Catherine Harrington

Tolerability of paliperidone: a meta-analysis of randomized, controlled trials

Balancing tolerability and efficacy of medications can be problematic for clinicians when assessing appropriate therapy for patients. For antipsychotic therapy, this can be especially challenging because of the hazardous movement and metabolic effects associated with them. Paliperidone is an atypical antipsychotic used for the treatment of schizophrenia and schizoaffective disorder. A systematic review of the literature for the tolerability of the drug, paliperidone, was performed. A total of 15 articles met the criteria for inclusion representing a total of 3779 patients. Data combination was conducted using the Mantel–Haenszel method, random effects model at 95% confidence. Adverse events with the greatest incidence in the paliperidone population were any treatment emergent adverse event (68%), extra-pyramidal symptoms (23%), headache (14%), insomnia (11%), somnolence (9%), tachycardia (9%) and weight gain (8%). Reported events most likely related to paliperidone [largest attributable risks (AR)] were extra-pyramidal symptoms (AR=10), reduction in acute psychosis (AR=8), any treatment emergent adverse event (AR=6), tachycardia (AR=4), and weight gain (AR=4). Events where incidence was entirely because of paliperidone (incidence equals AR) were hypersalivation (3), dysarthria (2), and sexual dysfunction (1). Reported events totally unrelated to paliperidone (AR=0) included anxiety, asthenia, constipation, depression, dyspepsia, glucose related events, and vomiting. Overall, a 50% reduction in treatment emergent psychosis was seen in schizophrenic patients treated with paliperidone, however the reduction of a psychotic event is about equal to the occurrence of an adverse event with paliperidone.

The Incidence of Akathisia in the Treatment of Schizophrenia with Aripiprazole, Asenapine and Lurasidone: A Meta-Analysis.

Akathisia is a troubling side effect that leads to non-adherence with antipsychotic regimens. Second generation antipsychotics (SGAs) tend to cause less akathisia than older agents but the risk still exists and rates vary between agents. Little is known about the incidence of akathisia among the newer SGAs. The purpose of this study was to conduct a meta-analysis of akathisia incidence rates for three of the newer SGAs: aripiprazole, asenapine, and lurasidone. Data were drawn from published and unpublished clinical trials comparing the drug of interest to either placebo or another SGA in adults with schizophrenia. Twenty-four studies (11 aripiprazole, 5 asenapine, and 8 lurasidone) provided incidence rates for akathisia and related nervous system events. Data showed that the relative risk (RR) of akathisia was double that of controls, with lurasidone having the highest individual RR at 2.7 [CI: 2-3.6]. Sensitivity analysis changed the RR of akathisia to less than 10%. The RR of akathisia was still elevated (1.75 [1.4-2.1]) when these drugs were compared only to actives (older SGAs). Agitation and anxiety RRs were also higher with the newer SGAs as compared to the older SGAs. Previous theory suggests antagonism of serotonin (5-HT)2A receptors may decrease akathisia risk. Expectations were that aripiprazole, asenapine and lurasidone would have a low incidence of akathisia, as all display strong antagonism at 5-HT2A. However, in this study all three had a significantly higher risk of akathisia compared to placebo or other SGAs. This suggests the pathophysiology of akathisia involves other receptors and is multifactorial.

Marketing Retail Health Clinics: Challenges and Controversies Arising From a Health Care Innovation

Since their founding in 2000, retail-based health care clinics, also called convenient care clinics, have flourished but continue to generate controversy. This article examines the literature with respect to the industrys background, establishment of industry standards, types of services offered, marketing of retail health clinics, industry growth with new target markets, and patient demographics. It also examines the growing relationship with insurers and third-party payers, quality-of-care concerns by medical associations, and legal regulations and their potential impact on industry growth nationwide.

Adverse Drug Events Related to Ziprasidone: A Meta‐analysis of Randomized, Placebo‐Controlled Trials

Study Objective. To assess the drug‐related risk of adverse events associated with ziprasidone.

An updated systematic review and meta-analysis on the efficacy and tolerability of dipeptidyl peptidase-4 inhibitors in patients with type 2 diabetes with moderate to severe chronic kidney disease

