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Translational Psychiatry Feb 2020Antidepressants exhibit similar efficacy, but varying tolerability, in randomized controlled trials. Predicting tolerability in real-world clinical populations may...
Antidepressants exhibit similar efficacy, but varying tolerability, in randomized controlled trials. Predicting tolerability in real-world clinical populations may facilitate personalization of treatment and maximize adherence. This retrospective longitudinal cohort study aimed to determine the extent to which incorporating patient history from electronic health records improved prediction of unplanned treatment discontinuation at index antidepressant prescription. Clinical data were analyzed from individuals from health networks affiliated with two large academic medical centers between March 1, 2008 and December 31, 2014. In total, the study cohorts included 51,683 patients with at least one International Classification of Diseases diagnostic code for major depressive disorder or depressive disorder not otherwise specified who initiated antidepressant treatment. Among 70,121 total medication changes, 16,665 (23.77%) of them were followed by failure to return; maximum risk was observed with paroxetine (27.71% discontinuation), and minimum with venlafaxine (20.78% discontinuation); Mantel-Haenzel χ (8 df) = 126.44, p = 1.54e-23 <1e-6. Models incorporating diagnostic and procedure codes and medication prescriptions improved per-medication Areas Under the Curve (AUCs) to a mean of 0.69 [0.64-0.73] (ranging from 0.62 for paroxetine to 0.80 for escitalopram), with similar performance in the second, replication health system. Machine learning applied to coded electronic health records facilitates identification of individuals at high-risk for treatment dropout following change in antidepressant medication. Such methods may assist primary care physicians and psychiatrists in the clinic to personalize antidepressant treatment on the basis not solely of efficacy, but of tolerability.
Topics: Antidepressive Agents; Depressive Disorder, Major; Humans; Longitudinal Studies; Paroxetine; Retrospective Studies
PubMed: 32066733
DOI: 10.1038/s41398-020-0716-y -
MedRxiv : the Preprint Server For... Feb 2023Paroxetine is an older "selective" serotonin reuptake inhibitor (SSRI) that is notable for its lack of selectivity, resulting in a cholinergic adverse-effect profile,...
INTRODUCTION
Paroxetine is an older "selective" serotonin reuptake inhibitor (SSRI) that is notable for its lack of selectivity, resulting in a cholinergic adverse-effect profile, especially among older adults (65+).
METHODS
Paroxetine prescription rates and costs per state were ascertained from the Medicare Specialty Utilization and Payment Data. States' annual prescription rate, corrected per thousand Part D enrollees, outside 95% confidence interval were considered significantly different from the average.
RESULTS
There was a steady decrease in paroxetine prescriptions (-34.52%) and spending (-16.69%) from 2015-2020 but a consistent, five-fold state-level difference. From 2015-2020, Kentucky (194.9, 195.3, 182.7, 165.1, 143.3, 132.5) showed significantly higher prescriptions rates relative to the national average, and Hawaii (42.1, 37.9, 34.3, 31.7, 27.7, 26.6) showed significantly lower prescription rates. North Dakota was often a frequent elevated prescriber of paroxetine (2016: 170.7, 2018: 143.3), relative to the average. Neuropsychiatry and geriatric medicine frequently prescribed the largest amount of paroxetine prescriptions, relative to the number of providers in that specialty, from 2015-2020.
DISCUSSION
Despite the American Geriatrics Society prohibition against paroxetine use in the older adults and many effective treatment alternatives, paroxetine was still commonly used in this population, especially in Kentucky and North Dakota and by neuropsychiatry and geriatric medicine. These findings provide information on the specialty types and states where education and policy reform would likely have the greatest impact on improving adherence to the paroxetine prescription recommendations.
PubMed: 36824839
DOI: 10.1101/2023.02.15.23285973 -
American Journal of Translational... 2022To systematically evaluate the clinical efficacy of acupuncture combined with paroxetine in the treatment of depression. (Review)
Review
OBJECTIVE
To systematically evaluate the clinical efficacy of acupuncture combined with paroxetine in the treatment of depression.
