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Introduction: Gastroesophageal reflux disease (GERD) is a chronic disease of the esophagus characterized by the regurgitation of stomach contents into the esophagus, causing troublesome symptoms and/or complications. Among patients with GERD, around 30% of patients have visible mucosal damage, while 70% have normal esophageal mucosa. Accordingly, the optimal pharmacological treatment of GERD should address different disease manifestations, including symptoms, the mucosal damage when present, and possible chronic complications, including strictures, Barrett's esophagus, and esophageal adenocarcinoma. Areas covered: Available medical treatments for GERD include proton pump inhibitors (PPIs), potassium-competitive acid blockers (PCABs), histamine receptor antagonists (H2-RAs), prokinetics, and mucosal protectants, such as alginates, hyaluronic acid/chondroitin-sulfate, and poliprotect. Each compound has its own advantages and disadvantages, and knowledge of expected benefits and tips for their use is paramount for the success of treatment. In addition, the appropriateness of indications for initiating treatment is also crucial to achieve positive results when managing GERD patients. Expert opinion: PPIs, PCABs, H2-RAs, prokinetics, and mucosal protectants can all be used in patients with GERD, but careful assessment of patients' characteristics as well as advantages and disadvantages of each therapeutic compound is essential to ensure successful treatment of GERD. [ABSTRACT FROM AUTHOR]

Introduction: Persistent genital arousal disorder/genitopelvic dysesthesia (PGAD/GPD) is a rare, yet debilitating disease, which has been included in ICD-11. Pharmacotherapy in PGAD/GPD is a mixed blessing – drugs may either alleviate symptoms or worsen/induce them. Therefore, we aim at offering both an overview of pharmacological approaches to treat this disorder, including treatment failures, and to highlight drugs that may induce or worsen symptoms. We include all available data published so far as well as data from an own registry. Areas covered: The international registries have not recorded any completed or ongoing trials on pharmacotherapy of PGAD/GPD. We refer to case reports, case series, online surveys, and data from our own registry that includes 90 subjects with PGAD/GPD. Expert Opinion: There is weak evidence (level 4) that some drugs such as SSRIs, SNRIs, cannabinoids, and anticonvulsants (pregabalin and gapabentin) may alleviate symptoms in PGAD/GPD. However, serotonergic drugs may also induce or worsen PGAD/GPD during administration or termination, as observed in 28% of cases. In conclusion, the pharmacotherapy of PGAD/GPD is still in its infancy just like the etiopathological understanding of the disease. Clinicians should be aware of PGAD/GPD, conduct careful diagnostics, and discuss an individual treatment plan with the patient. [ABSTRACT FROM AUTHOR]

The efficacy of non-pharmacotherapeutic treatment of obstructive sleep apnea, a highly prevalent condition with serious cardiometabolic and neurocognitive health consequences, is well established. Supplementing traditional treatment strategies with medications can improve symptoms and reduce side effects. Efforts to identify medications that target the causes of sleep apnea have met with mixed success. However, this remains a worthwhile objective for researchers to pursue, given the potential benefit pharmacotherapy could bring to those patients who reject or struggle to adhere to existing treatments. This article presents the case for obstructive sleep apnea pharmacotherapy including drugs that reduce the occurrence of apnea events, such as weight loss agents, ventilation activators and muscle and nervous system stimulants, drugs that alleviate symptoms, such as wake-promoting agents for excessive daytime sleepiness, and drugs that improve adherence to existing treatments, such as hypnotics. Literature was accessed from PubMed between 1 March 2024 and 18 April 2024. Exciting recent advances in both our understanding of obstructive sleep apnea pathology and in the techniques used to identify therapeutic agents and their targets combine to embolden a positive outlook for the expanded use of drugs in tackling this consequential disease. [ABSTRACT FROM AUTHOR]

Hypertrophic cardiomyopathy (HCM) is a heterogeneous genetic heart disease with an estimated prevalence in the general population of 0.2% to 0.6%. Clinically, HCM can range from no symptoms to severe symptoms such as heart failure or sudden cardiac death. Currently, the management of HCM involves lifestyle modifications, familial screening, genetic counseling, pharmacotherapy to manage symptoms, sudden cardiac death risk assessment, septal reduction therapy, and heart transplantation for specific patients. Multicenter randomized controlled trials have only recently explored the potential of cardiac myosin inhibitors (CMIs) such as mavacamten as a directed pharmacological approach for managing HCM. We will assess the existing medical treatments for HCM: beta-blockers, calcium channel blockers, disopyramide, and different CMIs. We will also discuss future HCM pharmacotherapy guidelines and underline this patient population's unfulfilled needs. Mavacamten is the first-in-class CMI approved by the FDA to target HCM pathophysiology specifically. Mavacamten should be incorporated into the standard therapy for oHCM in case of symptom persistence despite using maximally tolerated beta blockers and/or calcium channel blockers. Potential drug-drug interactions should be assessed before initiating this drug. More studies are needed on the use of CMIs in patients with kidney and/or liver failure and pregnant/breastfeeding patients. [ABSTRACT FROM AUTHOR]