Objective: This updated meta-analysis determines the effect of dipeptidyl peptidase-4 inhibitors on glycemic and tolerability outcomes in patients with type 2 diabetes mellitus and chronic kidney disease with glomerular filtration rate of ⩽60 mL/min or on dialysis. Methods: In all, 14 citations were identified from multiple databases. Qualitative assessments and quantitative analyses were performed. Results: There were 2261 participants, 49–79 years of age, 49% men and 44% Caucasians. In seven placebo-comparator studies, reduction in hemoglobin A1c at weeks 12–24 was 0.55% (95% confidence interval: −0.68 to −0.43), P < 0.00001). In three sulfonylurea-comparator studies, dipeptidyl peptidase-4 inhibitors did not significantly reduce hemoglobin A1c at weeks 52–54 (−0.15% (95% confidence interval: −0.32 to 0.02)). In one sitagliptin versus albiglutide study, albiglutide significantly reduced hemoglobin A1c in patients with moderate renal impairment (−0.51%). A similar reduction in hemoglobin A1c was seen with sitagliptin versus vildagliptin (−0.56% vs −0.54%). Compared with placebo or sulfonylurea, dipeptidyl peptidase-4 inhibitors did not significantly reduce hemoglobin A1c after 12 and 54 weeks in patients on dialysis. Hypoglycemia was reported by ~30% of patients in both dipeptidyl peptidase-4 inhibitors and placebo groups over 24–52 weeks. While hypoglycemia was more common with a sulfonylurea at 52–54 weeks (risk ratio: 0.46 (95% confidence interval: 0.18 to 1.18)), there was significant heterogeneity (I2 = 87%). Limitations included high drop-out rate from most studies and small number of active-comparator studies. Conclusions: Dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease caused a modest reduction in hemoglobin A1c versus placebo, but not when compared with sulfonylureas or albiglutide, or when used in patients on dialysis. Additional active-comparator studies are needed to further elucidate the role of dipeptidyl peptidase-4 inhibitors in patients with chronic kidney disease stages 3–5 or on dialysis.

The role of paliperidone extended release for the treatment of bipolar disorder

Background Bipolar disorder (BD) is a chronic, relapsing, episodic mental illness associated with other psychiatric comorbidities. There is a substantial economic burden with BD, which makes it challenging to treat. The aim of this review is to evaluate the pharmacology, clinical efficacy, and safety data related to paliperidone extended release (ER) for the treatment of BD. Methods A literature search was performed from January 1966 through January 2012 using PreMEDLINE, MEDLINE, EMBASE, IPA, and ClinicalTrials.gov to identify articles in English regarding the pharmacology, clinical efficacy, and safety of paliperidone ER in acute mania or mixed episodes or in the maintenance treatment of BD I. Results There are currently three published studies relating to the use of paliperidone ER for the treatment of BD. Two of these evaluated paliperidone ER as monotherapy for acute mania, while the other assessed its role as adjunct with a mood stabilizer. Conclusion According to the limited available evidence, paliperidone at higher doses of ER 9–12 mg/day may be a safe and efficacious treatment option for acute episodes of mania in BD. A once-daily dose formulation may improve patient adherence to treatment; however, the cost of paliperidone ER, which is higher than that of generically available second-generation antipsychotics (such as olanzapine and risperidone), and a lack of alternative dosage forms (ie, liquid, intramuscular) compared with other agents may limit its usefulness in the treatment of BD. The role of paliperidone ER as an adjunctive agent or for long-term use requires further investigation.

Banning Tobacco Sales at the Retail Pharmacy: Natural Evolution of Drug Store As Responsible Health Provider Or Effective Marketing Strategy?

CVS Health has taken a strategic marketing move by banning tobacco sales. They risk losing customers who buy medications and cigarettes at their drugstores. They estimate they will lose 2 billion dollars by banning cigarette sales. CVS Health believes they will benefit from being regarded as health care partner by insurers and banning cigarette sales is an important step in being recognized as such. The Affordable Care Act expanded access to pharmacy-based medical clinics, increased affordability of medications, and expanded the clinical role of pharmacists. CVS Health is positioning itself to take advantage of these changes.

The association of vitamin D deficiency and glucose control among diabetic patients

Objective To evaluate the association between the level of vitamin D and glycemic control among patients with diabetes. Research design and method We analyzed data collected from NHANES 2003–2006. We included only non-pregnant adult diabetic persons 18 years or older. Participants who had vitamin D level less than 20 ng/ml were considered as having vitamin D deficiency. Participants were considered to have a glucose control if the HbA1c level was less than 7% [53 mmol/L]. We used student’s t test to compare the difference in HbA1c means between people with Diabetes with and without a vitamin D deficiency. We used a multivariate logistic regression model to predict the relationship between glucose control and vitamin D deficiency. We used race/ethnicity, BMI, age, gender, type of diabetic medication used, having health insurance or not, and comorbid conditions (hypertension, anemia, cholesterol, liver disease, and kidney disease) as control variables. Results The study population included a total of 929 non-institutionalized, non-pregnant, diabetic adult persons. About 57% of patients with diabetes had a vitamin D deficiency. Blacks (non-Hispanic patients) with diabetes had the highest rate of vitamin D deficiency (79%). The unadjusted means of HbA1c were significantly different between diabetic patients with no vitamin D deficiency and those with a vitamin D deficiency (7.06% [54 mmol/L], 7.56 % [59 mmol/L], respectively, P < 0.0001). Multivariate adjustment showed a small but not significant, increase in odds (11%) of having uncontrolled diabetes in patients with a vitamin D deficiency after adjustment for other factors. