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Journal of Clinical Psychopharmacology
Topics: Humans; Antipsychotic Agents; Lurasidone Hydrochloride; Asthma; Piperazines; Female; Male; Schizophrenia; Adult
PubMed: 38820328
DOI: 10.1097/JCP.0000000000001871 -
Journal of Psychiatric Practice May 2024Prescriptions for atypical antipsychotics in children and adolescents are increasing globally. However, a precise understanding of the clinical variables and evidence...
OBJECTIVE
Prescriptions for atypical antipsychotics in children and adolescents are increasing globally. However, a precise understanding of the clinical variables and evidence that prescribers consider before using these agents is lacking. While empirical literature on the long-term safety and efficacy of these medications is available, the literature concerning their use in these younger age groups is relatively sparse. In this study, we examined the current prescribing patterns of medical professionals employed by a public health service in Australia.
METHODS
A survey examining their current practice when prescribing atypical antipsychotics to children and adolescents was completed by 103 physicians. Questions were asked about commonly prescribed atypical antipsychotics, indications, dose ranges, target symptoms, duration of treatment, and the evidence base(s) used when making treatment decisions.
RESULTS
Physicians prescribed atypical antipsychotics for a wide range of indications in this age group, with the most common agents being risperidone, quetiapine, and olanzapine. Adverse effects were reported as the main reason for treatment discontinuation. More than half of the respondents indicated that the most common source of guidance/evidence they referred to when initiating prescriptions were peers or expert opinion.
CONCLUSIONS
Children and adolescents were prescribed a number of atypical antipsychotics for a variety of indications, with variable perceived confidence and a relatively heavy reliance on "own or peer experience" as opposed to good quality evidence. Challenges exist for both prescribers and policymakers, and further "head-to-head" studies are needed in this age group to ensure that a balance is maintained between therapeutic benefit and safety.
Topics: Humans; Antipsychotic Agents; Adolescent; Practice Patterns, Physicians'; Australia; Child; Male; Female; Drug Prescriptions; Risperidone; Surveys and Questionnaires; Olanzapine
PubMed: 38819247
DOI: 10.1097/PRA.0000000000000785 -
Annals of General Psychiatry May 2024Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to... (Review)
Review
Personality disorders (PD) are described as enduring patterns of markedly deviant and pervasive inner experiences and behaviors, with onset in adolescence, which lead to severe distress or impairment. Patients suffering from major depressive disorder (MDD) display higher rates of comorbidity with personality disorders, often complicating the treatment, and worsening the outcomes. Borderline personality disorder (BPD) is the most common of PD and is frequently associated with MDD, with which shares several features. The most part of research agrees on the fact that comorbid BPD in MDD patients quite doubles the poor response to treatments. Moreover, no treatment strategy stands out currently to emerge as more effective in these cases, thus urging the call for the need of new approaches. Herein, we revise the current literature on BPD, its neurobiology and comorbidity with MDD, as well as the more recent treatment strategies used. Then, based on its pharmacology, we propose a possible role of trazodone as a valuable tool to approach comorbid BPD-MDD.
PubMed: 38816843
DOI: 10.1186/s12991-024-00507-z -
Kidney360 May 2024Cisplatin is an effective first line therapy for a variety of cancers. Cisplatin is highly emetogenic and resulting volume depletion can contribute to acute kidney...
BACKGROUND
Cisplatin is an effective first line therapy for a variety of cancers. Cisplatin is highly emetogenic and resulting volume depletion can contribute to acute kidney injury (AKI). Anti-emetic drugs such as 5-hydroxytryptamine type 3 receptor antagonists (5-HT3RAs) are commonly prescribed to prevent this complication. Preclinical studies suggest first generation 5-HT3RAs may alter the renal clearance and increase cisplatin toxicity. This retrospective study evaluated whether different 5-HT3RAs modify the risk of AKI in patients receiving cisplatin.
METHODS
Patients with cancer who received cisplatin between January 1, 2010 and December 31, 2016 were included. Patients over 18 years old with available data for baseline and post-treatment serum creatinine, cisplatin cumulative dose, and administration of 5-HT3RAs including first generation (ondansetron, granisetron, and ramosetron) and second generation (palonosetron) were analyzed. AKI defined as 1.5x increase in serum creatinine. Fisher's exact and Wilcoxon rank-sum tests were used to assess univariable associations between baseline covariates and AKI, and logistic regression for multivariable associations with AKI.