Benign Prostate Hyperplasia (BPH) significantly impacts men's health and quality of life, with its prevalence rising with age. This review critically examines the cost-effectiveness of pharmacological interventions for BPH to optimize patient outcomes and healthcare resource utilization. This review explores the integration of cost-effectiveness analysis (CEA) into clinical practice, balancing clinical efficacy with economic efficiency in BPH management. We performed a critical literature search, including recent studies on the economic evaluation of BPH treatments, focusing on pharmacotherapies such as alpha-blockers and 5-alpha reductase inhibitors. Additionally, we discussed the concept of CEA and evaluated the role of medicinal reconciliation and the avoidance of polypharmacy in favor of optimal BPH treatment. Cost-effectiveness analysis is crucial for evaluating BPH treatments, with evidence suggesting a shift towards surgical interventions may offer greater long-term economic benefits. However, these models must be applied cautiously, considering clinical evidence and patient preferences to ensure equitable and patient-centric healthcare. [ABSTRACT FROM AUTHOR]

The introduction of targeted therapy and immunotherapy has tremendously changed the clinical outcomes and prognosis of cancer patients. Despite innovative pharmacological therapies and improved radiotherapy (RT) techniques, patients continue to suffer from side effects, of which oral mucositis (OM) is still the most impactful, especially for quality of life. We provide an overview of current advances in cancer pharmacotherapy and RT, in relation to their potential to cause OM, and of the less explored and more recent literature reports related to the best management of OM. We have analyzed natural/antioxidant agents, probiotics, mucosal protectants and healing coadjuvants, pharmacotherapies, immunomodulatory and anticancer agents, photobiomodulation and the impact of technology. The discovery of more precise pathophysiologic mechanisms of CT and RT-induced OM has outlined that OM has a multifactorial origin, including direct effects, oxidative damage, upregulation of immunologic factors, and effects on oral flora. A persistent upregulated immune response, associated with factors related to patients' characteristics, may contribute to more severe and long-lasting OM. The goal is strategies to conjugate individual patient, disease, and therapy-related factors to guide OM prevention or treatment. Despite further high-quality research is warranted, the issue of prevention is paramount in future strategies. [ABSTRACT FROM AUTHOR]

Penile squamous cell carcinoma (PSCC), a rare genitourinary cancer, is associated with poor outcomes due to limited treatment effectiveness, especially in advanced stages. While chemotherapy and/or surgery remain the standard of care, emerging therapies like immunotherapy, targeted therapy, and human papillomavirus (HPV) directed therapies show promise. Key to advancing treatment is understanding the immune microenvironment to gain insights into tumor resistance mechanisms and potential therapeutic targets. The scarcity of data on PSCC is a major obstacle in advancing research for this rare cancer. Future research should prioritize collaborative efforts across various research centers and countries. Enhancing data sharing and pooling resources can lead to a more comprehensive understanding of PSCC, ultimately supporting the development of precision medicine strategies tailored to this specific cancer type. This collaborative approach is essential for making significant strides in PSCC treatment and care. [ABSTRACT FROM AUTHOR]

The pharmacotherapy of asthma is a dynamic process that changes as our knowledge of the underlying pathophysiology and treatment of this disease continues to evolve. This implies the need for continuous revision of the recommendations of asthma guidelines and strategies. This review summarizes the latest key practical information on the pharmacological management of asthma in adults. We provide the background to the 2023 update of the GINA strategy report, focusing on changes and discussing areas of uncertainty. We review current and emerging pharmacotherapy for uncontrolled asthma, including synthetic agents and new biologics, and provide expert perspectives and opinions on the treatment of uncontrolled asthma. The current pharmacological treatment of asthma, based on a step-by-step, control-based approach, with ICSs, LABAs and LAMAs being the mainstay generally provides good symptom control. Biologic therapies are often effective in treating T2high severe asthma. However, there is still room for improvement, such as the discovery of new molecules that specifically target chronic inflammation and, most importantly, the ability to provide solutions to the various areas of uncertainty that still exist. Also finding solutions to improve the accessibility and affordability of rescue ICS in resource-constrained settings is critical. [ABSTRACT FROM AUTHOR]

