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Our immune system acts to protect us in times of stress and traumatic injury. As part of the immune response, the body produces various cytokines, which mediate or modulate immune functions. Such cytokines include tumor necrosis factor (TNF) and interleukin 6 (IL-6) and IL-17. These cytokines can also act on the nervous system to influence pain perception. TNF-α triggers an inflammatory response and two forms of programmed cell death, apoptosis and necroptosis, depending on the pathological state. For individuals with chronic conditions relating to immune deficiency, the actions of these cytokines can present as chronic pain states, significantly altering quality of life. One attractive potential solution for treating this immune linked pain is by altering signaling pathways of pain-enhancing cytokines. Infliximab and etanercept are TNF inhibitors that are currently on the market for use in the treatment of chronic pain. Secukinumab and tocilizumab serve as IL inhibitors, utilized for a similar purpose. These novel immunotherapies have shown efficacy in numerous clinical studies with acceptable side effect profiles. In this review, we summarize the pharmacological profiles of these drugs and discuss their usage in treating chronic pain.

Worldwide, hypertension is the leading risk factor for cardiovascular disease and death. An estimated 122 million people, per the American Heart Association in 2023, have been diagnosed with this common condition. It is generally agreed that the primary goal in the treatment of hypertension is to reduce overall blood pressure to below 140/90 mmHg, with a more optimal goal of 130/80 mmHg. Common medications for treating hypertension include calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, beta-blockers, and diuretics. CCBs are one of the most widely studied agents and are generally recommended as first-line therapy alone and in combination therapies. This is largely based on the vast knowledge of CCB mechanisms and their minimal side effect profile. CCBs can be separated into two classes: dihydropyridine and non-dihydropyridine. Non-dihydropyridine CCBs act on voltage-dependent L-type calcium channels of cardiac and smooth muscle to decrease muscle contractility. Dihydropyridine CCBs act by vasodilating the peripheral vasculature. For many patients with only mild increases in systolic and diastolic blood pressure (e.g., stage 1 hypertension), the medical literature indicates that CCB monotherapy can be sufficient to control hypertension. In this regard, CCB monotherapy in those with stage 1 hypertension reduced renal and cardiovascular complications compared to other drug classes. Combination therapy with CCBs and angiotensin receptor blockers or angiotensin-converting enzyme inhibitors has been shown to be an effective dual therapy based on recent meta-analyses. This article is a review of calcium channel blockers and their use in treating hypertension with some updated and recent information on studies that have re-examined their use. As for new information, we tried to include some information from recent studies on hypertensive treatment involving calcium channel blockers.

Abstract Etizolam is a thienodiazepine derivative which produces an anxiolytic effect similar to benzodiazepines such as alprazolam (Xanax). Like classic benzodiazepines, etizolam has a high affinity towards the GABAA receptor, and allosterically potentiates the effects of GABA resulting in neuronal hyperpolarization related to chloride influx. When taken in therapeutic doses, etizolam produces a similar effect to Xanax. Counterfeit Xanax tablets contain variable amounts of etizolam. Tablets with high amounts of etizolam can cause toxicity if ingested, especially when combined with other substances. When toxic symptoms occur in patients, they may include severe sedation, unconsciousness, and depression of the medullary respiratory center. In this regard, there is the potential for death. Additionally, the rise in fake Xanax tablets containing etizolam and other counterfeit medications has been exacerbated by the difference in regulations regarding these substances in different countries as well as the illegal drug trade. Healthcare providers may also play a role through the over- or underprescribing of certain medications. Thus, in order to combat the rise in counterfeit medications such as fake Xanax, international cooperation, regulation, and enforcement of laws pertaining to the manufacture, prescription, and distribution of these substances are needed.

Abstract Chronic pain, a complex and debilitating condition, involves intricate interactions between central and peripheral inflammatory processes. Cytokines, specifically tumor necrosis factor (TNF) and interleukins (IL), are key mediators in the initiation and maintenance of chronic pain states. Sensory neurons expressing receptors for cytokines like TNF, IL-1, and IL-6 are implicated in peripheral sensitization, contributing to increased signaling of painful sensations. The potential of targeting TNF and IL for therapeutic intervention in chronic pain states is the focus of this review, with preclinical and clinical evidence supporting the use of TNF and IL modulators for pain management. The physiological and pathological roles of TNF in neuropathic pain is complex. Experimental evidence highlights the effectiveness of TNF modulation in mitigating pain symptoms in animal models and displays promising outcomes of clinical trials with TNF inhibitors, such as infliximab and etanercept. ILs, a diverse group of cytokines, including IL-1, IL-6, and IL-17, are discussed for their contributions to chronic pain through inflammation and peripheral sensitization. Specific IL modulators, such as secukinumab and tocilizumab, have shown potential in managing chronic neuropathic pain, as demonstrated in various studies and clinical trials. The pharmacokinetics, safety profiles, and challenges associated with TNF and IL modulators highlight the need for cautious medication monitoring in clinical practice. Comparative evaluations have revealed distinct efficacy and safety profiles among different cytokine modulators, emphasizing the need for personalized approaches based on the specific underlying causes of pain. Further research is necessary to elucidate the intricate mechanisms by which cytokines contribute to chronic pain, as well as to understand why they may affect pain differently in various contexts. Additionally, long-term safety profiles of cytokine modulators require more thorough investigation. This continued exploration holds the promise of enhancing our comprehension of cytokine modulation in chronic pain and shaping more potent therapeutic strategies for the future.

Neuropathic pain is an increasingly common disease affecting millions of individuals worldwide. Refractory pain poses a significant impact on patients’ quality of life, financial and economic stability, and social interaction. Numerous effective modalities for treatment of refractory neuropathic pain are presently available. Currently, many options provide symptomatic treatment but are associated with an unfavorable side effect profile and increased risk of addiction. The present investigation reviews current medical management for refractory neuropathic pain including the use of antidepressants, anticonvulsants, gabapentinoids and opioid therapy, as well as interventional pain procedures such as spinal cord stimulation (SCS) and intrathecal targeted drug delivery. While multidisciplinary management with lifestyle modification and pharmacologic regimens remains at the forefront of treating many of these patients, interventional modalities are growing in popularity and have been demonstrated to be highly efficacious. In this regard, continued understanding of the pathophysiology surrounding refractory neuropathic pain has led to the development of interventional procedures and better outcomes for patients suffering from refractory neuropathic pain. When and if patients fail conservative therapy, interventional techniques are desirable alternatives for pain management. SCS and intrathecal targeted drug delivery are important tools for the treatment of refractory neuropathic pain. In summary, treatment modalities for refractory neuropathic pain are evolving with demonstrated efficacy. This review aims to outline the efficacy of various interventional procedures for refractory neuropathic pain in comparison to traditional drug therapies.

