Search

The continued rise in the availability of illicit opioids and opioid-related deaths in the United States has left physicians, researchers, and lawmakers desperate for solutions to this ongoing epidemic. The research into therapeutic options for the treatment of opioid use disorder (OUD) began with the introduction of methadone in the 1960s. The approval of oral naltrexone initially showed much promise, as the drug was observed to be highly potent in antagonizing the effects of opioids while producing no opioid agonist effects of its own and having a favorable side effect profile. Patients that routinely take their naltrexone reported fewer days of heroin use and had more negative drug tests than those without treatment. Poor outcomes in OUD patients treated with naltrexone have been directly tied to short treatment time. Studies have shown that naltrexone given orally vs. as an implant at the 6-month interval showed a higher non-compliance rate among those who used oral medications at the 6-month mark and a slower return to use rate. There were concerns that naltrexone could possibly worsen negative symptoms seen in opiate use disorder related to blockade of endogenous opioids that are important for pleasurable stimuli. Studies have shown that naltrexone demonstrated no increase in levels of anxiety, depression and anhedonia in participants and another study found that those treated with naltrexone had a significant reduction in mental health-related hospitalizations. The latter study also concluded that there was no increased risk for mental health-related incidents in patients taking naltrexone via a long-acting implant. Although not yet FDA approved in the United States, naltrexone implant has shown promising results in Europe and Australia and may provide a novel treatment option for opioid addiction.

Attention-deficit Hyperactivity Disorder is one of the most common childhood mental health disorders, affecting about 5.6% of the population worldwide. Several studies have specifically shown a high prevalence of comorbid mood disorders, such as depression and bipolar disorder (BD), in those diagnosed with ADHD. Several common symptoms of ADHD are also found in BD, which are characterized by alternating periods of euthymia and mood disturbances. The inattention and impulsivity of ADHD can be seen in manic and hypomanic episodes of BD. Over the past decade, there has been an increased interest in research between the correlation of ADHD and pediatric bipolar disorder (PBD) in children. Some experts hypothesize that more children are comorbidly diagnosed with ADHD and PBD because of how many clinicians treat children with ADHD. Other factors, which may affect the dual diagnoses of ADHD and PBD, are overlapping diagnostic criteria for the two disorders, the inevitable biases seen when one disorder is diagnosed without the other, and related risk factors leading to prodromal relationships. By examining clinical trials, a better understanding of whether ADHD and PBD have a stepwise progression or if other factors influence these comorbidities, such as blurred lines of diagnostic criteria. Those with ADHD are also at an increased risk of impairment at work and in social settings. This manuscript explores both progression of this disease and its clinical connections to other disorders.

Psychiatric disorders, in general, have a high prevalence of sexual problems, whether from the psychopathology of the disorder itself, pre-existing or co-morbid sexual disorder or from side effects of the treatment for mental disorders. Many patients report an already existing sexual dysfunction at the onset of diagnosis. The risk association for developing sexual dysfunction in patients with schizophrenia includes antipsychotic use and resulting hyperprolactinemia, age, gender, and disease severity. Medication side effects lead to nonadherence, and relapses lead to structural changes in the brain, treatment resistance, and worsening of symptoms. Findings in certain studies propose serum prolactin and thyroid-stimulating hormone measurement as a tool for assessing patients with schizophrenia for sexual dysfunction. Regarding specific symptoms, females especially reported decreased desire at baseline and galactorrhea after treatment. The findings of this review, therefore, suggest that sexual dysfunction may be present in patients with schizophrenia before starting antipsychotic treatment and that patients, especially those who are female, are likely to develop hyperprolactinemia with antipsychotic treatment. Aripiprazole may be an emergent treatment for sexual dysfunction in those who use antipsychotics. It is important for patients to consider sexual dysfunction prior to prescribing antipsychotics. Since sexual dysfunction can impact a patient’s quality of life and affect treatment adherence, it is important for physicians to be aware and monitor patients for symptoms.

Benzodiazepines (BZDs) are among one of the most widely prescribed drug classes in the United States. BZDs are a class of psychoactive drugs known for their depressant effect on the central nervous system (CNS). They quickly diffuse through the blood–brain barrier to affect the inhibitory neurotransmitter GABA and exert sedative effects. Related to their rapid onset and immediate symptom relief, BZDs are used for those struggling with sleep, anxiety, spasticity due to CNS pathology, muscle relaxation, and epilepsy. One of the debilitating side effects of BZDs is their addictive potential. The dependence on BZDs generally leads to withdrawal symptoms, requiring careful tapering of the medication when prescribed. Regular use of BZDs has been shown to cause severe, harmful psychological and physical dependence, leading to withdrawal symptoms similar to that of alcohol withdrawal. Some of these withdrawal symptoms can be life threatening. The current treatment for withdrawal is through tapering with clonazepam. Many drugs have been tested as a treatment for withdrawal, with few proving efficacious in randomized control trials. Future research is warranted for further exploration into alternative methods of treating BZD withdrawal. This call to action proves especially relevant, as those seeking treatment for BZD dependence and withdrawal are on the rise in the United States.

Catatonia is a syndrome that has been associated with several mental illness disorders but that has also presented as a result of other medical conditions. Schizophrenia and other psychiatric disorders such as mania and depression are known to be associated with catatonia; however, several case reports have been published of certain medical conditions inducing catatonia, including hyponatremia, cerebral venous sinus thrombosis, and liver transplantation. Neuroleptic Malignant Syndrome and anti-NMDA receptor encephalitis are also prominent causes of catatonia. Patients taking benzodiazepines or clozapine are also at risk of developing catatonia following the withdrawal of these medications—it is speculated that the prolonged use of these medications increases gamma-aminobutyric acid (GABA) activity and that discontinuation may increase excitatory neurotransmission, leading to catatonia. The treatment of catatonia often involves the use of benzodiazepines, such as lorazepam, that can be used in combination therapy with antipsychotics. Definitive treatment may be found with electroconvulsive therapy (ECT). Aberrant neuronal activity in different motor pathways, defective neurotransmitter regulation, and impaired oligodendrocyte function have all been proposed as the pathophysiology behind catatonia. There are many clinical challenges that come with catatonia and, as early treatment is associated with better outcomes, it becomes imperative to understand these challenges. The purpose of this manuscript is to provide an overview of these challenges and to look at clinical studies regarding the pathophysiology, diagnosis, and treatment of as well as the complications and risk factors associated with catatonia.

Opioid use disorder is a well-established and growing problem in the United States. It is responsible for both psychosocial and physical damage to the affected individuals with a significant mortality rate. Given both the medical and non-medical consequences of this epidemic, it is important to understand the current treatments and approaches to opioid use disorder and acute opioid overdose. Naloxone is a competitive mu-opioid receptor antagonist that is used for the reversal of opioid intoxication. When given intravenously, naloxone has an onset of action of approximately 2 min with a duration of action of 60–90 min. Related to its empirical dosing and short duration of action, frequent monitoring of the patient is required so that the effects of opioid toxicity, namely respiratory depression, do not return to wreak havoc. Nalmefene is a pure opioid antagonist structurally similar to naltrexone that can serve as an alternative antidote for reversing respiratory depression associated with acute opioid overdose. Nalmefene is also known as 6-methylene naltrexone. Its main features of interest are its prolonged duration of action that surpasses most opioids and its ability to serve as an antidote for acute opioid overdose. This can be pivotal in reducing healthcare costs, increasing patient satisfaction, and redistributing the time that healthcare staff spend monitoring opioid overdose patients given naloxone.

