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Innovations in Clinical Neuroscience Apr 2020: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF.... (Review)
Review
: This paper sought to identify the instruments used to measure depression in heart failure (HF) and elucidate the impact of treatment interventions on depression in HF. The Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines were followed. Studies published from 1988 to 2018 covering depression and HF were identified through the review of the PubMed and PsycINFO databases using the keywords: "depres*" AND "heart failure." Two authors independently conducted a focused analysis, identifying 27 studies that met the specific selection criteria and passed the study quality checks. Patient-reported questionnaires were more commonly adopted than clinician-rated questionnaires, including the Beck Depression Inventory, the Patient Health Questionnaire (PHQ-9), and the Hospital Anxiety and Depression Scale. Six common interventions were observed: antidepressant medications, collaborative care, psychotherapy, exercise, education, and other nonpharmacological interventions. Except for paroxetine, selective serotonin reuptake inhibitors failed to show a significant difference from placebo. However, the collaborative care model including the use of antidepressants showed a significant decrease in PHQ-9 score after one year. All of the psychotherapy studies included a variation of cognitive behavioral therapy and patients showed significant improvements. The evidence was mixed for exercise, education, and other nonpharmacological interventions. This study suggests which types of interventions are more effective in addressing depression in heart failure patients.
PubMed: 32802590
DOI: No ID Found -
International Journal of Women's Health 2022Most women experience vasomotor symptoms (VMS) during their menopausal transition. Menopausal hormone therapy (HT) is the most effective treatment for VMS, but some... (Review)
Review
Most women experience vasomotor symptoms (VMS) during their menopausal transition. Menopausal hormone therapy (HT) is the most effective treatment for VMS, but some women choose not to use HT or have contraindications to using HT. Non-hormonal treatment options should be offered to these symptomatic menopausal women. Multiple large randomized controlled trials have demonstrated statistically significant reductions in hot flash severity and/or frequency with the use of selective serotonin reuptake inhibitors (SSRIs) and serotonin norepinephrine reuptake inhibitors (SNRIs). To date, paroxetine mesylate remains the only non-hormonal treatment that has been approved by the United States Food and Drug Administration (FDA) for the management of moderate to severe postmenopausal vasomotor symptoms. Lower doses are needed to reduce VMS than those used to treat anxiety or depression, which is beneficial since side effects are typically dose dependent. The recommended dosage is 7.5 mg once daily at bedtime. Dose dependent side effects include nausea, fatigue, and dizziness. Knowing potential medication interactions is critical such as with medications that can lead to serotonin syndrome, concomitant use with monoamine oxidase inhibitors and being aware of p450 drug metabolism is essential for patients taking drugs that utilize the CYP2D6 enzyme for metabolism including tamoxifen. This review discusses in detail the available data supporting the use of paroxetine for the treatment of VMS, including side effects and considerations regarding prescribing. A discussion of other emerging treatments is included as well, including estetrol, oxybutynin and neurokinin 3 (NK3) receptor antagonists.
PubMed: 35300283
DOI: 10.2147/IJWH.S282396 -
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 -
Indian Journal of Dermatology 2022Selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressant medications for the treatment of depression and other psychiatric disorders due to...
Selective serotonin reuptake inhibitors (SSRI) are the most prescribed antidepressant medications for the treatment of depression and other psychiatric disorders due to their efficacy, tolerability, and safety profile. The dermatological side-effects or cutaneous reactions due to SSRI class of antidepressants is rare. Though there were few case reports of SSRI-induced rash due to fluoxetine, paroxetine, and sertraline, the evidence associated with escitalopram, the highly prescribed antidepressant is comparatively less. The identification and reporting of the drug-related side-effects/adverse drug reactions either serious or non-serious is very important as it will be helpful in understanding, reviewing, and educating the drug-related information before starting medication to the patient.
PubMed: 35656231
DOI: 10.4103/ijd.ijd_1140_20 -
Biomedicine & Pharmacotherapy =... Aug 2023In this study, we have investigated the anti-depressant effects of the fruit Areca catechu L. (ACL) and elucidated its potential underlying mechanism using a rat model...