Acromegaly is a condition most commonly diagnosed in the fifth decade of life and has numerous treatment options. In this regard, Mycapssa® is the first FDA-approved oral octreotide capsule for treating acromegaly, combining the efficacy of the somatostatin receptor ligand, octreotide, with the ease of a twice-daily oral capsule. Where surgical treatment is not an option, somatostatin analogs, including octreotide, are the first line of medical treatment for acromegaly, requiring regular subcutaneous or intramuscular injections administered by a patient’s healthcare provider. Octreotide capsules (Mycapssa®) provide an alternative to these somatostatin receptor ligand injections by combining octreotide with other excipients to produce a transient permeability enhancer technology that improves paracellular transport of octreotide across the gastrointestinal wall into the small intestine. Across multiple trials, including open-label (CH-ACM-01), double-blind placebo-controlled (CHIASMA OPTIMAL), and open-label extension of the trial period (CHIASMA OPTIMAL OLE), Mycapssa® octreotide capsules maintained a consistent biochemical normalization of IGF-1 and GH levels, safety profiles similar to injected somatostatin receptor ligands, and patient preference to continued treatment with octreotide capsules. While clinical trial data supports the use of octreotide capsules (Mycapssa®) in the pharmacological management of GH and IGF-1 levels, very little data exist regarding the drug’s efficacy, tolerability, and use in female or pediatric-specific populations. A better understanding of the efficacy, application, and role of oral octreotide capsules in the long-term medical management of acromegaly in a diversity of populations is imperative to best determine the risks/benefits for the clinician.

Abstract Tianeptine is an antidepressant drug approved for the treatment of major depressive disorder in countries other than the US. It is classified as an atypical tricyclic antidepressant and has shown potential benefits in addressing anxiety and irritable bowel disease. However, it is important to note that tianeptine is not approved for any use by the United States Federal Drug Administration (FDA). Despite its lack of approval by the FDA, tianeptine has been distributed online and at small retail locations. The term “gas station drugs” refers to a wide range of substances typically available for purchase from gas stations, corner stores, bodegas, mini marts, smoke shops, and the Internet. These substances may be produced commercially by drug manufacturers or in clandestine laboratories to mimic the effects of more well-known illicit/controlled substances such as marijuana, cocaine, opioids, etc. Tianeptine has made its way to convenience stores and gas station shelves, branded as “Zaza” and “Tianna Red.” It can also be obtained online from independent vendors without a prescription. Misuse of tianeptine can lead to euphoric, opioid-like highs with the potential for chronic users to develop dependence and tolerance. Overdose and use in suicide attempts have also been documented. This manuscript is a narrative review, highlighting the dangers of tianeptine and other gas station drugs and underscoring the urgent need to regulate these substances.

Abstract Introduction Chronic refractory low back and lower extremity pain recalcitrant to conservative management and epidural injections secondary to postsurgery syndrome, spinal stenosis, and disc herniation are sometimes managed with percutaneous adhesiolysis. Consequently, this systematic review and meta-analysis was undertaken to assess the efficacy of percutaneous adhesiolysis in managing low back and lower extremity pain. Methods A systematic review and meta-analysis of randomized controlled trials (RCTs) utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist was performed. A comprehensive literature search of multiple databases from 1966 to July 2022, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included trials, meta-analysis, and best evidence synthesis was performed. The primary outcome measure was a significant reduction in pain (short term up to 6 months and long term more than 6 months). Results The search identified 26 publications, with 9 trials meeting the inclusion criteria. The results of dual-arm and single-arm analyses showed significant improvement in pain and function at 12 months. Opioid consumption was also significantly reduced at 6 months with dual-arm analysis, whereas single-arm analysis showed a significant decrease from baseline to treatment at the 3-, 6-, and 12-month analyses. At 1 year follow-up, seven of seven trials were positive for improvements in pain relief, function, and diminution of opioid use. Discussion Based on the present systematic review of nine RCTs, the evidence level is I to II, with moderate to strong recommendation for percutaneous adhesiolysis in managing low back and lower extremity pain. The limitations of the evidence include paucity of literature, lack of placebo-controlled trials, and the majority of the trials studying post lumbar surgery syndrome. Conclusion The evidence is level I to II or strong to moderate based on five high-quality and two moderate-quality RCTs, with 1 year follow-up that percutaneous adhesiolysis is efficacious in the treatment of chronic refractory low back and lower extremity pain.

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common neurodevelopmental disorders, characterized by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), which is marked by symptoms such as inappropriate levels of inattention, hyperactivity, and impulsivity that can affect academic, social, and personal functioning in children and adolescents. This review summarizes clinical trials demonstrating the effectiveness of Alpha-2 agonists in reducing symptoms of inattention, hyperactivity, and impulsivity in children with ADHD. Studies were identified through a systematic search of PubMed and Cochrane databases. However, these medications’ long-term safety and efficacy remain uncertain, with a lack of data on their effects on growth, cardiovascular function, and other adverse events. Further studies are required to determine these medications’ optimal dose and treatment duration. Methods: Medications that target the noradrenergic system, such as Alpha-2 agonists, have been increasingly used as a treatment option for ADHD, with guanfacine and clonidine being two of the most commonly used medications. They function by selectively targeting Alpha-2 adrenergic receptors in the brain leading to improved attention and reduced hyperactivity and impulsivity symptoms in children with ADHD. Results: Clinical trials have demonstrated the effectiveness of Alpha-2 agonists in treating ADHD in children by reducing symptoms of inattention, hyperactivity, and impulsivity. However, these medications’ long-term safety and efficacy still need to be completely understood. Due to a lack of information on the effects of Alpha-2 agonists on growth, cardiovascular function, and other long-term adverse events, more studies must investigate the optimal dose and treatment duration for these medications. Conclusions: Despite these concerns, Alpha-2 agonists remain a valuable treatment option for ADHD in children, especially those unable to tolerate stimulant medications or who have coexisting conditions such as tic disorders. Future research should continue to explore the safety and efficacy of Alpha-2 agonists in the long term. In conclusion, Alpha-2 agonists show promise as a treatment for ADHD in children; however, the safety and efficacy of these drugs in the long term are not yet completely understood. Additional studies are required to investigate the optimal dose and treatment duration for these medications in their use as a treatment for this debilitating disease.