Phenothiazines, a diverse class of drugs, can be used to treat multiple mental health and physical conditions. Phenothiazines have been used for decades to treat mental illnesses, including schizophrenia, mania in bipolar disorder, and psychosis. Additionally, these drugs offer relief for physical illnesses, including migraines, hiccups, nausea, and vomiting in both adults and children. Further research is needed to prove the efficacy of phenothiazines in treating physical symptoms. Phenothiazines are dopaminergic antagonists that inhibit D2 receptors with varying potency. High potency phenothiazines such as perphenazine are used to treat various psychiatric conditions such as the positive symptoms of schizophrenia, the symptoms of psychosis, and mania that can occur with bipolar disorder. Low/mid potency phenothiazines such as chlorpromazine antipsychotic drugs that have been used to treat schizophrenia and schizophrenia-like disorders since the 1950s and are utilized in numerous disease states. The present investigation aims to elucidate the effects of phenothiazines in clinical practice.

This review aims to assess the relationship between interstitial cystitis (IC) and significant traumatic events or PTSD. It was shown that there is a strong correlation between past trauma and the development of interstitial cystitis, as well as a much higher incidence of PTSD in patients diagnosed with IC. It was also established that for individuals with early traumatic experiences, the more likely the development of IC later in life, and with more severe symptoms and adverse effects on quality of life. We describe three distinct hypotheses for the possible physiologic mechanism for development of IC with relation to mental health and trauma, although definitive evidence in this area is still lacking, which poses interesting avenues for further research. This review also revealed an apparent lack of, and need for, trauma informed care and screening for PTSD in patients diagnosed with IC or other chronic pain syndromes.

Major Depressive Disorder (MDD) is a major cause of disability worldwide and is associated with serious lasting impairment. A leading hypothesis of the pathophysiology of MDD is the monoamine deficiency hypothesis which suggests that depression is caused by depletion of serotonin, norepinephrine, or dopamine in the central nervous system. Serotonin is the most widely studied neurotransmitter in the pathophysiology of depression, with studies showing that reduced central serotonin synthesis leads to depressive symptoms in individuals at risk for depression. Selective Serotonin Reuptake Inhibitors (SSRI) inhibit serotonin reuptake and subsequently increase the amount of serotonin available in synapses. Common side effects of SSRIs include increased suicidality of patients under the age of 25, sexual dysfunction, anxiety, dizziness, weight gain, gastrointestinal distress, and headache. Other side effects include prolonging the QT interval, coagulopathy, and the risk of serotonin syndrome, as well as SSRI discontinuation syndrome. Sites of increased bleeding related to SSRI use have been reported to occur in the upper gastrointestinal tract, as well as intracranially. Based on the current literature, three studies have found that SSRIs are not associated with increased bleeding and/or increased perioperative risk, while others have demonstrated that SSRIs are associated with an increased risk in perioperative use. The inhibition of serotonin reuptake can affect platelet aggregation since platelets also express the serotonin transporter. SSRIs can result in decreased storage of serotonin in platelet dense granules. Increased serotonin can also increase gastric acid secretion, which increases the risk for ulceration. SSRIs in combination with NSAIDs also show a significantly increased risk of upper GI bleeding. Some studies show an increased bleeding risk from 30% to 70% when taking a combination of vitamin K antagonists and SSRIs in hospitalized patients. Related to the high prevalence of conditions that are treated with SSRIs, the bleeding risk associated with this class of medication merits further study.

# Background Depression is a common disorder that affects millions globally and is linked to reduced quality of life and mortality. Its pathophysiology is complex and there are several forms of treatment proposed in the literature with differing side effect profiles. Many patients do not respond to treatment which warrants augmentation with other treatments and the investigation of novel treatments. One of these treatments includes testosterone therapy which evidence suggests might improve depressed mood in older patients with low levels of testosterone and helps restore physical impairments caused by age-related hormonal changes. # Objective The objective of this review is to synthesize information regarding clinical depression, its treatment options, and the efficacy and safety of testosterone treatment for the treatment of depression. # Methods This review utilized comprehensive secondary and tertiary data analysis across many academic databases and published work pertaining to the topic of interest. # Results Within some subpopulations such as men with dysthymic disorder, treatment resistant depression, or low testosterone levels, testosterone administration yielded positive results in the treatment of depression. Additionally, rodent models have shown that administering testosterone to gonadectomized male animals reduces symptoms of depression. Conversely, some studies have found no difference in depressive symptoms after treatment with testosterone when compared with placebo. It was also noted that over administration of testosterone is associated with multiple adverse effects and complications. # Conclusion The current evidence provides mixed conclusions on the effectiveness of testosterone therapy for treating depression. More research is needed in adult men to see if declining testosterone levels directly influence the development of depression.

The intention of utilizing chaperones during sensitive physical exams is to show respect to the patient, while simultaneously providing protection to both the patient and the medical provider. Despite clinical practice recommendations to offer chaperones for sensitive urologic exams, there is no data regarding the consistency of chaperone utilization. Our aim was to summarize the patient and provider perspectives on the role of chaperones in urology as well as identify barriers to implement chaperone consistency. In the present investigation, we conducted a systematic review of prospective, case-control, and retrospective studies and followed the PRISMA 2020 guidelines for data reporting. Studies were identified from PubMed, MEDLINE, and PMC using the Medical Subject Headings (MeSH) terms “chaperones, patient”, “chaperones, medical”, and keywords “chaperones”, and “urology”. Studies were included if they addressed patient/provider perspectives on chaperone utilization in urology specifically and were excluded if they investigated perspectives on chaperone utilization in other specialties. Preliminary study identification yielded 702 studies, 9 of which were eligible for this review after applying the inclusion and exclusion criteria. Of these, 4 studies focused on the patient perspective and 5 focused on the provider perspective. The percentage of patients that did not have a chaperone present during their urologic exam ranged from 52.9-88.5%. A greater proportion of these patients were male. Patients (59%) prefer a family member compared to a staff member as a chaperone. Physicians (60%) prefer staff member chaperones compared to family members. One study reported that 25.6% of patients did not feel comfortable to ask for a chaperone if they were not offered one. Two studies reported the percentage of patients who believed chaperones should be offered to all urology patients, ranging from 73-88.4%. Three studies reported the use of chaperones in the clinic which ranged from 5-72.5%. Two studies reported chaperone utilization documentation, ranging between 16-21.3%. Two studies reported the likelihood of chaperone utilization depending on gender of the physician, showing that male physicians were more likely to utilize chaperones and were 3x more likely to offer chaperones to their patients compared to female physicians. Research suggests that there are differing perspectives between patients and physicians regarding the specific role and benefits chaperones offer during a sensitive urologic examination, as well as differences in preferences of who should perform the role of the chaperone. While more work needs to be done to bridge the divide between clinical practice and patient/physician preferences, the act of offering chaperones to urologic patients, regardless if they want to utilize a chaperone for their examination is respectful of patient privacy and decision making.

Monoamine oxidase inhibitors (MAOI) are a class of drugs that were originally developed for the treatment of depression but have since been expanded to be used in management of affective and neurological disorders, as well as stroke and aging-related neurocognitive changes. Ranging from irreversible to reversible and selective to non-selective, these drugs target the monoamine oxidase (MAO) enzyme and prevent the oxidative deamination of various monoamines and catecholamines such as serotonin and dopamine, respectively. Tyramine is a potent releaser of norepinephrine (NE) and is found in high concentrations in foods such as aged cheeses and meats. Under normal conditions, NE is unable to accumulate to toxic levels due to the presence of MAO-A, an enzyme that degrades neurotransmitters, including NE. When MAO-A is inhibited, the capacity to handle tyramine intake from the diet is significantly reduced causing the brain to be vulnerable to overstimulation of postsynaptic adrenergic receptors with as little as 8-10 mg of tyramine ingested and can result in life-threatening blood pressure elevations. In addition to adverse reactions with certain foods, both older and newer MAOIs can negatively interact with both sympathomimetic and serotonergic drugs. In general, patients on a MAOI want to avoid two types of medications: those that can elevate blood pressure via sympathomimetic actions (e.g., phenylephrine and oxymetazoline) and those that can increase serotonin levels via 5-HT reuptake inhibition (e.g., dextromethorphan, chlorpheniramine, and brompheniramine). Illicit drugs that stimulate the central nervous system such as ecstasy (MDMA, 3,4-methylenedioxymethamphetamine) act as serotonin releasers. Patient involvement is also crucial to ensure any interaction within the healthcare setting includes making other providers aware of a MAOI prescription as well as avoiding certain OTC medications that can interact adversely with MAOIs.

