-
Scientific Reports Jul 2023Rhabdomyolysis is a syndrome potentially fatal and has been associated with selective serotonin reuptake inhibitors (SSRIs) treatment in a few case reports. Herein, we...
Rhabdomyolysis is a syndrome potentially fatal and has been associated with selective serotonin reuptake inhibitors (SSRIs) treatment in a few case reports. Herein, we purpose to establish the correlation between SSRIs use and rhabdomyolysis using the U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database. We conducted an analysis on reports that were submitted to the FAERS database during the period between January 1, 2004, and December 31, 2022. Four algorithms, including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayes geometric mean (EBGM), were employed to quantify the signals of rhabdomyolysis associated with SSRIs. In total, 16,011,277 non-duplicated reports were obtained and analyzed. Among 33,574 reports related to rhabdomyolysis, SSRIs were classified as primary suspected drug in 889 cases. Disproportionality analysis identified a positive signal between rhabdomyolysis and SSRIs (ROR: 2.86, 95% CI 2.67-3.05; PRR: 2.84, χ: 1037.16; IC = 1.39; EBGM = 2.64). Among six SSRIs, fluvoxamine had the strongest signal (ROR: 11.64, 95% CI 8.00-16.93; PRR: 11.38, χ: 265.51; IC = 2.41; EBGM = 8.31), whereas no significant signal of rhabdomyolysis was detected for paroxetine (ROR: 1.83, 95% CI 1.55-2.15; PRR: 1.82, χ: 53.82; IC = 0.73; EBGM = 1.59). After excluding cases co-administered with statins, the signal of rhabdomyolysis associated with SSRIs remains significant. Our analysis reveals that there are differences in safety signals among six SSRIs in respect to the risk of rhabdomyolysis, with fluvoxamine displaying the highest risk signal, while paroxetine did not show a significant signal. Given the potentially lethal nature of rhabdomyolysis, healthcare professionals should inform patients of the potential risk of rhabdomyolysis associated with SSRIs prior to initiating treatment.
Topics: United States; Humans; Selective Serotonin Reuptake Inhibitors; Bayes Theorem; Pharmacovigilance; Fluvoxamine; Paroxetine; Adverse Drug Reaction Reporting Systems; Rhabdomyolysis; United States Food and Drug Administration
PubMed: 37507539
DOI: 10.1038/s41598-023-39482-y -
Fundamental & Clinical Pharmacology Jun 2024Pharmacologic management of mental health illnesses in patients receiving dialysis is complex and lacking data. (Review)
Review
BACKGROUND
Pharmacologic management of mental health illnesses in patients receiving dialysis is complex and lacking data.
OBJECTIVE
Our objective was to synthesize published data for the treatment of depression, bipolar and related disorders, schizophrenia or psychotic disorders, and anxiety disorders in adults receiving hemodialysis or peritoneal dialysis.
METHODS
We undertook a scoping review, searching the following databases: Medline, Embase, CINAHL, PsycINFO, Cochrane Library, Scopus, and Web of Science. Data on patients who received only short-term dialysis, a kidney transplant, or non-pharmacologic treatments were excluded.
RESULTS
Seventy-three articles were included: 41 focused on depression, 16 on bipolar disorder, 13 on schizophrenia and psychotic disorders, 1 on anxiety disorders, and 2 addressing multiple mental health illnesses. The majority of depression studies reported on selective serotonin reuptake inhibitors (SSRIs) as a treatment. Sertraline had the most supporting data with use of doses from 25 to 200 mg daily. Among the remaining SSRIs, escitalopram, citalopram, and fluoxetine were studied in controlled trials, whereas paroxetine and fluvoxamine were described in smaller reports and observational trials. There are limited published data on other classes of antidepressants and on pharmacological management of anxiety. Data on treatment for patients with bipolar disorder or schizophrenia and related disorders are limited to case reports.
CONCLUSION
Over half of the studies included were case reports, thus limiting conclusions. More robust data are required to establish effect sizes of pharmacological treatments prior to providing specific recommendations for their use in treating mental health illnesses in patients receiving dialysis.