Nonalcoholic fatty liver disease (NAFLD) is the most common hepatic disease affecting almost 30% of the world population. Approximately 25% of people with NAFLD develop nonalcoholic steatohepatitis (NASH), the fulminant version of the disease. Diabetes mellitus is present in 22.5% of people with NAFLD and 44.60% of individuals with NASH. This review was undertaken to examine the current contribution of glucagon-like peptide 1 (GLP-1) receptor agonists to the pharmacotherapy of diabetic nonalcoholic steatohepatitis. The author analyzed the current status of GLP-1 receptor agonists for pharmacotherapy of diabetic NASH. Research data and literature reports were taken from the database and or websites of Diabetes UK, American Diabetes Association, ClinicalTrials.gov, PubMed, and Scopus. The keywords utilized included type 2 diabetes, GLP-1, NASH, NAFLD, and clinical trials. Since diabetic NASH is associated with obesity, diabetes mellitus, oxidative stress and inflammation, drugs capable of mitigating all of these conditions simultaneously, are most ideal for the treatment of diabetic NASH. These drugs include (in order of relevance), GLP-1 receptor agonists, GLP-1 and GIP dual receptor agonists, sodium-glucose co-transporter-2 (SGLT2) inhibitors, and pioglitazone. The future, FDA-approved drug for diabetic NASH treatment will likely be GLP-1 agonist, which could be used as monotherapy or in combination with other drugs. [ABSTRACT FROM AUTHOR]

Postural tachycardia syndrome (POTS) is a disorder characterized by a constellation of symptoms including lightheadedness, fatigue, and palpitations when upright, associated with an increase in the heart rate (HR) of > 30 beats per minute when changing from a lying down to standing position or head-up tilt position and not associated with orthostatic hypotension. The causes as well as the management of POTS are not quite fully understood. We performed a literature review on the diagnosis and management of POTS, and this article includes an overview of novel pharmacotherapeutic options for the treatment of (POTS), although an effective treatment has not been established. POTS is a clinical syndrome characterized by a constellation of symptoms that are nonspecific. No single etiology or unified hypothesis could be identified. In fact, multiple pathophysiological mechanisms have been proposed, and none of the suggested medications have been approved by the FDA for this indication. Further understanding of the autonomic nervous system and its adjustment to standing position is needed to provide better management strategies. [ABSTRACT FROM AUTHOR]

Disruptive Mood Dysregulation Disorder (DMDD) was officially introduced as a new diagnostic entity in the Diagnostic and Statistical Manual of Mental Disorder, Fifth Edition (DSM-5), under the category of depressive disorders. A comprehensive overview and a critical commentary on the currently investigated psychopharmacological approaches for the treatment of DMDD have been here provided. Behavioral and psychosocial interventions should be considered as first-line treatment strategies. When ineffective or partially effective, psychopharmacological strategy is recommended. Overall, pharmacological strategy should be preferred in those individuals with psychiatric comorbidities (e.g. ADHD). Indeed, so far published studies on pharmacological strategies in DMDD are scant and heterogeneous (i.e. age, assessment tools, symptomatology profile, comorbidity, and so forth). Therefore, DMDD psychopharmacological guidelines are needed, particularly to guide clinicians toward the patient's typical symptom profile who could benefit from psychopharmacological strategy. [ABSTRACT FROM AUTHOR]

Clinical presentation of both insomnia and obstructive sleep apnea (COMISA) is common. Approximately 30% of clinical cohorts with OSA have insomnia symptoms and vice versa. The underlying pathophysiology of COMISA is multifactorial. This poses a complex clinical challenge. Currently, there are no clinical guidelines or recommendations outside of continuous positive airway pressure (CPAP) therapy and cognitive behavioral therapy for insomnia (CBTi). Clinically translatable precision medicine approaches to characterize individual causes or endotypes may help optimize future pharmacological management of COMISA. This review article provides an up-to-date account of COMISA and its consequences, the underlying pathophysiology of sleep apnea, insomnia and COMISA, current treatment approaches and limitations, pharmacotherapy targets and future priorities. There are multiple promising emerging therapies, but clinical trial data specifically in COMISA populations are lacking. This is a priority for future investigation to inform development of evidence-based guidelines. Pharmacotherapies, particularly for insomnia, do not target the underlying causes of the disorder thus, are indicated for short-term use only and should remain second line. Future multidisciplinary research should be directed toward the multifactorial nature of COMISA and the challenges of adapting COMISA treatment in clinical practice and overcoming the practical barriers that health-care providers and consumers encounter. [ABSTRACT FROM AUTHOR]

