Aripiprazole lauroxil, a novel injectable long-acting antipsychotic treatment for adults with schizophrenia: A comprehensive review

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

Aripiprazole lauroxil, a novel injectable long-acting antipsychotic treatment for adults with schizophrenia: A comprehensive review

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

Alternative Options for Complex, Recurrent Pain States Using Cannabinoids, Psilocybin, and Ketamine: A Narrative Review of Clinical Evidence

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-HT. 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

Ozanimod to treat relapsing forms of multiple sclerosis: A comprehensive review of disease, drug efficacy and side effects

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

Ozanimod to treat relapsing forms of multiple sclerosis: A comprehensive review of disease, drug efficacy and side effects

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

Midazolam nasal spray to treat intermittent, stereotypic episodes of frequent seizure activity: pharmacology and clinical role, a comprehensive review.

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

Opicapone, a Novel Catechol-O-methyl Transferase Inhibitor, for Treatment of Parkinson\u27s Disease Off Episodes

Parkinson\u27s Disease (PD) is a common neurodegenerative disorder and the leading cause of disability. It causes significant morbidity and disability through a plethora of symptoms, including movement disorders, sleep disturbances, and cognitive and psychiatric symptoms. The traditional pathogenesis theory of PD involves the loss of dopaminergic neurons in the substantia nigra (SN). Classically, treatment is pursued with an assortment of medications that are directed at overcoming this deficiency with levodopa being central to most treatment plans. Patients taking levodopa tend to experience off episodes with decreasing medication levels, causing large fluctuations in their symptoms. These off episodes are disturbing and a source of morbidity for these patients. Opicapone is a novel, peripherally acting Catechol-O-methyl transferase (COMT) inhibitor that is used as adjunctive therapy to carbidopa/levodopa for treatment and prevention of off episodes. It has been approved for use as an adjunct to levodopa since 2016 in Europe and has recently (April 2020) gained FDA approval for use in the USA. By inhibiting COMT, opicapone slows levodopa metabolism and increases its availability. Several clinical studies demonstrated significant improvement in treatment efficacy and reduction in duration of off episodes. The main side effect demonstrated was dyskinesia, mostly with the 100mg dose, which is higher than the approved, effective dose of 50mg. Post-marketing surveillance and analysis are required to further elucidate its safety profile and contribute to patient selection. This paper reviews the seminal and latest evidence in the treatment of PD off episodes with the novel drug Opicapone, including efficacy, safety, and clinical indications

Transcranial Magnetic Stimulation for Post-traumatic Stress Disorder

Post-traumatic stress disorder (PTSD) is a psychiatric disorder that causes significant functional impairment and is related to altered stress response and reinforced learned fear behavior. PTSD has been found to impact three functional networks in the brain: default mode, executive control, and salience. The executive control network includes the dorsolateral prefrontal cortex (DLPFC) and lateral PPC. The salience network involves the anterior cingulate cortex, anterior insula, and amygdala. This latter network has been found to have increased functional connectivity in PTSD. Transcranial Magnetic Stimulation (TMS) is a technique used in treating PTSD and involves stimulating specific portions of the brain through electromagnetic induction. Currently, high-frequency TMS applied to the left dorsolateral prefrontal cortex (DLPFC) is approved for use in treating major depressive disorder (MDD) in patients who have failed at least one medication trial. In current studies, high-frequency stimulation has been shown to be more effective in PTSD rating scales posttreatment than low-frequency stimulation. The most common side effect is headache and scalp pain treated by mild analgesics. Seizures are a rare side effect and are usually due to predisposing factors. Studies have been done to assess the overall efficacy of TMS. However, results have been conflicting, and sample sizes were small. More research should be done with larger sample sizes to test the efficacy of TMS in the treatment of PTSD. Overall, TMS is a relatively safe treatment. Currently, the only FDA- approved to treat refractory depression, but with the potential to treat many other conditions

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

Revising a 5th Grade Curriculum using Interactive Notebooks

Revising a 5th Grade Curriculum using Interactive Notebook