Introduction. Ties between the endocrine system and mental health are undeniably a consistent point of interest in modern day medicine. Furthermore, mental disturbances due to hormonal changes following childbirth have been mentioned in medical literature since Hippocrates. Considering the dramatic endocrine, paracrine and autocrine changes that occur during gestation, labour and postnatal phase, hormonal theories are not to be ignored in the treatment of postpartum disorders. Results. Reproductive hormones are known to modulate behavioural, emotional and cognitive response, therefore rapid changes in estradiol and progesterone plasma concentrations during pregnancy and labour create a vulnerable terrain leading towards postpartum disorders. New research shows that women suffering from postpartum disorders have abnormal neural responses, suggesting a neuroendocrine explanation for postpartum syndromes. Conclusion. To facilitate further research in this area, we present new information on several hormonal interactions and the psychiatric response involved in pregnancy and labour, offering an interdisciplinary outlook on pregnancy and postpartum disorders. There is enough evidence to suggest that estradiol, progesterone, oxytocin, cortisol and thyroid hormones are some of many hormones involved in postpartum syndromes and tackling their perinatal imbalance with pharmacological substituents or antagonists could be useful as an adjuvant form of treatment in future patients.
The aim of this overview was to outline the pathophysiology, common comorbidities and current therapeutic modalities in the treatment/management of restless legs syndrome (RLS) a sensorimotor neurological disorder. The main symptom in RLS is a compelling compulsion to move the legs and a sense of restlessness at rest most commonly occurring during the night and improving with movement. The prevalence of secondary RLS among comorbid conditions such as idiopathic pulmonary fibrosis, end-stage renal disease, irritable bowel syndrome and attention deficit/hyperactivity disorder have further elucidated our understanding of the role of the iron-dopamine hypothesis as an etiopathogenetic hallmark in RLS and the efficacy of therapeutic approaches in milder to more severe forms. Currently, RLS treatment uses only symptomatic agents, since a disease-modifying therapy does not yet exist. The phenomena of rebound and augmentation have become central phenomena in overcoming the pharmacotherapeutic challenges when treating with dopaminergic agents in RLS. Considering alternative nonpharmacological therapies, especially for the treatment of RLS in pregnancy has a significant role and positive clinical outcome for patients in controlling symptoms.
Background: clozapine (CLZ) use is precarious due to its neurological, cardiovascular, and hematological side effects; however, it is the gold standard in therapy-resistant schizophrenia (TRS) in adults and is underused. Objective: to examine the most recent CLZ data on (a) side effects concerning (b) recent pharmacological mechanisms, (c) therapy benefits, and (d) the particularities of the COVID-19 pandemic. Data sources: a search was performed in two databases (PubMed and Web of Science) using the specific keywords “clozapine” and “schizophrenia”, “side effects”, “agranulocytosis”, “TRS”, or “bipolar affective disorder (BAF)” for the last ten years. Study eligibility criteria: clinical trials on adults with acute symptoms of schizophrenia or related disorders. Results: we selected 37 studies, randomized controlled trials (RCTs), and clinical case series (CCS), centered on six main topics in the search area: (a) CLZ in schizophrenia, (b) CLZ in bipolar disorder, (c) side effects during the clozapine therapy, (d) CLZ in pregnancy, (e) CLZ in early-onset schizophrenia, and (f) CLZ therapy and COVID-19 infection. Limitations: we considered RCTs and CCS from two databases, limited to the search topics. Conclusions and implications of key findings: (a) clozapine doses should be personalized for each patient based on pharmacogenetics testing when available; the genetic vulnerability postulates predictors of adverse reactions’ severity; patients with a lower genetic risk could have less frequent hematological monitoring; (b) a CLZ-associated risk of pulmonary embolism imposes prophylactic measures for venous thromboembolism; (c) convulsive episodes are not an indication for stopping treatment; the plasma concentration of clozapine is a better side effect predictor than the dosage; (d) COVID-19 infection may enhance clozapine toxicity, generating an increased risk of pneumonia. Therapy must be continued with the proper monitoring of the white blood count, and the clozapine dose decreased by half until three days after the fever breaks; psychiatrists and healthcare providers must act together.
Aggressive behavior is one of the main characteristics of different psychiatric disorders such as: personality disorders (antisocial personality disorder, borderline personality disorder), schizophrenia, intermittent explosive disorder, post-traumatic stress disorder, bipolar disorder, depression, alcohol/substance induced psychiatric disorders. Epidemiological evidence shows that always there is a higher risk of violence and aggressivity among patients with psychiatric disorders compared with general population. Researchers have tried many times to narrow the theories that can explain such a behavior, starting from models that involve a link between illness and aggression going up to external-environmental factors including the therapeutic relation in the hospital. Even if the majority of studies are centered on intoxications (with alcohol or other substances that potentiate the aggressive behavior) we will highlight another somatic dimension linked with this behavior. In the following review we summarize the hormonal imbalances that have been noted to accompany aggressive behavior in different psychiatric disorders. Several studies have been made starting even at the age of ten corelating hormone cortisol with increase aggression, but patients with psychiatric disorders have a higher sensitivity in linking hormonal imbalance with their behavior.
Alpha-lipoic acid (ALA, thioctic acid), a naturally-occurring essential dithiol compound, has become a common ingredient in many pharmaceutical and food supplement products (FSP), used in oxidative stress-dependent pathologies; oral bioavailability of ALA is limited by pharmacokinetic particularities that reduce its therapeutic efficacy-reduced solubility, lack of gastric stability and hepatic degradation, doubled by formulation hinders. The objectives were to develop a solid oral 600 mg ALA FSP to obtain an optimal pharmaceutical profile compared to a reference listed drug (RLD) with a similarity factor f2 50. A comparative dissolution study was performed; an HPLC method was used for ALA quantification. After planning combinatory simulations (formulation stage), two prototype formulas (#1 and #2) were manufactured and further optimized by adjusting ALA physical characteristics and the excipients quantities (#3 and #4) in order to achieve the Quality Target Product Profile. A misshapen of ALA’s in vitro release was observed for #3 Formula (f2 = 31.6); the optimal profile was obtained for Formula #4 (f2 = 58.5). A simple quantitative formula is not enough to assure good ALA bioavailability; the formulation needs multiple compounding modulations under physicochemical compatibility algorithms, with multiple dissolution profiles testing back-ups. It is essential to ensure a formulation with an in vitro dissolution comparable with the RLD, allowing the compound to reach its target level to assure the optimum claimed antioxidant activity of ALA at the cellular level, even for food supplement formulations.
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