METHODS
The research literature on the treatment of depression with acupuncture and moxibustion combined with paroxetine was collected using keywords in PubMed, Embase, Web of Science, Cochrane Library, CNKI, World Wide Web, Chinese Biomedical Literature and other public publication databases. Collaborative screening of literature was performed according to pre-established inclusion and exclusion criteria. The data in the literature were extracted, the quality of the literature was evaluated, and the RevMan software was used for statistical analysis.
RESULTS
This study finally included 21 research papers involving 1733 clinical patients. The main evaluation indicators for clinical patients were Hamilton Depression Rating Scale (HAMD), total clinical response rate, Rating Scale for Side Effects (SERS) and Treatment Emergent Symptom Scale (TESS). SERS was developed by Asberg. The Chinese version was revised by Zhang Mingyuan (Chairman of the Chinese Medical Association Mental Health Society) et al. The SERS is divided into 14 items, all of which use a 4-point scoring method (none, mild, moderate and severe, respectively). This scale is mainly used to assess the side effects of antidepressants. TESS was compiled by the NIMH of the United States in 1973. It has the most comprehensive items and the widest coverage among the scales of its kind, including not only common adverse symptoms and signs, but also several laboratory test results. Meta-analysis of the above results showed that compared with the control group, the acupuncture combined with paroxetine treatment group showed lower HAMD score (WMD=-4.18 [-5.04, -3.31], P<0.001), higher total response rate (OR=4.01 [3.01, 5.33], P<0.001), lower SERS score (WMD=-2.54 [-4.58, -0.51], P<0.001) and lower TESS score (WMD=-4.39 [-5.15, -3.62], P<0.001), and the differences were statistically significant.
CONCLUSION
The therapeutic effect of acupuncture combined with paroxetine on depression is better than that of conventional drug treatment, and its safety is comparable to that of conventional treatment.
PubMed: 36628233
DOI: No ID Found -
Pakistan Journal of Medical Sciences 2023To evaluate the effects of paroxetine hydrochloride combined with idebenone on inflammatory factors and antioxidant molecules in the treatment of depression after...
OBJECTIVES
To evaluate the effects of paroxetine hydrochloride combined with idebenone on inflammatory factors and antioxidant molecules in the treatment of depression after ischemic stroke.
METHODS
Randomized controlled trial was adopted on 80 patients with depression after ischemic stroke were randomly divided into two groups, with 40 patients in each group at Xingtai Sanli Health Quannan Clinic from March 17, 2019 to December 20, 2021. Both groups were given basic treatment. On this basis, the control group was treated with paroxetine hydrochloride, while the study group was treated with paroxetine hydrochloride combined with idebenone. The clinical efficacy was evaluated using the Hamilton Rating Scale for Depression (HRSD) before and after treatment. Additionally, the difference in HRSD score after treatment and the improvement in inflammatory factors and antioxidant molecules were compared and analyzed between the two groups.
RESULTS
After treatment, the HRSD score of the study group was significantly improved compared with that of the control group ( 0.00). The effective rate was 82.5% in the study group, which was significantly higher than 62.5% in the control group ( 0.04). After treatment, TNF-a, CRP and IL-6 in the study group were significantly lower than those in the control group (= 0.00). Serum SOD, TAC and CAT levels in the study group were significantly higher than those in the control group after treatment (SOD and TAC, 0.00; CAT, 0.01). The incidence of adverse reactions was 37.5% in the study group and 25% in the control group. Although the incidence of adverse reactions in the study group was higher than that in the control group, the difference was not statistically significant ( 0.23).
CONCLUSION
Paroxetine hydrochloride combined with idebenone in the treatment of depression after ischemic stroke can significantly improve HRSD score, enhance clinical efficacy, reduce the levels of inflammatory factors, and increase the levels of antioxidant factors, without a significant increase in adverse reactions. Therefore, it is a safe and effective treatment method.
