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Urology Journal Nov 2021The purpose of this study was to compare the effectiveness of Dapoxetine, and Paroxetine as well as Dapoxetine/Tadalafil and Paroxetine/Tadalafil combinational... (Randomized Controlled Trial)
Randomized Controlled Trial
PURPOSE
The purpose of this study was to compare the effectiveness of Dapoxetine, and Paroxetine as well as Dapoxetine/Tadalafil and Paroxetine/Tadalafil combinational therapies, for the treatment of patients with premature ejaculation.
MATERIALS AND METHODS
In this clinical trial study, 120 patients with premature ejaculation were randomly divided into 4 groups: The first group was treated with Paroxetine (Pa), while the second group received Dapoxetine(Da). The third group received Paroxetine combined with Tadalafil(PT) whereas the fourth group's treatment involved the use of Dapoxetine and Tadalafil(DT) for one month. In the next 2 and 4 weeks, the cases were evaluated in terms of ejaculation duration, frequency of intercourse per week, and drug side effects.
RESULTS
The mean age of the Da, Pa, PT, DT groups was 32 ± 6.9, 32.4 ± 7.2, 31.6 ± 1.9, and 32.9 ± 7.7 years, respectively. There was a significant difference between the Da and DT groups (p = .029) in the ejaculation latency in the 4-week follow-up. In the two weeks follow-up, a significant difference was observed between DA and DT (p = 0.043), Pa and PT (p = 0.006), and Pa and DT groups (p = 0.004) in terms of ejaculation latency. Four weeks after the intervention, a significant difference was detected in the intercourse frequency of Da and PT groups (p =0.033), Pa and PT groups (p = 0.043), Pa and DT groups (p = 0.02), and Da and DT groups (p = 0.016).
CONCLUSION
Combination therapy (Tadalafil plus Paroxetine or Dapoxetine) was more effective in IELT (Intra ejaculation latency time) than mono-therapy especially in younger patients despite its slightly more side effects.
Topics: Benzylamines; Ejaculation; Humans; Male; Naphthalenes; Paroxetine; Premature Ejaculation; Selective Serotonin Reuptake Inhibitors; Tadalafil; Treatment Outcome
PubMed: 34773634
DOI: 10.22037/uj.v18i.6644 -
Adicciones Apr 2022This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical... (Review)
Review
This review synthesizes the pharmacological and psychosocial interventions that have been conducted in comorbid anxiety disorders and SUDs while also providing clinical recommendations about which intervention elements are helpful for addressing substance use versus anxiety symptoms in patients with these co-occurring conditions. The best evidence from randomized controlled trials was used to evaluate treatment options. The strength of recommendations was described using the GRADE approach. Clinical trials are only available for posttraumatic stress disorder (PTSD) and for social anxiety. Concerning the comorbid substance use, all the studies have included patients with alcohol use, none of them have dealt with cocaine, cannabis or nicotine use. Although some treatments have shown benefit for anxiety symptoms without benefits for alcohol or other substance use, only limited pharmacological approaches have been assayed (sertraline, desipramine, paroxetine, buspirone, naltrexone and disulfiram). Our results suggest that 1) we can (weakly) recommend the use of desipramine over paroxetine to alleviate symptoms of anxiety in patients with a PTSD and alcohol use; 2) In these patients, the use of naltrexone to reduce symptoms of anxiety is also recommended (weak strength); and 3) SSRI antidepressants vs placebo can be recommended to reduce alcohol use (weak recommendation). Our review highlights the need for more research in this area and for larger, multisite studies with generalizable samples to provide more definite guidance for clinical practice.
Topics: Adult; Anxiety Disorders; Desipramine; Humans; Naltrexone; Paroxetine; Substance-Related Disorders
PubMed: 34171105
DOI: 10.20882/adicciones.1548 -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Aug 2022To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis.
METHODS
Databases of PubMed, Cochrane Library, EMBASE, Web of Science, PsycINFO, CBM, CNKI and Wanfang Data were searched for randomized controlled trials (RCT) related to antidepressants in treatment of children and adolescents with depression from inception to December 2021. Quality assessment and data extraction from the included RCTs were performed. Statistical analyses of efficacy and tolerability were conducted with Stata 15.1 software. Surface under the cumulative ranking (SUCAR) was used to rank the value of the antidepressants.
