-
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 -
Pharmacoepidemiology and Drug Safety Jun 2018Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this...
PURPOSE
Co-prescription of paroxetine/fluoxetine (a strong CYP2D6 inhibitor) in metoprolol (a CYP2D6 substrate) users is common, but data on the clinical consequences of this drug-drug interaction are limited and inconclusive. Therefore, we assessed the effect of paroxetine/fluoxetine initiation on the existing treatment with metoprolol on the discontinuation and dose adjustment of metoprolol among elderly.
METHODS
We performed a cohort study using the University of Groningen IADB.nl prescription database (www.IADB.nl). We selected all elderly (≥60 years) who had ever been prescribed metoprolol and had a first co-prescription of paroxetine/fluoxetine, citalopram (weak CYP2D6 inhibitor), or mirtazapine (negative control) from 1994 to 2015. The exposure group was metoprolol and paroxetine/fluoxetine co-prescription, and the other groups acted as controls. The outcomes were early discontinuation and dose adjustment of metoprolol. Logistic regression was applied to estimate adjusted odds ratios (OR) and 95% confidence intervals (CI).
RESULTS
Combinations of metoprolol-paroxetine/fluoxetine, metoprolol-citalopram, and metoprolol-mirtazapine were started in 528, 673, and 625 patients, respectively. Compared with metoprolol-citalopram, metoprolol-paroxetine/fluoxetine was not significantly associated with the early discontinuation and dose adjustment of metoprolol (OR = 1.07, 95% CI:0.77-1.48; OR = 0.87, 95% CI:0.57-1.33, respectively). In comparison with metoprolol-mirtazapine, metoprolol-paroxetine/fluoxetine was associated with a significant 43% relative increase in early discontinuation of metoprolol (OR = 1.43, 95% CI:1.01-2.02) but no difference in the risk of dose adjustment. Stratified analysis by gender showed that women have a significantly high risk of metoprolol early discontinuation (OR = 1.62, 95% CI:1.03-2.53).
CONCLUSION
Paroxetine/fluoxetine initiation in metoprolol prescriptions, especially for female older patients, is associated with the risk of early discontinuation of metoprolol.
Topics: Aged; Aged, 80 and over; Citalopram; Cohort Studies; Cytochrome P-450 CYP2D6; Cytochrome P-450 CYP2D6 Inhibitors; Dose-Response Relationship, Drug; Drug Interactions; Drug Prescriptions; Drug Therapy, Combination; Female; Fluoxetine; Humans; Male; Metoprolol; Middle Aged; Mirtazapine; Netherlands; Paroxetine
PubMed: 29575226
DOI: 10.1002/pds.4422 -
Biomedicine & Pharmacotherapy =... Jan 2022Doxorubicin (DOX) is an effective anticancer drug. However, its use is hampered by the development of very mortal cardiomyopathy. Here, we investigate whether the...
Doxorubicin (DOX) is an effective anticancer drug. However, its use is hampered by the development of very mortal cardiomyopathy. Here, we investigate whether the co-administration of the antidepressant paroxetine (P), known to exert beneficial cardiovascular effects, would provide effective cardioprotection. Experiments were performed in male Wistar rats randomly assigned to control group (0.5 mL/kg 0.9% NaCl, i.v., n = 7), DOX group (DOX 5 mg /kg i.v., n = 23) and DOX+P group (DOX 5 mg/kg, i.v. plus P 10 mg/kg p.o. daily, beginning five days before DOX administration and during the follow-up period, n = 11). Rats' body weight and echocardiography parameters were monitored before and after drug/vehicle administration. Cardiac histology was performed post-mortem, as well as beta1-adrenergic receptor (β-AR), beta2-adrenergic receptor (β-AR), G protein-coupled receptor kinases type 2 (GRK2), type 3 (GRK3), beta-arrestin 1, and beta-arrestin 2 gene expression using RT-qPCR. DOX-treated rats exhibited bad general condition, adynamia, loss of body weight, and low survival. Echocardiography revealed two phenotypes: cardiomyopathy with left ventricular (LV) hypertrophy (DOX-HCM) and cardiomyopathy with LV dilation (DOX-DCM). In DOX-HCM rats only, there was an increased GRK2 and GRK3 gene expression and synthesis. DOX+P co-treated rats exhibited good general condition, normal spontaneous behaviour, gained weight over time, had increased survival, and preserved LV morphology and contractility. In these rats, gene expression and synthesis of GRK2 and GRK3 were decreased, while β-AR and β-AR were increased. Present results show for the first time that P effectively reduces DOX-induced cardiotoxicity and enhances survival.