PubMed: 36694748
DOI: 10.12669/pjms.39.1.5679 -
Brazilian Journal of Medical and... 2018The aim of this study was to investigate the efficacy, acceptability, and tolerability of antidepressants in treating post-stroke depression (PSD) by performing a... (Meta-Analysis)
Meta-Analysis Review
The aim of this study was to investigate the efficacy, acceptability, and tolerability of antidepressants in treating post-stroke depression (PSD) by performing a network meta-analysis of randomized controlled trials of the current literature. Eligible studies were retrieved from online databases, and relevant data were extracted. The primary outcome was efficacy as measured by the mean change in overall depressive symptoms. Secondary outcomes included discontinued treatment for any reason and specifically due to adverse events. Fourteen trials were eligible, which included 949 participants and 9 antidepressant treatments. Few significant differences were found for all outcomes. For the primary outcome, doxepin, paroxetine, and nortriptyline were significantly more effective than a placebo [standardized mean differences: -1.93 (95%CI=-3.56 to -0.29), -1.39 (95%CI=-2.59 to -0.21), and -1.25 (95%CI=-2.46 to -0.04), respectively]. Insufficient evidence exists to select a preferred antidepressant for treating patients with post-stroke depression, and our study provides little evidence that paroxetine may be the potential choice when starting treatment for PSD. Future studies with paroxetine and larger sample sizes, multiple medical centers, and sufficient intervention durations is needed for improving the current evidence.
Topics: Antidepressive Agents; Depressive Disorder; Female; Humans; Male; Network Meta-Analysis; Placebo Effect; Randomized Controlled Trials as Topic; Reproducibility of Results; Stroke; Time Factors; Treatment Outcome
PubMed: 29742266
DOI: 10.1590/1414-431x20187218 -
Aging Oct 2023G protein-coupled receptor kinase-2 (GRK2) is involved in TGF-β1-induced activation of lung fibroblasts, which could give rise to the pathogenesis of pulmonary...
G protein-coupled receptor kinase-2 (GRK2) is involved in TGF-β1-induced activation of lung fibroblasts, which could give rise to the pathogenesis of pulmonary fibrosis. Paroxetine (PRXT) serves as a selective GRK2 inhibitor which is widely used to treat anxiety and depression for several decades. However, whether PRXT could inhibit TGF-β1-induced activation of lung fibroblasts and combat bleomycin-induced pulmonary fibrosis remains unclear. Here, we investigated the effects of PRXT on pulmonary fibrosis in C57/BL6 caused by bleomycin as well as on the activation of murine primary lung fibroblasts stimulated with TGF-β1. The results demonstrated that PRXT markedly improved the pulmonary function and 21-day survival in bleomycin-induced mice. Meanwhile, PRXT significantly decreased collagen deposition, inflammation, and oxidative stress in lung tissues from bleomycin-induced mice. Furthermore, we found that PRXT could inhibit the protein and mRNA expression of GRK2 and Smad3 in lung tissues from bleomycin-induced mice. experiments also PRXT could inhibit cell activation and collagen synthesis in a concentration-dependent manner in TGF-β1-induced lung fibroblasts. In addition, we found that Smad3 overexpression by adenovirus transfection could offset anti-fibrotic and antioxidative effects from PRXT in TGF-β1-induced lung fibroblasts, which showed no effects on the protein expression of GRK2. In conclusion, PRXT mediates the inhibition of GRK2, which further blocks the transcription of Smad3 in TGF-β1-induced lung fibroblasts, providing an attractive therapeutic target for pulmonary fibrosis.
Topics: Mice; Animals; Pulmonary Fibrosis; Bleomycin; Transforming Growth Factor beta1; Paroxetine; Lung; Fibroblasts; Collagen; Mice, Inbred C57BL
PubMed: 37815883
DOI: 10.18632/aging.205092 -
Nephro-urology Monthly Jan 2016Several recent studies have investigated the therapeutic role of phosphodiesterase type 5 (PDE5) inhibitors in premature ejaculation (PE) used in the treatment of...