Palliative care is intended to relieve caregivers of physical, psychological, and even spiritual elements of care. One of the most prevalent issues facing this form of care is a lack of healthcare resources and structures to deal with an aging population. This aging population is placing a strain on the healthcare system, prompting a need for a shift in system management. A potential answer to this issue may be the Multi-Agent System (MAS). This category of computerized networking system was created by programmers to gather relevant health information on a patient and allow for the system to act with other agents to decide the best course for disease management. It can also allow for a multidisciplinary healthcare team to make more informed plans of actions for their patients by providing accurate and up-to-date information resulting from a greater synergetic mesh. MASs could fulfill the demands of a rising chronic illness population and deliver high-quality care, indicating a major paradigm shift within the US. In this review, we will evaluate the aging population and contributing factors, palliative care and the need for the multi-agent system, and clinical considerations involving examples from healthcare systems both on and beyond US shores.

Telemedicine, telehealth, and E-health all offer significant benefits for pain management and healthcare services by fostering the physician–patient relationship in otherwise challenging circumstances. A critical component of these artificial-intelligence-based health systems is the “agent-based system”, which is rapidly evolving as a means of resolving complicated or straightforward problems. Multi-Agent Systems (MAS) are well-established modeling and problem-solving modalities that model and solve real-world problems. MAS’s core concept is to foster communication and cooperation among agents, which are broadly considered intelligent autonomous factors, to address diverse challenges. MAS are used in various telecommunications applications, including the internet, robotics, healthcare, and medicine. Furthermore, MAS and information technology are utilized to enhance patient-centered palliative care. While telemedicine, E-health, and MAS all play critical roles in managing chronic pain, the published research on their use in treating chronic pain is currently limited. This paper discusses why telemedicine, E-health, and MAS are the most critical novel technologies for providing healthcare and managing chronic pain. This review also provides context for identifying the advantages and disadvantages of each application’s features, which may serve as a useful tool for researchers.

Background: Exogenous melatonin is commonly used to treat insomnia, other sleep problems, and numerous medical illnesses, including Alzheimer’s disease, autism spectrum disorder, and mild cognitive impairment in adults and children. There is evolving information regarding issues with the use of chronic melatonin. Methods: The present investigation was a narrative review. Results: Melatonin usage has risen dramatically in recent years. Many countries only allow melatonin prescriptions. In the United States (U.S.), it is classified as a dietary supplement accessible over the counter and can be derived from animals, microorganisms, or, most commonly, made synthetically. No regulatory agency oversees its manufacturing or sale in the U.S. melatonin concentration of marketed preparations varies widely between product labels and manufacturers. Melatonin’s ability to induce sleep is detectable. However, it is modest for most people. Sleep length appears to be less important in sustained-release preparations. The optimal dosage is unknown, and routinely used amounts vary substantially. Melatonin’s short-term negative effects are minimal, resolve at medicine cessation, and do not usually prevent usage overall. Much research on long-term melatonin administration has found no difference between exogenous melatonin and placebo in terms of long-term negative effects. Conclusion: Melatonin at low to moderate dosages (approximately 5–6 mg daily or less) appears safe. Long-term usage appears to benefit certain patient populations, such as those with autism spectrum disorder. Studies investigating potential benefits in reducing cognitive decline and increased longevity are ongoing. However, it is widely agreed that the long-term effects of taking exogenous melatonin have been insufficiently studied and warrant additional investigation.

While driving under the influence of drugs, drivers are more likely to be involved in and cause more accidents than drivers who do not drive under the influence. Ketamine is derived from phencyclidine and acts as a noncompetitive antagonist and allosteric modulator of N-methyl-D-aspartate receptors. Ketamine has been used to treat a variety of psychiatric disorders, with the most notable being treatment-resistant depression. With the rise of at-home ketamine treatment companies, the safety of unsupervised administration remains under evaluation. A study with ketamine and a ketamine-like medication, rapasitnel, showed that those who were given ketamine experienced more sleepiness and had decreased self-reported motivation and confidence in their driving abilities. Moreover, there seem to be significant differences in the acute versus persistent effects of ketamine, as well as the anesthetic versus subanesthetic doses, both in terms of effects and outcomes. These divergent effects complicate the clinical uses of ketamine, specifically involving driving, drowsiness, and cognitive abilities. This review aims to describe not only the various clinical uses of ketamine but also the potentially detrimental effects of driving under the influence, which should be understood to help with counseling the patients who use these substances, both for their well-being and to protect public safety.

Vocal fold implants (VFI) are used to manage glottis insufficiency, restore proper vocal cord functioning, and prevent aspiration. Implants with different physical properties are made from various materials. Patients with VFI present challenging airways. Perioperative physicians should recognize several considerations when confronting airway management in the setting of VFI. A preoperative assessment of patients with a VFI by a multidisciplinary team specialized in airway management is crucial. The best-fitting endotracheal tube and intubation technique can minimize the risk of implant displacement. The present investigation provides different options for airway management in the setting of VFI and describes solutions for special situations such as lung isolation and difficult intubation. An algorithm is presented as a visual tool to help anesthesiologists who encounter such patients for safe airway management while preserving the VFI.

Heavy societal stigma of certain conditions has created an environment where individuals may be hesitant to seek professional care. Urology is a specialized field that focuses on many of these conditions that society has deemed taboo to discuss. In this review, we address barriers that have prevented patients from seeking urologic care in order to better understand and elucidate important concerns within development of the physician-patient relationship. Recognizing these concerns can also assist in public health outreach approaches to motivate patients for seeking urologic care. The scope of this review was limited to three highly prevalent conditions affecting both men and women, including urinary incontinence, erectile dysfunction, and genitourinary syndrome of menopause.

The increasing prevalence of stimulant use disorder (StUD) involving methamphetamine and cocaine has been a growing healthcare concern in the United States. Cocaine usage is associated with atherosclerosis, systolic and diastolic dysfunction, and arrhythmias. Furthermore, approximately one of every four MIs is cocaine-induced among patients aged 18 to 45. Methamphetamine use has been associated with nerve terminal damage in the dopaminergic system resulting in impaired motor function, cognitive decline, and co-morbid psychiatric disorders. Current treatment options for StUD are extremely limited, and there are currently no FDA-approved pharmacotherapies. Behavioral interventions are considered first-line treatment; however, in a recent meta-analysis comparing behavioral treatment options for cocaine, contingency management programs provided the only significant reduction in use. Current evidence points to the potential of various neuromodulation techniques as the next best modality in treating StUD. The most promising evidence thus far has been transcranial magnetic stimulation which several studies have shown to reduce risk factors associated with relapse. Another more invasive neuromodulation technique being studied is deep-brain stimulation, which has shown promising results in its ability to modulate reward circuits to treat addiction. Results showing the impact of transcranial magnetic stimulation (TMS) in the treatment of StUD are limited by the lack of studies conducted and the limited understanding of the neurological involvement driving addiction-based diseases such as StUD. Future studies should seek to provide data on consumption-reducing effects rather than craving evaluations.

