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Biological Psychiatry Mar 1995
Topics: Akathisia, Drug-Induced; Clonazepam; Depressive Disorder; Dose-Response Relationship, Drug; Drug Administration Schedule; Drug Therapy, Combination; Humans; Male; Middle Aged; Neurologic Examination; Paroxetine; Propranolol
PubMed: 7748986
DOI: 10.1016/0006-3223(94)00158-Y -
BMJ (Clinical Research Ed.) May 1997
Topics: Aged; Antidepressive Agents, Second-Generation; Chemical and Drug Induced Liver Injury; Female; Humans; Paroxetine
PubMed: 9161313
DOI: 10.1136/bmj.314.7091.1387a -
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 -
The International Journal of... Apr 2022Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter...
BACKGROUND
Venlafaxine is a dual serotonin (5-HT) and norepinephrine reuptake inhibitor. The specific dose at which it begins to efficiently engage the norepinephrine transporter (NET) remained to be determined. Paroxetine is generally considered as a selective 5-HT reuptake inhibitor but exhibits some affinity for NET. Atomoxetine is a NET inhibitor but also has some affinity for the 5-HT reuptake transporter (SERT).
METHODS
This study examined the effects of forced titration of venlafaxine from 75 to 300 mg/d, paroxetine from 20 to 50 mg/d, or atomoxetine from 25 to 80 mg/d in 32 patients with major depressive disorder. Inhibition of SERT was estimated using the depletion of whole-blood 5-HT. Inhibition of NET was assessed using the attenuation of the systolic blood pressure produced by i.v. injections of tyramine.
RESULTS
All 3 medications significantly reduced 5-HT levels at the initiating regimens: venlafaxine and paroxetine by approximately 60% and atomoxetine by 16%. The 3 subsequent regimens of venlafaxine and paroxetine reduced 5-HT levels by over 90%, but the highest dose of atomoxetine only reached a 40% inhibition. Atomoxetine dose dependently inhibited the tyramine pressor response from the lowest dose, venlafaxine from 225 mg/d, and paroxetine left it unaltered throughout.
CONCLUSION
These results confirm that venlafaxine and paroxetine are potent SERT inhibitors over their usual therapeutic range but that venlafaxine starts inhibiting NET only at 225 mg/d, whereas paroxetine remains selective for SERT up to 50 mg/d. Atomoxetine dose dependently inhibits NET from a low dose but does not inhibit SERT to a clinically relevant degree.
Topics: Antidepressive Agents, Second-Generation; Atomoxetine Hydrochloride; Cyclohexanols; Depressive Disorder, Major; Humans; Norepinephrine; Norepinephrine Plasma Membrane Transport Proteins; Paroxetine; Serotonin; Selective Serotonin Reuptake Inhibitors; Tyramine; Venlafaxine Hydrochloride
PubMed: 34958348
DOI: 10.1093/ijnp/pyab086 -
Frontiers in Immunology 2023Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental...
BACKGROUND
Up to 40 per cent of people with active inflammatory bowel disease (IBD) also suffer from mood disorders such as anxiety and depression. Notwithstanding, the fundamental biological pathways driving depression in IBD remain unknown.
METHODS
We identified 33 core genes that drive depression in IBD patients and performed consensus molecular subtyping with the NMF algorithm in IBD. The CIBERSORT were employed to quantify the immune cells. Metabolic signature was characterized using the "IOBR" R package. The scoring system (D. score) based on PCA. Pre-clinical models are constructed using DSS.
RESULTS
Using transcriptome data from the GEO database of 630 IBD patients, we performed a thorough analysis of the correlation between IBD and depression in this research. Firstly, the samples were separated into two different molecular subtypes (D. cluster1 and D. cluster2) based on their biological signatures. Moreover, the immunological and metabolic differences between them were evaluated, and we discovered that D. cluster2 most closely resembled IBD patients concomitant with depression. We also developed a scoring system to assess the IBD-related depression and predict clinical response to anti-TNF- therapy, with a higher D. score suggesting more inflammation and worse reaction to biological therapies. Ultimately, we also identified through animal experiments an antidepressant, paroxetine, has the added benefit of lowering intestinal inflammation by controlling microorganisms in the digestive tract.
