather than direct disposal. Overall, the results indicated significant spatiotemporal variations depending on the location, and the PNMLs of most biomarkers increased during the first wave of the COVID-19 pandemic (spring of 2020). However, no clear spatial patterns were revealed related to the pandemic.
PubMed: 37640073
DOI: 10.1016/j.scitotenv.2023.166586 -
Neurochemistry International Oct 2023Antidepressants are used to treat depression and some anxiety disorders, including use in pregnant patients. The pharmacological actions of these drugs generally...
Antidepressants are used to treat depression and some anxiety disorders, including use in pregnant patients. The pharmacological actions of these drugs generally determine the uptake and metabolism of a series of neurotransmitters, such as serotonin, norepinephrine, or dopamine, along with an increase in BDNF expression. However, many aspects of antidepressant action remain unknown, particularly whether antidepressants interfere with normal neurodevelopment when taken by pregnant women. In order to reveal cellular and molecular implications crucial to the functioning of pathways related to antidepressant effects, we performed an investigation on neuronally differentiating human SH-SY5Y cells. To our knowledge, this is the first time human SH-SY5Y cells in cultures of purely neuronal cells induced by controlled differentiation with retinoic acid are followed by short-term 48-h exposure to 0.1-10 μM escitalopram or venlafaxine. Treatment with antidepressants (1 μM) did not affect the electrophysiological properties of SH-SY5Y cells. However, the percentage of mature neurons exhibiting voltage-gated sodium currents was substantially higher in cultures pre-treated with either antidepressant. After exposure to escitalopram or venlafaxine, we observed a concentration-dependent increase in activity-dependent BDNF promoter IV activation. The assessment of neurite metrics showed significant down-regulation of neurite outgrowth upon exposure to venlafaxine. Identified changes may represent links to molecular processes of importance to depression and be involved in neurodevelopmental alterations observed in postpartum children exposed to antidepressants antenatally.
Topics: Child; Female; Humans; Pregnancy; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Line, Tumor; Escitalopram; Neuroblastoma; Neuronal Outgrowth; Neurons; Venlafaxine Hydrochloride
PubMed: 37451345
DOI: 10.1016/j.neuint.2023.105571 -
Psychopharmacology Feb 2024The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
The selective serotonin and norepinephrine reuptake inhibitor venlafaxine is among the most prescribed antidepressant drugs worldwide and, according to guidelines, its dose titration should be guided by drug-level monitoring of its active moiety (AM) which consists of venlafaxine (VEN) plus active metabolite O-desmethylvenlafaxine (ODV). This indication of therapeutic drug monitoring (TDM), however, assumes a clear concentration/effect relationship for a drug, which for VEN has not been systematically explored yet.
OBJECTIVES
We performed a systematic review and meta-analysis to investigate the relationship between blood levels, efficacy, and adverse reactions in order to suggest an optimal target concentration range for VEN oral formulations for the treatment of depression.
METHODS
Four databases (MEDLINE (PubMed), PsycINFO, Web of Science Core Collection, and Cochrane Library) were systematically searched in March 2022 for relevant articles according to a previously published protocol. Reviewers independently screened references and performed data extraction and critical appraisal.
RESULTS
High-quality randomized controlled trials investigating concentration/efficacy relationships and studies using a placebo lead-in phase were not found. Sixty-eight articles, consisting mostly of naturalistic TDM studies or small noncontrolled studies, met the eligibility criteria. Of them, five cohort studies reported a positive correlation between blood levels and antidepressant effects after VEN treatment. Our meta-analyses showed (i) higher AM and (ii) higher ODV concentrations in patients responding to VEN treatment when compared to non-responders (n = 360, k = 5). AM concentration-dependent occurrence of tremor was reported in one study. We found a linear relationship between daily dose and AM concentration within guideline recommended doses (75-225 mg/day). The population-based concentration ranges (25-75% interquartile) among 11 studies (n = 3200) using flexible dosing were (i) 225-450 ng/ml for the AM and (ii) 144-302 ng/ml for ODV. One PET study reported an occupancy of 80% serotonin transporters for ODV serum levels above 85 ng/ml. Based on our findings, we propose a therapeutic reference range for AM of 140-600 ng/ml.