Overactive bladder (OAB) is a common syndrome in adults. Current pharmacologic treatment includes antimuscarinic agents and β-3 adrenoceptor agonists. For non-responders to oral medication, intravesical injection of botulinum toxin A (BoNT-A) is an effective option. However, these treatments have potential adverse events and should be cautiously selected for appropriate patients. This review presents the recently published results of clinical trials and studies for patients with OAB and the underlying pathophysiology of OAB. Appropriate medical therapy based on pathophysiology of OAB is also presented. Literature search from Pubmed from 2001 to 2023 including clinical background, pharmacology, and clinical studies for OAB medications. Treatment of OAB syndrome with any antimuscarinic or β-3 adrenoceptor agonist is feasible as a first-line approach. For patients with suboptimal therapeutic effect to full-dose antimuscarinics or mirabegron, combination with both drugs can improve efficacy. Intravesical BoNT-A 100-U injection provides therapeutic effects for refractory OAB. Patients who are refractory to initial pharmacotherapies should be investigated for the underlying pathophysiology; then an appropriate medication can be added, such as an α1-blocker or anti-inflammatory agents. Patient education about behavioral modification and therapies should always be provided with oral medication or BoNT-A injection for OAB patients. Overactive bladder (OAB) causes urgency, frequency, and nocturia, and greatly impacts quality of life. Pharmacological treatment with antimuscarinics, beta-3 adrenoceptor agonists, or in combination can effective improve OAB symptoms. In cases of treatment failure, searching for underlying causes and switching to the other treatment modalities such as Botox injection are also feasible to relieve the bothersome bladder symptoms. [ABSTRACT FROM AUTHOR]

Uterine fibroids are the most common noncancerous tumors in women of childbearing age. This review was developed to evaluate the current role of gonadotropin-releasing hormone (GnRH) agonists and antagonists in the therapy of symptomatic uterine fibroids. There is a great need for alternative methods for surgical treatment of uterine fibroids. Hormonal therapy remains the first-line treatment option for most patients. GnRH analogs (agonists and antagonists) modulate the pulsatile release of GnRH. This review summarizes the available literature concerning pharmacologic principles underlying the mechanism of action of GnRH and its analogs, as well as individual therapeutic applications to which these drugs have been applied. In many cases, it is possible to try to treat uterine fibroids pharmacologically. Both groups of GnRH analogs are used in therapy, agonists instead as a preparation for surgery, and antagonists as a drug for long-term use. It is essential to develop this path further and look for at least long-term-release systems or new methods of administering these drugs. It is also important from the patient's perspective to search for possible drugs that may have an additive effect of decreasing side effects when combined with GnRH analogs. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) represents the histological entity of prostate cell proliferation, which inflicts a gradually increasing obstruction of the bladder outlet and is accompanied by a progressing manifestation of lower urinary tract symptoms (LUTS). BPH management algorithm includes conservative measures, pharmaceutical agents, and surgical procedures. A comprehensive literature review was performed using PubMed, Scopus, and Google Scholar databases to identify publications written in English, analyzing BPH pharmaceutical treatment. The search was conducted from January 2000 to January 2023. Six main drug classes can be administered, either as monotherapy or in combination. Furthermore, the authors provide current direction of research on future medications, which focuses on a more etiological interference to the BPH pathophysiological mechanism. The available medications represent an effective first-line step of BPH/LUTS therapy. Currently, the administration of BPH medications is tailored to patient/disease characteristics and entails long-time adherence to therapy. The emergence of new surgical modalities, which combine significantly lower morbidity compared to standard procedures and more durable effects than the available medications, seems to challenge the current treatment algorithm. More direct comparisons and the increasing experience with these surgical modalities will delineate the switch points between various therapy levels along the BPH management sequence. [ABSTRACT FROM AUTHOR]

Crohn's disease (CD) mostly affects the terminal ileum and ileocecal region and up to 80% of patients end up requiring surgery. Previously reserved for complicated or refractory forms, surgery is now considered as an alternative to medical treatment in localized ileocecal disease. This review examines factors associated with response to medical treatment and those associated with the need for surgery in ileocecal CD to identify the patients' profile for whom pharmacotherapy might be enough. Factors associated with the recurrence and the postoperative complications are also reviewed to help the clinician identify patients for whom medical therapy might be preferred. LIR!C study long-term follow-up data show that 38% of infliximab-treated patients were still treated with infliximab at the end of their follow-up, while 14% had switched to another biologic or had received immunomodulator or corticosteroid and 48% had CD-related surgery. Only the combination with an immunomodulator was associated with a greater likelihood of continuing infliximab. Patients with ileocecal CD for whom pharmacotherapy might be sufficient are probably those with no risk factors for CD-related surgery. In addition, patients with high risk of recurrence or of post-operative complications may benefit more from medical treatment than from surgery. [ABSTRACT FROM AUTHOR]