CONCLUSIONS
This study highlights that IBD patients with or without depression show significant variations and antidepressant paroxetine may help reduce intestinal inflammation.
Topics: Humans; Paroxetine; Depression; Tumor Necrosis Factor Inhibitors; Inflammatory Bowel Diseases; Anti-Inflammatory Agents; Antidepressive Agents; Inflammation
PubMed: 36923403
DOI: 10.3389/fimmu.2023.1145070 -
ELife Jul 2020Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of...
Antidepressants target the serotonin transporter (SERT) by inhibiting serotonin reuptake. Structural and biochemical studies aiming to understand binding of small-molecules to conformationally dynamic transporters like SERT often require thermostabilizing mutations and antibodies to stabilize a specific conformation, leading to questions about relationships of these structures to the bonafide conformation and inhibitor binding poses of wild-type transporter. To address these concerns, we determined the structures of ∆N72/∆C13 and ts2-inactive SERT bound to paroxetine analogues using single-particle cryo-EM and x-ray crystallography, respectively. We synthesized enantiopure analogues of paroxetine containing either bromine or iodine instead of fluorine. We exploited the anomalous scattering of bromine and iodine to define the pose of these inhibitors and investigated inhibitor binding to Asn177 mutants of ts2-active SERT. These studies provide mutually consistent insights into how paroxetine and its analogues bind to the central substrate-binding site of SERT, stabilize the outward-open conformation, and inhibit serotonin transport.
Topics: Cryoelectron Microscopy; Crystallography, X-Ray; Humans; Molecular Structure; Paroxetine; Protein Structure, Tertiary; Serotonin; Serotonin Plasma Membrane Transport Proteins; Selective Serotonin Reuptake Inhibitors
PubMed: 32618269
DOI: 10.7554/eLife.56427 -
Psychoneuroendocrinology Oct 2021Selective serotonin reuptake inhibitors (SSRI) show high efficacy in treating depression, however during treatment side effects, like for instance sexual dysfunction,...
Selective serotonin reuptake inhibitors (SSRI) show high efficacy in treating depression, however during treatment side effects, like for instance sexual dysfunction, may appear, decreasing compliance. In some cases, this condition will last after drug discontinuation, leading to the so-called post-SSRI sexual dysfunction (PSSD). The etiology of PSSD is still unknown, however a role for neuroactive steroids may be hypothesized. Indeed, these molecules are key physiological regulators of the nervous system, and their alteration has been associated with several neuropathological conditions, including depression. Additionally, neuroactive steroids are also involved in the control of sexual function. Interestingly, sexual dysfunction induced by SSRI treatment has been also observed in animal models. On this basis, we have here evaluated whether a subchronic treatment with paroxetine for two weeks and/or its withdrawal (i.e., a month) may affect the levels of neuroactive steroids in brain areas (i.e., hippocampus, hypothalamus, and cerebral cortex) and/or in plasma and cerebrospinal fluid of male rats. Data obtained indicate that the SSRI treatment alters neuroactive steroid levels and the expression of key enzymes of the steroidogenesis in a brain tissue- and time-dependent manner. Indeed, these observations with the finding that plasma levels of neuroactive steroids are not affected suggest that the effect of paroxetine treatment is directly on neurosteroidogenesis. In particular, a negative impact on the expression of steroidogenic enzymes was observed at the withdrawal. Therefore, it is possible to hypothesize that altered neurosteroidogenesis may also occur in PSSD and consequently it may represent a possible pharmacological target for this disorder.
Topics: Animals; Hippocampus; Male; Neurosteroids; Paroxetine; Rats; Selective Serotonin Reuptake Inhibitors; Sexual Dysfunction, Physiological
PubMed: 34325207
DOI: 10.1016/j.psyneuen.2021.105364 -
Cancer Causes & Control : CCC Feb 2014Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and...
PURPOSE
Re-examine association of fluoxetine and paroxetine with risk of testicular cancer noted in drug screening, with 4 years more follow-up and expanded study of these and other antidepressant drugs.