BACKGROUND
Several recent studies have investigated the therapeutic role of phosphodiesterase type 5 (PDE5) inhibitors in premature ejaculation (PE) used in the treatment of erectile dysfunction.
OBJECTIVES
In the present research, the efficacy of paroxetine alone and paroxetine plus tadalafil was compared in patients referred because of premature ejaculation.
PATIENTS AND METHODS
This quasi-experimental study was performed on 100 consecutive 17 to 49-year-old potent men with premature ejaculation and without any clear organic disease. All patients had lifelong PE with an intravaginal ejaculation latency time (IELT) shorter than 1.5 minutes. Informed consent was obtained from all patients who were randomly divided into two groups using a computer-generated random tabulation list. In group A, patients received 10 mg paroxetine daily, in addition to four hours before planned sexual activity. In group B, 10 mg paroxetine was taken daily, plus 10 mg tadalafil one hour before planned sexual activity. The duration of the intervention was six months and patients were evaluated for IELT three and six months after the beginning of therapy.
RESULTS
The mean age of patients in groups A and B were 33 ± 9.6 and 31.2 ± 9.3 years, respectively (P = 0.368). The mean number of intercourses were 1.08 ± 0.6 and 1.12 ± 0.6 per week in groups A and B, respectively (P = 0.791). Mean IELT at the 3-month follow up in groups A and B was 4.5 ± 1.5 and 5 ± 2.4 minutes, respectively (P = 0.285) and at the 6-month follow up was 4.8 ± 1 and 5.3 ± 2 minutes, respectively (P = 0.278).
CONCLUSIONS
The results of the study show that tadalafil can increase the mean IELT and can be used for treatment of premature ejaculation in combination with paroxetine.
PubMed: 26981497
DOI: 10.5812/numonthly.32286 -
Parasites & Vectors Jan 2021Serotonin is a phylogenetically ancient molecule that is widely distributed in most metazoans, including flatworms. In addition to its role as a neurotransmitter,...
BACKGROUND
Serotonin is a phylogenetically ancient molecule that is widely distributed in most metazoans, including flatworms. In addition to its role as a neurotransmitter, serotonin acts as a morphogen and regulates developmental processes. Although several studies have focused on the serotonergic nervous system in parasitic flatworms, little is known on the role of serotonin in flatworm development.
METHODS
To study the effects of serotonin on proliferation and development of the cestode Echinococcus multilocularis, we cloned the genes encoding the E. multilocularis serotonin transporter (SERT) and tryptophan hydroxylase (TPH), analyzed gene expression by transcriptome analysis and whole mount in situ hybridization (WMISH) and performed cell culture experiments.
RESULTS
We first characterized orthologues encoding the SERT and TPH, the rate-limiting enzyme in serotonin biosynthesis. WMISH and transcriptomic analyses indicated that the genes for both SERT and TPH are expressed in the parasite nervous system. Long-term treatment of parasite stem cell cultures with serotonin stimulated development towards the parasite metacestode stage. Mature metacestode vesicles treated with serotonin showed increased rates of incorporation of the thymidine analogue 5-ethynyl-2'-deoxyuridine (EdU), indicating stimulated cell proliferation. In contrast, treatment with the selective serotonin reuptake inhibitor paroxetine strongly affected the viability of parasite cells. Paroxetine also caused structural damage in metacestode vesicles, suggesting that serotonin transport is crucial for the integrity of parasite vesicles.
CONCLUSIONS
Our results indicate that serotonin plays an important role in E. multilocularis development and proliferation, providing evidence that the E. multilocularis SERT and TPH are expressed in the nervous system of the protoscolex. Our results further suggest that the E. multilocularis SERT has a secondary role outside the nervous system that is essential for parasite integrity and survival. Since serotonin stimulated E. multilocularis metacestode development and proliferation, serotonin might also contribute to the formation and growth of the parasite in the liver.
