Benjamin Chavez

An Update on Central Nervous System Stimulant Formulations in Children and Adolescents with Attention-Deficit/Hyperactivity Disorder

Objective To review recent literature on the different stimulant preparations regarding efficacy and safety in children and adolescents with attention-deficit/hyperactivity disorder (ADHD) and describe advantages and disadvantages of the many available dosage formulations. Data Sources Literature retrieval was performed through PubMed/MEDLINE (2005–December 2008) using the terms methylphenidate, amphetamines, central nervous system stimulants, and attention-deficit/hyperactivity disorder. In addition, reference citations from publications identified were reviewed and drug manufacturers were contacted for any possible additional references. Study Selection And Data Extraction Double-blind clinical trials found using the search criteria listed above were included for review. Open-label studies and studies prior to 2005 were included if no double-blind trials were published for that formulation within the time period reviewed. Data Synthesis The literature reviewed here demonstrates the efficacy and safety of stimulant medications in children and adolescents with ADHD. However, there are 19 different formulations of stimulants, leading to confusion and errors in prescribing and dispensing of these drugs. Knowing and understanding the advantages and disadvantages of the different formulations can lead to individualized treatment. Formulations like Concerta, Focalin-XR, Adderall-XR, and Vyvanse provide the convenience of once-daily dosing. Each of these provides varying amount of stimulants at different times of the day. Vyvanse has a unique delivery system that may lower the risk of patients abusing their medication. Daytrana gives patients more control over their dosing by being able to choose when the patch is removed; it is also a feasible alternative for children who cannot swallow pills. For patients who cannot swallow tablets or capsules, the capsules of Focalin-XR, Adderall-XR, Metadate-CD, and Ritalin-LA can be opened and sprinkled on applesauce. Conclusions Stimulants are effective medications to treat the symptoms of ADHD. The multiple available dosage forms allow for individualization of treatment.

Atypical Antipsychotics in Children with Pervasive Developmental Disorders

The treatment of pervasive developmental disorders (PDDs) is a challenging task, which should include behavioral therapy modifications as well as pharmacologic therapy. There has been a lack of data on using medications in children with PDDs until recent years. Within the last 10 years, an increase in clinical research has attempted to provide efficacy and safety data to support the use of medications in children with PDDs. Double-blinded and open-label research of atypical antipsychotics has been of particular focus.Evidence shows that atypical antipsychotics (AAs) may be useful in treating certain symptoms associated with PDDs, such as aggression, irritability, and self-injurious behavior. This article reviews the literature regarding the use of AAs in children with PDDs. Of the AAs, risperidone has the largest amount of evidence with five published double-blinded, placebo-controlled trials and nine open-label trials. These risperidone trials have consistently shown improvements in aggression, irritability, self-injurious behavior, temper tantrums, and quickly changing moods associated with autistic disorder and other PDDs. Data for the other AAs are limited, but ziprasidone and aripiprazole appear to be promising treatment options. Based on clinical trials, olanzapine and quetiapine have shown minimal clinical benefit and a high incidence of weight gain and sedation. It should be noted that all AAs do have a risk of metabolic syndrome, and patients should be monitored appropriately while receiving these medications.Overall, AAs can be beneficial in alleviating behavioral symptoms, and should be considered an appropriate therapeutic option, as part of a comprehensive treatment strategy, for children with PDD.

Role of Risperidone in Children with Autism Spectrum Disorder

Objective: To review the clinical trials investigating the efficacy and safety of risperidone in the treatment of children with autism spectrum disorder (ASD). Data Sources: Searches of MEDLINE/PubMed (1992–February 2006) were conducted, as well as an extensive manual review of journals, using the key words autism and risperidone. Study Selection and Data Extraction: Only double-blind, placebo-controlled trials were included for review. Data Synthesis: ASD is the most common of the pervasive developmental disorders. The main characteristics (core symptoms) of autism are impairment in social skills, problems communicating, and stereotypical movements. Behavioral manifestations or maladaptive behaviors include aggression, irritability, hyperactivity, inattention, impulsivity, tantrums, and self-injurious behavior. Conclusions: Based on the data examined, risperidone appears efficacious and safe for treating certain behavioral aspects of autism including irritability, aggression, hyperactivity, and stereotypy. It does not appear to be as effective for the treatment of the core symptoms of autism.