RESULTS
Of 8703 patients identified with cisplatin exposure, 6889 were included. A total of 3881 (56.3%) patients received at least one 5-HT3RA, including palonosetron (3750, 54.4%), ondansetron (1399, 20.3%) and granisetron (11, 0.2%). AKI developed in 1666 (24.2%) patients following cisplatin. Patients who received any 5-HT3RAs were less likely to experience AKI as compared to patients that did not (22.6% vs 26.2%, p=0.001). Older age, male gender, African ethnicity, and cumulative cisplatin dose were univariately associated with higher risk for AKI (P<0.001). After adjusting for these variables, use of any of these antiemetic drugs was protective for AKI (OR 0.84, 95% CI: 0.75, 0.94; P= 0.003) with no difference detected between type of 5-HT3RA.
CONCLUSION
Nephrotoxicity continues to be a concern following cisplatin therapy. Given its emetogenic nature, use of antiemetic drugs such as 5-HT3RAs can lessen emesis and lower risk of kidney injury. This retrospective analysis supports use of any 5-HT3RAs to lower risk of AKI.
PubMed: 38814726
DOI: 10.34067/KID.0000000000000464 -
Scientific Reports May 2024The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial...
The relation of antipsychotics with severe Coronavirus Disease 19 (COVID-19) outcomes is a matter of debate since the beginning of the pandemic. To date, controversial results have been published on this issue. We aimed to prove whether antipsychotics might exert adverse or protective effects against fatal outcomes derived from COVID-19. A population-based retrospective cohort study (January 2020 to November 2020) comprising inpatients (15,968 patients) who were at least 18 years old and had a laboratory-confirmed COVID-19 infection. Two sub-cohorts were delineated, comprising a total of 2536 inpatients: individuals who either had no prescription medication or were prescribed an antipsychotic within the 15 days preceding hospitalization. We conducted survival and odds ratio analyses to assess the association between antipsychotic use and mortality, reporting both unadjusted and covariate-adjusted results. We computed the average treatment effects, using the untreated group as the reference, and the average treatment effect on the treated, focusing solely on the antipsychotic-treated population. Among the eight antipsychotics found to be in use, only aripiprazole showed a significant decrease in the risk of death from COVID-19 [adjusted odds ratio (OR) = 0.86; 95% CI, 0.79-0.93, multiple-testing adjusted p-value < 0.05]. Importantly, these findings were consistent for both covariate-adjusted and unadjusted analyses. Aripiprazole has been shown to have a differentiated beneficial effect in protecting against fatal clinical outcome in COVID-19 infected individuals. We speculate that the differential effect of aripiprazole on controlling immunological pathways and inducible inflammatory enzymes, that are critical in COVID19 illness, may be associated with our findings herein.
Topics: Humans; Aripiprazole; COVID-19; Male; Female; Antipsychotic Agents; Middle Aged; Retrospective Studies; Aged; SARS-CoV-2; COVID-19 Drug Treatment; Adult; Aged, 80 and over
PubMed: 38811612
DOI: 10.1038/s41598-024-60297-y -
Medicinal Research Reviews May 20245-HT1A receptor (5-HT1A-R) is a serotoninergic G-protein coupled receptor subtype which contributes to several physiological processes in both central nervous system and... (Review)
Review
5-HT1A receptor (5-HT1A-R) is a serotoninergic G-protein coupled receptor subtype which contributes to several physiological processes in both central nervous system and periphery. Despite being the first 5-HT-R identified, cloned and studied, it still represents a very attractive target in drug discovery and continues to be the focus of a myriad of drug discovery campaigns due to its involvement in numerous neuropsychiatric disorders. The structure-activity relationship studies (SAR) performed over the last years have been devoted to three main goals: (i) design and synthesis of 5-HT1A-R selective/preferential ligands; (ii) identification of 5-HT1A-R biased agonists, differentiating pre- versus post-synaptic agonism and signaling cellular mechanisms; (iii) development of multitarget compounds endowed with well-defined poly-pharmacological profiles targeting 5-HT1A-R along with other serotonin receptors, serotonin transporter (SERT), D2-like receptors and/or enzymes, such as acetylcholinesterase and phosphodiesterase, as a promising strategy for the management of complex psychiatric and neurodegenerative disorders. In this review, medicinal chemistry aspects of ligands acting as selective/preferential or multitarget 5-HT1A-R agonists and antagonists belonging to different chemotypes and developed in the last 7 years (2017-2023) have been discussed. The development of chemical and pharmacological 5-HT1A-R tools for molecular imaging have also been described. Finally, the pharmacological interest of 5-HT1A-R and the therapeutic potential of ligands targeting this receptor have been considered.