Erectile dysfunction (ED) affects between 12.9% and 28.1% of men worldwide, presenting a strong aged-correlated prevalence. Several pharmacological treatments are currently available for ED, which can be classified into oral, injection, and topical/intraurethral therapies. Extensive research on PubMed/MEDLINE until February 2023 was performed. For each of the aforementioned drug classes, available molecules, and formulations, their efficacy and most common adverse events as well as general guidelines on prescription were investigated and extensively described. A glimpse into future directions regarding ED pharmacotherapy is also present. In recent years, there have been significant developments in pharmacological treatments for ED. It is essential for physicians to identify the best treatment option for patients based on their preferences and sexual habits. The treatment approach for ED has shifted from a sequential to a parallel paradigm, where all treatment options are available as first-line therapies. While there are promising regenerative therapies for ED, such as shockwaves and platelet-rich plasma injections, pharmacological treatment is still the most effective option for most patients. [ABSTRACT FROM AUTHOR]

Major depressive disorder remains a major challenge due to its biopsychosocial burden with increased morbidity and mortality. Despite successful treatment options for the acute episode, recurrence rates are high, on average four times in a life span. Both pharmacological as non-pharmacological evidence-based therapeutic options to prevent and treat recurrent depression are discussed. Although some risk factors for recurrence are well known, better evidence is needed. Antidepressant medication should be continued after acute treatment at its full therapeutic dose for longer periods, at least 1 year. There are no clear differences between classes of antidepressant medication when treatment is focused on preventing relapse. Bupropion is the only antidepressant with a proven efficacy to prevent recurrence in seasonal affective disorder. Recent findings conclude maintenance subanesthetic ketamine and esketamine treatment can be effective in sustaining antidepressant effect following remission. Furthermore, the pharmacological approach must be integrated with lifestyle interventions, especially aerobic exercise. Finally, combining pharma- and psychotherapy seems to improve outcome. Network and complexity sciences will help to decrease the high recurrence rates of MDD by developing more integrative and personalized approaches. [ABSTRACT FROM AUTHOR]

Aphasia is a common, long-lasting aftermath of stroke lesions. There is an increased integration of pharmacotherapy as an adjunctive strategy to speech and language therapy (SLT) for post-stroke aphasia (PSA). Nevertheless, more research in pharmacotherapy for acute and chronic PSA is necessary, including the election of drugs that target different neurotransmitter systems and deficits in specific language domains. This article updates the role of pharmacotherapy for PSA, focusing the spotlight on some already investigated drugs and candidate agents deserving of future research. Refining the precision of drug election would require using multimodal biomarkers to develop personalized treatment approaches. There is a solid need to devise feasible randomized controlled trials adapted to the particularities of the PSA population. The emergent role of multimodal interventions combining one or two drugs with noninvasive brain stimulation to augment SLT is emphasized. Pharmacotherapy can improve language deficits not fully alleviated by SLT. In addition, the 'drug-only' approach can also be adopted when administering SLT is not possible. The primary goal of pharmacotherapy is reducing the overall aphasia severity, although targeting language-specific deficits (i.e. naming, spoken output) also contributes to improving functional communication. Unfortunately, there is still little information for recommending a drug for specific language deficits. [ABSTRACT FROM AUTHOR]

Lennox-Gastaut syndrome (LGS) is a severe childhood-onset epileptic encephalopathy, characterized by multiple seizure types, generalized slow spike-and-wave complexes in the EEG, and cognitive impairment. Seizures in LGS are typically resistant to treatment with antiseizure medications (ASMs). Tonic/atonic ('drop') seizures are of particular concern, due to their liability to cause physical injury. We summarize evidence for current and emerging ASMs for the treatment of seizures in LGS. The review focuses on findings from randomized, double-blind, placebo-controlled trials (RDBCTs). For ASMs for which no double-blind trials were identified, lower quality evidence was considered. Novel pharmacological agents currently undergoing investigation for the treatment of LGS are also briefly discussed. Evidence from RDBCTs supports the use of cannabidiol, clobazam, felbamate, fenfluramine, lamotrigine, rufinamide, and topiramate as adjunct treatments for drop seizures. Percentage decreases in drop seizure frequency ranged from 68.3% with high-dose clobazam to 14.8% with topiramate. Valproate continues to be considered the first-line treatment, despite the absence of RDBCTs specifically in LGS. Most individuals with LGS will require treatment with multiple ASMs. Treatment decisions should be individualized and take into account adverse effects, comorbidities, general quality of life, and drug interactions, as well as individual efficacy. [ABSTRACT FROM AUTHOR]