Abstract Introduction The COVID-19 pandemic resulted in major disruptions in all aspects of human life including a decline of medical services utilized during 2020. An analysis of the impact of COVID-19 pandemic showed an 18.7% reduction in utilization patterns of interventional techniques in managing chronic pain in the Medicare population from 2019 to 2020. However, specific changes in utilization patterns of facet joint interventions have not been studied. Thus, we sought to assess the utilization patterns including an update of facet joint interventions from 2018 to 2020, with analysis of the impact of COVID-19 pandemic in managing chronic spinal pain utilizing facet joint interventions in the fee-for-service Medicare population of the United States. Methods The present investigation was designed to assess utilization patterns and variables of facet joint interventions, in managing chronic spinal pain from 2010 to 2020 in the fee-for-service (FFS) Medicare population in the United States (US), and how the COVID-19 pandemic impacted these utilization patterns. Data for the analysis were obtained from the master database from the Centers for Medicare & Medicaid Services (CMS) physician/supplier procedure summary from 2000 to 2020. Results Results of this analysis showed significant impact of COVID-19 with overall decrease of 18.5% of all facet joint interventions per 100,000 Medicare population compared to 20.2 and 20.5% decrease for lumbar and cervical facet joint injections, 15 and 13.1% decrease per 100,000 Medicare population of lumbosacral and cervicothoracic facet joint neurolysis procedures. The results are significant in that comparative analysis from 2000 to 2010 and 2010 to 2019 showing an annual increase of 14.4 vs. 2.2%, illustrating a decelerating pattern. There were also significant growth patterns noted with decreases in facet joint injections and nerve blocks compared to facet joint neurolytic procedures. Conclusions This analysis shows a significant effect of COVID-19 producing an overall decrease in utilization of facet joint interventions relative to pre-COVID data. Further, the analysis demonstrates continued deceleration of utilization patterns of facet joint interventions compared to the periods of 2000–2010 and 2010–2019.

Abstract Since the early 2010s, synthetic opioids have significantly contributed to overall opioid-related overdose mortalities. For point of reference, of the 68,630 opioid-related deaths recorded in 2020, 56,516 involved synthetic opioids. During much of this period, fentanyl has been the most commonly used synthetic opioid. This time when fentanyl was the most popular opioid has been called the “third wave” of the opioid crisis, partly because it led to a sharp rise in deaths from overdoses. Other synthetic opioids, such as carfentanil, protonitazene, and isotonitazene, have also become more widely diverted for nonmedical used. Carfentanil is an even more potent fentanyl derivative that was initially used in the mid-1980s as a general anesthetic for large animals such as elephants. Related to its strong affinity for mu opioid receptors, carfentanil is still utilized in medicine and science today as a radiotracer for positron emission tomography imaging. Protonitazene and isotonitazene belong to a novel class of synthetic opioids called benzimidazoles that were manufactured in the 1950s as novel analgesics. These agents have come under recent scrutiny as designer synthetic opioids becoming more prevalent. However, to date, there is incomplete data regarding the prevalence of synthetic opioids, as traditional toxicology screenings may not be sensitive to detect these compounds at such low doses post-mortem, particularly when blood is drawn from the periphery instead of central tissues such as the brain, lung, or heart. This narrative review aims to highlight the clinical challenges presented by these new synthetic opioids.

Abstract Introduction Pain is a global phenomenon encompassing many subtypes that include neuropathic, musculoskeletal, acute postoperative, cancer, and geriatric pain. Traditionally, opioids have been a mainstay pharmacological agent for managing many types of pain. However, opioids have been a subject of controversy with increased addiction, fatality rates, and cost burden on the US healthcare system. Cannabinoids have emerged as a potentially favorable alternative or adjunctive treatment for various types of acute and chronic pain. This narrative review seeks to describe the efficacy, risks, and benefits of cannabinoids as an adjunct or even potential replacement for opioids in the treatment of various subtypes of pain. Methods In June of 2022, we performed a comprehensive search across multiple databases for English-language studies related to the use of cannabinoids in the treatment of various types pain: neuropathic pain, musculoskeletal pain, acute postoperative pain, cancer pain, and geriatric pain. Data from meta-analyses, systematic reviews, and randomized control trials (RCTs) were prioritized for reporting. We sought to focus our reported analysis on more recent literature as well as include older relevant studies with particularly notable findings. Results There is conflicting evidence for the use of cannabinoids in the management of pain. While cannabinoids have shown efficacy in treating specific chronic pain subtypes such as neuropathic pain, fibromyalgia pain, and geriatric pain, they do not show as clear benefit in acute postoperative and the majority of musculoskeletal pain syndromes. Data trends towards cannabinoids having a positive effect in treating cancer pain, but results are not as conclusive. To date, there is a paucity of data comparing cannabinoids directly to opioids for pain relief. Overall, the side effects of cannabinoids appear to be relatively mild. However, there is still potential for addiction, altered brain development, psychiatric comorbidities, and drug–drug interactions. Conclusion Cannabinoids may be effective in specific subtypes of pain, but current evidence and guidelines do not yet support its use as the first-line treatment for any type of acute or chronic pain. Rather, it may be considered a good adjunct or alternative for patients who have failed more typical or conservative measures. Additional studies are needed with standardized forms of cannabinoids, route of delivery, and dosing for greater-powered analysis. Providers must weigh the individualized patient risks, benefits, and concurrent medication list in order to determine whether cannabinoids are appropriate for a patient’s pain treatment plan.

Objectives The potentially different effects of commonly used anaesthetic agents propofol and sevoflurane on T-cell immune function and Th cell differentiation were investigated in patients with severe mycoplasmal pneumonia (SMPP) undergoing fibreoptic bronchoscopy.Methods Sixty children (2–12 years of age) with SMPP were randomized into the sevoflurane group and the propofol group. Patients in the sevoflurane group were anaesthetised with inhalational sevoflurane and intravenous remifentanil. Patients in the propofol group were anaesthetised with intravenous propofol and remifentanil. Patients in both groups underwent fibreoptic bronchoscopy and lavage therapy. We compared the clinical outcomes, cellular immunity function, and Th cell differentiation into Th1 and Th2 levels in both groups.Results There was no significant difference in clinical outcomes and hospital stay between the two groups (7.94 vs 7.36, p > .05). However, the CD3+ T cells, CD4+ T cells, and CD4+/CD8+ in the propofol group were significantly higher than those in the sevoflurane group (T1 51.96 vs 48.33, T2 58.08 vs 55.31, p

Lower Urinary Tract Symptoms (LUTS) are frequently present in the general population as patients age with approximately a third of individuals experiencing LUTS during their lifetime. LUTS can be further defined as having any of the following symptoms: urinary hesitancy, straining, nocturia, increased urination frequency, and dysuria. LUTS has the potential for patients to contribute their symptoms to what can normally occur as we age. This can lead to a decrease in patients seeking care and could negatively impact patients’ health-related quality of life (HRQL). In conjunction with LUTS, we obtained from our analysis that LUTS and depression are closely related and worsening depressive symptoms may increase the severity of LUTS. We also discerned three categories of factors that can yield major depression namely adversity, internalizing, and externalizing factors. Within these categories, trauma, social support, genetic factors, and minimal education appeared to increase the risk of depression in patients. With the recent increase in mental health awareness and more access to mental health care amid the COVID-19 Pandemic, further screening, and collaboration between providers to treat both urological and psychiatric symptoms could improve patient outcomes. It is important for providers to have an increased understanding of the mental and physical impact both LUTS and depression can have on patients’ wellbeing. This has the potential to help patients be more open about their symptoms with the aim of better addressing LUTS and depression to positively impact their HRQL.