RESULTS
A total of 33 RCTs were included in 32 articles, involving 6949 patients. There are 13 antidepressants used in total, including amitriptyline, vilazodone, fluoxetine, selegiline, paroxetine, imipramine, desipramine, sertraline, nortriptyline, escitalopram, citalopram, venlafaxine and duloxetine. The results of network meta-analysis showed that the efficacy of duloxetine ( =1.95, 95% 1.41-2.69), fluoxetine ( =1.73, 95% 1.40-2.14), venlafaxine ( =1.37, 95% 1.04-1.80) and escitalopram ( =1.48, 95% : 1.12-1.95) were significantly higher than that of placebos (all <0.05); the probability cumulative ranks were duloxetine (87.0%), amitriptyline (83.3%), fluoxetine (79.0%), escitalopram (62.7%), etc. The results showed that the intolerability of patients receiving imipramine ( =0.15, 95% 0.08-0.27), sertraline ( =0.33, 95% 0.16-0.71), venlafaxine ( =0.35, 95% 0.17-0.72), duloxetine ( =0.35, 95% 0.17-0.73) and paroxetine ( =0.52, 95% 0.30-0.88) were significantly higher than that of placebos (all <0.05), and the probability cumulative ranks were imipramine (95.7%), sertraline (69.6%), venlafaxine (68.6%), duloxetine (68.2%), etc. Conclusion: Among 13 antidepressants, duloxetine, fluoxetine, escitalopram and venlafaxine are significantly better than placebo in terms of efficacy, but duloxetine and venlafaxine are less well tolerated.
Topics: Adolescent; Child; Humans; Venlafaxine Hydrochloride; Duloxetine Hydrochloride; Fluoxetine; Sertraline; Paroxetine; Amitriptyline; Imipramine; Depression; Escitalopram; Network Meta-Analysis; Depressive Disorder, Major; Antidepressive Agents
PubMed: 37202104
DOI: 10.3724/zdxbyxb-2022-0145 -
European Neuropsychopharmacology : the... Jan 2023Antidepressant drugs are prescribed to patients with depressive, anxiety disorders, and other conditions. Evidence about antidepressant discontinuation syndrome (ADS)... (Review)
Review
Antidepressant drugs are prescribed to patients with depressive, anxiety disorders, and other conditions. Evidence about antidepressant discontinuation syndrome (ADS) and related outcomes is sparse, although potentially burdensome in some patients. The present state-of-the-art review aims to appraise the most current evidence about ADS critically. ADS has been documented for most antidepressant drugs, although most literature focuses on selective serotonin reuptake inhibitors prescribed for depression. While down-titration cannot exclude the chance of ADS, it is nonetheless warranted in the clinical setting, especially for short half-life and sedative compounds such as paroxetine. Integrative management with concurrent pharmacotherapy and psychotherapy may minimize the eventual unpleasant effects arising within the discontinuation process. In addition, patient-tailored interventions and education should be part of the discontinuation strategy. Future research must rely on broadly accepted definitions for ADS and related phenomena such as antidepressant withdrawal and shed further light on the underpinning neurobiology. Discriminating between ADS-related phenomena and relapse of depression is likewise warranted, along with a neuroscience-based nomenclature instead of a class one.
Topics: Humans; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Paroxetine; Anxiety Disorders; Anxiety; Substance Withdrawal Syndrome
PubMed: 36345093
DOI: 10.1016/j.euroneuro.2022.10.005 -
JAMA Feb 2008Only about 60% of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor (SSRI).... (Randomized Controlled Trial)
Randomized Controlled Trial
Switching to another SSRI or to venlafaxine with or without cognitive behavioral therapy for adolescents with SSRI-resistant depression: the TORDIA randomized controlled trial.
CONTEXT
Only about 60% of adolescents with depression will show an adequate clinical response to an initial treatment trial with a selective serotonin reuptake inhibitor (SSRI). There are no data to guide clinicians on subsequent treatment strategy.
OBJECTIVE
To evaluate the relative efficacy of 4 treatment strategies in adolescents who continued to have depression despite adequate initial treatment with an SSRI.
DESIGN, SETTING, AND PARTICIPANTS
Randomized controlled trial of a clinical sample of 334 patients aged 12 to 18 years with a primary diagnosis of major depressive disorder that had not responded to a 2-month initial treatment with an SSRI, conducted at 6 US academic and community clinics from 2000-2006.
INTERVENTIONS
Twelve weeks of: (1) switch to a second, different SSRI (paroxetine, citalopram, or fluoxetine, 20-40 mg); (2) switch to a different SSRI plus cognitive behavioral therapy; (3) switch to venlafaxine (150-225 mg); or (4) switch to venlafaxine plus cognitive behavioral therapy.
MAIN OUTCOME MEASURES
Clinical Global Impressions-Improvement score of 2 or less (much or very much improved) and a decrease of at least 50% in the Children's Depression Rating Scale-Revised (CDRS-R); and change in CDRS-R over time.
