Role of Medium Chain Triglycerides (Axona®) in the Treatment of Mild to Moderate Alzheimer's Disease.

Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors or N-methyl-D-aspartate (NMDA) receptor antagonists provides symptomatic relief but do not prevent its progression. Thus, additional approaches aimed at slowing the progression of the disease have been investigated. Reports detailing reduced brain glucose metabolism in the early stages of AD led to the hypothesis that alternate energy sources aimed at increasing neuronal metabolism may protect neurons and thus benefit patients with AD. Medium-chain triglycerides (MCTs) are metabolized to ketone bodies that serve as an alternative source of energy for neurons. Data from clinical trials suggest that MCTs improve cognition in patients with mild to moderate AD in apolipoprotein E4-negative patients. Adverse events observed were mild and included minor gastrointestinal problems such as diarrhea, dyspepsia, and flatulence. However, since genomic profiles are not routinely conducted in patients with AD in a clinical setting, the role of MCTs in clinical practice seems to be minimal.

Exenatide as a novel weight loss modality in patients without diabetes.

OBJECTIVE: To evaluate the potential role of exenatide for weight loss in overweight or obese adults without diabetes. DATA SOURCES: PubMed (1946-August 2012) and EMBASE (1974-August 2012) were used to conduct a literature search utilizing the terms exenatide, weight loss, obesity, and overweight. Additional references were identified by bibliographic review of relevant articles. STUDY SELECTION AND DATA EXTRACTION: Studies assessing the use of exenatide in adult subjects without type 2 diabetes or polycystic ovary syndrome and reporting effects on body weight were included. DATA SYNTHESIS: Five studies were identified that reported use of exenatide in nondiabetic adults and included weight change as an outcomes measure. In all 5 of these studies, subjects taking exenatide experienced statistically significant weight loss, which ranged from 2.0 ± 2.8 to 5.1 ± 0.5 kg. Two of the trials were randomized, placebo-controlled studies; 1 trial was a randomized, open-label investigation; 1 study had a prospective, open-label cohort design; and the remaining study was a chart review. Adverse events experienced with exenatide were primarily gastrointestinal in nature, although each trial reported the drug to be well tolerated. CONCLUSIONS: Obesity continues to be a national epidemic, while choices for effective pharmacologic treatments are extremely limited. Exenatide appears to have promising effects on weight in overweight or obese adults without type 2 diabetes. Further investigations with large, placebo-controlled trials assessing long-term weight loss as a primary outcome are warranted.

An update in options for the treatment of pain: a review of new opioid formulations.

In the past 2 decades, there has been a significant increase in the use of opioids for the management of chronic nonmalignant pain. This increase in usage has led to concerns of misuse and abuse of opioids. Also, many of the available opioid options were previously only available as oral tablets or capsules, further limiting treatment options for health care providers. Several new opioid formulations have been developed to address and prevent the misuse and abuse of opioids via tampering in the United States. In addition, alternative delivery systems have been developed to provide physicians with more options to provide adequate pain management for those with chronic pain. This article reviews new opioid options for the treatment of pain management and requirements of the Risk Evaluation and Mitigation Strategies program.

Considerations for the use of proton-pump inhibitors in older adults.

OBJECTIVE: To investigate current concerns regarding the use of proton-pump inhibitors (PPIs) in older adults. DATA SOURCES: A literature search was conducted in MEDLINE (1948 to April week 3 2011) to identify relevant publications. Key words searched included proton-pump inhibitor, safety, adverse events, elderly, and older adults. Additional data sources were obtained through a bibliographic review of selected articles. DATA SELECTION: Relevant studies conducted in older adults published in English that examined risks associated with the use of PPIs were included in this review. DATA SYNTHESIS: The older adult population in the United States is growing at an astounding rate. With the increase in age, there are many factors that make the elderly susceptible to acid-related gastrointestinal disorders that require treatment with PPIs. However, PPI use in the elderly has been shown to lead to a number of health concerns. Recent data have shown that PPI use is associated with an increased risk of fractures, Clostridium difficile infection, community-acquired pneumonia, vitamin and mineral deficiencies, and drug interactions. These concerns will be further investigated and weighed against the benefits of PPI use in this population. CONCLUSIONS: Patient-specific characteristics must be taken into consideration when recommending and/or prescribing PPIs to older adults.