PubMed: 38877814
DOI: 10.1111/fcp.13022 -
Journal of Biomolecular Structure &... 2024Several generations of anti-epileptic drugs (AEDs) are available but have several associated side effects apart from a limited success rate. Drug repositioning...
Several generations of anti-epileptic drugs (AEDs) are available but have several associated side effects apart from a limited success rate. Drug repositioning strategies have gained importance in the last two decades owing to lower failure rates and economic burden. Drugs with similar side effect profiles may share a common mechanism of action and thus can be linked to other disease treatments. The present study was carried out to identify the newly approved drug candidate(s) as AEDs using clinical side-effects drug repositioning strategy. The clinical side effect similarity of drugs available in the SIDER v4.1 database was estimated against common side effects of 5 major marketed AEDs, using the 'dplyr' package library in the R. Further drugs were filtered based on Blood Brain Barrier permeability prediction and FDA-approval status. Molecular docking studies were performed for selected 26 hits (drugs) against previously identified epilepsy target receptors: Voltage-gated sodium channel α2 (Nav1.2), GABA receptor α1-β1 (GABAr α1-β1), and Voltage-gated calcium channel α-1 G (Cav3.1). Only 2 drugs (Ziprasidone and Paroxetine) showed better binding affinities against studied epilepsy receptors Nav1.2, GABAr α1-β1, and Cav3.1, than their corresponding standard AEDs, i.e. Carbamazepine, Clonazepam, and Pregabalin, respectively. Ziprasidone reportedly showed seizure-like symptoms in ∼3% of patients and was hence omitted from further study. The MDS study of docked complexes of Paroxetine with selected epilepsy target receptors showed stable RMSD values and better interaction energies. The study reveals Paroxetine as a potential candidate to be repurposed for 1st line epileptic seizure medication.Communicated by Ramaswamy H. Sarma.
Topics: Humans; Drug Repositioning; Molecular Docking Simulation; Paroxetine; Anticonvulsants; Epilepsy; Piperazines; Thiazoles
PubMed: 37042987
DOI: 10.1080/07391102.2023.2199874 -
Acta Psychiatrica Scandinavica Jan 2024Antipsychotics (AP) have been used to augment antidepressant (AD) medication in treatment-resistant depression. In this study we examined factors (including severity of...
BACKGROUND
Antipsychotics (AP) have been used to augment antidepressant (AD) medication in treatment-resistant depression. In this study we examined factors (including severity of depression and initial antidepressant) affecting AP augmentation, as well as which APs were initiated as augmentation in young adults.
METHODS
Data were extracted from Finnish nationwide registers. Of persons aged 18-29 years diagnosed with a depression during 2004-2017 we focused on incident AD users (who initiated AD 6 months before and after the diagnosis) whose severity level of depression was recorded (N = 21,966). AP augmentation was studied during 1 year after diagnosis of depression. Persons diagnosed with severe depression with psychotic features (n = 1486) were excluded from main analyses and analyzed separately.
RESULTS
Overall, 8.4% of new antidepressant users initiated AP augmentation. Risk of augmentation increased with severity of depression as 3.9%, 5.8%, and 14.0% of persons with mild, moderate, and severe depression, respectively, initiated augmentation. Male sex, comorbid anxiety and personality disorders, substance abuse and selfharm/suicide attempt were positively associated with augmentation. Compared to citalopram, use of tricyclic antidepressant, paroxetine and venlafaxine were associated with increased risk of augmentation, while use of bupropion was associated with a decreased risk. Quetiapine and risperidone were the most common APs used in augmentation. Among persons with severe depression with psychotic features, use of sertraline was associated with AP augmentation, whereas use of fluoxetine decreased risk of augmentation.
CONCLUSIONS
Use of APs as augmentation of AD therapy was common in severe depression. Comorbidities had only a small effect to augmentation, but selection of initial AD was more closely associated to risk of augmentation. Interestingly, use of bupropion decreased risk of augmentation, which warrants further studies, as well as the decrease in risk of augmentation when fluoxetine in case of psychotic depression was used.