PubMed: 38808959
DOI: 10.1002/med.22049 -
Journal of Cancer Research and Clinical... May 2024The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with... (Randomized Controlled Trial)
Randomized Controlled Trial
A prospective randomized controlled clinical trial investigating the efficacy of low-dose olanzapine in preventing nausea and vomiting associated with oxaliplatin-based and irinotecan-based chemotherapy.
OBJECTIVE
The aim of this study is to assess the clinical efficacy of a 5 mg dosage of olanzapine in preventing chemotherapy-induced nausea and vomiting (CINV) associated with moderately emetogenic chemotherapy (MEC) among female patients diagnosed with gastrointestinal tract tumors.
METHODS
Patients undergoing the oxaliplatin/irinotecan chemotherapy regimen were enrolled in this prospective controlled study. The olanzapine group received a 5 mg dosage of olanzapine along with palonosetron and dexamethasone, while the control group received a standard two-combination regimen consisting of dexamethasone and palonosetron. The primary endpoints included the total protection (TP) rates for the entire age group and the subgroup aged 60 years and above. Secondary endpoints encompassed the total protection rates during the acute and delayed phases within the two age brackets, as well as the total control (TC) rates and complete remission (CR) rates across all three phases (total, acute, and delayed). Additionally, the study involved the assessment of quality of life and the collection of adverse events associated with the interventions.
RESULTS
1) Regarding the primary endpoint, the total phase TP rates within both the entire age group and the age group exceeding 60 years demonstrated superiority in the olanzapine group when compared to the control group (66.7% vs 37.25%, P = 0.003; 68.8% vs 44.4%, P = 0.044). 2) In terms of secondary endpoints, the olanzapine group exhibited superior acute phase TP rates in both age brackets when compared to the control group (P < 0.05). The olanzapine group also demonstrated higher delayed-phase TP rates, TC rates across all three phases, and CR rates within the two age brackets, although the differences were not statistically significant (P > 0.05). Furthermore, the quality of life in the olanzapine group surpassed that of the control group for both age brackets (P < 0.05), characterized by enhanced appetite and a higher incidence of drowsiness in the patients treated with olanzapine when compared to those in the control group (P < 0.05).
CONCLUSION
Olanzapine can enhance CINV induced by MEC regimen in female patients across all age groups, including the elderly, and therefore improve the quality of life for these patients.
CLINICAL TRIAL REGISTRATION
https://www.chictr.org.cn/index.html , identifier: ChiCTR20000368269, 25/08/2020.
Topics: Humans; Olanzapine; Female; Middle Aged; Nausea; Vomiting; Antineoplastic Combined Chemotherapy Protocols; Prospective Studies; Oxaliplatin; Irinotecan; Aged; Adult; Antiemetics; Gastrointestinal Neoplasms; Palonosetron; Quality of Life; Dexamethasone
PubMed: 38806870
DOI: 10.1007/s00432-024-05712-7 -
Behavioural Brain Research Jul 2024The hippocampus has a central role in regulating contextual processes in memory. We have shown that pharmacological inactivation of ventral hippocampus (VH) attenuates...
The hippocampus has a central role in regulating contextual processes in memory. We have shown that pharmacological inactivation of ventral hippocampus (VH) attenuates the context-dependence of signaled active avoidance (SAA) in rats. Here, we explore whether the VH mediates intertrial responses (ITRs), which are putative unreinforced avoidance responses that occur between trials. First, we examined whether VH inactivation would affect ITRs. Male rats underwent SAA training and subsequently received intra-VH infusions of saline or muscimol before retrieval tests in the training context. Rats that received muscimol performed significantly fewer ITRs, but equivalent avoidance responses, compared to controls. Next, we asked whether chemogenetic VH activation would increase ITR vigor. In male and female rats expressing excitatory (hM3Dq) DREADDs, systemic CNO administration produced a robust ITR increase that was not due to nonspecific locomotor effects. Then, we examined whether chemogenetic VH activation potentiated ITRs in an alternate (non-training) test context and found it did. Finally, to determine if context-US associations mediate ITRs, we exposed rats to the training context for three days after SAA training to extinguish the context. Rats submitted to context extinction did not show a reliable decrease in ITRs during a retrieval test, suggesting that context-US associations are not responsible for ITRs. Collectively, these results reveal an important role for the VH in context-dependent ITRs during SAA. Further work is required to explore the neural circuits and associative basis for these responses, which may be underlie pathological avoidance that occurs in humans after threat has passed.