OBJECTIVES
In this study, we have investigated the anti-depressant effects of the fruit Areca catechu L. (ACL) and elucidated its potential underlying mechanism using a rat model of chronic unpredictable mild stress (CUMS).
METHODS
CUMS was induced in rats to establish a depression animal model for 28 days. According to the baseline sucrose preference, the male rats were divided into 6 different groups. They were treated with paroxetine hydrochloride, ACL, and water once a day until the behavioral tests were performed. The levels of corticosterone (CORT), malondialdehyde (MDA), catalase (CAT), and total superoxide dismutase (T-SOD) in serum were detected using a commercial kit, and the concentrations of 5-hydroxytryptamine (5-HT) and dopamine (DA) monoamine neurotransmitters in the brain tissues were detected by liquid chromatography-tandem mass spectrometry. doublecortin (DCX) expression in the hippocampal dentate gyrus (DG) was determined by immunofluorescence, and the relative abundance of brain-derived neurotrophic factor (BDNF), TrkB, PI3K, p-AKT/AKT, PSD-95, and p-GSK-3β/GSK-3β of brain tissues were assayed by western blot.
RESULTS
ACL markedly increased sucrose preference, decreased the immobility time, and shortened the feeding latency of CUMS-induced rats. CUMS induction resulted in marked changes in the contents of the monoamine neurotransmitters (5-HT and DA) in the hippocampus and cortex of brain tissues and the levels of CORT, MDA, CAT, and T-SOD in serum, whereas ACL administration alleviated these considerable changes. ACL promoted DCX expression in DG and increased the protein levels of BDNF, TrkB, PI3K, p-AKT/AKT, PSD-95, and p-GSK-3β/GSK-3β in the brains of CUMS-induced rats.
CONCLUSIONS
Our results indicated that ACL may improve depression-like behaviors in CUMS-induced rats by decreasing the hyperfunction and oxidative stress of the hypothalamic-pituitary-adrenal axis, stimulating hippocampal neurogenesis, and activating the BDNF signaling pathway.
Topics: Rats; Male; Animals; Depression; Antidepressive Agents; Brain-Derived Neurotrophic Factor; Areca; Glycogen Synthase Kinase 3 beta; Hypothalamo-Hypophyseal System; Proto-Oncogene Proteins c-akt; Serotonin; Pituitary-Adrenal System; Signal Transduction; Hippocampus; Corticosterone; Dopamine; Sucrose; Neurotransmitter Agents; Phosphatidylinositol 3-Kinases; Stress, Psychological; Disease Models, Animal; Behavior, Animal
PubMed: 37245336
DOI: 10.1016/j.biopha.2023.114459 -
Neurology and Therapy Apr 2023Patients with depression require thorough clinical assessment, which should include symptom profile, severity and staging, personality factors, antecedent and concurrent...
Patients with depression require thorough clinical assessment, which should include symptom profile, severity and staging, personality factors, antecedent and concurrent psychiatric comorbidity, physical comorbidity, neurocognitive function, exposure to stressors in early life (e.g. trauma) or recently (e.g. bereavement), and protective factors. The presence of anxiety symptoms in a depressed patient is associated with more severe depression, increased suicidality and worse outcomes compared with non-anxious depression. A network meta-analysis of antidepressant treatments found that agomelatine, citalopram, amitriptyline, escitalopram, mirtazapine, paroxetine, venlafaxine and vortioxetine were all significantly more effective than other antidepressants for the treatment of depression, and that agomelatine, citalopram, escitalopram, fluoxetine, sertraline and vortioxetine were better tolerated than other antidepressants. Agomelatine has been shown to have two major effects-relieving depressive symptoms, and supporting symptomatic and functional recovery-and these benefits have been demonstrated in patients with depression as well as in patients with generalised anxiety disorder, including those with more severe symptoms. Agomelatine has also been shown to be efficacious and well tolerated in patients with depression plus concomitant anxiety symptoms. A pooled analysis of data from six agomelatine studies of depression (three placebo-controlled and three with active comparators-fluoxetine, sertraline and venlafaxine) found that agomelatine was significantly more effective than placebo at relieving the anxiety subscore on the Hamilton Depression Rating Scale, and that the difference between agomelatine and placebo was even more marked in the subgroup of patients with severe anxiety symptoms at baseline. Irrespective of the pharmacotherapy used in patients with depression, the likelihoods of response and remission are increased when pharmacotherapy is combined with psychotherapy, with this approach being more effective than either pharmacotherapy or psychotherapy alone. Persistence with treatment is important, and clinicians should therefore encourage patients to keep trying to obtain relief.