Efficacy and safety of deep brain stimulation as an adjunct to pharmacotherapy for the treatment of Parkinson disease.

OBJECTIVE: To review the literature describing the efficacy and safety of deep brain stimulation (DBS) as an adjunct to pharmacotherapy and to determine the best treatment option for patients with Parkinson disease (PD). DATA SOURCES: Literature was obtained through MEDLINE/PubMed (1948-September, week 2, 2011) and a bibliographic review of relevant articles. Key words included Parkinson disease, medication, pharmacotherapy, surgery, deep brain stimulation, and best medical therapy. STUDY SELECTION AND DATA EXTRACTION: Five English-language studies that compared the efficacy of DBS as an adjunct to pharmacologic treatment versus pharmacologic treatment alone in patients with PD met our inclusion criteria and were selected for this review. DATA SYNTHESIS: PD is a progressive neurodegenerative disease with limited treatment options, and levodopa is considered the pharmacologic gold standard. However, long-term levodopa use leads to decreased efficacy and increased incidence of adverse effects. Hence, DBS has been investigated as an adjunctive option for patients with PD both to overcome the adverse events of levodopa as well as to treat the disease. DBS, when used in conjunction with pharmacologic therapy, has resulted in improved motor function and quality of life in several trials compared with medication alone. Its benefit is limited by adverse events that are generally more frequent and severe than those with pharmacotherapy alone. Study limitations included small patient population and/or weak design. CONCLUSIONS: DBS may be an option as adjunct therapy in patients whose symptoms are no longer controlled with maximum pharmacologic therapy, but benefits of surgery must be weighed against the risks.

Proton Pump Inhibitor use in Hospitalized Patients: Is Overutilization Becoming a Problem?

Proton pump inhibitors (PPIs) are among the most common classes of medications prescribed. Though they were previously thought of as safe, recent literature has shown risks associated with their use including increased risk for Clostridium difficile infection, pneumonia, and fractures. Due to these risks, it is important to determine if PPIs are being used appropriately. This review evaluates seven studies in hospitalized patients. Additionally, this review evaluates literature pertaining to recently discovered adverse reactions; all studies found PPIs are being overutilized. Findings highlight the importance of evaluating appropriate therapy with these agents and recommending discontinuation if a proper indication does not exist.

Rosiglitazone and pioglitazone for the treatment of Alzheimer's disease.

OBJECTIVE: To review the literature on the efficacy and safety of rosiglitazone and pioglitazone for the treatment of Alzheimer's disease (AD). DATA SOURCES: Literature was accessed through MEDLINE (1948-August 2011 week 2) and EMBASE (1980-2011 week 32) using the search terms rosiglita-zone, pioglitazone, and Alzheimer's disease. Results were limited to studies conducted in humans and published in English. STUDY SELECTION AND DATA EXTRACTION: Clinical trials evaluating the efficacy and safety of rosiglitazone or pioglitazone in patients with AD were critically evaluated. DATA SYNTHESIS: The mechanism for development of AD has been linked to both inflammation and decreased insulin sensitivity. Because of this, rosiglitazone and pioglitazone have been evaluated as potential treatments for AD because of their insulin-sensitizing and antiinflammatory effects. Five clinical trials were evaluated (3 assessing rosiglitazone, 2 assessing pioglitazone); 1 trial evaluating rosiglitazone demonstrated a beneficial effect on cognition in patients with probable AD. However, the largest randomized, double-blind, placebo-controlled trials conducted to date failed to demonstrate a difference between rosiglitazone and placebo when assessing primary endpoints. Two small trials evaluating pioglitazone produced conflicting results regarding efficacy in AD; numerous limitations make results difficult to interpret. The safety of these agents was also evaluated in these trials; edema was seen more commonly in patients receiving rosiglitazone or pioglitazone than in those receiving placebo; however, each drug was generally well tolerated. CONCLUSIONS: Results from clinical trials and current safety data suggest that rosiglitazone should not be used for the treatment of AD. Application of results from trials evaluating pioglitazone in the treatment of AD is limited because of major trial limitations; therefore, it should not be recommended at this time. Although these drugs are not commonly used in the treatment of AD, further pharmacoepidemiologic studies are warranted before their use can be recommended.