CONCLUSION
VEN TDM within a range of 140 to 600 ng/ml (AM) will increase the probability of response in nonresponders. A titration within the proposed reference range is recommended in case of non-response at lower drug concentrations as a consequence of VEN's dual mechanism of action via combined serotonin and norepinephrine reuptake inhibition. Drug titration towards higher concentrations will, however, increase the risk for ADRs, in particular with supratherapeutic drug concentrations.
Topics: Humans; Antidepressive Agents; Depression; Desvenlafaxine Succinate; Norepinephrine; Reference Values; Serotonin; Venlafaxine Hydrochloride
PubMed: 37857898
DOI: 10.1007/s00213-023-06484-7 -
Pharmacopsychiatry Mar 2024CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on...
INTRODUCTION
CYP2D6 and CYP2C19 functional status as defined by genotype is modulated by phenoconversion (PC) due to pharmacokinetic interactions. As of today, there is no data on the effect size of PC for CYP2C19 functional status. The primary aim of this study was to investigate the impact of PC on CYP2C19 functional status.
METHODS
Two patient cohorts (total n=316; 44.2±15.4 years) were investigated for the functional enzyme status of CYP2C19 applying two different correction methods (PC, PC) as well as serum concentration and metabolite-to-parent ratio of venlafaxine, amitriptyline, mirtazapine, sertraline, escitalopram, risperidone, and quetiapine.
RESULTS
There was a decrease in the number of normal metabolizers of CYP2C19 and an increase in the number of poor metabolizers. When controlled for age, sex, and, in the case of amitriptyline, venlafaxine, and risperidone, CYP2D6 functional enzyme status, an association was observed between the CYP2C19 phenotype/functional enzyme status and serum concentration of amitriptyline, sertraline, and escitalopram.
DISCUSSION
PC of CYP2C19 changes phenotypes but does not improve correlations with serum concentrations. However, only a limited number of patients received perturbators of CYP2C19. Studies with large numbers of patients are still lacking, and thus, it cannot be decided if there are minor differences and which method of correction to use. For the time being, PC is relevant in individual patients treated with CYP2C19-affecting drugs, for example, esomeprazole. To ensure adequate serum concentrations in these patients, this study suggests the use of therapeutic drug monitoring.
Topics: Humans; Cytochrome P-450 CYP2D6; Venlafaxine Hydrochloride; Amitriptyline; Pharmacogenetics; Sertraline; Risperidone; Escitalopram; Cytochrome P-450 CYP2C19; Genotype
PubMed: 38354747
DOI: 10.1055/a-2248-6924 -
American Journal of Translational... 2023To determine the efficacy of venlafaxine combined with agomelatine in elderly patients with depression and observe the changes in S-100 calcium binding protein B...
OBJECTIVE
To determine the efficacy of venlafaxine combined with agomelatine in elderly patients with depression and observe the changes in S-100 calcium binding protein B (S-100B) and glial fibrillary acidic protein (GFAP) before and after treatment.
METHODS
The data of 142 elderly patients with depression treated in Affiliated Hospital of Gansu Medical College between January 2020 and January 2022 were retrospectively studied. Among the patients, 62 treated with venlafaxine were assigned to a control group, and 80 treated with agomelatine combined with venlafaxine were assigned to an observation group. In addition, 50 patients with suspected meningitis who were treated in Affiliated Hospital of Gansu Medical College over the same time span were enrolled into a normal group. The two groups of patients were compared in terms of clinical efficacy after treatment and the changes in S100B and GFAP before and after treatment. The diagnostic value of S100B and GFAP in patients with depression was explored. Additionally, the changes in Repeatable Battery for the Assessment of Neuropsychological Status (RBANS) score before and after treatment were compared between the two groups, and the adverse drug reaction rate was also compared.