# Purpose of Review Migraines are prevalent and cause significant morbidity, decline in quality of life and healthcare costs universally. Treatment options are varied, but efficacy is limited. This review centers on Eptinezumab-jjmr, a humanized monoclonal specific to CGRP for the prevention of migraines in adults. Herein presented are the science and mechanism of action, indication and clinical evidence for use. # Recent Findings Migraines are severe, recurrent headaches, which are either episodic or chronic in nature. The pain is severe, often accompanied by co-morbid symptoms, such as photophobia, phonophobia, nausea and emesis, and is limiting in nature. It is a prevalent disorder that causes significant, worldwide disability, morbidity, suffering, and costs. The pathophysiology of migraines is actively studied, though recent research points to an initiating event causing migraine generation, that is then propagated by other brain regions, a significant one being the trigeminocervical complex. This is driven by biochemical transmitters, chiefly CGRP. This discovery led to the development of CGRP-targeting drugs, including gepants (small molecular antagonists) and anti-CGRP antibodies, such as Eptinezumab-jjmr. Traditional therapy includes preventative and abortive treatment; however, adherence with preventative treatment has been historically poor, and certain types of abortive therapy carry risks and side effects that preclude them from a large patient population. Moreover, traditional therapy often falls short in migraine therapy. CGRP antagonist, including Eptinezumab, aims to cover the gaps in migraine therapy. We present here evidence to support the safe and effective use of Eptinezumab for the prevention of migraines. # Summary Migraines are a prevalent primary headache disorder causing significant morbidity worldwide. Traditional abortive and preventative treatments fall short for many patients. Eptinezumab is part of new generation of CGRP-targeting medications and has shown significant evidence to support its use for the prevention of migraines. Further research is required to properly compare eptinezumab with existing pharmacotherapy and update guidelines on the appropriate combinations of therapies that are not available and the correct patient selection for each.

Disparities in prostate cancer (PCa) exist at all stages: screening, diagnosis, treatment, outcomes, and mortality. Although there are a multitude of complex biological (e.g., genetics, age at diagnosis, PSA levels, Gleason score) and nonbiological (e.g., socioeconomic status, education level, health literacy) factors that contribute to PCa disparities, nonbiological factors may play a more significant role. One understudied aspect influencing PCa patients is mental health related to the quality of life. Overall, PCa patients report poorer mental health than non-PCa patients and have a higher incidence of depression and anxiety. Racial disparities in mental health, specifically in PCa patients, and how poor mental health impacts overall PCa outcomes require further study.

Migraine is a common form of primary headache, affecting up to 1 in every 6 Americans. The pathophysiology is an intricate interplay of genetic factors and environmental influence and is still being elucidated in ongoing studies. The trigeminovascular system is now known to have a significant role in the initiation of migraines, including the release of pain mediators such as CGRP and substance P. Traditional treatment of migraine is usually divided into acute and preventive treatment. Acute therapy includes non-specific therapy, such as NSAIDs and other analgesics, which may provide relief in mild to moderate migraines. 5-HT1 agonists may provide relief in severe migraine, but are not universally effective and carry a significant side-effect profile with frequent redosing requirement. Prophylactic therapy may reduce the occurrence of acute migraine attacks in selected patients, but does not completely eliminate it. More recently, CGRP antagonism has been studied and shown to be effective in both abortion and prevention of migraine. Novel medications, targeting CGRP, divide into CGRP antibodies and receptor antagonists (gepants). Rimegepant, a second-generation gepant, has shown efficacy in several clinical trials in treating acute migraine. Ongoing trials are also evaluating its role in migraine prophylaxis, and results are promising. It is also generally safer for use than existing options, does not appear to increase the chance of developing chronic migraines, and carries a very tolerable side effects profile. It is a part of a growing arsenal in migraine treatment, and may present the silver bullet for treatment of this disease.

Even as prescription opioid dispensing rates have begun to decrease, the use of illicit opioids such as heroin and fentanyl has increased. Thus, the end of the opioid epidemic is not in sight, and treating patients that are addicted to opioids remains of utmost importance. Currently, the primary pharmacotherapies used to treat opioid addiction over the long term are the opioid antagonist naltrexone, the partial-agonist buprenorphine, and the full agonist methadone. Naloxone is an antagonist used to rapidly reverse opioid overdose. While these treatments are well-established and used regularly, the gravity of the opioid epidemic necessitates that all possible avenues of treatment be explored. Therefore, in this narrative review, we analyze current literature regarding use of the alternative medications ketamine, noribogaine, and cannabinoids in treating patients suffering from opioid use disorder. Beyond its use as an anesthetic, ketamine has been shown to have many applications in several medical specialties. Of particular interest to the subject at hand, ketamine is promising in treating individuals addicted to opioids, alcohol, and cocaine. Therapeutically administered cannabinoids have been proposed for the treatment of multiple illnesses. These include, but are not limited to epilepsy, Parkinson's disease, multiple sclerosis, chronic pain conditions, anxiety disorders, and addiction. The cannabinoid dronabinol has been seen to have varying effects. High doses appear to reduce withdrawal symptoms but this comes at the expense of increased adverse side effects such as sedation and tachycardia. Noribogaine is a weak MOR antagonist and relatively potent KOR agonist, which may explain the clinical anti-addictive effects. More research should be done to assess the viability of these medications for the treatment of OUD and withdrawal.

Management of mental health illnesses and needs are important in fostering psychosocial support, interprofessional coordination, and greater adherence to treatment protocols in the field of urology. This can be especially true for mental health conditions that may greatly impact the presentation of a patient in the healthcare setting with urologic symptoms. This review describes the history, epidemiology, pathophysiology, clinical presentation, and treatment of somatic symptom disorder, illness anxiety disorder, compulsive sexual behavior/hypersexuality, factitious disorder, malingering symptoms, and conversion disorder in the realm of urology. Given the newly updated psychiatric diagnoses in the *Diagnostic and Statistical Manual of Mental Disorders*, fifth edition, there has been a lack of studies reviewing how these illnesses may present in a urology patient encounter. Additionally, as these mental health illnesses may carry a rare incidence compared to other well-known mental health illness such as generalized depression or generalized anxiety disorder, we have found that the lack of provisions and recognition of the diseases can prolong the timeline for diagnosis and lead to an increased cost in both healthcare and quality of life of patients with these mental health illnesses. This review provides awareness on these mental health conditions which may greatly impact patient history and presentation within the field of urology. Additionally, urologic care providers may have an improved understanding of interdisciplinary management of such illnesses and the common symptoms patients may present with such diseases.