Bronchiectasis has become a growing concern of chronic airway disease because of the enormous socioeconomic burden. Four cardinal interdependent components – impaired airway defense, recurrent airway infections, inflammatory response, and airway damage, in conjunction with the underlying etiology, have collectively played a role in modulating the vicious vortex of the pathogenesis and progression of bronchiectasis. Current pharmacotherapy aims to target at these aspects to break the vicious vortex. The authors retrieve and review, in MEDLINE, Web of Science and ClinicalTrials.gov registry, the studies about pharmacotherapy for bronchiectasis from these aspects: antibiotics, mucoactive medications, bronchodilators, anti-inflammatory drug, and etiological treatment. Future drug development and clinical trials of bronchiectasis need to pay more attention to the different phenotypes or endotypes of bronchiectasis. There is a need for the development of novel inhaled antibiotics that could reduce bacterial loads, improve quality-of-life, and decrease exacerbation risks. More efforts are needed to explore the next-generation neutrophil-targeted therapeutic drugs that are expected to ameliorate respiratory symptom burden, reduce exacerbation risks, and hinder airway destruction in bronchiectasis. [ABSTRACT FROM AUTHOR]

Endometriosis is a benign chronic inflammatory disease responsible for debilitating pain and decreased quality of life. The traditional treatment is based on estroprogestins, progestins, GnRH analogs, and surgery. Recently, aromatase inhibitors (AIs) demonstrated good efficacy in controlling symptoms and size of endometriotic implants, mostly because they suppress extraovarian estrogen synthesis, which can enhance the hypoestrogenic state ameliorating symptoms of endometriosis. Phase I, II, III and IV trials, on the use of AIs used for the treatment of endometriosis, have been retrieved. The pharmacokinetics and pharmacodynamics of third-generation non-steroidal AIs have also been investigated. A MEDLINE search has been performed using the following MeSH keywords: 'endometriosis,' aromatase inhibitors,' 'therapy,' and 'treatment'. The timeframe was from 2010 up to November 2022 including reviews, systematic reviews, reports, case series, and retrospective or prospective trials. AIs have shown good clinical efficacy in combination with hormonal therapy in disease control, and they represent a promising second-line therapy in selected patients, yet more research is needed on alternative drug delivery systems and better control of adverse effects. In postmenopausal women in which surgery is contraindicated, AIs represent an excellent treatment option. Their application in routine clinical practice remains limited by adverse effects. [ABSTRACT FROM AUTHOR]

Although sodium-glucose cotransporter-2 (SGLT2) inhibitors have risen in popularity for managing heart failure (HF) and chronic kidney disease (CKD), little guidance is available for the management of patients with an overlap of HF and CKD. Following a brief review of the cardiorenal effects of SGLT2 inhibitors, this narrative review focused on the published clinical evidence pertaining to the cardiovascular and renal efficacy of SGLT2 inhibitors in patients with HF and CKD, including both randomized controlled trials and real-world observational studies. Real-world considerations of using SGLT2 inhibitors in these patients were also reviewed. Although no randomized controlled trial has specifically studied the use of SGLT2 inhibitors in patients with HF and CKD, evidence from existing trials is largely sufficient to demonstrate that SGLT2 inhibitors are efficacious in these patients, in whom these agents should be initiated early to maximally slow declines in renal function. Further studies should focus on better guiding the timing of initiating SGLT2 inhibitors, improving these agents' cost-effectiveness, and bettering equity of access to these agents. Further areas of study may include the prognostic implications of SGLT2 inhibitors-induced changes in biomarker levels (e.g. natriuretic peptides), and the potentials of SGLT1 inhibition. [ABSTRACT FROM AUTHOR]

Lower-sodium oxybate (LXB) is a novel formulation that is approved by the US Food and Drug Administration (FDA) to treat cataplexy and excessive daytime sleepiness (EDS) in adult patients and children ≥7 years with narcolepsy. LXB contains 92% less sodium than sodium oxybate (SXB), which adds 550–1640 mg of sodium/day at usual doses of 3–9 g/day. The FDA has declared LXB to be clinically superior to SXB due to greater safety by reducing the chronic sodium load. Narcolepsy patients have high comorbidities for hypertension and cardiovascular disease conditions, which can be adversely affected by high sodium intake. This drug review discusses narcolepsy, current and upcoming pharmacotherapy, and LXB chemistry, pharmacodynamics, pharmacokinetics, and metabolism. Published results from LXB's phase 1 studies, a phase 3 study, and two post-marketing studies are reviewed. Databases searched included PubMed, Google Scholar, Lexi-Comp, Scopus, Science, and Ovid. LXB is efficacious in treating daytime sleepiness and cataplexy in adults and children ≥7 years with narcolepsy. Using LXB instead of SXB formulations may benefit narcolepsy patients with cardiovascular comorbidities and hypertension, but long-term studies are needed to prove it. [ABSTRACT FROM AUTHOR]