Topics: Animals; Cell Proliferation; Echinococcus multilocularis; Gene Expression; Gene Expression Profiling; Helminth Proteins; In Situ Hybridization; Larva; Nervous System; Paroxetine; Serotonin; Serotonin Antagonists; Serotonin Plasma Membrane Transport Proteins; Tryptophan Hydroxylase
PubMed: 33407815
DOI: 10.1186/s13071-020-04533-0 -
Progress in Neuro-psychopharmacology &... Jul 2023Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Post-traumatic stress disorder (PTSD) is a mental disorder that can emerge after an individual experiences a traumatic event such as physical abuse, sexual/relationship violence, combat exposure, witnessing death, or serious injury. This study aimed to identify the most suitable drugs for the management of PTSD based on a network meta-analysis (NMA).
METHODS
Six databases (Ovid Medline, EMBase, CENTRAL, PsycINFO, Ovid Health and Psychosocial Instruments, and Web of Science) were searched from inception to September 6, 2022.
RESULTS
Thirty articles with a total of 5170 participants were included. Compared with placebo, active drugs including olanzapine (SMD = -0.66, 95% CI: -1.19 to -0.13), risperidone (SMD = -0.23, 95% CI: -0.42 to -0.03), quetiapine (SMD = -0.49, 95% CI: -0.93 to -0.04), venlafaxine (SMD = -0.29, 95% CI: -0.42 to -0.16), sertraline (SMD = -0.23, 95% CI: -0.34 to -0.11), paroxetine (SMD = -0.48, 95% CI: -0.60 to -0.36) and fluoxetine (SMD = -0.27, 95% CI: -0.42 to -0.12), significantly reduced the total clinician-administered PTSD scale score.
CONCLUSION
The results of this study support the use of paroxetine, venlafaxine, and quetiapine as first-line treatment for PTSD. In addition, quetiapine is recommended for patients with PTSD affected by symptoms of hyperarousal and re-experience disorder. Clinicians should prescribe medications based on the severity of PTSD symptoms and other conditions to develop the best treatment strategy for this patient population.
Topics: Humans; Stress Disorders, Post-Traumatic; Cognitive Behavioral Therapy; Paroxetine; Quetiapine Fumarate; Venlafaxine Hydrochloride; Network Meta-Analysis
PubMed: 36934999
DOI: 10.1016/j.pnpbp.2023.110754 -
Heart, Lung & Circulation May 2016Heart failure is a significant global health problem, which is becoming worse as the population ages, and remains one of the biggest burdens on our economy. Despite... (Review)
Review
Heart failure is a significant global health problem, which is becoming worse as the population ages, and remains one of the biggest burdens on our economy. Despite significant advances in cardiovascular medicine, management and surgery, mortality rates remain high, with almost half of patients with heart failure dying within five years of diagnosis. As a multifactorial clinical syndrome, heart failure still represents an epidemic threat, highlighting the need for deeper insights into disease mechanisms and the development of innovative therapeutic strategies for both treatment and prevention. In this review, we discuss conventional heart failure therapies and highlight new pharmacological agents targeting pathophysiological features of the failing heart, for example, non-coding RNAs, angiotensin receptor-neprilysin inhibitors, cardiac myosin activators, BGP-15 and molecules targeting GRK2 including M119, gallein and paroxetine. Finally, we address the disparity between phase II and phase III clinical trials that prevent the translation of emerging HF therapies into new and approved therapies.
Topics: Angiotensin Receptor Antagonists; Cardiac Myosins; Clinical Trials, Phase II as Topic; Clinical Trials, Phase III as Topic; Cyclohexanes; G-Protein-Coupled Receptor Kinase 2; Heart Failure; Humans; Neprilysin; Oximes; Paroxetine; Piperidines; RNA, Untranslated; Xanthenes
PubMed: 26993094
DOI: 10.1016/j.hlc.2016.01.002