Special considerations for the use of insulin in older adults.

OBJECTIVE: The goal of this article is to provide guidance in prescribing insulin for older adults. BACKGROUND: The prevalence of diabetes increases with age, with almost 30% of the elderly population diagnosed with this metabolic disorder. Along with the well-documented microvascular and microvascular complications of diabetes, older adults are at increased risk of numerous other complications, such as dementia, risk of falling, frailty, and incontinence. DATA SYNTHESIS: Whether designing a new insulin regimen or adjusting an existing regimen, many factors must be considered; these include advantages and disadvantages of each insulin option; adverse events, particularly hypoglycemia and increased risk of falls; and comorbid conditions. When assessing insulin options for older adults, a thorough evaluation of key features, such as the pharmacokinetics and timing of administration in relation to meals, along with cost, will assist clinicians in selecting an appropriate regimen. Hypoglycemia and risk of falls are increased in older adults; tight glycemic goals must be weighed against the risk of these adverse events. The presence of comorbid conditions may interfere with older adults' ability to inject insulin and monitor their blood sugar appropriately. Specialized devices, such as insulin pens, may offer a means to assist older adults with their insulin therapy. CONCLUSION: Prescribing insulin to older patients must be individualized and tailored to meet the needs of each individual.

Thienopyridines in Acute Coronary Syndrome.

OBJECTIVE: To evaluate the safety and efficacy of the thienopyridines in order to identify their current place in therapy for the treatment of acute coronary syndrome (ACS). DATA SOURCES: Literature was accessed through MEDLINE (1966-October 2010 week 1), EMBASE (1980-2010 week 40), and a bibliographic review of published articles using the search terms acute coronary syndrome, clopidogrel, and prasugrel. Articles were limited to clinical trials conducted in humans and published in the English language. STUDY SELECTION AND DATA EXTRACTION: Head-to-head clinical trials evaluating the safety and efficacy of the thienopyridines in patients with ACS were critically reviewed. Trials evaluating ticlopidine were excluded due to its limited clinical use. DATA SYNTHESIS: Thienopyridines are an integral part of the treatment of ACS. Prior to the approval of prasugrel, clopidogrel was considered the agent of choice due to safety concerns associated with ticlopidine. A randomized controlled trial comparing prasugrel and clopidogrel has demonstrated superior efficacy with prasugrel, and post hoc analyses suggest additional benefit with prasugrel is derived in patients with ST-segment elevation myocardial infarction and patients with diabetes. However, safety concerns exist linking prasugrel with an increased risk of bleeding, which diminishes its advantage in elderly patients, underweight patients, and those with a history of stroke. Pharmacokinetic and pharmacodynamic studies discussing differences in response variability, platelet inhibition, interactions with proton pump inhibitors, and genetic factors between the thienopyridines are numerous, although more clinical data are needed to determine clinical implications. CONCLUSIONS: Clinical trial data have suggested prasugrel is superior to clopidogrel at preventing ischemic events in patients with ACS undergoing percutaneous coronary intervention. However, this coincides with an increased risk of bleeding. Clinicians must carefully interpret the current evidence, including limitations in study design and pharmacologic differences between agents, in order to balance the risks and benefits as new data become available.

Dexlansoprazole in the treatment of esophagitis and gastroesophageal reflux disease.