Topics: Animals; Avoidance Learning; Male; Hippocampus; Muscimol; Female; Rats; GABA-A Receptor Agonists; Rats, Long-Evans; Clozapine
PubMed: 38806099
DOI: 10.1016/j.bbr.2024.115071 -
Journal of Medicinal Chemistry Jun 2024Development of more efficacious medications with improved safety profiles to manage and treat multiple forms of pain is a critical element of healthcare. To this end, we...
Development of more efficacious medications with improved safety profiles to manage and treat multiple forms of pain is a critical element of healthcare. To this end, we have designed and synthesized a novel class of tetracyclic pyridopyrroloquinoxalinone derivatives with analgesic properties. The receptor binding profiles and analgesic properties of these tetracyclic compounds were studied. Systematic optimizations of this novel scaffold culminated in the discovery of the clinical candidate, (6,10)-8-[3-(4-fluorophenoxy)propyl]-6,7,8,9,10,10-hexahydro-1-pyrido[3',4':4,5]pyrrolo[1,2,3-]quinoxalin-2(3)-one (compound , ITI-333), which exhibited potent binding affinity to serotonin 5-HT ( = 8.3 nM) and μ-opioid receptors (MOR, = 11 nM) and moderate affinity to adrenergic α ( = 28 nM) and dopamine D ( = 50 nM) receptors. ITI-333 acts as a 5-HT receptor antagonist, a MOR partial agonist, and an adrenergic α receptor antagonist. ITI-333 exhibited dose-dependent analgesic effects in rodent models of acute pain. Currently, this investigational new drug is in phase I clinical development.
Topics: Animals; Humans; Analgesics; Structure-Activity Relationship; Administration, Oral; Pain; Mice; Male; Rats; Drug Discovery; Rats, Sprague-Dawley; Biological Availability; Receptors, Opioid, mu; Pyridines; Pyrroles
PubMed: 38805667
DOI: 10.1021/acs.jmedchem.4c00480 -
Pain Physician May 2024Flupentixol and melitracen are being investigated for their potential effectiveness in managing persistent idiopathic facial pain (PIFP), based on their mechanisms of... (Observational Study)
Observational Study
BACKGROUND
Flupentixol and melitracen are being investigated for their potential effectiveness in managing persistent idiopathic facial pain (PIFP), based on their mechanisms of action as dopamine receptor antagonists and noradrenaline/serotonin reuptake inhibitors, respectively. The efficacy and safety of flupentixol and melitracen (FM) tablets in treating PIFP were retrospectively analyzed at our hospital.
OBJECTIVES
The aim of this study is to determine the effectiveness and safety of FM tablets in treating PIFP.
STUDY DESIGN
Retrospective unicentric cohort design.
SETTING
An academic university hospital.
METHODS
A retrospective analysis was conducted on a cohort comprising 128 patients with a definite diagnoses of PIFP who were treated with FM tablets (flupentixol 0.5 mg and melitracen 10 mg tablet, >= 4 tablets/d) from January 2022 through May 2023 at an academic university hospital. Baseline conditions were statistically described, and Numeric Rating Scale (NRS-11) scores of pain levels before and during treatment were collected. Pain relief rates were calculated. Differences in baseline characteristics between responsive and unresponsive patients were evaluated using statistical tests. Additionally, the side effects experienced during treatment were summarized.
RESULTS
Among the included 128 patients, 105 (82.0%) patients achieved pain relief (pain NRS-11 score reduction rate >= 50%). The median treatment onset time was 3 (1-7) days. NRS-11 scores of responsive patients at week 2, week 4, week 8, and week 12 were significantly lower than the baseline NRS-11 scores (P < 0.001), regardless of their Hamilton Depression Rating Scale score. Pain duration was the only factor that related to responsiveness (Wilcoxon rank sum test, P < 0.001; logistic regression, P = 0.001). No serious side effects that could affect patients' lives were observed during the first week of treatments.
LIMITATIONS
Due to its retrospective nature, this study is limited by its lack of a randomized control. The lack of data on nonresponders who did not achieve significant pain relief hinders assessing overall change and the placebo effects'. Patients previously treated with antidepressants were excluded, making it hard to determine if FM tablets were a better treatment for PIFP. Additionally, the small sample size in a single center may be influenced by chance variation in pain relief.
CONCLUSIONS
FM tablets showed its potential in the management of PIFP with considerable efficacy and safety. Early administration of FM tablets after a PIFP diagnosis may result in a high possibility of pain relief.
Topics: Humans; Retrospective Studies; Male; Female; Middle Aged; Facial Pain; Adult; Flupenthixol; Tablets; Aged; Treatment Outcome
PubMed: 38805533
DOI: No ID Found