Bupropion had been in use since the late 1980s as an unconventional treatment for depression. Unlike other antidepressants, bupropion has no serotonergic activity and inhibits the reuptake of norepinephrine and dopamine. The drug has been used to treat depression, Attention Deficit Hyperactivity Disorder (ADHD), and smoking cessation. This investigation reviews the pharmacokinetic and pharmacodynamic effects of bupropion and its mechanisms of action and interactions with other drugs. We evaluated the efficacy of major on and off-label uses of bupropion, focusing on the indications, benefits, and adverse effects. Our review demonstrates that bupropion is superior to placebo and non-inferior to SSRIs such as escitalopram in treating major depressive disorder. More research is needed to determine positive patient-centered outcomes such as increases in quality of life. In the case of ADHD, the evidence for efficacy is mixed with poorly conducted randomized clinical trials, small sample sizes, and a lack of long-term assessments. The same is true in the case of bipolar disorder in which there is still limited and controversial data available on bupropion's safety and efficacy. In the case of smoking cessation, bupropion is found to be an effective anti-smoking drug with synergistic benefits when used as a combination therapy. We conclude that bupropion has the potential to provide benefit for a subset of patients who do not tolerate other typical antidepressants or anti-smoking therapies or for those whose treatment goals align with bupropion's unique side effect profile, such as smokers who wish to quit and lose weight. Additional research is needed to determine the drug's full clinical potential, particularly in the areas of adolescent depression and combination therapy with varenicline or dextromethorphan. Clinicians should use this review to understand the varied uses of the drug and identify the situations and patient populations in which bupropion can lend its greatest benefit.

As tranquilizers, benzodiazepines have a wide range of clinical uses. Recently, there has been a significant rise in the number of novel psychoactive substances, including designer benzodiazepines. Flubromazolam(8-bromo-6-(2-fluorophenyl)-1-methyl-4H-[1,2,4]triazolo[4,3-a][1,4]benzodiazeZpine) is a triazolo-analogue of flubromazepam. The most common effects noted by recreational users include heavy hypnosis and sedation, long-lasting amnesia, and rapid development of tolerance. Other effects included anxiolysis, muscle-relaxing effects, euphoria, loss of control, and severe withdrawals. Clonazolam, or 6-(2-chlorophenyl)-1-methyl-8-nitro-4H-[1,2,4]triazolo[4,3-α]-[1,4]-benzodiazepine, is a triazolo-analog of clonazepam. It is reported to be over twice as potent as alprazolam. Deschloroetizolam (2-Ethyl-9-methyl-4-phenyl-6H-thieno[3,2-f][1,2,4]triazolo[4,3-a][1,4]diazepine) is part of the thienodiazepine drug class, which, like benzodiazepines, stimulates GABA-A receptors. Meclonazepam ((3S)-5-(2-chlorophenyl)-3-methyl-7-nitro-1,3-dihydro-1,4-benzodiazepin-2-one) is a designer benzodiazepine with additional anti-parasitic effects. Although it has proven to be an efficacious therapy for schistosomiasis, its sedative side effects have prevented it from being marketed as a therapeutic agent. The use of DBZs has been a subject of multiple recent clinical studies, likely related to increasing presence and availability on the internet drug market and lack of regulation. Many studies have aimed to identify the prevalence of DBZs and their effects on those using them. This review discussed these designer benzodiazepines and the dangers and adverse effects that the clinician should know.

Epilepsy is a complex neurological condition with numerous etiologies and treatment options. In a subset of these patients, sudden unexpected death can occur, and to date, there are numerous explanations as to the pathophysiological mechanisms and how to mitigate these catastrophic outcomes. Approximately 2.3 million Americans have epilepsy, and nearly 150,000 people develop the condition each year. Sudden unexpected death in epilepsy (SUDEP) accounts for 2–18% of all epilepsy-related deaths and this is equivalent to one death in 1000 person-years of diagnosed epilepsy. It is more common in young adults aged 20–45. Seizures in the past year; the absence of terminal remission in the last five years; increased seizure frequency, particularly GTCS; and nocturnal seizures are the most potent modifiable risk factors for SUDEP. Patients not receiving any antiepileptic drug therapy are at higher risk of SUDEP. Patient education on medication compliance; care plans for seizure clusters (rescue medicines); epilepsy self-management programs; and lifestyle changes to avoid seizure-triggering factors, including avoiding excessive alcohol use and sleep deprivation, should be provided by health care providers. Continued research into SUDEP will hopefully lead to effective interventions to minimize occurrences. At present, aggressive control of epilepsy and enhanced education for individuals and the public are the most effective weapons for combating SUDEP. This narrative review focuses on updated information related to SUDEP epidemiology; pathophysiology; risk factor treatment options; and finally, a discussion of important clinical studies. We seek to encourage clinicians who care for patients with epilepsy to be aggressive in controlling seizure activity and diligent in their review of risk factors and education of patients and their families about SUDEP.

Stimulants are effective in treating attention-deficit/hyperactivity disorder (ADHD). Psychiatrist Charles Bradley first made this discovery in 1937 when he found that children treated with amphetamines showed improvements in school performance and behavior. Between 1995 and 2008, stimulants to treat ADHD increased six-fold among American adults and adolescents at an annual rate of 6.5%. Stimulants without a prescription, known as nonmedical use or misuse, have also increased. The highest rates of nonmedical prescription drug misuse in the United States are seen most notably in young adults between 18 and 25 years, based on data from the Substance Abuse and Mental Health Services Administration in 2021. Aside from undergraduate students, nonmedical prescription stimulant use is prevalent among medical students worldwide. A recent literature review reported the utilization of stimulants without a prescription in 970 out of 11,029 medical students. The percentages of medical students across the country misusing stimulants varied from 5.2% to 47.4%. Academic enhancement, reported in 50% to 89% of college students with stimulant misuse, is the most common reason for nonmedical stimulant use. With the increasing use of stimulants among adolescents and adults, it is unclear what long-term outcomes will be since little data are available that describe differences in how side effects are experienced for prescribed and non-prescribed users. The present narrative review focuses on these adverse effects in this population and the reasonings behind misuse and nonmedical use.