OBJECTIVE: To describe the pharmacology, pharmacokinetics, and efficacy of dexlansoprazole in the treatment of heartburn associated with nonerosive gastroesophageal reflux disease (GERD) and healing and maintenance of healing of all grades of erosive esophagitis (EE). DATA SOURCES: Literature searches were conducted using MEDLINE Ovid (1950-December 2009, week 4) and EMBASE (1980-2009, week 53) using the term dexlansoprazole. References from articles obtained from the search were evaluated for other relevant citations. STUDY SELECTION AND DATA EXTRACTION: All articles published in English evaluating the pharmacology, pharmacokinetics, efficacy, and adverse effect profile of dexlansoprazole were selected for inclusion. DATA SYNTHESIS: Dexlansoprazole is the newest addition to the proton pump inhibitor (PPI) class and is approved for the treatment of heartburn associated with nonerosive GERD, healing of all grades of EE, as well as maintenance of healing of EE. Dexlansoprazole has a unique dual delayed-release formulation, which releases drug at 2 points in time; the first peak occurs 1-2 hours after administration and the second occurs within 4-5 hours after administration. In Phase 3 trials conducted in adults, researchers found that dexlansoprazole increases rates of healing of EE, as well as the maintenance of healing, compared to lansoprazole. Relief of heartburn symptoms was comparable among the dexlansoprazole and lansoprazole treatment groups. Common adverse effects of dexlansoprazole are similar to those of the other PPIs, including diarrhea, abdominal pain, nausea, upper respiratory infection, vomiting, and flatulence. CONCLUSIONS: Dexlansoprazole provides another treatment option for the management of EE and symptoms of heartburn. Considering that the cost of dexlansoprazole is not favorable, further studies evaluating potential advantages over other agents are necessary to define the role of dexlansoprazole in the treatment of these conditions.

The role of pramlintide for weight loss.

OBJECTIVE: To evaluate the weight-loss effects of pramlintide. DATA SOURCES: A literature search was conducted in MEDLINE (1950-October week 4, 2009), International Pharmaceutical Abstracts (1970-October 2009), and Evidence Based Medicine Database (1991-2009 week 44) to identify relevant publications. Key words searched included pramlintide, weight loss, obesity, and overweight. Additional data sources were obtained through a bibliographic review of selected articles. STUDY SELECTION/DATA EXTRACTION: All studies conducted on humans and published in English that examined the effects of pramlintide on body weight as a primary or secondary endpoint were selected for analysis. DATA SYNTHESIS: Pramlintide is a human amylin analog approved by the Food and Drug Administration for use in conjunction with insulin therapy in patients with type 1 or 2 diabetes. In addition to its glucoregulatory actions, pramlintide has been shown to increase satiety and, therefore, decrease caloric intake via a central mechanism. Several studies show that this translates into statistically significant weight loss in overweight or obese patients with type 1 or 2 diabetes; patients with type 1 diabetes lost up to 1.7 kg over 1 year with pramlintide 60 microg 3 times daily, while patients with type 2 diabetes experienced a placebo-subtracted weight loss of up to 3.7 kg after 16 weeks of pramlintide 120-240 microg administered 3 times daily. Preliminary trials assessing the use of pramlintide for weight loss in obese patients without diabetes have demonstrated weight loss of up to 8 kg after 1 year. In all studies, the drug was generally well tolerated, with nausea being the most commonly reported adverse effect. CONCLUSIONS: Based on preliminary evidence, pramlintide facilitates modest weight loss in obese or overweight patients with and without diabetes. However, current trials were limited by inconsistent study design, dosing, and patient population.

Role of huperzine a in the treatment of Alzheimer's disease.

OBJECTIVE: To review the role of huperzine A in the treatment of Alzheimer's disease (AD). DATA SOURCES: A literature search was conducted through MEDLINE (1950-September week 2, 2008), EMBASE (all years), Google Scholar, International Pharmaceutical Abstracts, and a bibliographic review of relevant articles. Key words included huperzine, huperin, Huperzia serrata, and Alzheimer's disease. STUDY SELECTION AND DATA EXTRACTION: All clinical trials published in the English language that evaluated huperzine A in patients with AD were included in this review. Articles published in Chinese were included when English abstracts or electronic translation technology were available. DATA SYNTHESIS: AD is a progressive neurodegenerative brain disorder for which there is no cure; available therapies only decrease cognitive decline. Huperzine A, an alkaloid derived from Chinese club moss (H. serrata), acts as a selective inhibitor of acetylcholinesterase and may also display neuroprotective properties. Preliminary data suggest that huperzine A may improve cognition; studies ranging from 8 to 12 weeks have found improvements in the Mini-Mental State Examination score of 1-5 points. CONCLUSIONS: Although use of huperzine A has shown promising results in patients with AD, data supporting its use are limited by weak study design. Largescale, randomized, placebo-controlled trials are necessary to establish the role of huperzine A in the treatment of AD.