PubMed: 37115460
DOI: 10.1007/s40120-023-00470-z -
Clinical Psychopharmacology and... Aug 2023Restless legs syndrome (RLS) is a chronic progressive movement disorder characterized by abnormal sensations, especially at rest and at night, as the need and urge to...
Restless legs syndrome (RLS) is a chronic progressive movement disorder characterized by abnormal sensations, especially at rest and at night, as the need and urge to move the lower extremity. It has been reported that RLS severity and frequency increase in patients with anxiety and depression. It has been reported that serotonin-noradrenaline reuptake inhibitors such as venlafaxine and selective serotonin reuptake inhibitors such as citalopram, fluoxetine, paroxetine, and sertraline can cause RLS symptoms. No adverse effects of vortioxetine on RLS have been reported in the literature. In this case series, we report the effect of vortioxetine in patients with RLS with symptoms of depression and anxiety. In this case series, the effect of adding vortioxetine to treatment on RLS symptoms is reported in 7 patients (5 female). After the use of vortioxetine, 5 of 7 patients' symptoms regressed without the need to start a separate drug for primary movement disorder. In conclusion, we believe that studies should be conducted to investigate the efficacy of vortioxetine in the treatment of RLS. Therefore, randomized controlled studies are needed to determine the effect and safety of vortioxetine on RLS symptoms.
PubMed: 37424427
DOI: 10.9758/cpn.22.1021 -
Frontiers in Pharmacology 2022To evaluate the efficacy and tolerability of pharmacotherapies for postpartum depression (PPD). We performed a computerized search of MEDLINE (Ovid and PubMed),...
To evaluate the efficacy and tolerability of pharmacotherapies for postpartum depression (PPD). We performed a computerized search of MEDLINE (Ovid and PubMed), Embase, Cochrane Library, Web of Science, and Google Scholar to identify eligible randomized controlled trials (RCTs) before 31 March 2022. We calculated standardized mean differences (SMDs) for continuous outcomes and odds ratios (ORs) for dichotomous outcomes with the random-effects model. The tolerability of antidepressants in terms of early dropouts was investigated. The surface under the cumulative ranking curve (SUCRA) was used for ranking the outcomes. Quality assessment of the included studies was performed using the Cochrane Collaboration's tool. A total of 11 studies with 944 participants were included in this network meta-analysis, involving nine antidepressants. With respect to efficacy, only estradiol and brexanolone were significantly more effective than the placebo ( < 0.05), and the calculated SUCRA indicated that estradiol (94.3%) had the highest probability ranking first for reducing the PPD, followed by paroxetine (64.3%) and zuranolone (58.8%). Regarding tolerability, a greater percentage of patients treated with brexanolone experienced early dropout as compared to those treated with most other antidepressants. Only estradiol and brexanolone showed significantly higher efficacy than the placebo. According to the SUCRA ranking, estradiol, paroxetine, and zuranolone were the three best antidepressants. Concerning acceptability in terms of early dropouts, brexanolone was less well-tolerated than other antidepressants.
PubMed: 36506537
DOI: 10.3389/fphar.2022.950004 -
Frontiers in Pharmacology 2021Depression is a common mental disorder. Its treatment with selective serotonin reuptake inhibitors (SSRIs) is effective only in a fraction of patients, and...