Topics: Animals; Antibiotics, Antineoplastic; Cardiomyopathies; Cardiotonic Agents; Cardiotoxicity; Doxorubicin; Gene Expression Regulation; Male; Paroxetine; Rats; Rats, Wistar; Selective Serotonin Reuptake Inhibitors; Ventricular Remodeling
PubMed: 34781149
DOI: 10.1016/j.biopha.2021.112411 -
Frontiers in Neuroendocrinology Oct 2022Postpartum depression is a common mental disease in obstetric puerperium. Its etiology is not completely clear, and its clinical manifestations are complex. It has... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postpartum depression is a common mental disease in obstetric puerperium. Its etiology is not completely clear, and its clinical manifestations are complex. It has serious adverse effects on the body and mind of mothers and infants. Treatment should also follow the principle of individualization. Preliminary studies have shown that traditional chinese medicine prescriptions combined with paroxetine is effective in treating postpartum depression. In order to better determine the therapeutic effect, further exploration was carried out.
HYPOTHESIS
Does the study better evaluate the therapeutic effect and provide data support for clinical promotion?
STUDY DESIGN
The search comes from using the following electronic databases established until January 2022.
STUDY RESULTS
The meta analysis results show that paroxetine combined with traditional chinese medicine prescriptions can reduce the Hamilton Depression Scale (HAMD) score [WMD = -7.35, 95 % CI (-10.84, -3.87), P<0.001] and Edinburgh Postpartum Depression Scale (EPDS) score [WMD = -3.24, 95 % CI (-5.96, -0.53), P < 0.001].And better than paroxetine treatment alone in terms of improving clinical efficacy [RR = 1.22, 95 % CI (1.16, 1.30), P < 0.001].
CONCLUSIONS
Based on the combination of paroxetine and traditional chinese medicine prescriptions in the treatment of postpartum depression, there is a certain clinical effect, and a strong research design and a certain number of RCTs are required at the same time. Future research should clarify the specific composition and composition of traditional Chinese medicine prescriptions.
Topics: Female; Humans; Paroxetine; Depression, Postpartum; Medicine, Chinese Traditional; Randomized Controlled Trials as Topic; Prescriptions; Depression
PubMed: 35926637
DOI: 10.1016/j.yfrne.2022.101019 -
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 -
The Cochrane Database of Systematic... Sep 2014Postnatal depression is a common disorder that can have adverse short- and long-term effects on maternal morbidity, the new infant and the family as a whole. Treatment... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Postnatal depression is a common disorder that can have adverse short- and long-term effects on maternal morbidity, the new infant and the family as a whole. Treatment is often largely by social support and psychological interventions. It is not known whether antidepressants are an effective and safe choice for treatment of this disorder. This review was undertaken to evaluate the effectiveness of different antidepressants and to compare their effectiveness with other forms of treatment, placebo or treatment as usual. It is an update of a review first published in 2001.
OBJECTIVES
To assess the effectiveness of antidepressant drugs in comparison with any other treatment (psychological, psychosocial or pharmacological), placebo or treatment as usual for postnatal depression.
SEARCH METHODS
We searched the Cochrane Depression, Anxiety and Neurosis Group's Specialized Register (CCDANCTR) to 11 July 2014. This register contains reports of relevant randomised controlled trials (RCTs) from the following bibliographic databases: The Cochrane Library (all years), MEDLINE (1950 to date), EMBASE, (1974 to date) and PsycINFO (1967 to date). We also searched international trial registries and contacted pharmaceutical companies and experts in the field.
SELECTION CRITERIA
We included RCTs of women with depression with onset up to six months postpartum that compared antidepressant treatment (alone or in combination with another treatment) with any other treatment, placebo or treatment as usual.
DATA COLLECTION AND ANALYSIS
Two review authors independently extracted data from the trial reports. We requested missing information from investigators wherever possible. We sought data to allow an intention-to-treat analysis. Random effects meta-analyses were conducted to pool data where sufficient comparable studies were identified.
MAIN RESULTS
We included six trials with 596 participants in this review. All studies had a randomised controlled parallel group design, with two conducted in the UK, three in the US and one in Israel. Meta-analyses were performed to pool data on response and remission from studies comparing antidepressants with placebo. No meta-analyses could be conducted for other comparisons due to the small number of trials identified.Four studies compared selective serotonin reuptake inhibitors (SSRIs) with placebo (two using sertraline, one using paroxetine and one using fluoxetine; 233 participants in total). In two of these studies both the experimental and placebo groups also received psychological therapy. Pooled risk ratios based on data from three of these studies (146 participants) showed that women randomised to SSRIs had higher rates of response and remission than those randomised to placebo (response: RR 1.43, 95% CI 1.01 to 2.03; remission: RR 1.79, 95% CI 1.08 to 2.98); the fourth study did not report data on response or remission.One study (254 participants) compared antidepressant treatment with treatment as usual (for the first four weeks) followed by listening visits. The study found significantly higher rates of improvement in the antidepressant group than treatment-as-usual group after the first four weeks, but no difference between antidepressants and listening visits at the later follow-up. In addition, one study comparing sertraline with nortriptyline (a tricyclic antidepressant) found no difference in effectiveness (109 participants).Side effects were experienced by a substantial proportion of women, but there was no evidence of a meaningful difference in the number of adverse effects between treatment arms in any study. There were very limited data on adverse effects experienced by breastfed infants, with no long-term follow-up. All but one of the studies were assessed as being at high or uncertain risk of attrition bias and selective outcome reporting. In particular, one of the placebo-controlled studies had over 50% drop-out.