RESULTS
The patient group showed higher cerebrospinal fluid (CSF) levels of S100B and GFAP than the control group (P < 0.001). The areas under the curve (AUC) of CSF S100B and GFAP for diagnosing depression were 0.833 and 0.925, respectively, and the AUC of the combination of the two was 0.967, which was larger than that of CSF S100B or GFAP alone (P < 0.001). Additionally, the control group showed lower clinical efficacy than the observation group (P < 0.001). After treatment, the observation group exhibited lower CSF levels of S100B and GFAP than the control group (P < 0.001), and demonstrated higher RBANS score than the control group (P < 0.001). The difference in adverse drug reaction rate was not significant between the control group and the observation group (P > 0.05).
CONCLUSION
S100B and GFAP can be used as diagnostic indicators of depression. Agomelatine plus venlafaxine are superior to venlafaxine alone in the treatment of depression. The combination can contribute to better S100B and GFAP levels, and take a more obvious role in alleviating disease symptoms, thereby improving the cognitive function and overall well-being of patients.
PubMed: 37692959
DOI: No ID Found -
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 Lancet. Psychiatry Jul 2024Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Antidepressant discontinuation symptoms are becoming an increasingly important part of clinical practice, but the incidence of antidepressant discontinuation symptoms has not been quantified. An estimate of antidepressant discontinuation symptoms incidence could inform patients and clinicians in the discontinuation of treatment, and provide useful information to researchers in antidepressant treatments. We aimed to assess the incidence of antidepressant discontinuation symptoms in patients discontinuing both antidepressants and placebo in the published literature.
METHODS
We systematically searched Medline, EMBASE, and CENTRAL from database inception until Oct 13, 2022 for randomised controlled trials (RCTs), other controlled trials, and observational studies assessing the incidence of antidepressant discontinuation symptoms. To be included, studies must have investigated cessation or tapering of an established antidepressant drug (excluding antipsychotics, lithium, or thyroxine) or placebo in participants with any mental, behavioural, or neurodevelopmental disorder. We excluded studies in neonates, and those using antidepressants for physical conditions such as pain syndromes due to organic disease. After study selection, summary data extraction, and risk of bias evaluation, data were pooled in random-effects meta-analyses. The main outcome was the incidence of antidepressant discontinuation symptoms after discontinuation of antidepressants or placebo. We also analysed the incidence of severe discontinuation symptoms. Sensitivity and meta-regression analyses tested a selection of methodological variables.
FINDINGS
From 6095 articles screened, 79 studies (44 RCTs and 35 observational studies) covering 21 002 patients were selected (72% female, 28% male, mean age 45 years [range 19·6-64·5]). Data on ethnicity were not consistently reported. 16 532 patients discontinued from an antidepressant, and 4470 patients discontinued from placebo. Incidence of at least one antidepressant discontinuation symptom was 0·31 (95% CI 0·27-0·35) in 62 study groups after discontinuation of antidepressants, and 0·17 (0·14-0·21) in 22 study groups after discontinuation of placebo. Between antidepressant and placebo groups of included RCTs, the summary difference in incidence was 0·08 [0·04-0·12]. The incidence of severe antidepressant discontinuation symptoms after discontinuation of an antidepressant was 0·028 (0·014-0·057) compared with 0·006 (0·002-0·013) after discontinuation of placebo. Desvenlafaxine, venlafaxine, imipramine, and escitalopram were associated with higher frequencies of discontinuation symptoms, and imipramine, paroxetine, and either desvenlafaxine or venlafaxine were associated with a higher severity of symptoms. Heterogeneity of results was substantial.
INTERPRETATION
Considering non-specific effects, as evidenced in placebo groups, the incidence of antidepressant discontinuation symptoms is approximately 15%, affecting one in six to seven patients who discontinue their medication. Subgroup analyses and heterogeneity figures point to factors not accounted for by diagnosis, medication, or trial-related characteristics, and might indicate subjective factors on the part of investigators, patients, or both. Residual or re-emerging psychopathology needs to be considered when interpreting the results, but our findings can inform clinicians and patients about the probable extent of antidepressant discontinuation symptoms without causing undue alarm.
FUNDING
None.
Topics: Humans; Antidepressive Agents; Incidence; Substance Withdrawal Syndrome; Randomized Controlled Trials as Topic
PubMed: 38851198
DOI: 10.1016/S2215-0366(24)00133-0