# Purpose of Review Headaches, especially migraines, are one of the most pervasive neurological disorders affecting up to 15.9% of the population. Current methods of migraine treatment include lifestyle changes, pharmacologic, and minimally invasive techniques such as peripheral nerve stimulation (PNS) and pericranial nerve blocks (PNB). # Recent Findings PNBs are used to treat and prevent migraines and involves injection of local anesthetics with or without corticosteroids. PNBs include the greater occipital, supraorbital, supratrochlear, lesser occipital, auriculotemporal, sphenopalantine ganglion, and cervical root nerve blocks. Of the PNBs, the most extensively studied is the greater occipital nerve block (GONB) which has been shown to be an efficacious treatment for migraines, trigeminal neuralgia, hemi-crania continua, and post-lumbar puncture, post-concussive, cluster, and cervicogenic headaches but not medication overuse and chronic tension type headaches. # Summary In this review, we aim to summarize the recent literature on PNBs and their efficacy in the treatment of migraines including a brief discussion of peripheral nerve stimulation.

Burning mouth syndrome is a condition characterized by a painful burning sensation in the oral mucosa lasting at least 3-6 months with no definitive etiology. The pathophysiology is not well understood, though there appears to be a connection with other neuropsychiatric conditions such as depression, anxiety, and mood disorders. We briefly discuss our experience with a patient who suffered from this conidtion and how it was treated with mandibular and maxillary nerve blocks after failing more conservative pharmacological options.

# Purpose of Review Meralgia paresthetica (MP) is a condition characterized by paresthesias, neuropathic pain, and alterations in sensorium of the anterolateral thigh secondary to impingement of the lateral femoral cutaneous nerve (LFCN). MP is generally diagnosed by clinical history and is often a diagnosis of exclusion. When diagnosis remains a challenge, diagnostic modalities such as ultrasound, MRI, electromyography, and nerve conduction studies have been utilized as an adjunct. This review summarizes the most recent medical literature regarding MP, its pathophysiology, presentation, and current treatment options. # Recent Findings Treatment options for patients with MP range from lifestyle modifications and conservative management to surgical procedures. Initial management is often conservative with symptoms managed with medications. When conservative management fails, the next step is regional blocks followed by surgical management. The conflicting data for treatment options for MP highlight how the evidence available does not point to a single approach that's universally effective for treating all patients with MP. # Summary Despite the apparent success at treating MP with regional blocks and surgical interventions, much remains to be known about the dosing, frequency, and optimal interventions due to the inconclusive results of current studies. Further research including randomized controlled trials are needed to better understand the most optimal treatment options for MP including studies with a larger number of participants.

Recently dubbed Long COVID or Long-Haul COVID, those recovering from the initial COVID-19 infection may maintain clinical signs for longer than two or more weeks following the initial onset of the infection. The virus can gain entry into the CNS through axonal transport mediated through the olfactory nerve or hematogenous spread and can also cross the blood–brain barrier to access the temporal lobe and the brainstem. The neurologic and neuropsychiatric symptoms associated with COVID-19 patients are becoming a highly studied area due to the increased frequency of reported cases. Multiple hospital case series and observational studies have found a headache to be a common symptom among patients who are symptomatic with the SARS-CoV-2 virus. The headache described by many of these patients is similar to new daily persistent headache (NDPH). NDPH potentially develops in response to pro-inflammatory cytokines during a persistent systemic or CNS inflammation, mostly due to the initial infection. The treatments investigated were high-dose steroids, tetracycline derivatives, onabotulinum toxin type A, and long-term multidrug regimens. Among the identified symptoms of post-COVID-19 viral illness, fatigue appears to be the most ubiquitous. High-dose vitamin C is currently a suggested therapy proposed for its antioxidant, anti-inflammatory, and immunomodulatory properties. The mental health consequences of this diagnosis are being identified among large portions of COVID-19 survivors. Among these consequences, cases of major depressive disorder (MDD) and anxiety are being reported and closely examined. The aim of this narrative review is to highlight the neurological and psychiatric symptoms that have been associated with Long-Haul COVID and their possible treatments.

In recent decades, the United States has seen a substantial increase in the number of people diagnosed with substance use disorder (SUD). Both SUDs and COVID-19 separately have had, and continue to have, a widespread impact on our society. While they are two distinct entities, they are intricately related and have been shown to influence one another. Lockdown mandates intended to enhance public safety produced unintended consequences for people with SUDs by decreasing access to treatment and disrupting their current care. Telehealth could offer a solution to this disruption as its utilization expands the provider’s reach and increases access to treatment in underserved populations, including those with SUDs. The use of telemedicine seems to result in higher rates of patient satisfaction, compliance, and treatment retention rates while maintaining the need for social distancing. Even when pandemic restrictions resolve, telehealth can continue to provide invaluable benefits to individuals with addiction, particularly those in rural America. In summary, ongoing research regarding telehealth delivery and the expansion of telehealth is a byproduct of the pandemic and can advance the American healthcare system beyond the days of COVID-19. This manuscript will review studies regarding the use of telehealth in SUD with the hope that further research within and beyond the COVID-19 pandemic will lead to the increased use of telehealth by those involved in and those receiving care for SUDs.

With emerging information about the potential for morbidity and reduced life expectancy with long-term use of opioids, it is logical to evaluate nonopioid analgesic treatments to manage pain states. Combinations of drugs can provide additive and/or synergistic effects that can benefit the management of pain states. In this regard, tetrahydrocannabinol (THC) and cannabidiol (CBD) modulate nociceptive signals and have been studied for chronic pain treatment. Psilocybin, commonly known as “magic mushrooms”, works at the serotonin receptor, 5-HT2A. Psilocybin has been found in current studies to help with migraines since it has a tryptamine structure and works similarly to triptans. Psilocybin also has the potential for use in chronic pain treatment. However, the studies that have looked at alternative plant-based medications such as THC, CBD, and psilocybin have been small in terms of their sample size and may not consider the demographic or genetic differences in the population because of their small sample sizes. At present, it is unclear whether the effects reported in these studies translate to the general population or even are significant. In summary, additional studies are warranted to evaluate chronic pain management with alternative and combinations of medications in the treatment of chronic pain.