AUTHORS' CONCLUSIONS
The evidence base for this review was very limited, with a small number of studies and little information on a number of important outcomes, particularly regarding potential effects on the child. Risk of bias, for example from high attrition rates, as well as low representativeness of participants (e.g. exclusion of women with severe or chronic depression in several trials) also limit the conclusions that can be drawn.Pooled estimates for response and remission found that SSRIs were significantly more effective than placebo for women with postnatal depression. However the quality of evidence contributing to this comparison was assessed as very low owing to the small sample size for this comparison (146 participants from three studies), the risk of bias in included studes and the inclusion of one study where all participants in both study arms additionally received psychological therapy. There was insufficient evidence to conclude whether, and for whom, antidepressant or psychological/psychosocial treatments are more effective, or whether some antidepressants are more effective or better tolerated than others. There is also inadequate evidence on whether the benefits of antidepressants persist beyond eight weeks or whether they have short- or long-term adverse effects on breastfeeding infants.Professionals treating women with severe depression in the postnatal period will need to draw on other evidence, including trials among general adult populations and observational studies of antidepressant safety when breastfeeding (although the potential for confounding in non-randomised studies must be considered). More RCTs are needed with larger sample sizes and longer follow-up, including assessment of the impact on the child and safety of breastfeeding. Further larger-scale trials comparing antidepressants with alternative treatment modalities are also required.
Topics: Adult; Antidepressive Agents, Second-Generation; Clinical Trials as Topic; Depression, Postpartum; Female; Fluoxetine; Humans; Nortriptyline; Paroxetine; Randomized Controlled Trials as Topic; Selective Serotonin Reuptake Inhibitors; Sertraline
PubMed: 25211400
DOI: 10.1002/14651858.CD002018.pub2 -
Frontiers in Pharmacology 2022Paroxetine is one of the most potent selective serotonin reuptake inhibitors (SSRIs) approved for treating depression, panic disorder, and obsessive-compulsive disorder....
Pharmacokinetics of immediate and sustained-release formulations of paroxetine: Population pharmacokinetic approach to guide paroxetine personalized therapy in chinese psychotic patients.
Paroxetine is one of the most potent selective serotonin reuptake inhibitors (SSRIs) approved for treating depression, panic disorder, and obsessive-compulsive disorder. There is evidence linking genetic polymorphisms and nonlinear metabolism to the Paroxetine's pharmacokinetic (PK) variability. The purpose of the present study was to develop a population PK (PPK) model of paroxetine in Chinese patients, which was used to define the paroxetine's PK parameters and quantify the effect of clinical and baseline demographic factors on these PK characteristics. The study included 184 inpatients with psychosis (103 females and 81 males), with a total of 372 serum concentrations of paroxetine for PPK analyses. The total daily dosage ranged from 20 to 75 mg. One compartment model could fit the PKs characterize of paroxetine. Covariate analysis revealed that dose, formulation, and sex had a significant effect on the PK parameters of paroxetine; however, there was no evident genetic influence of enzymes on paroxetine concentrations in Chinese patients. The study determined that the population's apparent distribution volume (V/F) and apparent clearance (CL/F), respectively, were 8850 and 21.2 L/h. The CL/F decreased 1-2-fold for each 10 mg dose increase, whereas the different formulations caused a decrease in V/F of 66.6%. Sex was found to affect bioavailability (F), which decreased F by 47.5%. Females had higher F values than males. This PPK model described data from patients with psychosis who received paroxetine immediate-release tablets (IR-T) and/or sustained-release tablets (SR-T). Paroxetine trough concentrations and relative bioavailability were different between formulations and sex. The altered serum concentrations of paroxetine resulting from individual variants and additive effects need to be considered, to optimize the dosage regimen for individual patients.
PubMed: 36172189
DOI: 10.3389/fphar.2022.966622 -
World Psychiatry : Official Journal of... Oct 2022
PubMed: 36073700
DOI: 10.1002/wps.21026 -
Clujul Medical (1957) 2015To evaluate the effects of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite, 4-hydroxyatomoxetine-O-glucuronide, after coadministration of...