Safety and Efficacy of Quetiapine in Bipolar Depression

Objective: To review the clinical data investigating the efficacy and safety of quetiapine in bipolar depression. Data Sources: Searches of MEDLINE and PubMed (1977–July 2009) were conducted using the key words quetiapine and bipolar depression. The references of literature found were cross-referenced. The pharmaceutical company that produces quetiapine was contacted to obtain the posters for the EMBOLDEN I and EMBOLDEN II trials. Study Selection and Data Extraction: Only double-blind, placebo-controlled trials were included for review, as well as any subanalyses of the literature that matched this criterion. Data Synthesis: There was a total of 5 double-blind, placebo-controlled trials and 5 subanalyses reviewed. The results of these data demonstrated quetiapines efficacy in the treatment of depressive phases of bipolar disorder, including statistically significant improvement in the Montgomery-Åsberg Depression Rating Scale (MADRS). In the trials reviewed in this article, the change in MADRS scores ranged from -15.4 to -16.94 within the quetiapine groups, and from -10.26 to -11.93 in the placebo groups. There were also statistically significant improvements in the Hamilton Anxiety Rating Scale, the Short Form of the Quality of Life Enjoyment and Satisfaction Questionnaire, the Pittsburgh Sleep Quality Index, and the Sheehan Disability Scale. All of these trials had a duration of 8 weeks and therefore cannot be applied to the long-term use of quetiapine in bipolar depression. The most common adverse events were sedation, somnolence, and dry mouth. The overall dropout rates for the trials reviewed ranged from 24% to 47%. Conclusions: Based on the literature reviewed here, quetiapine appears to be a safe and efficacious short-term treatment option for bipolar depression. Patients with bipolar type I showed greater improvement on the MADRS than those with bipolar type II. Patients with a rapid-cycling disease course showed an improvement in depressive symptoms, regardless of bipolar type.

Adjustments to diabetes medications in response to increases in hemoglobin a1c: an epidemiologic study.

Objective: The primary objective was to assess associations between increases in glycated hemoglobin (HbA1c) levels and medication adjustments among patients with diabetes. A secondary objective was to measure the effect of adjustments on subsequent HbA1c levels. Methods: A retrospective analysis of administrative data from a large health insurer in Hawaii of 7654 patients with diabetes mellitus type II, HbA1c levels greater than 7%, and who were taking oral diabetic medications. Patients were eligible if they had an HbA1c measurement in 2009, a prior measure 30 or more days previously, and at least 30 days of follow-up to identify medication adjustments. Patients were classified into 3 groups based on their extent of change in HbA1c levels. Patients were followed to determine the frequency of medication adjustments and to observe the possible benefit of making adjustments on subsequent HbA1c levels. Results: Medication adjustments were the exception, occurring among less than a fourth of patients. Compared with patients without HbA1c increases, patients with <1% HbA1c increases made adjustments 20% more frequently, and patients with increased HbA1c levels of 1% or more made adjustments 60% more frequently. Patients with similar HbA1c increases were more likely to adjust their medications if they had higher baseline HbA1c levels. Medication adjustments were mostly for oral diabetes medications; insulin use was seldom initiated, and then primarily by patients with HbA1c levels of 9% or higher. Patients with medication adjustments averaged about 0.40% lower HbA1c levels when reassessed after 120 days or more. Conclusion: The results show limited responsiveness to increases in HbA1c levels and a low initiation rate of insulin use. Patients adjusting their medications, however, had clinically significant improvements in their HbA1c levels. Clinical inertia and patient concerns are discussed as factors possibly limiting the frequency of medication adjustments.

Efficacy with High-Dose Aripiprazole After Olanzapine-Related Metabolic Disturbances

Objective: To report a case in which a patient tolerated and responded to high-dose aripiprazole and lost weight after having been on olanzapine for several years; a secondary objective is to discuss the use of aripiprazole dosages at higher than those recommended in the products labeling. Case Summary: A 57-year-old man with a 30 year history of schizophrenia had been taking olanzapine for 4 years, with the dosage titrated to 20 mg/day, to control the psychosis. After he had gained significant weight with olanzapine (the highest was 102.7 kg), his treatment was switched to aripiprazole. The patient required a high dose of aripiprazole (60 mg/day) to achieve full control of the psychiatric symptoms, and during aripiprazole therapy, he lost the weight he had gained while on olanzapine, weighing 85.9 kg within 7 months after the therapy switch. Discussion: Dosages of atypical antipsychotics higher than those recommended by the Food and Drug Administration are often used in clinical practice for refractory patients, despite the lack of evidence. The literature available on this subject is limited to small, double-blind trials; open-label trials; and case reports. Although certain patients may benefit from higher doses of atypical antipsychotics, the lack of evidence limits their use. Conclusions: High-dose aripiprazole (60 mg/day) was well tolerated and controlled this patients symptoms effectively. In addition, he lost weight that was gained while being treated with olanzapine. High-dose aripiprazole may be beneficial and safe in refractory patients; however, large, double-blind, randomized clinical trials are needed.

Febuxostat for the treatment of gout

Introduction: Gout is a rheumatologic condition associated with elevated serum uric acid levels and deposition of monosodium urate crystals in joints and soft tissues. The xanthine oxidase inhibitor, allopurinol, has historically been the principle agent utilized for reducing elevated uric acid levels and treating underlying cause of gout symptoms; the availability of febuxostat, a newer non-purine selective xanthine oxidase inhibitor, represents an alternative therapy for those patients with contraindications or intolerance to allopurinol. Areas covered: This article reviews the published literature on the pharmacologic characteristics and clinical safety and efficacy data on the use of febuxostat in the treatment of gout. A literature search of MEDLINE and MEDLINE In-Process & Other Non-Indexed Citations Databases (1996–November 2014) was conducted utilizing the key words ‘febuxostat’, ‘allopurinol’, and ‘gout’. All published articles regarding febuxostat were evaluated. References of selected articles, data from poster presentations, and abstract publications were additionally reviewed. Expert opinion: Febuxostat has shown benefit with respect to symptomatic relief and uric acid level reduction. The safety profile of this agent makes it an ideal alternative in those patients with contraindications to or who are intolerant of allopurinol.