Topics: Male; Young Adult; Humans; Fluoxetine; Depression; Bupropion; Antidepressive Agents; Antipsychotic Agents; Depressive Disorder, Major
PubMed: 37985246
DOI: 10.1111/acps.13633 -
Journal of Affective Disorders Jan 2024Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in... (Randomized Controlled Trial)
Randomized Controlled Trial
Omega-3 supplementation improves depressive symptoms, cognitive function and niacin skin flushing response in adolescent depression: A randomized controlled clinical trial.
BACKGROUND
Depressive disorder in adolescents is a major health problem with inadequate treatment. Omega-3 (ω3) polyunsaturated fatty acids are a promising adjuvant therapy in adult depression. The primary objective of this study was to investigate the efficacy of adjuvant ω3 treatment on depressive symptoms in adolescent depression. Secondarily, we explored the effects of ω3 on cognitive function and memory and niacin skin flushing response (NSFR), as their robust associations with adolescent depression.
METHODS
A total of 71 adolescents with depression (aged 13-24; 59.2 % female) were randomly assigned to receive ω3 plus Paxil (n = 34) or Paxil alone (n = 37) for 12 weeks. Primary outcome was depression severity according to scores on Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes were cognitive function and memory, and NSFR.
RESULTS
Significant improvements in depressive symptoms over time (p = 0.00027 at week 12) were observed in the ω3 + Paxil group compared with Paxil group. Additionally, in the ω3 + Paxil group, significant improvements in memory over time, and greater cognitive function and NSFR were also observed compared with the Paxil group; the NSFR was negatively correlated with MADRS scores at baseline.
LIMITATIONS
The trial was open label; thus, the outcome measures should be viewed as preliminary since inherent bias in outcomes due to the potential of a placebo effect.
CONCLUSIONS
Our results demonstrate that adjuvant ω3 treatment is effective for reducing depressive symptoms as well as improving cognitive function, memory and the NSFR; these results suggest ω3 is a promising adjuvant treatment for adolescent depression.
Topics: Adult; Adolescent; Female; Humans; Male; Niacin; Depression; Paroxetine; Cognition; Dietary Supplements
PubMed: 38190276
DOI: 10.1016/j.jad.2023.10.151 -
Heliyon May 2024To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the...
AIM
To investigate whether SJF functions in similar manner as the key substance in the inflammatory process, soluble epoxide hydrolase (sEH) inhibitor, to inhibit the arachidonic acid metabolic pathway and nuclear factor kappa-B(NF-κB) signal path in the hippocampi of postpartum depression rats.
METHODS
The rats were subcutaneous injected estradiol benzoate and progesterone to build PPD rat model. SJF, paroxetine hydrochloride and sEH inhibitor (AUDA) were used to treat PPD rats for 3 weeks. Then the morphological changes of hippocampi and various proteins were observed after that behavioral test were conducted in all 36 SD rats in six group: SJF, paroxetine, AUDA, PPD, sham and normal group.
RESULTS
Weight, results of sucrose preference, upright times, total and center squares crossing decreased significantly (P < 0.01), whereas immobility time increased (P < 0.01). Results above were reversed in animals that in the SJF, paroxetine and AUDA groups. Hippocampal neurons in PPD rats partially degenerated with narrowed nuclei, increased autophagy and mitochondria bound to lysosomes were visible while the autophagy of hippocampal neurons in the paroxetine and AUDA group decreased, with a small amount of lysosomes. sEH, COX-2, 5-LOX, TNF-α, IL-1, IL-6, NF-κB p65, and Cor increased in hippocampi of PPD rats while EETs and 5-HT decreased. Protein expressions of Ibal, GFAP, p-IκBα, p65, and p-p65(S536)increased in PPD animals. Those changes were reversed by SJF, paroxetine and AUDA. Gene expressions of TNF-α, IL-1β, IL-6, 5-LOX, COX-2 and p65 increased in PPD rats and the changes of expression in these genes were reversed by paroxetine and AUDA. SJF reversed the gene expression changes of COX-2, TNF-α, and IL-1β.
