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Clinical Psychopharmacology and... Feb 2023Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate... (Review)
Review
Paroxetine and Sertraline are the only medications approved in posttraumatic stress disorder (PTSD). However, about 60% of traumatized patients fail to show an adequate clinical response. Second generation antipsychotics are recommended as second-line monotherapy or third-line augmentation strategies and quetiapine appears as one of the most used and promising agents. Up to date, no reviews assessed the efficacy of quetiapine in the treatment of PTSD. We aimed to assess the effectiveness and general safety of quetiapine on PTSD. A systematic review was conducted following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) and Cochrane guidelines, selecting studies that evaluated the efficacy of quetiapine on global or specific PTSD symptomatology. Ten studies (n = 894) were considered eligible for qualitative synthesis: one case report, one case series, one prospective cohort study, 3 open-label trials, 3 retrospective studies, one randomized controlled trial. Quetiapine was effective on global PTSD symptomatology assessed in 6 studies as well as on re-experiencing (4/4 studies), avoidance (4/3 studies) and hyperarousal (4/4 studies), flashbacks (2/2 studies), depressive (4/4 studies), anxiety (1/1 studies), psychotic (3/3 studies), insomnia (4/5 studies), nightmares (3/3 studies) specific symptoms and PTSD domains. Sedation was among the most frequently observed adverse effects and the main cause of drug discontinuation. Preliminary findings support the efficacy of quetiapine in ameliorating symptoms relative to PTSD and its overall safety. However, quetiapine use in PTSD cannot be recommended yet as studies mainly rely on open-label, retrospective studies or case series.
PubMed: 36700311
DOI: 10.9758/cpn.2023.21.1.49 -
Biochemical Pharmacology Oct 2023Prolonged vasoconstrictor signalling found in hypertension, increases arterial contraction, and alters vessel architecture by stimulating arterial smooth muscle cell...
Prolonged vasoconstrictor signalling found in hypertension, increases arterial contraction, and alters vessel architecture by stimulating arterial smooth muscle cell (ASMC) growth, underpinning the development of re-stenosis lesions and vascular remodelling. Vasoconstrictors interact with their cognate G protein coupled receptors activating a variety of signalling pathways to promote smooth muscle proliferation. Here, angiotensin II (AngII) and endothelin 1 (ET1), but not UTP stimulates ASMC proliferation. Moreover, siRNA-mediated depletion of endogenous GRK2 expression, or GRK2 inhibitors, compound 101 or paroxetine, prevented AngII and ET1-promoted ASMC growth. Depletion of GRK2 expression or inhibition of GRK2 activity ablated the prolonged phase of AngII and ET-stimulated ERK signalling, while enhancing and prolonging UTP-stimulated ERK signalling. Increased GRK2 expression enhanced and prolonged AngII and ET1-stimulated ERK signalling, but suppressed UTP-stimulated ERK signalling. In ASMC prepared from 6-week-old WKY and SHR, AngII and ET1-stimulated proliferation rates were similar, however, in cultures prepared from 12-week-old rats AngII and ET1-stimulated growth was enhanced in SHR-derived ASMC, which was reversed following depletion of GRK2 expression. Furthermore, in ASMC cultures isolated from 6-week-old WKY and SHR rats, AngII and ET1-stimulated ERK signals were similar, while in cultures from 12-week-old rats ERK signals were both enhanced and prolonged in SHR-derived ASMC, and were reversed to those seen in age-matched WKY-derived ASMC following pre-treatment of SHR-derived ASMC with compound 101. These data indicate that the presence of GRK2 and its catalytic activity are essential to enable pro-proliferative vasoconstrictors to promote growth via recruitment and activation of the ERK signalling pathway in ASMC.