RESULTS
Cognitive behavioral therapy plus a switch to either medication regimen showed a higher response rate (54.8%; 95% confidence interval [CI], 47%-62%) than a medication switch alone (40.5%; 95% CI, 33%-48%; P = .009), but there was no difference in response rate between venlafaxine and a second SSRI (48.2%; 95% CI, 41%-56% vs 47.0%; 95% CI, 40%-55%; P = .83). There were no differential treatment effects on change in the CDRS-R, self-rated depressive symptoms, suicidal ideation, or on the rate of harm-related or any other adverse events. There was a greater increase in diastolic blood pressure and pulse and more frequent occurrence of skin problems during venlafaxine than SSRI treatment.
CONCLUSIONS
For adolescents with depression not responding to an adequate initial treatment with an SSRI, the combination of cognitive behavioral therapy and a switch to another antidepressant resulted in a higher rate of clinical response than did a medication switch alone. However, a switch to another SSRI was just as efficacious as a switch to venlafaxine and resulted in fewer adverse effects.
TRIAL REGISTRATION
clinicaltrials.gov Identifier: NCT00018902.
Topics: Adolescent; Citalopram; Cognitive Behavioral Therapy; Combined Modality Therapy; Cyclohexanols; Depressive Disorder, Major; Drug Resistance; Female; Fluoxetine; Humans; Male; Paroxetine; Selective Serotonin Reuptake Inhibitors; Treatment Outcome; Venlafaxine Hydrochloride
PubMed: 18314433
DOI: 10.1001/jama.299.8.901 -
Frontiers in Immunology 2022G protein-coupled receptor (GPCR) kinase 2 (GRK2), which phosphorylates agonist-occupied GPCRs to promote their desensitization, has been investigated as an attractive...
G protein-coupled receptor (GPCR) kinase 2 (GRK2), which phosphorylates agonist-occupied GPCRs to promote their desensitization, has been investigated as an attractive therapeutic target for cardiovascular and metabolic diseases. Several GRK2-targeted inhibition strategies have been reported including the use of direct pharmacological inhibitors such as paroxetine (a widely prescribed antidepressant) and its analogs such as compound CCG258747. Cross-linking of high affinity IgE receptor (FcϵRI) on mast cells (MCs) and the resulting degranulation causes anaphylaxis and allergic asthma. Using gene silencing strategy, we recently showed that GRK2 contributes to FcεRI signaling and MC degranulation. The purpose of this study was to determine if the GRK2 inhibitors paroxetine and CCG258747 modulate FcεRI-mediated MC responses and . Utilizing rat basophilic leukemia (RBL-2H3) cells and primary mouse lung MCs (LMCs), we found that paroxetine and CCG258747 inhibit FcϵRI-mediated calcium mobilization and degranulation. Furthermore, intravenous administration of paroxetine and CCG258747 in mice resulted in substantial reduction of IgE-mediated passive cutaneous anaphylaxis. Unlike LMCs, human cutaneous MCs abundantly express a novel GPCR known as MRGPRX2 (mouse; MRGPRB2). We found that in contrast to their inhibitory effects on FcεRI-mediated MC responses, both paroxetine and CCG258747 induce calcium mobilization and degranulation in RBL-2H3 cells stably expressing MRGPRX2 but not in untransfected cells. Furthermore, paroxetine and CCG258747 induced degranulation in peritoneal MCs from Wild-type (WT) mice and caused increased cutaneous vascular permeability , but these responses were substantially reduced in mice. Additionally, upon intradermal injection, paroxetine also induced neutrophil recruitment in WT but not mice. These findings suggest that in addition to their potential therapeutic utility against cardiovascular and metabolic disorders, paroxetine-based GRK2-inhibitors may serve to modulate IgE-mediated anaphylaxis and to enhance cutaneous host defense by harnessing MC's immunomodulatory property through the activation of MRGPRX2/MRGPRB2.
Topics: Rats; Mice; Humans; Animals; Mast Cells; Anaphylaxis; Paroxetine; Receptors, IgE; Calcium; Receptors, G-Protein-Coupled; Immunoglobulin E; Nerve Tissue Proteins; Receptors, Neuropeptide
PubMed: 36275707
DOI: 10.3389/fimmu.2022.1032497 -
BMJ Clinical Evidence Nov 2007Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission... (Review)
Review
INTRODUCTION
Up to one in five people may have generalised anxiety disorder (GAD) at some point, and most have other health problems. Less than half of people have full remission after 5 years. GAD may have a genetic component, and has also been linked to previous psychological or other trauma.
METHODS AND OBJECTIVES
We conducted a systematic review and aimed to answer the following clinical question: What are the effects of treatments for GAD? We searched: Medline, Embase, The Cochrane Library and other important databases up to February 2006 (Clinical Evidence reviews are updated periodically, please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA).
RESULTS
We found 52 systematic reviews, RCTs, or observational studies that met our inclusion criteria.
CONCLUSIONS
In this systematic review we present information relating to the effectiveness and safety of the following interventions: abecarnil, antidepressants (imipramine, opipramol, paroxetine, sertraline, escitalopram and venlafaxine), antipsychotic drugs (trifluoperazine), applied relaxation, benzodiazepines, buspirone, cognitive behavioural therapy, hydroxyzine, kava, and pregabalin.