CONCLUSION
SJF may have an analogous effect as sEH inhibitor to relieve depressive symptoms by suppressing inflammatory signaling pathways in hippocampi of PPD rats, which involves AA metabolic pathway and NF-κB signal pathway.
PubMed: 38726147
DOI: 10.1016/j.heliyon.2024.e29978 -
Neuropharmacology Dec 2023The study aimed to investigate the functional connectivity (FC) between the cerebellum and intrinsic cerebral networks in patients with panic disorder (PD), and to...
The study aimed to investigate the functional connectivity (FC) between the cerebellum and intrinsic cerebral networks in patients with panic disorder (PD), and to observe changes in the cerebellar-cerebral FC following pharmacotherapy. Fifty-four patients with PD and 54 healthy controls (HCs) underwent clinical assessments and functional magnetic resonance imaging scans before and after a 5-week paroxetine treatment. Seed-based cerebellar-cerebral FC was compared between the PD and HC groups, as well as between patients with PD before and after treatment. Additionally, the correlations between FC and clinical features of PD were analyzed. Compared to HCs, patients with PD had altered cerebellar-cerebral FC in the default mode, affective-limbic, and sensorimotor networks. Moreover, a negative correlation between cerebellar-insula disconnection and the severity of depressive symptoms in patients with PD (Pearson correlation, r = -0.424, p = 0.001, Bonferroni corrected) was found. After treatment, most of the enhanced FCs observed in patients with PD at baseline returned to levels similar to those observed in HCs. However, the reduced FC at baseline did not significantly change after treatment. The findings suggest that patients with PD have specific deficits in resting-state cerebellar-cerebral FC and that paroxetine may improve PD by restoring the balance of cerebellar-cerebral FC. These findings emphasize the crucial involvement of cerebellar-cerebral FC in the neuropsychological mechanisms underlying PD and in the potential pharmacological mechanisms of paroxetine for treating PD.
PubMed: 37652260
DOI: 10.1016/j.neuropharm.2023.109692 -
BMC Psychiatry Sep 2023Appropriate medication is very important for pilots with acute stress disorder. Improper medication can not only affect the physical and mental health of the pilots but...
BACKGROUND
Appropriate medication is very important for pilots with acute stress disorder. Improper medication can not only affect the physical and mental health of the pilots but can also endanger flight safety. Hence, we aimed to quickly and effectively relieve symptoms and restore cognitive function by forming a consensus of Chinese experts on the pharmacological treatment of acute stress disorder in pilots using the Delphi method.
METHODS
Relevant literature was searched to enumerate the current status of pharmacological treatment of acute stress disorder in pilots, followed by two rounds of expert consultation and discussion according to the listed status of the survey using the Delphi method. A descriptive statistical method was used to analyze the basic information, authority coefficients, concentration of opinions, and survey items of the experts to develop a consensus on the pharmacological treatment of acute stress disorder in pilots.
RESULTS
A total of 16 experts in psychiatry, pharmacology, and aerospace medicine from different provinces and cities across China were invited for consultation. The recovery rate of the two rounds of consultation was 100%, and the expert authority coefficients were 0.897 and 0.906, respectively. Kendall's coefficient of concordance of indicators at all levels was 0.564-0.594 (p < 0.01). Based on the number of votes received, alprazolam tablets (16), eszopiclone tablets (15), and lorazepam tablets (14) were recommended for the treatment of excitatory psychomotor symptoms of acute stress disorder; paroxetine tablets (15) and sertraline tablets (15) were available for psychomotor depressive symptoms; olanzapine tablets (15), olanzapine orally disintegrating tablets (14), and quetiapine fumarate tablets (14) were selected for psychotic symptoms.
CONCLUSIONS
This study formed a consensus on rapid and effective pharmacological treatment for different symptoms of acute stress disorder pilots, which provides a reference for clinical treatment.