Dhat syndrome is a culture-bound psychiatric syndrome most commonly found in the Indian subcontinent. It has been characterized as the experiential fear of losing semen through ejaculation, nocturnal emission, or other means. While Dhat syndrome is common in the Indian subcontinent, given the lack of representativeness, generalizability, and closer connection to Ayurvedic system, there have been limited studies or recognition of symptoms among healthcare providers around the world. In this review, we describe Dhat syndrome, its epidemiology, risk factors, comorbidities, diagnosis, treatment, and its management. For patients with Dhat syndrome, it becomes important to appreciate how generalized depression and anxiety may persist alongside the disorder and those symptoms can be common and non-specific. Related to its strong cultural connection with South Asia such as the belief on Dhat’s role in health and vitality influence, it also becomes important to recognize that the syndrome can be found in other populations and the importance of cultural humility and nonconfrontational approach for patient care. In summary, this review provides an informative understanding of Dhat syndrome for non-Indian clinicians who may not be prepared for a patient encounter with vague somatic symptoms in the context of semen loss. Treatment for Dhat syndrome is the same as treatments for major depressive disorder.

An intranasal formulation of midazolam, Nayzilam, has been FDA-approved to treat intermittent, stereotypic episodes of frequent seizure activity. Nayzilam is easy to administer and can quickly treat seizures that occur outside of the hospital. The intra-nasal route of administration allows non-medical personal to administer the drug which makes it more accessible and user-friendly in the event of a seizure. Many studies have indicated quick cessation of seizures with Nayzilam compared to rectal diazepam, which has been the standard of care treatment. Nayzilam has been proven to be safe and effective for acute seizures in children, deeming it a revolutionary alternative in times where intravenous administration is not possible.

For decades, chronic pain was managed with an almost conventional approach of using a wide range of analgesic spectrum, surgical approaches and complex interventional pain techniques to modulate or even interrupt pain pathways. These different approaches carry many pharmacological hazards together with the lack of efficacy and safety of many interventional and surgical management techniques for chronic pain have mandated searching for other effective therapies including alternative treatments. Cannabinoids are naturally occurring substances that are derived from Cannabis sativa L. The usage of cannabinoids and their related synthetic chemical compounds has emerged as a choice in the management of different chronic pain conditions is being evaluated, however, the efficacy is still not consistently established. In the present investigation, therefore, we discuss the different aspects related to cannabinoids and their implications in the management of chronic pain conditions. This review will also discuss the safety profile of the cannabinoids together with the legal considerations that hinder their use in different countries.

The monoamine hypothesis of depression attributes the symptoms of major depressive disorders to imbalances of serotonin, noradrenaline, and dopamine in the limbic areas of the brain. The preferential targeting of serotonin receptor (SERT) by selective serotonin reuptake inhibitors (SSRIs) has offered an opportunity to reduce the range of these side effects and improve patient adherence to pharmacotherapy. Clozapine remains an effective drug against treatment-resistant schizophrenia, defined as failing treatment with at least two different antipsychotic medications. Patients with schizophrenia who display a constellation of negative symptoms respond poorly to antipsychotic monotherapy. Negative symptoms include the diminution of motivation, interest, or expression. Conversely to the depressive symptomology of interest presently, supplementation of antipsychotics with SSRIs in schizophrenic patients with negative symptoms lead to synergistic improvements in the function of these patients. Fluvoxamine is one of the most potent inhibitors of CYP1A2 and can lead to an increase in clozapine levels. Similar increases in serum clozapine were detected in two patients taking sertraline. However, studies have been contradictory as well, showing no such increases, which are worrying. Clinicians should be aware that clozapine levels should be monitored with any coadministration with SSRIs.

Psychosis, a break in reality which is manifested as hallucinations, delusions or the disruption in thought process, is the hallmark of schizophrenia. Despite novel pharmacotherapy advancements of antipsychotic medications that have resulted in some patients having the ability to return to social settings and thereby decreasing psychotic symptoms and reducing hospital admissions, there is still a sub-population of patients who remain symptomatic. Treatment-resistant schizophrenia is defined as failure of treatment with at least two different antipsychotics with the proper length of treatment and titration. Clozapine has been heralded as a drug to resolve the puzzle of treatment-resistant schizophrenia. Clozapine has one side effect that is well known, being the development of agranulocytosis. However, there is another side effect that can limit clozapine’s use and can also be life-threatening. Recently, at the end of January 2020, the FDA issued a communications statement which “[strengthened] an existing warning that constipation caused by the schizophrenia medicine clozapine can, uncommonly, progress to serious bowel complications.” After identifying ten cases of constipation from between 2006 to 2016 that progressed to hospitalization, surgery, and even death, the FDA focused their attention on this often overlooked, common side effect, especially when considering the strong anticholinergic effects of clozapine. Although patients are screened by their physicians for agranulocytosis by weekly lab monitoring, constipation is also a complication that needs to be identified and treated. Much like opioid-induced constipation, constipation can also be reduced with the use of laxatives and reduction in the co-prescribing of anticholinergic therapies with clozapine.

Depression is the most prevalent psychiatric disorder in the world, affecting 4.4% of the global population. Despite an array of treatment modalities, depressive disorders remain difficult to manage due to many factors. Beginning with the introduction of fluoxetine to the United States in 1988, selective serotonin reuptake inhibitors (SSRIs) quickly became a mainstay of treatment for a variety of psychiatric disorders. The primary mechanism of action of SSRIs is to inhibit presynaptic reuptake of serotonin at the serotonin transporter, subsequently increasing serotonin at the postsynaptic membrane in the serotonergic synapse. The six major SSRIs that are marketed in the USA today, fluoxetine, citalopram, escitalopram, paroxetine, sertraline, and fluvoxamine, are a group of structurally unrelated molecules that share a similar mechanism of action. While their primary mechanism of action is similar, each SSRI has unique pharmacokinetics, pharmacodynamics, and side effect profile. One of the more controversial adverse effects of SSRIs is the black box warning for increased risk of suicidality in children and young adults aged 18–24. There is a lack of understanding of the complexities and interactions between SSRIs in the developing brain of a young person with depression. Adults, who do not have certain risk factors, which could be confounding factors, do not seem to carry this increased risk of suicidality. Ultimately, when prescribing SSRIs to any patient, a risk–benefit analysis must factor in the potential treatment effects, adverse effects, and dangers of the illness to be treated. The aim of this review is to educate clinicians on potential adverse effects of SSRIs.

Keratoconjunctivitis sicca (“dry eye”) is a common (14%–30% of adults over age 48) though difficult to treat condition that causes both discomfort and disability with associated dryness, pain, and visual disturbances. Etiology is not clearly understood but is likely varied, with a subset of patients suffering from chronic neuropathic pain referred to as “burning eye syndrome.” This review of existing literature summarizes the clinical presentation, natural history, pathophysiology, and treatment modalities of burning eye syndrome. Chronicity of burning eye syndrome is likely secondary to increased nociception from the cornea, decrease in inhibitory signals, and nerve growth factor expression alterations. Treatment centers around symptomatic alleviation and reduction of inflammation. Conservative treatments focus on well-being and perception and include exercise, acupuncture, and cognitive behavioral therapy. Topical treatment consists of the anti-adhesion T-cell antagonist lifitegrast, corticosteroids, and cyclosporine; all have moderate efficacy and good safety. Autologous serum eye drops are a second-line topical that may promote corneal and neural healing on top of symptomatic relief. When these treatments fail, patients may trial neuromodulation with transcranial magnetic stimulation. Despite general treatment safety, more research is needed to develop novel approaches to this condition, possibly focusing more directly on the neurological component.