Manic and psychotic symptoms following subcutaneous leuprolide in a male patient with no prior psychiatric history.

To the Editor: Leuprolide is a synthetic luteinizing hormone– releasing hormone (LHRH) agonist used in the treatment of advanced prostate cancer. It is available as an immediate-release intramuscular injection, a depot suspension for intramuscular injection, and an extended-release suspension for subcutaneous injection. After a 45-mg dose of subcutaneous leuprolide, 99.1% of patients experience clinical castration by day 28, defined as serum testosterone levels < 50 ng/mL.1 In addition to this decrease in serum testosterone levels, decreases in sex hormone–binding globulin and estradiol are also seen.1,2 Although there have been reports3,4 of emotional lability, depression, and anxiety with LHRH agonists, the data are not consistent. Furthermore, all published reports on psychiatric side effects of LHRH agonists have been exclusively in female patients. The package insert1 of leuprolide depot subcutaneous injection does list anxiety, depression, and delusions as occurring in less than 5% of patients. Here, we describe a case of a 65-year-old man with no prior psychiatric history who developed manic and psychotic symptoms after receiving a 45-mg subcutaneous injection of leuprolide. This is the only case available in the literature that describes a male patient experiencing such severe psychiatric symptoms in association with leuprolide.

The Safety and Efficacy of Methylphenidate and Dexmethylphenidate in Adults with Attention Deficit/Hyperactivity Disorder

Objective To review the literature on the safety and efficacy of methylphenidate, OROS-methylphenidate, methylphenidate ER, and dexmethylphenidate in adults with Attention-Deficit/Hyperactivity Disorder (ADHD). To analyze the effects of different doses of methylphenidate, its various formulations, and methylphenidate on efficacy and safety in this population. Data Sources Literature retrieval was performed through Pubmed/MEDLINE (Up to May 2010) using the terms methylphenidate, dexmethylphenidate, and attention-deficit hyperactivity disorder. In addition, reference citations from publications identified were reviewed. Study Selection and Data Extraction Double-blinded, placebo-controlled clinical trials, as well as crossover and open-label trials found using the search criteria listed above were included for review. Case reports were not included in this review. Data Synthesis Attention-deficit/hyperactivity disorder (ADHD) is a psychiatric condition that is commonly seen in children and adolescents, that persists into adulthood for about 50% of patients. Methylphenidate and dexmethylphenidate are often prescribed to treat the symptoms associated with ADHD. The literature validating the safety and efficacy of methylphenidate and dexmethylphenidate in children and adolescents with ADHD is substantial. However, the literature specifically addressing the safety and efficacy of these medications in the adult population is less extensive and prescribing is often anecdotal based on child and adolescent data. Understanding the literature regarding methylphenidate and dexmethylphenidate and its effects in adults can enhance evidence-based medicine (EBM) and improve treatment outcomes Conclusion Methylphenidate and dexmethylphenidate are safe and effective medications to treat the symptoms of ADHD in adults. Based on the literature, increased doses are associated with better treatment response with moderate safety concerns. The different dosage forms available enable individualization of treatment.

Monitoring of Recommended Metabolic Laboratory Parameters Among Medicaid Recipients on Second-Generation Antipsychotics in Federally Qualified Health Centers:

Background: In 2004, a consensus statement outlining recommended metabolic monitoring for patients prescribed second-generation antipsychotics (SGAs) was published. More than a decade later, suboptimal adherence rates to these recommendations continue to be reported, which could lead to long-term and costly complications. Objectives: To define the prevalence of appropriately monitored Medicaid patients receiving care at federally qualified health centers (FQHCs) prescribed SGAs. Methods: This was a retrospective study examining electronic health record and Medicaid claims data to assess the rates of glucose and lipid monitoring for patients prescribed SGAs from January 2014 to August 2016 in a FQHC. Prescription and laboratory claims for patients receiving care at 4 FQHCs were reviewed. Descriptive statistics were used to evaluate the primary outcome. Results: A total of 235 patients were included in the analysis. Patients initiated on SGA therapy (n = 92) had baseline glucose and lipid monitoring rates of 50% and 23%, respectively. The 3-month monitoring rates were 37% for glucose and 26% for lipids, whereas annual rates were 71% and 40%, respectively. Patients continuing SGA therapy (n = 143) had annual glucose and lipid monitoring rates of 67% and 44%. Conclusions: Medicaid patients at FQHCs initially prescribed SGAs have low baseline and 3-month metabolic monitoring, whereas annual monitoring was comparable to previously published studies. Adults receiving chronic care at a FQHC were more likely to receive glucose monitoring. Those with type 2 diabetes mellitus and/or hyperlipidemia were more likely to receive glucose and lipid monitoring.