Topics: Anxiety Disorders; Citalopram; Cognitive Behavioral Therapy; Double-Blind Method; Humans; Paroxetine; Remission Induction; Sertraline
PubMed: 19450347
DOI: No ID Found -
The Primary Care Companion For CNS... Jan 2018
Topics: Humans; Paroxetine; Selective Serotonin Reuptake Inhibitors
PubMed: 29381271
DOI: 10.4088/PCC.17l02113 -
Drug Design, Development and Therapy 2023Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated...
BACKGROUND
Osteoarthritis (OA), a common chronic joint disease, is characterized by cartilage degeneration and subchondral bone reconstruction. NF-κB signaling pathway-activated inflammation and NLRP3-induced pyroptosis play essential roles in the development of OA. In this study, we examine whether paroxetine can inhibit pyroptosis and reduce osteoclast formation, thereby delaying the destruction of knee joints.
METHODS
We employed high-density cultures, along with quantitative polymerase chain reactions and Western blotting techniques, to investigate the effects of paroxetine on extracellular matrix synthesis and degradation. The expression levels of NF-κB and pyroptosis-related signaling pathway proteins were examined by Western blotting and immunofluorescence. Furthermore, the impact of paroxetine on RANKL-induced osteoclast formation was evaluated through TRAP staining and F-actin ring fluorescence detection. To investigate the role of paroxetine in vivo, we constructed a mouse model with destabilization of the medial meniscus (DMM) surgery. Safranin O-Fast Green staining, Hematoxylin-Eosin staining, and immunohistochemistry were conducted to observe the extent of knee joint cartilage deformation. In addition, TRAP staining was used to observe the formation of osteoclasts in the subchondral bone.
RESULTS
In the in vitro experiments with ATDC5, paroxetine treatment attenuated IL-1β-induced activation of the pyroptosis-related pathway and suppressed extracellular matrix catabolism by inhibiting the NF-kB signaling pathway. In addition, paroxetine treatment decreased the expression of RANKL-induced osteoclast marker genes and reduced osteoclast formation. In animal experiments conducted in vivo, mice treated with paroxetine exhibited thicker knee cartilage with a smoother surface compared to the DMM group. Additionally, the formation of osteoclasts in the subchondral bone was reduced in the paroxetine-treated mice. Further analysis revealed that paroxetine treatment played a role in preserving the balance of the extracellular matrix and delaying knee joint degeneration.
CONCLUSION
Paroxetine can inhibit pyroptosis and reduce osteoclast formation via inhibiting the NF-κB signaling pathway, suggesting that it may have therapeutic effects in patients with OA.
Topics: Animals; Mice; NF-kappa B; Chondrocytes; Osteoclasts; Paroxetine; Pyroptosis; Signal Transduction; Osteoarthritis, Knee
PubMed: 37605762
DOI: 10.2147/DDDT.S417598 -
Ecotoxicology and Environmental Safety Jul 2023Paroxetine (PRX) is a common antidepressant drug which widely existence in natural environment. Numerous studies in the past few decades have focused on the beneficial...
Paroxetine (PRX) is a common antidepressant drug which widely existence in natural environment. Numerous studies in the past few decades have focused on the beneficial effects of PRX on depression, however, the toxic properties and the potential mechanisms remain unclear. In this study, zebrafish embryos were exposed to 1.0, 5.0, 10 and 20 mg/L of PRX from 4 to 120-hour-post-fertilization (hpf), and it showed that PRX exposure caused adverse effects in zebrafish embryos, including decreased body length, blood flow velocity, cardiac frequency, cardiac output and increased burst activity and atria area. Meanwhile, the Tg (myl7: EGFP) and Tg (lyz: DsRed) transgenic zebrafish were used to detect the cardiotoxicity and inflammation response of PRX. Moreover, the heart development associated genes (vmhc, amhc, hand2, nkx2.5, ta, tbx6, tbx16 and tbx20) and inflammatory genes (IL-10, IL-1β, IL-8 and TNF-α) were up-regulated after PRX challenge. In addition, Aspirin was used to alleviate the PRX-induced heart development disorder. In conclusion, our study verified the PRX induced inflammatory related cardiotoxicity in larva zebrafish. Meanwhile, the current study shown the toxic effects of PRX in aquatic organism, and provide for the environmental safety of PRX.
Topics: Animals; Zebrafish; Cardiotoxicity; Paroxetine; Larva; Embryo, Nonmammalian; Inflammation; Water Pollutants, Chemical; T-Box Domain Proteins; Zebrafish Proteins
PubMed: 37269614
DOI: 10.1016/j.ecoenv.2023.115096