Purpose of Review. This is a comprehensive review of the literature regarding the use of Aripiprazole lauroxil for schizophrenia. This review presents the background, evidence, and indications for using aripiprazole lauroxil to treat schizophrenia in the context of current theories on the development of schizophrenia. Recent Findings. Schizophrenia is a chronic mental health disorder that currently affects approximately 3.3 million people in the United States. Its symptoms, which must be present for more than six months, are comprised of disorganized behavior and speech, a diminished capacity to comprehend reality, hearing voices unheard by others, seeing things unseen by others, delusions, decreased social commitment, and decreased motivation. The majority of these symptoms can be managed with antipsychotic medication. Aripiprazole lauroxil is a long-acting intramuscular injection that works as a combination of partial agonist activity at D2 and 5-HT1A receptors combined with antagonist activity at 5-HT2A receptors. It can be dosed as a 4-, 6-, or 8-week injection, depending on oral dosage. Aripiprazole lauroxil was FDA approved in October of 2015. Summary. Schizophrenia is a severe psychiatric disorder if left untreated. There are multiple medications to help treat schizophrenia. One antipsychotic agent, aripiprazole lauroxil, offers long duration injections that optimize and improve compliance. Known side effects include weight gain, akathisia, neuroleptic malignant syndrome, tardive dyskinesia, and orthostatic hypotension. Aripiprazole lauroxil is an FDA-approved drug that can be administered monthly, every six weeks, or every two months and has been shown to be both safe and effective.

Purpose of Review: This is a comprehensive review of the literature regarding the use of paliperidone in the treatment of schizophrenia and schizoaffective disorder. It covers the background and presentation of schizophrenia and schizoaffective disorder, as well as the mechanism of action and drug information for paliperidone. It covers the existing evidence of the use of paliperidone for the treatment of schizophrenia and schizoaffective disorder. Recent Findings: Schizophrenia and schizoaffective disorder lead to significant cognitive impairment. It is thought that dopamine dysregulation is the culprit for the positive symptoms of schizophrenia and schizoaffective disorder. Similar to other second-generation antipsychotics, paliperidone has affinity for dopamine D2 and serotonin 5-HT2A receptors. Paliperidone was granted approval in the United States in 2006 to be used in the treatment of schizophrenia and in 2009 for schizoaffective disorder. Summary: Schizophrenia and schizoaffective disorder have a large impact on cognitive impairment, positive symptoms and negative symptoms. Patients with either of these mental illnesses suffer from impairments in everyday life. Paliperidone has been shown to reduce symptoms of schizophrenia and schizoaffective disorder.

Obesity has emerged as a widespread disease with epidemic proportions, necessitating effective management to enhance the overall health outcomes of patients. Medical intervention for weight loss becomes necessary when diet and exercise prove ineffective, and topiramate emerges as a potential treatment option for this global problem. Currently approved as an anti-epileptic and migraine prophylaxis medication, topiramate is frequently utilized as adjunctive therapy for patients with mood and eating disorders, as well as for alcohol use disorders. Its multifaceted mechanisms of action contribute to reducing neuronal excitation and enhancing neuronal inhibition. Given its variety of mechanisms, topiramate shows several off-label outcomes, including weight loss, for patients prescribed this medication. Although the specific mechanism of action concerning weight loss remains uncertain, various hypotheses have been reported. Notably, topiramate may contribute to weight loss by reducing calorie intake, decreasing fat gain, and lowering triglyceride and cholesterol levels. Additionally, its impact on reward pathways associated with food could play a role. Multiple clinical studies have supported the use of topiramate as a weight-loss medication. Notably, the medication demonstrates effectiveness in reducing body weight across different dosages and sustaining weight loss over time, outperforming alternative weight loss methods. Moreover, it was generally well-tolerated in clinical studies, with few side effects observed. In conclusion, topiramate offers promising potential as a weight loss solution and can be a valuable addition to the range of treatment options for combating obesity.

Psoriatic arthritis is a chronic debilitating autoimmune condition, and when diagnosed in patients before the age of eighteen, it is considered pediatric polyarticular juvenile idiopathic arthritis. Monoarticular or polyarticular psoriatic arthritis can be distinguished from other arthropathies by its unique cutaneous manifestations. With numerous treatments already in clinical practice, there are numerous options for treatment. The current literature indicates an elevated level of tumor necrosis factor is present in the epidermis of patients with psoriatic arthritis when compared with the general population. For this reason, anti-tumor necrosis factor therapies have become a hallmark option for psoriatic arthritis patients. Golimumab, a human monoclonal antibody tumor necrosis factor-alpha (TNF-a) receptor antagonist, was chosen as the focus therapy for this investigation. The mechanism of action behind anti-tumor necrosis factor-alpha blockers involves the binding of human TNF-a soluble and transmembrane proteins to competitively inhibit TNF-a from binding to its cellular receptors. The present investigation evaluated current treatment options available for both juvenile- and adult-onset psoriatic arthritis and compared them with the efficacy seen with golimumab use. Pediatric patients included children ages 2–17, while adult populations included adults 18–83 years old. The Food and Drug Administration has approved golimumab for the treatment of rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, ulcerative colitis, and polyarticular juvenile idiopathic arthritis. The results of four different studies reporting on the therapeutic effects and adverse events of golimumab use in psoriatic arthritis, juvenile psoriatic arthritis, juvenile idiopathic arthritis, and juvenile polyarticular arthritis were used for comparison. The meta-analysis referenced studies including children ages 2–17 with no reference mentioning children less than age 2. Based on the results of each study, it can be concluded that golimumab, a human monoclonal antibody that prevents the activation of cellular inflammatory reactions when it binds to the TNF-a receptor, is an effective option for patients with active psoriatic arthritis and psoriatic juvenile idiopathic arthritis and for patients who are no longer responding to their current treatment with adalimumab. Each study also reported minimal adverse events associated with golimumab use, and the drug can be safely used in the pediatric population.

Warfarin administration poses a notable challenge in clinical practice due to the increased susceptibility of patients to major bleeding, particularly when co-administered with other medications capable of modulating its metabolic pathways. Among these medications, antibiotics have been recognized as potential agents that can either induce or inhibit cytochrome P450-2C9, thereby impacting the effects of warfarin. A wealth of evidence from numerous studies consistently supports an elevated risk of serious bleeding in patients concurrently receiving antibiotics and warfarin therapy. This narrative review elucidates the intricate interactions between warfarin and various antibiotic classes. Notably, significant increases in the International Normalized Ratio (INR) were observed among warfarin-treated patients receiving penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides. Conversely, investigations have also demonstrated a reduction in INR levels in patients on warfarin when exposed to rifampin, a potent inducer of cytochrome P-450. Intriguingly, cephalosporin antibiotics and amoxicillin/clavulanate, despite not interfering with the cytochrome P450 system, exhibited a positive association with increased INR values. The findings of this narrative review underscore the importance of diligent monitoring in patients on warfarin requiring concomitant antibiotic therapy, as this surveillance strategy proves pivotal in mitigating the risk of major bleeding complications. Additionally, for patients necessitating cytochrome P450 inhibitors such as penicillin derivatives, fluoroquinolones, TMP-SMX, and macrolides, the consideration of dose reduction in warfarin therapy may confer substantial benefits in reducing the occurrence of major bleeding events. Similarly, patients who are co-administered rifampin alongside warfarin necessitate vigilant monitoring, with a potential need for escalating warfarin doses to counteract the risk of a hypercoagulable state.

Medical management of epilepsy seeks to eliminate or to reduce the frequency of seizures, help patients maintain a normal lifestyle, and maintain psychosocial and occupational activities, while avoiding the negative side effects of long-term treatment. Current FDA approved drugs have been shown to have similar efficacy; however, they all share a commonality of having side effects that have the potential to significantly reduce a patient’s quality of life. Cenobamate, a newly-FDA approved drug used to treat partial-onset seizures in adult patients, has demonstrated promise in that it works on two proposed mechanisms that are commonly associated with epilepsy. Cenobamate acts as a positive allosteric modulator of the GABAA ion channels and is effective in reducing repetitive neuronal firing by inhibition of voltage-gated sodium channels, although the complete mechanism of action is currently unknown. The efficacy of Cenobamate with its low toxicity and adverse drug reaction profile emphasizes the need to further evaluate antiepileptic therapies containing sulfamoylphenyl and/or carbamate moieties in their chemical structure. Recent studies have found more patients to be seizure free during the maintenance period when compared to placebo. The most common side effects reported in with Cenobamate are somnolence, dizziness, headache, nausea, and fatigue. There are currently ongoing phase III studies looking to further evaluate the long-term benefits of Cenobamate and investigate adverse events.