Anxiety disorders are the most prevalent psychiatric disorders among youth. Among the various anxiety disorders, generalized anxiety disorder is particularly prevalent. Youth with GAD appear at elevated risk of developing other anxiety disorders, mood disorder, and substance use disorders. Functional outcomes of youth with GAD can be improved through early recognition and treatment, thus promoting better longer-term outcomes. The current article summarizes evidence-based state-of-the-art pharmacotherapy for pediatric GAD based on open-label, randomized, and controlled trials. Two electronic databases (PubMed and Scopus) were systematically searched in April 2022 for relevant publications. The literature supports a combination of psychotherapy and pharmacotherapy as being associated with better outcomes when compared to mono-therapies. While longer-term follow-ups are limited, one such study does challenge this notion. Both selective serotonin reuptake inhibitors (SSRIs) and selective norepinephrine reuptake inhibitors (SNRIs) have been found across studies to have moderate effect sizes in the treatment of pediatric anxiety disorders. SSRIs continue to be a first-line intervention, whereas SNRIs may be considered a second-line treatment. While more evidence is needed, there are emerging data indicating that SSRIs are associated with a more rapid and greater reduction in anxiety symptoms when compared to SNRIs. [ABSTRACT FROM AUTHOR]

Interstitial lung disease (ILD) is a major cause of disease-related morbidity and one of the leading causes of mortality in patients with systemic sclerosis (SSc). Many patients will be diagnosed with SSc before the emergence of clinically meaningful ILD. Screening and early recognition of SSc-ILD allows prompt intervention and improved clinical outcomes. In recent years, clinical trial data from large well-designed randomized controlled trials have greatly enhanced our understanding of the natural history of SSc-ILD and risk factors for progressive disease. These advances have led to the emergence of treatment paradigms designed to address the management of both established and subclinical disease. The present review shall consider the findings of recent trials and implications for modern pharmacological management of SSc-ILD. Where relevant, knowledge gaps shall be highlighted to outline the potential focus of additional research in this field. Recent clinical trial data have confirmed beyond doubt the value of immunomodulatory treatment in SSc-ILD, and it is expected this shall translate into improved clinical outcomes in SSc-ILD. We need better methods of cohort enrichment for SSc-ILD clinical trials, and biomarker discovery may establish molecular signatures allowing more personalized approaches to SSc-ILD prevention and management. [ABSTRACT FROM AUTHOR]

Hirsutism is the presence of excessive body hair in a male pattern distribution in a woman, and can affect up to 20% of women. It can be associated with high levels of psychosocial and psychosexual morbidity. It is a common cause for presentation to medical staff, particularly endocrinologists, gynecologists, and dermatologists. The authors discuss the definition, causes, and diagnosis of hirsutism. Current and evolving pharmacotherapy is available for hirsutism with an evaluation of the available evidence, consensus opinions, and guidelines to date. Physical therapies that can be recommended in combination with medical pharmacotherapies are also outlined. Combined oral contraceptive pills (OCP) are recommended as first-line therapy. The addition of oral antiandrogens can be combined for severe cases. Antiandrogens and OCPs have been demonstrated to be the most effective pharmacotherapy available in improving hirsutism. Greater insight is being achieved in the use of antiandrogens and their role in managing hyperandrogenism states such as hirsutism. Insulin sensitizers such as metformin are found to be the least effective. Medical treatments for hirsutism often need to be combined with physical therapies for optimal management. Psychological support should be considered in patients with associated psychosocial morbidity. [ABSTRACT FROM AUTHOR]

Bardet–Biedl Syndrome (BBS) is a rare, multisystemic ciliopathy with an incidence of obesity of 89%. Mutations in genes encoding BBS proteins are linked to reduced leptin sensitivity of hypothalamic POMC neurons and reduced activation of the melanocortin-4 receptor (MC4R) pathway due to deficient α-MSH production by hypothalamic POMC neurons. The MC4R pathway is involved in controlling body weight and energy metabolism, and its disruption is linked to hyperphagia and obesity. Setmelanotide is an MC4R agonist that counteracts deficiencies in the MC4R pathway of individuals with BBS. Data from clinical trials were reviewed along with information available from setmelanotide's approval for treatment of obesity in people ages ≥6y with a clinical diagnosis of BBS. Setmelanotide is available as a daily injectable that can be used for amelioration of obesity in people with Bardet–Biedl syndrome. Its cost is substantial, which may limit its use, but among those who respond, setmelanotide can reduce body mass dramatically and potentially improve comorbid conditions associated with obesity. Setmelanotide treatment has generally tolerable side effects, primarily injection site reactions and nausea/vomiting that generally improve with continued use; almost all people using setmelanotide experience marked skin darkening due to off-target activation of cutaneous MC1R. [ABSTRACT FROM AUTHOR]