Role of metformin for weight management in patients without type 2 diabetes.

OBJECTIVE: To evaluate the efficacy and safety of metformin for weight management in overweight and obese patients without type 2 diabetes. DATA SOURCES: Literature was obtained through MEDLINE Ovid (1950-February week 3, 2008), EMBASE (all years), and a bibliographic review of relevant articles. Key words included metformin, obesity, overweight, and weight loss. STUDY SELECTION/DATA EXTRACTION: All studies published in the English language that evaluated the effects of metformin on weight in obese or overweight individuals were critically analyzed. Relevant articles were selected for inclusion in this review. DATA SYNTHESIS: Metformin is first-line pharmacotherapy in the treatment of overweight or obese patients with type 2 diabetes, with beneficial effects on weight in this population. Multiple trials have evaluated the effect of metformin on weight and other metabolic parameters in adults and adolescents without diabetes. Five of 12 trials in adults evaluated weight loss as a primary endpoint. Significant weight reduction was found in 4 of these studies; however, the trials were small and of weak design. Weight reduction was significant in 5 of the 6 adolescent trials; similarly, these studies were limited by weak study design and small patient population. Metabolic parameters (blood pressure, waist circumference, cholesterol parameters, insulin/glucose levels) often showed varying results. Metformin was well tolerated; gastrointestinal effects were the most frequently reported adverse effects. CONCLUSIONS: The weight loss effects of metformin in overweight or obese adults and adolescents without diabetes appear promising; however, trials have been limited by small patient populations and weak design. Metformin may also have a positive effect on metabolic parameters such as waist circumference, fasting insulin and glucose levels, and triglycerides. Further research involving large-scale trials that evaluate weight loss as a primary outcome is necessary to firmly establish the role of metformin in this population.

Pharmacotherapeutic options for overweight adolescents.

OBJECTIVE: To evaluate the safety and efficacy of current pharmacotherapeutic options for weight loss in overweight adolescents. DATA SOURCES: Literature was obtained through MEDLINE Ovid (1996-April 2007) and EMBASE Drugs and Pharmacology (1991-2nd quarter 2007) searches and a bibliographic review of published articles. Key words included adolescents, overweight, obesity, anti-obesity agents, drug therapy, orlistat, sibutramine, and metformin. STUDY SELECTION AND DATA EXTRACTION: All studies published in the English language that evaluated the use of pharmacotherapy for the treatment of overweight adolescents were critically analyzed; pertinent articles were selected for this review. DATA SYNTHESIS: Orlistat has been approved for use in adolescents between the ages of 12 and 16 years. The most frequently reported adverse effects of orlistat were gastrointestinal; reduced concentrations of fat-soluble vitamins were also observed. Of the 6 clinical trials published, 5 have shown statistically significant reductions in body mass index (BMI) from baseline, ranging from 0.55 to 4.09 kg/m2; one small trial failed to demonstrate significant weight reduction compared with placebo. Sibutramine has also been evaluated for use in overweight adolescents in 6 trials. Trials demonstrated a statistically significant reduction in BMI up to 5.6 kg/m2 (from baseline). Of concern is evidence indicating that sibutramine therapy may be associated with elevated blood pressure, increased pulse rate, depression, and suicidal ideations. Lastly, metformin has recently been evaluated for weight loss in overweight adolescents; small, short-term trials demonstrate modest reductions in weight and BMI. CONCLUSIONS: Orlistat has been proven both safe and effective for weight reduction in overweight adolescents. Sibutramine has also been proven effective in reducing weight in this population; however, the potential for severe adverse effects requires further investigation. Metformin has demonstrated promising results in small trials; its role in the treatment of overweight adolescents will remain investigational until further research is conducted.