Multiple sclerosis (MS) is a prevalent neurologic autoimmune disorder affecting two million people worldwide. Symptoms include gait abnormalities, perception and sensory losses, cranial nerve pathologies, pain, cognitive dysfunction, and emotional aberrancies. Traditional therapy includes corticosteroids for the suppression of relapses and injectable interferons. Recently, several modern therapies—including antibody therapy and oral agents—were approved as disease-modifying agents. Monomethyl fumarate (MMF, Bafiertam) is a recent addition to the arsenal available in the fight against MS and appears to be well-tolerated, safe, and effective. In this paper, we review the evidence available regarding the use of monomethyl fumarate (Bafiertam) in the treatment of relapsing-remitting MS.

While transfusion of blood and blood products is instinctively linked to the provision of emergent care, blood and blood products are also routinely used for the treatment of subacute and chronic conditions. Despite the efforts of the World Health Organization and others, developing countries are faced with a three-part problem when it comes to access to and delivery of transfusions: insufficient supply, excessive demand, and inadequate quality of available supply. Developing countries rely heavily on replacement and remunerated donors rather than voluntary nonremunerated donors due to concerns regarding donation- and transfusion-transmitted infection as well as local and cultural beliefs. While increased awareness of HIV and improved testing techniques have jointly reduced infection-related apprehensions and improved the quality of available blood and blood products, continued efforts are warranted to bolster testing for other bloodborne pathogens. Similarly, although prevalence rates of anemia are high in some areas of the world, success in adequate widespread management of these conditions has been limited. One of the keys to expanding access to high-quality blood and blood products is thus to improve medical management of conditions that would otherwise require transfusion. Through a three-pronged approach to address quantity, quality, and demand, developing countries can enable themselves to build toward self-sufficient blood management services and increased independence from the support of international organizations.

# Purpose of Review Attention deficit hyperactivity disorder (ADHD) is a widely diagnosed neurodevelopmental disorder giving rise to symptoms of hyperactivity, impulsivity, and inattentiveness that can impair daily functioning. Stimulants, such as methylphenidate and amphetamines, are the mainstay of treatment for ADHD. However, nonstimulant drugs such as viloxazine, atomoxetine, guanfacine, and clonidine are becoming more popular due to minimal adverse effects when compared to stimulants. # Recent Findings Viloxazine is a selective norepinephrine reuptake inhibitor (NRI) originally used to treat depression in adults with activity in both the noradrenergic as well as serotonergic pathways. Studies have demonstrated its efficacy for its use in the treatment of ADHD. Unlike stimulants, viloxazine has a decreased chance of substance abuse, drug dependance, and withdrawal symptoms upon the cessation of therapy. Additionally, dopamine levels in the nucleus accumbens after treatment with viloxazine are elevated considerably less in comparison with traditional stimulant ADHD treatments. Viloxazine provides an alternative, nonstimulant approach to treating ADHD. # Summary Viloxazine is a recently approved, non-stimulant medication functions by inhibiting the uptake of norepinephrine which has been seen to be decreased in patients with ADHD. When patients do not respond to first-line stimulants, cannot tolerate the side effects, or have contraindications to stimulants, viloxazine may be a nonstimulant option offering patients an increasing arsenal of medications to treat ADHD.

This article is a literature review of mental health concerns in non-oncologic urology patients. Pathologies represented in this review include Peyronie's Disease (PD), erectile dysfunction (ED), urinary incontinence and urinary tract infections (UTI), infertility, benign prostatic hyperplasia (BPH), kidney stones, and urinary retention. While there has been great interventional focus as of late for urogenitary malignancies (i.e. prostate cancer awareness with the Movember campaign), literature studies and intervention focused on non-oncologic urology patients has been limited. As such, we conducted a review on urology patients with non-oncologic pathologies as an effort to increase clinician awareness of mental health concerns among such patients, increase the comfort level for clinician communication on socially sensitive topics surrounding pathologies, and review ongoing interventions conducted within these pathologies. We outlined different ongoing Mental Health Illness (MHI) needs and treatments for various pathologies. Patients with non-cancerous urologic pathologies had lower quality of life and higher incidence of MHI than the general population. As such, in line with the American Urological Association recommendations, psychological and social support from peers, therapists, and healthcare providers further prove to be crucial for some subpopulations. The review also yielded pathology specific interventions such as group therapy for ED patients. Given the higher incidence of MHI in the patient population after the Covid-19 pandemic, MHI awareness in the sphere of non-oncologic urology treatment continues to be crucial when creating a collaborative treatment platform for patients.

Methamphetamine has been labeled "America's most dangerous drug" and has received significant public health attention. Stimulant addiction and tolerance are heavily documented in the literature; increasingly larger doses maintain euphoria in short time periods to withstand stimulant tolerance. Stimulant deaths are high in the United States and abroad. Between 2013 and 2019, deaths related to methamphetamine use quadrupled from 3,616 to 16,127. Methamphetamine use increased four-fold from 2015 to 2016. Due to this increase in methamphetamine use and its associated medical complications, the mortality rate associated with methamphetamine use has doubled over the past ten years. Cardiopulmonary symptoms include chest pain, palpitations, and shortness of breath. Methamphetamine-related myocardial infarction can also occur. Central nervous system symptoms include agitation, anxiety, delusions, hallucinations, and seizures. Methamphetamine-induced psychosis may unmask underlying psychiatric disorders. It can also cause cerebral vasculitis, which elicits cortical blindness and ischemic strokes. Methamphetamine-induced neurotoxicity in serotonergic systems is more diffuse, involving the striatum, hippocampus, septum, amygdala, and hypothalamus leading to mood changes, psychosis, and memory impairment. This narrative review will aim to highlight the adverse effects as well as the toxicity that can occur with methamphetamine use.

Ketamine is a common medical anesthetic and analgesic but is becoming more widely used as a recreational drug. Significant side effects on the urinary tract are associated with frequent recreational ketamine use most notably ketamine-induced cystitis (KIC). Regular ketamine consumption has been shown to increase the risk of cystitis symptoms by 3- to 4-fold, and cessation of ketamine use is usually associated with improvement of symptoms. Common KIC-related problems are urinary pain and discomfort, bladder epithelial barrier damage, reduced bladder storage and increased pressure, ureter stenosis, and kidney failure, all of which significantly impact patients' quality of life. Furthermore, it becomes a vicious cycle when KIC patients attempt to manage their urinary pain with increased ketamine use. The precise pathophysiology of KIC is still unknown but several theories exist, most of which highlight the inflammatory signaling pathways leading to bladder epithelium damage due to presence of ketamine in the urine. Empirical treatment options for KIC are available and consist of ketamine cessation, noninvasive therapies, and surgery, and should be decided upon based on the time course and severity of the disease. Of note, cessation of use is strongly recommended for all KIC patients, and should be supplemented with motivational interviews and psychological and social support. It is crucial for clinicians to be familiar with KIC diagnosis and treatment, and to be prepared to have informed discussions with ketamine-using patients about the potential health consequences of ketamine.