Topics: Animals; Rats; Angiotensin II; Cell Proliferation; Cells, Cultured; Hypertension; Muscle, Smooth, Vascular; Rats, Inbred SHR; Rats, Inbred WKY; Uridine Triphosphate; Vasoconstrictor Agents; G-Protein-Coupled Receptor Kinase 2
PubMed: 37690571
DOI: 10.1016/j.bcp.2023.115795 -
Cureus Aug 2023This meta-analysis was conducted to assess the effectiveness of topical anesthetics in preventing premature ejaculation. We conducted an online database search for... (Review)
Review
This meta-analysis was conducted to assess the effectiveness of topical anesthetics in preventing premature ejaculation. We conducted an online database search for original studies comparing topical anesthetic agents with placebo in patients with premature ejaculation. After selecting relevant articles, we extracted data on baseline characteristics and predetermined endpoints. Intravaginal ejaculatory latency time (IELT) was the primary outcome for efficacy. Mean differences and corresponding 95% confidence intervals were used to present continuous data. A random-effects model was used to pool the data, and subgroup analysis was performed based on the type of anesthetic agent used. Eleven randomized controlled trials were examined, involving a total of 2008 participants. After analyzing the combined results, it was found that Severance Secret (SS) cream (CJ CheilJedang Corporation, Seoul, South Korea) demonstrated significantly higher effectiveness than a placebo in increasing IELT (P = 0.001). Similarly, the topical eutectic mixture for premature ejaculation (TEMPE), lidocaine, and the eutectic mixture of local anesthetics (EMLA) were significantly more efficient than a placebo (P<0.00001; P = 0.0001; P<0.00001). Additionally, it was found that lidocaine gel was more efficient than paroxetine or sildenafil (P = 0.04; P<0.00001). In conclusion, topical anesthetics increase IELT in men with premature ejaculation more effectively than placebo, sildenafil, tadalafil, paroxetine, and dapoxetine.
PubMed: 37664322
DOI: 10.7759/cureus.42913 -
AMIA ... Annual Symposium Proceedings.... 2020The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is...
The development of novel drugs in response to changing clinical requirements is a complex and costly method with uncertain outcomes. Postmarket pharmacovigilance is essential as drugs often have under-reported side effects. This study intends to use the power of digital media to discover the under-reported side effects of marketed drugs. We have collected tweets for 11 different Drugs (Alprazolam, Adderall, Fluoxetine, Venlafaxine, Adalimumab, Lamotrigine, Quetiapine, Trazodone, Paroxetine, Metronidazole and Miconazole). We have compiled a vast adverse drug reactions (ADRs) lexicon that is used to filter health related data. We constructed machine learning models for automatically annotating the huge amount of publicly available Twitter data. Our results show that on average 43 known ADRs are shared between Twitter and FAERS datasets. Moreover, we were able to recover on average 7 known side effects from Twitter data that are not reported on FAERS. Our results on Twitter dataset show a high concordance with FAERS, Medeffect and Drugs.com. Moreover, we manually validated some of the under-reported side effect predicted by our model using literature search. Common known and under-reported side effects can be found at https://github.com/cbrl-nuces/Leveraging-digital-media-data-for-pharmacovigilance.
Topics: Diagnostic Tests, Routine; Drug-Related Side Effects and Adverse Reactions; Humans; Internet; Machine Learning; Pharmacovigilance; Social Media
PubMed: 33936417
DOI: No ID Found -
Forensic Sciences Research 2021Paroxetine is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression and anxiety disorders. In some epidemiological studies, slightly...
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) used in the treatment of depression and anxiety disorders. In some epidemiological studies, slightly increased risks of major malformations and cardiac malformations have been reported following paroxetine exposure in the first trimester of pregnancy. However, such findings have been inconsistent. There is only one report of any overdose of an SSRI during pregnancy, and that involved escitalopram. The aim of this case report was to describe the impact of a paroxetine overdose in the first trimester of pregnancy on the health of the foetus. A 21-year-old mother of one child who was pregnant with a second child was prescribed 20 mg/day paroxetine hydrochloride for the treatment of anxiety/depression. The patient ingested 15 or 16 20-mg tablets of paroxetine hydrochloride (300-320 mg) during the 5th week of pregnancy as a suicide attempt. Within 15 min of ingestion, she was admitted to hospital and treated for intoxication. No evidence of maternal SSRI intoxication was observed after treatment. The patient consulted our teratology information service for further risk assessment regarding possible major congenital malformations following the paroxetine overdose. We were unable to find previous reports of paroxetine overdose during pregnancy in the literature. The timely administration of the overdose treatment and the lack of maternal intoxication symptoms were considered positive for the foetal well-being, and the patient was referred for perinatology and psychiatry follow-ups. A healthy, 3 500-g male infant was born at 38 weeks' gestation, and his development at the age of 2 years was normal. This is the first reported case of paroxetine overdose during pregnancy. Comprehensive studies are needed to evaluate pregnancy outcomes after SSRI overdose.Key PointsThere are no reported data on paroxetine overdose during pregnancy.The aim of this case report was to describe the impact of a maternal paroxetine overdose in the first trimester of pregnancy on the health of the foetus. No evidence of maternal SSRI intoxication was observed.No congenital malformations or developmental disorders were observed in the child at 2 years of age.Comprehensive studies are needed to evaluate pregnancy outcomes following SSRI overdose.