Topics: Humans; Consensus; Delphi Technique; East Asian People; Olanzapine; Stress Disorders, Traumatic, Acute; Pilots
PubMed: 37684592
DOI: 10.1186/s12888-023-05145-5 -
Chinese Medical Journal Jun 2024G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present...
BACKGROUND
G protein-coupled receptor kinase 2 (GRK2) could participate in the regulation of diverse cells via interacting with non-G-protein-coupled receptors. In the present work, we explored how paroxetine, a GRK2 inhibitor, modulates the differentiation and activation of immune cells in rheumatoid arthritis (RA).
METHODS
The blood samples of healthy individuals and RA patients were collected between July 2021 and March 2022 from the First Affiliated Hospital of Anhui Medical University. C57BL/6 mice were used to induce the collagen-induced arthritis (CIA) model. Flow cytometry analysis was used to characterize the differentiation and function of dendritic cells (DCs)/T cells. Co-immunoprecipitation was used to explore the specific molecular mechanism.
RESULTS
In patients with RA, high expression of GRK2 in peripheral blood lymphocytes, accompanied by the increases of phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR). In animal model, a decrease in regulatory T cells (Tregs), an increase in the cluster of differentiation 8 positive (CD8+) T cells, and maturation of DCs were observed. Paroxetine, when used in vitro and in CIA mice, restrained the maturation of DCs and the differentiation of CD8+ T cells, and induced the proportion of Tregs. Paroxetine inhibited the secretion of pro-inflammatory cytokines, the expression of C-C motif chemokine receptor 7 in DCs and T cells. Simultaneously, paroxetine upregulated the expression of programmed death ligand 1, and anti-inflammatory cytokines. Additionally, paroxetine inhibited the PI3K-AKT-mTOR metabolic pathway in both DCs and T cells. This was associated with a reduction in mitochondrial membrane potential and changes in the utilization of glucose and lipids, particularly in DCs. Paroxetine reversed PI3K-AKT pathway activation induced by 740 Y-P (a PI3K agonist) through inhibiting the interaction between GRK2 and PI3K in DCs and T cells.
CONCLUSION
Paroxetine exerts an immunosuppressive effect by targeting GRK2, which subsequently inhibits the metabolism-related PI3K-AKT-mTOR pathway of DCs and T cell in RA.
PubMed: 38879805
DOI: 10.1097/CM9.0000000000003165 -
Cureus Dec 2023Symptoms caused by a selective serotonin reuptake inhibitor (SSRI) overdose are often mild and can be managed with supportive care and close monitoring, even when...
Symptoms caused by a selective serotonin reuptake inhibitor (SSRI) overdose are often mild and can be managed with supportive care and close monitoring, even when complicated by serotonin syndrome. There are limited pharmacokinetic data regarding massive overdoses of paroxetine, and the severity of an SSRI overdose is likely to be underestimated. We describe a fatal case of severe serotonin syndrome and acute respiratory distress syndrome (ARDS) following an overdose of controlled-release paroxetine. A 53-year-old male with depression presented with altered consciousness. He had ingested controlled-release paroxetine along with other medications. On arrival, he had ocular flutter and myoclonus, and blood examinations revealed acute kidney injury and rhabdomyolysis, which suggested serotonin syndrome. Computed tomography (CT) showed pharmacobezoars in the esophagus and stomach. Symptoms of serotonin syndrome and hypotension persisted despite administration of high doses of vasopressors with endotracheal intubation. We performed endoscopic decontamination to remove pharmacobezoars from the stomach. Finally, he developed severe ARDS and died due to respiratory failure on day 23. Sequential serum concentrations of paroxetine were 5.38 µg/mL at admission and 3.21 µg/mL on day 7, both above lethal levels. This case highlights the potential for fatal complications and prolonged toxicity in the case of a massive overdose of controlled-release paroxetine. We should recognize that such an overdose may be life-threatening and should consider aggressive interventions including endoscopic decontamination. A better understanding of the pharmacokinetics of a massive SSRI overdose would be helpful for optimal management.
PubMed: 38229825
DOI: 10.7759/cureus.50691