# Background Vasectomy is a procedure that results in permanent yet reversible sterility and remains a great contraceptive option for many. Previous research studies have highlighted frequency of vasectomy utilization, defining characteristics of individuals who opt for this method, various surgical techniques, and the risks and benefits associated with the procedure. What remains to be defined is why or why not individuals may experience post-vasectomy regret and whether the previous characteristics correlate. # Objective The objective of this review is to synthesize information regarding reasons individuals may regret their vasectomy and seek reversal, what options exist for accomplishing the reversal, and patients' fertility prognosis post-vasovasostomy. # Methods This review utilized a combination of secondary and tertiary data analysis across a wide scope of academic databases pertaining to the topic of interest. # Results Typically, most males who have sought a vasectomy are satisfied with their decision, however, approximately 6% of this population seeks reversal. Key factors influencing vasectomy regret include age at the time of vasectomy, parental status, pre- and post-operative relationship status, unresolved physical and psychosexual problems, and development of chronic scrotal pain following the procedure. Few options exist for vasectomy reversal including microsurgical reconstructive vasectomy reversal (VR) and sperm extraction for in vitro fertilization. There is no guarantee that fertility will be restored in any case but a major predictive factor for success is the time interval prior to reversal. # Conclusion Vasectomy is intended to be a permanent form of contraception; however, a minor chance remains that individuals may experience post-operative regret due to various factors. This warrants proper comprehensive counseling by the patient's provider regarding benefits and risks, procedural outcomes, opportunities for reversal, and fertility prognosis.

Urologic procedures (both open and minimally invasive) can cause pain due to the surgery itself, devices placed, and post-operative issues. Thus, pain management is important for every post-procedure recovery period. Opioid use post-surgery is common and often over-prescribed contributing to persistent use by patients. In this article, we review the extent of opioid use in pediatric urologic procedures, vasectomy, endourologic procedures, penile implantation, urogynecologic procedures, prostatectomy, nephrectomy, cystectomy, and scrotal/testicular cancer surgery. Generally, we have found that institutions do not have a standardized protocol with a set regimen to prescribe opioids, resulting in more opioids being prescribed than needed and patients not properly disposing of their unused prescriptions. However, many institutions recognize their opioid overuse and are implementing new multimodal opioid-sparing analgesics methods such as non-opioid peri-operative medications, minimally invasive robotic surgery, and nerve blocks or local anesthetics with varying degrees of success. By shedding light on these opioid-free methods and prescription protocols, along with improved patient education and counselling, we hope to bring awareness to institutions and decrease unnecessary opioid use.

COVID-19 caused a drastic change in clinical medicine around the globe. In the United States, telemedicine was rapidly adopted on a wide scale to minimize direct patient interaction and to reduce the spread of the COVID-19 virus. Telemedicine also went hand in hand with the rapid movement of working remotely. This has provided several challenges to chronic pain management clinics along with other subspecialties. Telemedicine has also opened opportunities for providing valuable care for patients with significant barriers to healthcare professionals. Given the benefits and downfalls of telemedicine, it is ultimately up to the provider who has an established patient-physician relationship and best understands the patient's limitations and healthcare needs who can best determine which patient population telemedicine is appropriate for and how frequently it can be utilized for each individual patient.

Gender dysphoria is defined by severe or persistent distress associated with an incongruence between one's gender identity and biological sex. It is estimated that 1.4 million Americans and 25 million people worldwide identify as transgender and that 0.6% of Americans experience gender dysphoria. The pathophysiology of gender dysphoria is multifactorial and incompletely understood. Genetics, androgen exposure, neuroanatomy, brain connectivity, history of trauma, parents with psychological disorders, and being raised by less than two parents are associated with gender dysphoria. Gender dysphoria most frequently presents in early teenage years but can present earlier or later. Anxiety and depression are the two most common comorbid diagnoses and may be the reason for presentation to medical care. Diagnosis is established through history and or validated questionnaires. Treatment includes psychosocial therapy, pharmacotherapy for underlying depression and/or anxiety, hormonal therapy, non-genital and/or genital feminization or masculinization operations. The frequency and severity of treatment related morbidity increases progressively as treatments go from conservative to more invasive. Gender dysphoria and its treatment is individualized and not completely understood.

# Purpose of Review Insomnia is a complex sleeping disorder that affects the lives of many individuals worldwide. Insomnia often occurs in the presence of coexisting comorbidities making it a complex disorder that requires a multifactorial approach to therapy. First-line therapy is cognitive-behavioral therapy for insomnia (CBT-I). Pharmacotherapy for insomnia falls into four classes based on mechanism of action: benzodiazepine receptor agonists (BZRAs), histamine receptor antagonists, melatonin receptor agonists, and dual orexin receptor antagonists (DORAs). # Recent Findings Daridorexant is a dual orexin type 1 and types 2 (OX~1~ and OX~2~) receptor antagonist that was recently approved by the US FDA for the treatment of adults suffering from insomnia. It was shown to be effective in reducing insomnia symptoms, increasing daytime functioning, and improving the overall quality of sleep. Daridorexant offers patients relief from insomnia while avoiding the severe side effects and dependency issues of traditional treatments like benzodiazepines and sedatives. # Summary In this article, we review the most recent data on insomnia treatments and summarize the safety and efficacy of daridorexant in treating insomnia.

Male sexual dysfunction is a series of conditions, most notably including erectile dysfunction (ED), Peyronie's disease (PD), and premature ejaculation (PE), defined by impaired sexual functioning. The prevalence of male sexual dysfunction increases with age and is relatively high with greater than 50% of men aged 40 to 70 describing some degree of erectile dysfunction. Risk factors for male sexual dysfunction include age, diabetes mellitus (DM), cancer, stroke, hypertension, penile trauma, depression, anxiety, and disturbance in central serotonin neurotransmission and 5-HT postsynaptic receptor functioning. Sexual questionnaires including the International Index of Erectile Dysfunction, Sexual Health Inventory for Men, and the Premature Ejaculation Diagnostic Tool are useful in screening for these disorders. Focused history and physical can establish diagnoses. For a condition to be diagnosed as male sexual dysfunction, the patient or their partner must view their sexual functioning as impaired. Treatment of male sexual dysfunction is etiology dependent. For ED, first-line therapy is a phosphodiesterase-5 inhibitor or mental health care for psychogenic ED. More complicated cases may be treated with injections, surgery, or shockwave therapy. PD is either treated with medications for pain management, collagenase clostridium histolyticum injection, corpoplasty, plication, or shockwave therapy. PE may be treated behaviorally or with SSRIs as first line medication.

This article is a systematic review of mental health in urologic oncology patients with prostate cancer (PCa), bladder cancer (BC), renal cell carcinoma (RCC), testicular cancer (TC), or penile cancer (PeCa). For all pathologies, a focus on increasing quality of life post-treatment demonstrated a positive impact in reducing Mental Health Illness (MHI) prevalence. Cancer specific mental health care may be given to patients to reduce suicide risk in BC patients and sexual identify and masculinity counseling may improve mental health for TC or PeCa patients. In order to better accommodate patient’s mental health needs when undergoing GU cancer treatment, we recommend incorporation of mental health metrics such as questionnaires to assess early treatment of MHI, a greater emphasis on psychosocial support with the patient’s loved ones, peers, and healthcare team, alongside advising healthy habits such as exercise which has been shown to drastically reduce MHI incidence across all pathologies. We hope that these measures conducted by urologists and oncologists, alongside possible coordination with psychiatrists and psychologists for psychotherapy, psychopharmacology, and neuro-stimulation treatment modems may be helpful in the long term to reduce MHI incidence in urology oncology patients. Given the higher incidence of MHI in oncology patients and in the patient population after the Covid-19 pandemic, MHI awareness in the sphere of urologic oncologic treatment continues to be crucial when creating a collaborative treatment platform for patients.