PubMed: 34868717
DOI: 10.1080/20961790.2021.1938802 -
Frontiers in Pharmacology 2022Adenosine (ADO) is an extracellular signaling molecule generated locally under conditions that produce ischemia, hypoxia, or inflammation. It is involved in modulating a...
Adenosine (ADO) is an extracellular signaling molecule generated locally under conditions that produce ischemia, hypoxia, or inflammation. It is involved in modulating a range of physiological functions throughout the brain and periphery through the membrane-bound G protein-coupled receptors, called adenosine receptors (ARs) AAR, AAR, AAR, and AAR. These are therefore important targets for neurological, cardiovascular, inflammatory, and autoimmune diseases and are the subject of drug development directed toward the cyclic adenosine monophosphate and other signaling pathways. Initially using public data for AAR agonists we generated and validated a Bayesian machine learning model (Receiver Operator Characteristic of 0.87) that we used to identify molecules for testing. Three selected molecules, crisaborole, febuxostat and paroxetine, showed initial activity using the HEK293 AAR Nomad cell line. However, radioligand binding, β-arrestin assay and calcium influx assay did not confirm this AAR activity. Nevertheless, several other AR activities were identified. Febuxostat and paroxetine both inhibited orthosteric radioligand binding in the µM range for AAR and AAR. In HEK293 cells expressing the human AAR, stimulation of cAMP was observed for crisaborole (EC 2.8 µM) and paroxetine (EC 14 µM), but not for febuxostat. Crisaborole also increased cAMP accumulation in AAR-expressing HEK293 cells, but it was weaker than at the AAR. At the human AAR, paroxetine did not show any agonist activity at 100 µM, although it displayed binding with a K value of 14.5 µM, suggesting antagonist activity. We have now identified novel modulators of AAR, AAR and AAR subtypes that are clinically used for other therapeutic indications, and which are structurally distinct from previously reported tool compounds or drugs.
PubMed: 35814244
DOI: 10.3389/fphar.2022.920643 -
European Review For Medical and... May 2023Premature ejaculation (PE) and erectile dysfunction (ED) are sexual dysfunction diseases affecting males. The phosphodiesterase type 5 (PDE5) inhibitors such as...
OBJECTIVE
Premature ejaculation (PE) and erectile dysfunction (ED) are sexual dysfunction diseases affecting males. The phosphodiesterase type 5 (PDE5) inhibitors such as tadalafil are used to treat ED whereas selective serotonin reuptake inhibitors (SSRIs) are preferred for PE. Most of the patients with ED also suffer from PE simultaneously. The combined drug therapies are commonly preferred as they favor elevated intra-vaginal ejaculation latency time (IELT) scores and improved sexual function. The study aimed to evaluate the efficacy and safety of daily paroxetine and tadalafil combination therapy in patients with PE and ED.
PATIENTS AND METHODS
A total of 81 PE patients with ED were enrolled in the study. Patients were treated with daily paroxetine 20 mg and tadalafil 5 mg for 4 weeks. Pre- and post-treatment IELT, premature ejaculation profile (PEP), and International Index of Erectile Function-Erectile Function (IIEF-EF) scores of the patients were analyzed.
