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Frontiers in Pharmacology 2024This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and...
OBJECTIVES
This study aimed to investigate the plasma and breastmilk concentrations for sertraline, citalopram and paroxetine for assessment of the Milk/Plasma (M/P) ratio and Absolute Infant Dose (AID), and to determine actual infant drug exposure through breastfeeding. Subsequently, informed recommendations will be formulated regarding the advisability of breastfeeding in women undergoing treatment with the three most widely used antidepressants.
METHODS
A pharmacokinetic study in lactating women and their infants using sertraline, citalopram or paroxetine was performed. Paired breastmilk and plasma samples and single point infant plasma samples were collected to determine antidepressant concentrations. An Area Under the Curve (AUC) based approach with the trapezoidal rule was used to calculate M/P ratios and AID for all three antidepressants by combining all measured concentrations for the same dose.
RESULTS
Thirty-seven lactating women and their infants participated in this study. 111 paired breastmilk and plasma samples and 37 single point infant plasma samples were collected. Detectable concentrations of sertraline, citalopram and paroxetine were present in all breastmilk samples. For sertraline and citalopram M/P ratio is above one, indicating higher breastmilk than plasma concentrations, however, drug exposure by breastmilk did not lead to detectable plasma drug levels in any of the 15 infants for sertraline, for nine (out of 13) infants for citalopram and for eight (out of nine) infants for paroxetine.
CONCLUSION
Given the well-known benefits of breastfeeding, our findings support breastfeeding of infants by mothers who are taking sertraline, citalopram or paroxetine is safe. Sertraline and paroxetine are the preferred antidepressants during breastfeeding, reaching mostly undetectable infant drug levels.
PubMed: 38841362
DOI: 10.3389/fphar.2024.1414677 -
Indian Dermatology Online Journal 2020Psychodermatological (PD) conditions encountered in dermatologic practice include primary psychiatric conditions such as delusions of parasitosis or secondary... (Review)
Review
Psychodermatological (PD) conditions encountered in dermatologic practice include primary psychiatric conditions such as delusions of parasitosis or secondary psychiatric conditions such as anxiety and depression due to dermatologic disease. The psychotropics include antipsychotic agents, anti-anxiety agents, antidepressants, and miscellaneous drugs such as anti convulsants. Anti psychotics are further divided into first-generation and second-generation drugs. Currently, second-generation drugs e.g., risperidone are preferred over first-generation drugs e.g., pimozide in delusional infestation owing to the side effect profile of the latter. Anti-anxiety agents include benzodiazepines used in acute anxiety and buspirone in chronic anxiety disorders. They are frequently prescribed along with antidepressants. Although dependence and necessity of tapering is a problem with benzodiazepines, delayed onset of action is a feature of buspirone. The commonly used antidepressants in dermatology include selective serotonin reuptake inhibitors (citalopram, escitalopram, fluoxetine, fluvoxamine, paroxetine, and sertraline), selective serotonin norepinephrine reuptake inhibitors (venlafaxine, desvenlefaxine, and duloxetine), norepinephrine dopamine reuptake inhibitors (bupropion), tricyclic antidepressants (doxepin, amitriptyline, imipramine, and clomipramine), and tetracyclic antidepressants (mirtazapine). Miscellaneous drugs include anticonvulsants such as gabapentin and pregabalin, naltrexone, and N-acetyl cysteine. The principles of PD treatment are first establish the psychiatric diagnosis, followed by initiating drug treatment. The choice of drugs is dependent on multiple factors such as side-effect profile, drug interactions, and co-morbid conditions. Usually, drugs are started at a low dose and gradually increased. A literature search was done in Pubmed, Google Scholar, and Medline databases, and articles on treatment were analyzed.
PubMed: 32695685
DOI: 10.4103/idoj.IDOJ_330_19 -
EClinicalMedicine Sep 2021Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are...
BACKGROUND
Although tinnitus has a prevalence between 20 and 42.8%, the currently recommended management for tinnitus, such as tinnitus support and psychologic therapies, are relatively time-consuming and expensive. Several new pharmacologic treatments designed for tinnitus patients without specific origin had been developed but their efficacy remains unclear.
METHODS
The current Network Meta-Analysis (NMA) of randomised controlled trials (RCTs) was conducted to evaluate the efficacy of different pharmacologic treatments for tinnitus management in tinnitus patients without specific or treatable origin (i.e. primary tinnitus). Databases were searched from inception to April 5, 2021. All network meta-analytic procedures were conducted under the frequentist model. We calculated the effect size of outcomes with different rating scales with standardized mean difference. PROSPERO registration: CRD42020177742.
FINDINGS
Overall, 36 RCTs were included with 2,761 participants. The main results revealed that pharmacologic interventions with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) and those with anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) were associated with superior improvement in tinnitus severity and response rate compared to placebo/control. Oral amitriptyline were associated with the highest improvement in tinnitus severity and the fourth highest response rate. None of the investigated interventions was associated with different changes in quality of life compared to placebo/control. All the investigated treatments were associated with similar drop-out rate to placebo/control.
INTERPRETATION
The current NMA suggests a potential role for treatments with brain-acting effect (for example, amitriptyline, acamprosate, and gabapentin) or anti-inflammation/anti-oxidant effect (for example, intra-tympanic dexamethasone injection plus oral melatonin) as the preferable effective treatments for tinnitus without specific or treatable origin.
FUNDING
none.