Buprenorphine, a novel long-acting analgesic, was developed with the intention of two purposes: analgesia and opioid use disorder. Regarding its pharmacodynamics, it is a partial agonist at mu receptors, an inverse agonist at kappa receptors, and an antagonist at delta receptors. For the purpose of analgesia, three formulations of buprenorphine were developed: IV/IM injectable formulation (Buprenex®), transdermal patch formulation (Butrans®), and buccal film formulation (Belbuca®). Related to opioid dependence, the formulations developed were subcutaneous extended release (Sublocade®), subdermal implant (Probuphine®), and sublingual tablets (Subutex®). Lastly, in order to avoid misuse of buprenorphine for opioid dependence, two combination formulations paired with naloxone were developed: film formulation (Suboxone®) and tablet formulation (Zubsolv®). In this review, we present details of each formulation along with their similarities and differences between each other and clinical considerations.

Alzheimer's disease (AD) is the most common form of dementia affecting millions of individuals, including family members who often take on the role of caregivers. This debilitating disease reportedly consumes 8% of the total United States healthcare expenditure, with medical and nursing outlays accounting for an estimated \$290 billion. Cholinesterase inhibitors and N-methyl-D-aspartate receptor antagonists have historically been the most widely used pharmacologic therapies for patients with AD; however, these drugs are not curative. The present investigation describes the epidemiology, pathophysiology, risk factors, presentation, and current treatment of AD followed by the role of the novel monoclonal antibody, Adulhelm, in the treatment of AD. Currently, Adulhelm is the only Food and Drug Administration (FDA) approved drug that acts to slow the progression of this disease. Adulhelm is an anti-amyloid drug that functions by selectively binding amyloid aggregates in both the oligomeric and fibrillar states. Studies show Adulhelm may help to restore neurological function in patients with AD by reducing beta-amyloid plaques and reestablishing neuronal calcium permeability. At present, there is concern the magnitude of this drug's benefit may only be statistically significant, although not clinically significant. Despite skepticism, Adulhelm has proven to significantly decrease amyloid in all cortical brain regions examined. With such high stakes and potential, further research into Adulhelm's clinical efficacy is warranted in the treatment of AD.

Attention deficit hyperactivity disorder (ADHD) is the most common neurodevelopmental disorder in childhood. Current treatment options for ADHD include pharmacological treatment (stimulants, non-stimulants, anti-depressants, anti-psychotics), psychological treatment (behavioral therapy with or without parent training, cognitive training, neurofeedback), and complementary and alternative therapies (vitamin supplementation, exercise). Central nervous system (CNS) stimulants are the primary pharmacological therapy used in treatment; however, these stimulant drugs carry a high potential for abuse and severe psychological/physical dependence. Viloxazine, a non-stimulant medication without evidence of drug dependence, is a selective norepinephrine reuptake inhibitor that has historically been prescribed as an anti-depressant medication. The extended-release (ER) form was approved by the US Food and Drug Administration (FDA) in April 2021 for the treatment of ADHD in pediatric patients aged 6-17 years. Phase 2 and 3 randomized control trials have demonstrated significant efficacy of viloxazine in improving ADHD symptoms versus placebo. Related to its long-standing use as an antidepressant, the safety profile and pharmacokinetics of viloxazine are well understood. Viloxazine appears to be a suitable alternative to current standard-of-care pharmacotherapy for ADHD, but the further investigation remains to be done in comparing its efficacy to that of current treatments.

Multiple myeloma (MM) is a hematologic malignancy characterized by excessive clonal proliferation of plasma cells. The treatment of multiple myeloma presents a variety of unique challenges due to the complex molecular pathophysiology and incurable status of the disease at this time. Given that MM is the second most common blood cancer with a characteristic and unavoidable relapse/refractory state during the course of the disease, the development of new therapeutic modalities is crucial. Belantamab mafodotin (belamaf, GSK2857916) is a first-in-class therapeutic, indicated for patients who have previously attempted four other treatments, including an anti-CD38 monoclonal antibody, a proteosome inhibitor, and an immunomodulatory agent. In November 2017, the FDA designated belamaf as a breakthrough therapy for heavily pretreated patients with relapsed/refractory multiple myeloma. In August 2020, the FDA granted accelerated approval as a monotherapy for relapsed or treatment-refractory multiple myeloma. The drug was also approved in the EU for this indication in late August 2020. Of note, belamaf is associated with the following adverse events: decreased platelets, corneal disease, decreased or blurred vision, anemia, infusion-related reactions, pyrexia, and fetal risk, among others. Further studies are necessary to evaluate efficacy in comparison to other standard treatment modalities and as future drugs in this class are developed.

Migraine is a neurobiological headache disorder that affects around 16% of adults in the United States. Medical treatment of mild to moderate migraines include non-prescription non-steroidal anti-inflammatory drugs, acetaminophen, or aspirin and caffeine-containing combination analgesics. Additionally, moderate to severe migraines and those that are mild to moderate that have not responded to analgesics can be treated with triptans, which are drugs specific for migraine treatment. Non-pharmacological treatments include cognitive behavioral therapy and relaxation training. Medications for the prevention of migraines have also been developed since they are more affective in offsetting the symptoms. Ubrogepant’s high specificity and selectivity for calcitonin gene-related peptide (CGRP) sets it apart from certain other drugs, which previously limited the treatment of migraines with or without aura due to their decreased selectivity. The most frequently reported side effects are oropharyngeal pain, nasopharyngitis, and headache. Most studies found that participants receiving Ubrogepant were free from pain within 2 h when compared to placebo. Patients taking Ubrogepant should avoid taking it when pregnant or with end stage renal disease. In summary, Ubrogepant has good tolerability and an overall favorable safety profile. It appears to hold promise for the acute treatment of migraines with or without aura in adults.

Multiple sclerosis (MS) is a prevalent and debilitating neurologic condition characterized by widespread neurodegeneration and the formation of focal demyelinating plaques in the central nervous system. Current therapeutic options are complex and attempt to manage acute relapse, modify disease, and manage symptoms. Such therapies often prove insufficient alone and highlight the need for more targeted MS treatments with reduced systemic side effect profiles. Ozanimod is a novel S1P (sphingosine-1-phosphate) receptor modulator used for the treatment of clinically isolated syndrome, relapsing–remitting, and secondary progressive forms of multiple sclerosis. It selectively modulates S1P1 and S1P5 receptors to prevent autoreactive lymphocytes from entering the CNS where they can promote nerve damage and inflammation. Ozanimod was approved by the US Food and Drug Administration (US FDA) for the management of multiple sclerosis in March 2020 and has been proved to be both effective and well tolerated. Of note, ozanimod is associated with the following complications: increased risk of infections, liver injury, fetal risk, increased blood pressure, respiratory effects, macular edema, and posterior reversible encephalopathy syndrome, among others. Further investigation including head-to-head clinical trials is warranted to evaluate the efficacy of ozanimod compared with other S1P1 receptor modulators.

Parkinson’s disease (PD) is a common neurodegenerative disorder that leads to significant morbidity and disability. PD is caused by a loss of dopaminergic, cholinergic, serotonergic, and noradrenergic neurons in the central nervous system (CNS), and peripherally; the syndromic parkinsonism symptoms of movement disorder, gait disorder, rigidity and tremor are mostly driven by the loss of these neurons in the basal ganglia. Unfortunately, a significant proportion of patients taking levodopa, the standard of care treatment for PD, will begin to experience a decrease in effectiveness at varying times. These periods, referred to as “off episodes”, are characterized by increased symptoms and have a detrimental effect on quality of life and disability. Istradefylline, a novel adenosine A2A receptor antagonist, is indicated as a treatment addition to levodopa/carbidopa in patients experiencing “off episodes”. It promotes dopaminergic activity by antagonizing adenosine in the basal ganglia. This review will discuss istradefylline as a treatment for PD patients with off episodes.