RESULTS
The mean IELT and PEP index scores, and mean IIEF-EF values improved after combination therapy (p<0.001 for each). When lifelong and acquired PE+ED patients were compared, significant improvements were observed in IELT, PEP, and IIEF-EF scores in both groups (p<0.001).
CONCLUSIONS
Even though the treatment methods are different, combined therapies to treat simultaneous PE and ED presence are effective compared to monotherapies. However, there is still no definitive treatment that can cure all subtypes of PE or ED.
Topics: Male; Female; Humans; Erectile Dysfunction; Premature Ejaculation; Paroxetine; Tadalafil; Retrospective Studies; Ejaculation; Phosphodiesterase 5 Inhibitors; Treatment Outcome
PubMed: 37203851
DOI: 10.26355/eurrev_202305_32335 -
Current Research in Toxicology 2022Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and noradrenergic and specific serotonergic antidepressants...
Selective serotonin reuptake inhibitors (SSRIs), serotonin and noradrenaline reuptake inhibitors (SNRIs), and noradrenergic and specific serotonergic antidepressants (NaSSAs) are broadly used for the treatment of depression. Depression is one of the most common psychiatric disorders in pregnant women and SSRIs are commonly prescribed for depression during pregnancy. The placenta regulates the transport of nutrients and oxygen between the maternal and fetal circulation, and is essential for the survival and growth of the fetus. The present study investigated the effects of antidepressants on human placental BeWo cells. BeWo cell viability was significantly decreased following exposure to sertraline (SSRI), paroxetine (SSRI), fluvoxamine (SSRI), and duloxetine (SNRI), whereas escitalopram (SSRI), venlafaxine (SNRI), and mirtazapine (NaSSA) showed little or no effects. Extracellular lactate dehydrogenase activity was increased by sertraline, paroxetine, fluvoxamine, and duloxetine, indicating toxicity to the cells. Sertraline increased the production of cellular reactive oxygen species (ROS) and decreased the mitochondrial membrane potential. Sertraline decreased the cellular ATP content in a time and concentration-dependent manner. Caspase-3/7 activity and apoptotic cells, detected using the phosphatidylserine-specific fluorescent probe Apotracker Green, were increased by sertraline. Our findings suggest that antidepressants, such as sertraline, paroxetine, fluvoxamine, and duloxetine, induce toxicity in human placental BeWo cells. Sertraline may induce ROS-dependent apoptosis in human placental cells. These results are useful for further studies to determine the optimal dosage of antidepressants for pregnant women.
PubMed: 35602006
DOI: 10.1016/j.crtox.2022.100073 -
Pharmacological Research Dec 2022Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in... (Review)
Review
Widespread musculoskeletal pain characterizes fibromyalgia (FM), accompanied by sleep, fatigue, and mood problems. Chronic stress and depression play a crucial role in the etiology and pathophysiology of FM. They may contribute to a dysregulation of the central pain mechanisms together with the neuroendocrine and immune systems. Pharmacological treatments are the first-line therapy to reduce the symptoms of FM. The US Food and Drug Administration (FDA) indicated gabapentinoid, pregabalin, duloxetine, and milnacipran for adult patients. An alternative approach is widely used, based on therapies including interventions in patient education, behavioral therapy, exercise, pain management, and a healthy diet. A systematic search was performed on PubMed, MEDLINE, EMBASE, and Web of Science databases. The authors established the selection, inclusion, and exclusion criteria. We found a total of 908 articles. This systematic review will include ten articles selected after excluding duplicates and reading the abstracts and full texts. All studies related the effect of drugs to various symptoms caused by fibromyalgia patients with depression, such as insomnia/sleepiness, depression, suicide, difficulty walking/working, pain, fatigue, and nervousness. Although, we concluded that antidepressant drugs are effective in treating depression and pain in fibromyalgia, further studies are needed to understand the etiology of this disease and to find a combination of therapies to increase tolerability and adherence of the patient to the drug, decreasing the adverse effects.
Topics: Adult; Humans; Fibromyalgia; Antidepressive Agents; Fatigue; Musculoskeletal Pain; Employment
PubMed: 36336218
DOI: 10.1016/j.phrs.2022.106547 -
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