BACKGROUND AND AIMS
To evaluate the effects of paroxetine on the pharmacokinetics of atomoxetine and its main metabolite, 4-hydroxyatomoxetine-O-glucuronide, after coadministration of atomoxetine and paroxetine in healthy volunteers.
METHODS
22 healthy volunteers, extensive metabolizers, took part in this open-label, non-randomized, clinical trial. The study consisted of two periods: Reference, when a single oral dose of 25 mg atomoxetine was administrated to each subject and Test, when 25 mg atomoxetine and 20 mg paroxetine were coadministered. Between the two periods, the volunteers received an oral daily dose of 20-40 mg paroxetine, for 6 days. Atomoxetine and 4-hydroxyatomoxetine-O-glucuronide plasma concentrations were determined within the first 48 hours following drug administration. The pharmacokinetic parameters of both compounds were assessed using a non-compartmental method and the analysis of variance aimed at identifying any statistical significant differences between the pharmacokinetic parameters of atomoxetine and its main metabolite, corresponding to each study period.
RESULTS
Paroxetine modified the pharmacokinetic parameters of atomoxetine. Cmax increased from 221.26±94.93 to 372.53±128.28 ng/mL, while AUC0-t and AUC0-∞ also increased from 1151.19±686.52 to 6452.37±3388.76 ng*h/mL, and from 1229.15±751.04 to 7111.74±4195.17 ng*h/mL respectively. The main metabolite pharmacokinetics was also influenced by paroxetine intake, namely Cmax, AUC0-t and AUC0-∞ decreased from 688.76±270.27 to 131.01±100.43 ng*h/mL, and from 4810.93±845.06 to 2606.04±923.88 and from 4928.55±853.25 to 3029.82 ±941.84 respectively.
CONCLUSIONS
Multiple-dose paroxetine intake significantly influenced atomoxetine and its active metabolite pharmacokinetics, causing a 5.8-fold increased exposure to atomoxetine and 1.6-fold reduced exposure to 4-hydroxyatomoxetine-O-glucuronide.
PubMed: 26733750
DOI: 10.15386/cjmed-488 -
Journal of Neurovirology Feb 2018Paroxetine and fluconazole have neuroprotective effects in an in vitro model of HIV protein-mediated neuronal injury. This study evaluated the safety, tolerability, and... (Randomized Controlled Trial)
Randomized Controlled Trial
Paroxetine and fluconazole have neuroprotective effects in an in vitro model of HIV protein-mediated neuronal injury. This study evaluated the safety, tolerability, and efficacy of both paroxetine and fluconazole for the treatment of HIV-associated neurocognitive disorder (HAND). A 24-week randomized double-blind, placebo-controlled 2 × 2 factorial design study was used. HIV+ individuals with cognitive impairment were enrolled in the 24-week trial. Participants were randomly assigned to one of four groups: (1) paroxetine 20 mg/day, (2) fluconazole 100 mg every 12 h, (3) paroxetine and fluconazole, or (4) placebo. Safety, tolerability, and efficacy were evaluated. Forty-five HIV+ individuals were enrolled. Medications were well tolerated. Compared to no paroxetine arms, HIV+ individuals receiving paroxetine showed improved NPZ8 summary scores, (mean change = 0.25 vs - 0.19, p = 0.049), CalCAP sequential test reaction time (mean change = 0.34 vs -0.23, p = 0.014), Trail Making Part B test performance (mean change = 0.49 vs - 0.33, p = 0.041), and FAS verbal fluency (mean change = 0.25 vs 0.02, p = 0.020) but a decline in the Letter number sequencing test (mean change = - 0.40 vs 0.26, p = 0.023). Biomarkers of cellular stress, inflammation, and neuronal damage were not affected by paroxetine. HIV+ individuals receiving fluconazole did not show a benefit in cognition and showed an increase in multiple markers of cellular stress compared to the no fluconazole arms. In conclusion, paroxetine was associated with improvement in a summary neuropsychological test measure and in several neuropsychological tests but worse performance in one neuropsychological test. Further studies of paroxetine for the treatment of HAND and to define its precise neuroprotective properties are warranted.
Topics: AIDS Dementia Complex; Adult; Anti-HIV Agents; Antidepressive Agents, Second-Generation; Antifungal Agents; Double-Blind Method; Drug Administration Schedule; Drug Repositioning; Factor Analysis, Statistical; Female; Fluconazole; HIV-1; Humans; Male; Middle Aged; Neuroprotective Agents; Neuropsychological Tests; Paroxetine; Patient Safety; Treatment Outcome
PubMed: 29063516
DOI: 10.1007/s13365-017-0587-z