Depression is a leading cause of disability globally, with a prevalence of 3.8% among the whole population, 5% of the adult population, and 5.7% of the elderly population over 60 years of age. There is evidence that depression is linked to certain neurodegenerative diseases, one being Alzheimer’s disease (AD). The efficacy of conventional antidepressants to treat depression in AD is conflicting, especially regarding selective serotonin reuptake inhibitors (SSRIs). A recent systemic review and meta-analysis of 25 randomized controlled trials including fourteen antidepressant medications showed no high efficacy in treating AD patients’ symptoms. However, ketamine, a nonselective N-methyl-D-aspartate (NMDA) receptor antagonist, can mediate a wide range of pharmacological effects, including neuroprotection, anti-inflammatory and anticancer properties, multimodal analgesia, and treatment of depression, suicidal attempts, and status epilepticus. Esketamine, which is ketamine formulated as a nasal spray, was approved by the Federal Drug Administration (FDA) in March 2019 as an adjuvant drug to treat treatment-resistant depression. NMDA receptor antagonists treat AD through offsetting AD-related pathological stimulation of subtypes of glutamate receptors in the central nervous system. Recent clinical findings suggest that ketamine may provide neuroprotection and reduce neuropsychiatric symptoms associated with AD. In the present investigation, we evaluate the potential role of ketamine and its postulated mechanism in AD management.

Schizophrenia is a psychotic disorder that exists at the more extreme end of a spectrum of diseases, and significantly affects daily functioning. Cardiovascular adverse effects of antipsychotic medications are well known, and include changes in blood pressure and arrhythmias. Sudden cardiac death is the leading cause of death worldwide, and antipsychotic medications are associated with numerous cardiac side effects. A possible link exists between antipsychotic medications and sudden cardiac death. Common prescribing patterns that may influence cardiovascular events include the use of multiple antipsychotics and/or additional drugs commonly prescribed to patients on antipsychotics. The results of this review reflect an association between antipsychotic drugs and increased risk of ventricular arrhythmias and sudden cardiac death by iatrogenic prolongation of the QTc interval. QTc prolongation and sudden cardiac death exist in patients taking antipsychotic monotherapy. The risk increases for the concomitant use of specific drugs that prolong the QTc interval, such as opioids, antibiotics, and illicit drugs. However, evidence suggests that QTc intervals may not adequately predict sudden cardiac death. In considering the findings of this narrative review, we conclude that it is unclear whether there is a precise association between antipsychotic polypharmacy and sudden cardiac death with QTc interval changes. The present narrative review warrants further research on this important potential association.

Pregnant women constitute a vulnerable population, with 25.3% of pregnant women classified as suffering from a psychiatric disorder. Since childbearing age typically aligns with the onset of mental health disorders, it is of utmost importance to consider the effects that antipsychotic drugs have on pregnant women and their developing fetus. However, the induction of pharmacological treatment during pregnancy may pose significant risks to the developing fetus. Antipsychotics are typically introduced when the nonpharmacologic approaches fail to produce desired effects or when the risks outweigh the benefits from continuing without treatment or the risks from exposing the fetus to medication. Early studies of pregnant women with schizophrenia showed an increase in perinatal malformations and deaths among their newborns. Similar to schizophrenia, women with bipolar disorder have an increased risk of relapse in antepartum and postpartum periods. It is known that antipsychotic medications can readily cross the placenta, and exposure to antipsychotic medication during pregnancy is associated with potential teratogenicity. Potential risks associated with antipsychotic use in pregnant women include congenital abnormalities, preterm birth, and metabolic disturbance, which could potentially lead to abnormal fetal growth. The complex decision-making process for treating psychosis in pregnant women must evaluate the risks and benefits of antipsychotic drugs.

Hypoactive sexual desire disorder (HSDD) is a persistent deficiency or absence of sexual fantasies and desire resulting in significant distress or interpersonal difficulty. Women with this disorder may display a lack of motivation for sexual activity, reduced responsiveness to erotic cues, a loss of interest during sexual activity, and avoidance of situations that could lead to sexual activity. The pathophysiology of HSDD is thought to be centered around inhibitory and excitatory hormones, neurotransmitters, and specific brain anatomy. Due to the multifactorial nature of HSDD, treatment can be complex and must attempt to target the biological and psychosocial aspects of the disorder. Bremelanotide is a melanocortin receptor agonist and has been recently approved by the FDA to treat HSDD. Bremelanotide is administered intranasally or as a subcutaneous injection. The recommended dosage of bremelanotide is 1.75 mg injected subcutaneously in the abdomen or thigh at least 45 min before sexual activity. Studies showed improvements in desire, arousal, and orgasm scores when 1.75 mg of bremelanotide was administered before sexual activity compared to a placebo. Bremelanotide is a promising way to treat HSDD.

The treatment of substance abuse with oxytocin is a novel approach to a challenging public health issue that continues to contribute to a growing economic cost for societies worldwide. Methamphetamine addiction is one of the leading causes of mortality worldwide, and despite advances in understanding the neurobiology of methamphetamine addiction, treatment options are limited. There are no medications that the Food and Drug Administration currently approves for stimulant use disorder. Off-label use of therapies for stimulant misuse include antidepressants, anxiolytics, and milder stimulants as replacement agents. Due to the shortcomings of these attempts to treat a complicated psychiatric disorder, recent attention to oxytocin therapy (OT) has gained momentum in clinical studies as a possible therapy in the context of social stress, social anxiety, social cognition, and psychosis. Oxytocin produces enhanced connectivity between cortical regions. The results from studies in rodents with OT suggest that central neuromodulation of oxytocin may be beneficial across transition states of stimulant dependence and may alleviate intense withdrawal symptoms. Studies of oxytocin in the context of other drugs of abuse, including cocaine, cannabis, and alcohol, also support the potential of oxytocin to treat stimulant use disorder, methamphetamine type. Methamphetamine abuse continues to be a significant cause of distress and dysfunction throughout the world. The effects of oxytocin on methamphetamine use outlined in this review should act as a catalyst for further investigation into the efficacy of treating stimulant use disorder, methamphetamine type with oxytocin in humans. More human-based research should initiate studies involving the long-term efficacy, side effects, and patient selection.

Koro syndrome is a multi-tiered disease presenting as an overwhelming belief that one's sex organs are shrinking into their body. Moderate to severe anxiety attacks are associated with the condition, along with a fear of imminent death. Koro is often culturally related and is most seen as an epidemic form in East and Southeast Asia, although it can present anywhere worldwide in its sporadic form. The condition typically affects young males who believe in sex-related myths, and many individuals can co-present with anxiety, depression, or even psychosis. Although most presentations of Koro are self-limiting, the condition is harmful for one's self-esteem and quality of life, and some individuals may go through extreme, physically injurious measures to prevent genital retraction. Treatments include the use of psychotherapy that has a sex education component, especially if the patient believes in culturally rooted myths. In sporadic Koro, it is believed that if the primary psychiatric disorder is treated with anxiolytics, antidepressants, sedatives, or psychotics, the secondary Koro-like symptoms will also fade. Additional investigation on the prevalence, pathogenesis, factors that correlate with treatment efficacy are needed to fully understand Koro syndrome.