PubMed: 34611615
DOI: 10.1016/j.eclinm.2021.101080 -
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 -
Current Neuropharmacology 2023People with epilepsy (PWE) are more likely to develop depression and both these complex chronic diseases greatly affect health-related quality of life (QOL). This... (Review)
Review
People with epilepsy (PWE) are more likely to develop depression and both these complex chronic diseases greatly affect health-related quality of life (QOL). This comorbidity contributes to the deterioration of the QOL further than increasing the severity of epilepsy worsening prognosis. Strong scientific evidence suggests the presence of shared pathogenic mechanisms. The correct identification and management of these factors are crucial in order to improve patients' QOL. This review article discusses recent original research on the most common pathogenic mechanisms of depression in PWE and highlights the effects of antidepressant drugs (ADs) against seizures in PWE and animal models of seizures and epilepsy. Newer ADs, such as selective serotonin reuptake inhibitors (SRRI) or serotonin-noradrenaline reuptake inhibitors (SNRI), particularly sertraline, citalopram, mirtazapine, reboxetine, paroxetine, fluoxetine, escitalopram, fluvoxamine, venlafaxine, duloxetine may lead to improvements in epilepsy severity whereas the use of older tricyclic antidepressant (TCAs) can increase the occurrence of seizures. Most of the data demonstrate the acute effects of ADs in animal models of epilepsy while there is a limited number of studies about the chronic antidepressant effects in epilepsy and epileptogenesis or on clinical efficacy. Much longer treatments are needed in order to validate the effectiveness of these new alternatives in the treatment and the development of epilepsy, while further clinical studies with appropriate protocols are warranted in order to understand the real potential contribution of these drugs in the management of PWE (besides their effects on mood).
Topics: Animals; Quality of Life; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Epilepsy; Seizures
PubMed: 35761500
DOI: 10.2174/1570159X20666220627160048 -
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 -
Therapeutic Advances in... 2023In patients attempting to discontinue their antidepressant medication, there have been no prospective studies on patterns of withdrawal as a function of the rate of...
BACKGROUND
In patients attempting to discontinue their antidepressant medication, there have been no prospective studies on patterns of withdrawal as a function of the rate of antidepressant reduction during the tapering trajectory, and moderators thereof.
OBJECTIVE
To investigate withdrawal as a function of gradual dose reduction.
DESIGN
Prospective cohort study.
METHODS
The sampling frame consisted of 3956 individuals in the Netherlands who received an antidepressant tapering strip between 19 May 2019 and 22 March 2022 in routine clinical practice. Of these, 608 patients, majorly with previous unsuccessful attempts to stop, provided daily ratings of withdrawal in the context of reducing their antidepressant medications (mostly venlafaxine or paroxetine), using hyperbolic tapering strips offering daily tiny reductions in dose.
RESULTS
Withdrawal in daily-step hyperbolic tapering trajectories was limited, and inverse to the rate of taper. Female sex, younger age, presence of one or more risk factors and faster rate of reduction over shorter tapering trajectories were associated with more withdrawal and differential course over time. Thus, sex and age differences were less marked early in the course of the trajectory, whereas differences associated with risk factors and shorter trajectories tended to peak early in the trajectory. There was evidence that tapering in weekly larger steps (mean per-week dose reduction: 33.4% of previous dose), in comparison with daily tiny steps (mean per-day dose reduction: 4.5% of previous dose or 25.3% per week), was associated with more withdrawal in trajectories of 1, 2 or 3 months, particularly for paroxetine and the group of other (non-paroxetine, non-venlafaxine) antidepressants.
CONCLUSION
Antidepressant hyperbolic tapering is associated with limited, rate-dependent withdrawal that is inverse to the rate of taper. The demonstration of multiple demographic, risk and complex temporal moderators in time series of withdrawal data indicates that antidepressant tapering in clinical practice requires a personalised process of shared decision making over the entire course of the tapering period.
PubMed: 37200818
DOI: 10.1177/20451253231171518 -
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 -
Frontiers in Cardiovascular Medicine 2021Paroxetine is a GRK2 inhibitor that has been widely used to treat depression and anxiety over the last few decades. The inhibition of GRK2 has been studied extensively ;...
INTRODUCTION
Paroxetine is a GRK2 inhibitor that has been widely used to treat depression and anxiety over the last few decades. The inhibition of GRK2 has been studied extensively ; however, evidence of its impact on heart failure remains scarce.
METHODS
To assess the association between paroxetine use and mortality in patients with heart failure. We conducted a retrospective longitudinal cohort study from 2008 to 2019, with a follow-up time of 28 days for all groups. This is a single-center study using the Medical Information Mart for Intensive Care IV database with 11,657 heart failure patients identified. We performed genetic matching to adjust for the covariates. Heart failure patients prescribed paroxetine for >24 h after hospital admission were categorized into the paroxetine group (77 patients), with remaining heart failure patients making up the matched control group (231 patients). The primary outcome was 28-day all-cause mortality from the date of hospital admission. Secondary outcomes included length of intensive care unit stay, length of hospital stay, and in-hospital mortality. The Kaplan-Meier survival estimator, logistic regression, Cox regression, and restricted mean survival time were used to detect the association between paroxetine therapy and outcomes.
RESULTS
Patients who received paroxetine during one hospital admission lived, on average, 0.7 lesser days (95% CI -2.53 to 1.1, = 0.46) than patients who did not use it in a 28-day truncation time point. Multivariable logistic regression, including all matched covariates, demonstrated that the adjusted odds ratio of 28-day mortality of the paroxetine administration group was 1.1 (95% CI 0.37-2.9, = 0.90). Multivariable Cox regression of 28-day mortality presented an adjusted hazard ratio of 1.00 (95% CI 0.42-2.62, = 0.92). Paroxetine was associated with an increased survival time at a 3,000-day truncation time point (203 days, 95% CI -305.69 to 817.8, = 0.37).
CONCLUSIONS
In patients with heart failure, treatment with paroxetine did not significantly reduce 28-day all-cause mortality.
PubMed: 35155607
DOI: 10.3389/fcvm.2021.794584