-
Medicine Aug 2023Paroxetine therapy has been used for treatment of patients with depression and Parkinson's disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Paroxetine therapy has been used for treatment of patients with depression and Parkinson's disease (dPD) in many clinical studies, but, the effects of paroxetine in dPD patients are not completely understood. The aim of this study was to systematically evaluate the effects of paroxetine therapy on depressive symptom and motor function in the treatment of dPD, in order to confer a reference for clinical practice.
METHODS
Randomized controlled trials (RCTs) of paroxetine for dPD published up to October, 2022 were retrieved. Standardised mean difference (SMD), odds ratio (OR), and 95% confidence interval (CI) were calculated and heterogeneity was measured with the I2 test. The outcomes of interest were as follows: the efficacy, Hamilton depression rating scale score, unified Parkinson's disease rating scale score, Hamilton anxiety rating scale score or adverse events.
RESULTS
Thirty-four RCTs with 2819 participants were included. Compared with control group, the pooled effects of paroxetine therapy on depression were (22 trials; OR 3.62, 95% CI 2.63 to 4.98, P < .00001) for antidepressant response (25 trials; SMD -2.14, 95% CI -2.73 to -1.56, P < .00001) for Hamilton depression rating scale score, the pooled effects of paroxetine therapy on motor function were (10 trials; OR 4.63, 95% CI 3.15 to 6.79, P < .00001) for anti-PD efficacy (18 trials; SMD -2.02, 95% CI -2.48 to -1.55, P < .00001) for total unified Parkinson's disease rating scale score. The Hamilton anxiety rating scale score showed significant decrease in the paroxetine treatment group compared to control group (10 trials; SMD -1.93, 95% CI -2.65 to -1.22, P < .00001). In addition, paroxetine therapy reduced the number of any adverse events obviously in dPD patients (twenty trials; OR 0.42, 95% CI 0.31 to 0.57, P < .00001).
CONCLUSIONS
Paroxetine therapy has clinical benefits for improvement of depressive symptom and motor function in dPD patients, moreover, it is of high drug safety. Further well-designed, multi-center RCTs needed to identify these findings.
Topics: Humans; Paroxetine; Parkinson Disease; Depression; Control Groups; Mental Status and Dementia Tests
PubMed: 37653795
DOI: 10.1097/MD.0000000000034687 -
BMJ Open Dec 2023Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
Adverse drug events associated with nortriptyline compared with paroxetine and alternative medications in an older adult population: a retrospective cohort study in Southern California.
OBJECTIVE
Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.
DESIGN
Retrospective cohort study.
SETTING
The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California.
PARTICIPANTS
Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018.
MAIN OUTCOME MEASURES
HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities.
RESULTS
Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin.
CONCLUSIONS
Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications.
Topics: Humans; Aged; Paroxetine; Nortriptyline; Citalopram; Fluoxetine; Sertraline; Venlafaxine Hydrochloride; Amitriptyline; Duloxetine Hydrochloride; Retrospective Studies; Escitalopram; Gabapentin; Drug-Related Side Effects and Adverse Reactions; Syncope
PubMed: 38154883
DOI: 10.1136/bmjopen-2023-076028 -
Psychiatry Research Jun 2024The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We... (Meta-Analysis)
Meta-Analysis
The relationship between the use of selective serotonin reuptake inhibitors (SSRIs) and suicide risk in patients with mental disorders remains controversial. We conducted a network meta-analysis to examine the effects of SSRIs on suicide risk in patients with mental disorders. A comprehensive search was conducted across PubMed, Web of Science, PsycINFO, CENTRAL, Wanfang Database, and China National Knowledge Infrastructure for articles published until December 19, 2023. The main outcomes were suicidal ideation and instances of suicidal behavior. We included 29 double-blind randomized trials in our analysis. The findings suggest that SSRIs primarily offer short-term protection against suicidal ideation. By week 2, paroxetine, fluoxetine, escitalopram, and non-SSRI treatments were linked to a decreased suicide risk compared with a placebo, with the exception of sertraline. This protective effect was diminished by week 8. In contrast, studies on instances of suicidal behavior from weeks 1 to 10 found no significant difference in efficacy between SSRIs, non-SSRIs, and placebo. These results indicate that SSRIs may offer short-term protection against suicidal ideation. However, their long-term effectiveness in mitigating suicidal ideation and preventing suicidal behaviors is limited.