Cancer cachexia is a multifactorial metabolic syndrome associated with a pathophysiology intertwined with increased inflammatory response, anorexia, metabolic dysregulation, insulin resistance, and hormonal alterations, which together generate a negative energy balance in favor of catabolism. The development of therapeutic strategies to treat cancer cachexia has always been related to clinical interventions with increased food intake/supplementation, physical exercise regimens, and/or medication to attenuate catabolism and increase the anabolic response. However, the approval of drugs by regulatory agencies has always been a challenge. This review outlines the main pharmacotherapy findings in cancer cachexia as well as the ongoing clinical trials that have evaluated changes in body composition and muscle function. The National Library of Medicine (PubMed) was used as search tool. The pharmacological therapy for cachexia should be focused on improving body composition, muscle function, and mortality, although none of the compounds used so far was able to demonstrate positive results beyond increased appetite and improvements in body composition. Ponsegromab (GDF15 inhibitor), a new compound that has just entered a phase II clinical trial, is a promising candidate to treat cancer cachexia and may produce exciting results if the study can be conducted as planned. [ABSTRACT FROM AUTHOR]

Non-ST-segment elevation acute coronary syndromes (NSTE-ACS), including non-ST-segment-elevation myocardial infarction (NSTEMI) and unstable angina, represent a leading cause of mortality worldwide, with important socio-economic consequences. NSTEMI accounts for the majority of acute coronary syndromes and usually develops on the background of a nonocclusive thrombus. We searched for relevant literature in the field in PubMed and clinicaltrials.gov as of July 2022. A number of pharmacotherapies are currently available for treatment and secondary prevention, mainly including antithrombotic, lipid-lowering and anti-inflammatory drugs. Pretreatment with aspirin, anticoagulant and statin therapy is of key importance in the preprocedural phase, while pretreating with an oral P2Y12 inhibitor is not routinely indicated in patients undergoing early invasive management. For patients undergoing percutaneous coronary revascularization, pharmacotherapy essentially consists of antithrombotic drugs, which should be carefully selected. Finally, antithrombotic, lipid-lowering and anti-inflammatory drugs are important components of long-term secondary prevention after a NSTE-ACS. This article reviews the evidence supporting recommendation on pharmacotherapy in patients presenting with a NSTE-ACS. Several randomized clinical trials are still ongoing and are expected to further inform scientific knowledge and clinical practice, with the final aim to improve the treatment of NSTE-ACS patients. [ABSTRACT FROM AUTHOR]

A large number of randomized controlled trials (RCTs) and observational studies on the pharmacotherapy of ADHD are available. Based on a search in PubMed and PsycInfo (up to 15 September 2022), this review addresses to which extent this body of research is currently able to inform routine prescribing practice, in terms of the choice of medication, titration strategy, augmentation treatments, and use of alternative, non-approved treatments. A growing body of evidence is informing prescribers on some, but certainly not all, aspects related to the pharmacological treatment of ADHD in the daily clinical practice, with important weaknesses/gaps that need to be addressed. First, evidence synthesis of RCTs is not able to inform decision-making at the individual patient level. Second, the maximum safe and effective doses, possibly beyond those currently recommended, are not well understood. Third, evidence from RCTs on augmenting strategies is still limited. Fourth, no novel agents with the same or higher effect size of stimulants, in terms of efficacy, but with better tolerability and lower abuse potential, have been found. Implementation of precision psychiatry approaches and stratification of patients in future RCTs will be key to, respectively, individualize the treatment strategies and test etiopathophysiology-based agents. [ABSTRACT FROM AUTHOR]

Introduction: Heart failure (HF) is a global health challenge that requires a multidisciplinary approach. Despite recent advances in pharmacological and interventional therapy, morbidity and mortality in these patients remain high. For this reason, and because of its interplay with other cardiovascular and non-cardiovascular diseases, HF represents a major area of research, with new trials being published every year and international guidelines constantly updated., Areas Covered: The authors review the current status and possible future developments in HF pharmacotherapy., Expert Opinion: The treatment of HF has made significant advances in recent years, and the current recommendations are based on large outcome trials. This has led to significant reductions in both mortality and morbidity, but the death rate remains unacceptably high. In this context, a patient-centered approach that considers comorbidities and specific clinical scenarios when dosing HF medication is essential. Prevention of hospital admissions for cardiac decompensation is of utmost importance in patients with HF as is the enablement of activities of daily living, an endpoint which has only recently been incorporated into major HF trials.