Depression is a common mental disorder. Its treatment with selective serotonin reuptake inhibitors (SSRIs) is effective only in a fraction of patients, and pharmacoresistance is increasing steadily. Intranasal (IN) drug delivery to the brain stands out as a promising strategy to improve current therapeutic approaches by operating as a shuttle to overcome the blood-brain barrier. This work aimed to simultaneously administer escitalopram and paroxetine by IN route to mice. For this purpose, three nanostructured lipid carriers (NLC1, NLC2, and BorNLC) and one nanoemulsion (NE) were tested for drug loading. After their characterization, investigation of their impact on nasal cell viability and SSRI permeability assays were performed, using a human nasal RPMI 2650 cell line in air-liquid interface. assays demonstrated that NLCs, including borneol (BorNLC), significantly increased escitalopram permeability ( < 0.01) and paroxetine recovery values ( < 0.05) in relation to the other formulations and non-encapsulated drugs. IN and intravenous (IV) pharmacokinetic studies performed with a single dose of 2.38 mg/kg demonstrated similar results for escitalopram brain-to-plasma ratios. IN administrations delayed escitalopram peak concentrations in the brain for 15-60 min and no direct nose-to-brain delivery was detected. However, encapsulation with BorNLC considerably decreased escitalopram exposure in the lungs (124 μg min/g) compared with free escitalopram by IN (168 μg min/g) and IV (321 μg min/g) routes. Surprisingly, BorNLC IN instillation increased concentration levels of paroxetine in the brain by five times and accelerated brain drug delivery. Once again, lung exposure was considerably lower with BorNLC (AUC = 0.433 μg min/g) than that with IV administration (AUC = 1.01 μg min/g) and non-encapsulated IN formulation (AUC = 2.82 μg min/g). Direct nose-to-brain delivery was observed for paroxetine IN administration with a direct transport percentage (DTP) of 56.9%. If encapsulated, it increases to 74.2%. These results clearly emphasize that nose-to-brain delivery and lung exposure depend on the formulation and on the characteristics of the drug under investigation. NLCs seem to be an advantageous strategy for nose-to-brain delivery of lipophilic molecules, since they reduce systemic and lung exposure, thereby decreasing adverse effects. For hydrophilic compounds, NLCs are particularly important to decrease lung exposure after IN administration.
PubMed: 34925013
DOI: 10.3389/fphar.2021.751321 -
Iranian Journal of Medical Sciences May 2022Hot flashes (HF) are a common symptom during the menopausal transition. It is therefore important to identify effective drugs that can alleviate HF. This study aimed to... (Review)
Review
The Efficacy and Safety of Selective Serotonin Reuptake Inhibitors and Serotonin-Norepinephrine Reuptake Inhibitors in the Treatment of Menopausal Hot Flashes: A Systematic Review of Clinical Trials.
BACKGROUND
Hot flashes (HF) are a common symptom during the menopausal transition. It is therefore important to identify effective drugs that can alleviate HF. This study aimed to systematically review published clinical trials on the efficacy and safety of selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs) in the treatment of HF in healthy menopausal women.
METHODS
In this systematic review, articles published during 2003-2019 in PubMed, MEDLINE, Web of Science, Scopus, Science Direct, PsycINFO, CINAHL, the Cochrane Central Register of Controlled Trials, and Google Scholar as well as Iranian databases such as SID, and Magiran were searched. The quality of the selected articles was assessed using the Jadad score calculation.
RESULTS
Thirty-six articles on randomized controlled trials were included in this study, out of which 27 articles had acceptable, and nine had weak methodological quality. Findings on SSRIs class of drugs indicated that escitalopram, paroxetine, and fluoxetine have higher efficacy and safety in the treatment of menopausal HF than other drugs. Studies on the effectiveness of sertraline, citalopram, and fluvoxamine are limited in number or show inconsistent results. Therefore, further high-quality studies are required to confirm their effectiveness in alleviating HF. Within the SNRIs class, venlafaxine and desvenlafaxine showed significant efficacy in the treatment of menopausal HF. However, studies on the effectiveness of duloxetine are also limited, which requires further research.
CONCLUSION
Most studies have indicated the efficacy and safety of some antidepressants, such as SSRIs and SNRIs, in decreasing the frequency and severity of HF. These drugs are therefore recommended for the treatment of menopausal HF.
Topics: Female; Hot Flashes; Humans; Iran; Menopause; Norepinephrine; Randomized Controlled Trials as Topic; Serotonin; Selective Serotonin Reuptake Inhibitors; Serotonin and Noradrenaline Reuptake Inhibitors
PubMed: 35634530
DOI: 10.30476/ijms.2020.87687.1817