METHODS
In the Kaiser Permanente Medical Care Program in Northern California, 906 men with testicular cancer diagnosed August 1996-December 2010 were compared with 38,253 matched controls with race/ethnicity recorded regarding receipt of antidepressant drugs at least 2 years before diagnosis or control index date. Analyses emphasized duration of use and histological subgroups.
RESULTS
With control for race/ethnicity and use of other antidepressant drugs, odds ratios (OR) and 95 % confidence intervals (CI) for associations with testicular cancer were as follows: fluoxetine 1.22 (0.88-1.71), paroxetine 1.19 (0.78-1.83), and 1.21 (0.92-1.58) for all serotonin reuptake inhibitors. There was no statistically significant association with risk of all testicular cancers or their histological subtypes for any individual drug or for tricyclics or all antidepressants combined except for citalopram with all testicular cancers 2.55 (1.43-4.52) and those of mixed histology 4.36 (1.50-12.68) and nefazodone with embryonal cancers 9.79 (1.85-51.81). These could readily be chance findings in the context of the many analyses that were performed. Duration of use was not associated with risk of the drugs and drug groups with sufficient numbers of exposed cases for analysis.
CONCLUSIONS
We found little evidence to support a testicular carcinogenic effect of fluoxetine, paroxetine, or other antidepressant drugs, but a weakly positive association is not ruled out. The signals in prior screening may have been due to chance and/or uncontrolled confounding.
Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antidepressive Agents, Second-Generation; California; Case-Control Studies; Cohort Studies; Depression; Female; Fluoxetine; Humans; Male; Middle Aged; Paroxetine; Selective Serotonin Reuptake Inhibitors; Testicular Neoplasms; Young Adult
PubMed: 24276357
DOI: 10.1007/s10552-013-0327-5 -
BMC Urology Jan 2019Paroxetine is one of the selective serotonin reuptake inhibitors (SSRIs) used in the treatment of premature ejaculation (PE). However, this use is not approved in many... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Paroxetine is one of the selective serotonin reuptake inhibitors (SSRIs) used in the treatment of premature ejaculation (PE). However, this use is not approved in many countries. The purpose of this systematic review and meta-analysis is to review the efficacy and safety of paroxetine for PE patients.
METHODS
We searched relevant randomized, controlled trials through May 2018, using PubMed, Embase and Cochrane Central Register. The main endpoint included intra-vaginal ejaculatory latency time (IELT) and side effects in the treatment of PE. Cochrane Collaboration's Revman software, version 5.3, was used for statistical analysis.
RESULTS
Out of 493 unique articles, a total of 19 randomized, controlled trials (RCTs) were reviewed. Quite a few RCTs were considered to have unclear risk of bias because of limited information. Pooled outcomes suggested that paroxetine was more effective than placebo, fluoxetine and escitalopram at increasing IELT (all p < 0.05). However, there existed a high level of heterogeneity in the paroxetine vs. fluoxetine groups and the paroxetine vs. placebo groups. Comparing paroxetine with tramadol, sertraline, phosphodiesterase 5 inhibitors (PDE5Is), local lidocaine gel, behaviour therapy or dapoxetine, we found that the increase in IELT was not statistically significant between groups. Paroxetine combined with tadalafil or behaviour therapy was more efficacious than paroxetine alone (all p < 0.05). Although the side effects in the combination group were more common than in the paroxetine alone group, the most common adverse events, such as nausea, muscle soreness, palpitation and flushing, were mild and tolerable. The main limitations of this systematic review and meta-analysis were the different definitions of PE and short follow-up times.
CONCLUSIONS
According to this systematic review and meta-analysis, paroxetine provided better efficacy than placebo, fluoxetine and escitalopram in the treatment of PE, with well-tolerated side effects. The combination group had better efficacy than the paroxetine alone group.
TRIAL REGISTRATION
This review was reported in agreement with the PRISMA statement and was registered on PROSPERO 2018CRD42018097014 .
Topics: Humans; Male; Paroxetine; Premature Ejaculation; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Treatment Outcome
PubMed: 30606186
DOI: 10.1186/s12894-018-0431-7 -
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