The present investigation summarizes relevant symptoms, differential diagnosis, imaging, and treatment options of Eagle Syndrome. A comprehensive literature review of peer-reviewed literature was employed utilizing most relevant databases. The diagnoses of Eagle Syndrome have recently increased because of increased awareness of physicians of Eagle Syndrome and the earlier identification of the cardinal symptoms of the disease. The most important symptoms are dysphagia in the setting of cervical neck pain, but there is a wide variety of symptomatology that make Eagle Syndrome a challenge to recognize and diagnose clinically. CT scan continues to be the standard of care for diagnosing Eagle Syndrome and CT Angiography has an important role in aiding diagnosis as well. Medical treatment options include steroids, antidepressants, and anticonvulsants however not all cases of Eagle Syndrome can be managed medically. Surgical approaches are varied but typically are either extraoral or transoral. This report aims to update providers on the important diagnostic criteria of Eagle Syndrome and how physicians can develop a treatment plan that addresses all the symptoms of patients with Eagle Syndrome because it can be treated safely and appropriately.

# Purpose of Review Seizures are a hyperexcitable, and hypersynchronous imbalance between excitatory and inhibitory factors (E/I imbalance) in neurotransmission, and epilepsy is the recurrent manifestation of seizures within a reasonable time frame and without being attributable to a reversible cause. Brivaracetam is a derivative of the antiepileptic agent, levetiracetam, that is used as adjuvant therapy for focal onset seizures. It was approved by the FDA in 2016 and has shown promising results with minimal adverse effect reactions in clinical trials. # Recent Findings Brivaracetam has been used in multiple clinical trials at various dosages in adults that have partial-onset seizures refractory to conventional treatment. A meta-analysis in 2016 showed that brivaracetam as adjunctive therapy was statically significant in its reduction of adults with drug-refractory seizure frequency.^1^ The most commonly reported adverse effects that patients who were taking brivaracetam experienced were somnolence, headache, and dizziness. Further studies are necessary to conclude long term efficacy and safety profile of brivaracetam. # Conclusion The treatment of epilepsy with pharmacologic agents is a difficult task due to balancing the efficacy of the drug with the side effect profile that will allow for the best quality of life for the patient. There are approximately 30 antiepileptic agents for clinicians to choose from. Brivaracetam is a novel antiepileptic agent that was approved for use by the FDA in 2016 and is showing promising results as monotherapy and adjunctive therapy in individuals with drug-refractory focal seizures while minimizing adverse drug reactions.

# Purpose of Review The present investigation is a comprehensive review regarding the use of Suvorexant for insomnia treatment. It covers the background, pathophysiology, and significance of addressing insomnia, the pharmaceutical details of Suvorexant, and its safety, efficacy, and implications in treating insomnia. We further discuss Suvorexant's role in targeting insomnia with other comorbidities. # Recent Findings Insomnia refers to poor quality and/or quantity of sleep. While there are many existing treatments such as benzodiazepines, melatonin agonists, TCAs, and atypical antipsychotics used to target various receptors involved in normal induction and maintenance of sleep, Suvorexant is an antagonist that specifically targets orexin receptors. Recent clinical studies suggest that Suvorexant is both clinically safe and effective. Quantity and quality of sleep are measured in various ways, yet the consensus points towards Suvorexant's effectiveness in improving sleep time, onset, latency, and quality compared to placebo. In addition to helping improve isolated insomnia, Suvorexant helps improve sleep in patients that have other comorbidities such as obstructive sleep apnea, Alzheimer's disease, dementia, acute stroke, and delirium. While Suvorexant is safe, there are still adverse effects associated with the drug that needs to be considered. The most common adverse effects include dizziness, somnolence, headaches, and cognitive impairment. # Summary Insomnia is a major public health concern that affects many people worldwide and has been linked to many adverse health outcomes. While there are existing treatments that target different receptors and pathways of normal sleep induction and maintenance, Suvorexant is a novel drug that targets dual orexin receptors. Its safety and efficacy, mechanism of action, pharmacokinetic parameters, and relative lack of rebound and withdrawal effects render suvorexant a reliable choice for the treatment of insomnia.

This is a review of the latest and seminal evidence in pediatric migraine. It covers the etiology and pathophysiology known today, and then will review treatment options, efficacy and safety, quality of data and indications. Though migraine is usually regarded as an infliction in adults, it is not uncommon in the pediatric population and affects up to 8% of children. Children may experience migraine differently than adults, and present not only with headache but also frequent gastrointestinal symptoms. They are frequently shorter in duration than in adults. Traditional migraine treatment in adults is less effective in children. In this population, adjunct therapies -- such as interventional techniques -- should be considered when traditional treatment fails, including Botulinum Toxin A (BTA) injections, peripheral nerve and ganglion blocks. BTA injections are FDA approved for migraine prophylaxis in adults, but currently not in children; however, recent evidence shows efficacy and safety in pediatric migraine management. Nerve blocks stop nociceptive afferent fibers through injection of local anesthetics, and it may be associated with the local injection of corticosteroids. Although more common in adults, recent data suggests they are safe and effective in children and adolescents. Blocking the sphenopalatine ganglion can be achieved through nasal approach, and achieves a similar action by blocking the entire ganglion. Interventional techniques may provide a key component in the alleviation of this otherwise debilitating chronic migraine pain. Though most studies have been performed in adults, new studies provide encouraging results for treatment in children.

# Background Amyloidosis is a group of diseases with the common pathophysiology of protein misfolding and aberrant deposition in tissue. There are both acquired and hereditary forms of this disease, and this review focuses on the latter hereditary transthyretin-mediated (hATTR). hATTR affects about 50,000 individuals globally and mostly appears as one of three syndromes - cardiac, polyneuropathy, and oculoleptomeningeal. Polyneuropathy is the most common form, and there is usually some overlap in individual patients. # Results Recently, novel therapeutic options emerged in the form of groundbreaking drugs, Patisiran and Inotersen, small interfering RNA molecules that target TTR and reduce the production of this protein. By targeting TTR mRNA transcripts, Inotersen decreases protein translation and production, reducing the deposition of misfolded proteins. It was shown to be both effective and safe for use and specifically formulated to concentrate in the liver -- where protein production takes place. # Conclusion hATTR is a rare, progressive, and debilitating disease. Its most common presentation is that of polyneuropathy, and it carries a very poor prognosis and a natural history conveying a median survival of \< 12 years. Novel therapeutic options are groundbreaking by providing disease-modifying specific, targeted therapies against TTR production and deposition. The use of RNA interference (RNAi) opens the door to the treatment of hereditary diseases by targeting them at the genetic level.

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.

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.

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.

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.

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.

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.