Topics: Selective Serotonin Reuptake Inhibitors; Humans; Randomized Controlled Trials as Topic; Suicidal Ideation; Network Meta-Analysis; Double-Blind Method; Suicide; Mental Disorders
PubMed: 38663222
DOI: 10.1016/j.psychres.2024.115917 -
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 -
Chinese Medical Journal Jun 2024G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present...
BACKGROUND
G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA).
METHODS
The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism.
RESULTS
In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (Tregs), an increase in the cluster of differentiation 8 positive (CD8+) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8+ T cells, and induced the proportion of Tregs. Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells.
CONCLUSION
Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cell in RA.
PubMed: 38879805
DOI: 10.1097/CM9.0000000000003165 -
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 -
Micromachines Jun 2023Selective serotonin re-uptake inhibitors (SSRIs) are one of the most commonly prescribed classes of antidepressants used for the treatment of moderate to severe... (Review)
Review
Selective serotonin re-uptake inhibitors (SSRIs) are one of the most commonly prescribed classes of antidepressants used for the treatment of moderate to severe depressive disorder, personality disorders and various phobias. This class of antidepressants was created with improved margins of safety. However, genetic polymorphism may be responsible for the high variability in patients' responses to treatment, ranging from failure to delayed therapeutic responses to severe adverse effects of treatment. It is crucial that the appropriate amount of SSRI drugs is administered to ensure the optimum therapeutic efficacy and intervention to minimise severe and toxic effects in patients, which may be the result of accidental and deliberate cases of poisoning. Determining SSRI concentration in human fluids and the environment with high sensitivity, specificity and reproducibility, and at a low cost and real-time monitoring, is imperative. Electrochemical sensors with advanced functional materials have drawn the attention of researchers as a result of these advantages over conventional techniques. This review article aims to present functional materials such as polymers, carbon nanomaterials, metal nanomaterials as well as composites for surface modification of electrodes for sensitive detection and quantification of SSRIs, including fluoxetine, citalopram, paroxetine, fluvoxamine and sertraline. Sensor fabrication, sensor/analyte interactions, design rationale and properties of functional material and the electrocatalytic effect of the modified electrode on SSRI detection are discussed.
PubMed: 37512646
DOI: 10.3390/mi14071334 -
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 -
Heliyon May 2024To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the...
AIM
To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the arachidonic acid metabolic pathway and nuclear factor kappa-B(NF-κB) signal path in the hippocampi of postpartum depression rats.
METHODS
The rats were subcutaneous injected estradiol benzoate and progesterone to build PPD rat model. SJF, paroxetine hydrochloride and sEH inhibitor (AUDA) were used to treat PPD rats for 3 weeks. Then the morphological changes of hippocampi and various proteins were observed after that behavioral test were conducted in all 36 SD rats in six group: SJF, paroxetine, AUDA, PPD, sham and normal group.
RESULTS
Weight, results of sucrose preference, upright times, total and center squares crossing decreased significantly (P < 0.01), whereas immobility time increased (P < 0.01). Results above were reversed in animals that in the SJF, paroxetine and AUDA groups. Hippocampal neurons in PPD rats partially degenerated with narrowed nuclei, increased autophagy and mitochondria bound to lysosomes were visible while the autophagy of hippocampal neurons in the paroxetine and AUDA group decreased, with a small amount of lysosomes. sEH, COX-2, 5-LOX, TNF-α, IL-1, IL-6, NF-κB p65, and Cor increased in hippocampi of PPD rats while EETs and 5-HT decreased. Protein expressions of Ibal, GFAP, p-IκBα, p65, and p-p65(S536)increased in PPD animals. Those changes were reversed by SJF, paroxetine and AUDA. Gene expressions of TNF-α, IL-1β, IL-6, 5-LOX, COX-2 and p65 increased in PPD rats and the changes of expression in these genes were reversed by paroxetine and AUDA. SJF reversed the gene expression changes of COX-2, TNF-α, and IL-1β.
CONCLUSION
SJF may have an analogous effect as sEH inhibitor to relieve depressive symptoms by suppressing inflammatory signaling pathways in hippocampi of PPD rats, which involves AA metabolic pathway and NF-κB signal pathway.
PubMed: 38726147
DOI: 10.1016/j.heliyon.2024.e29978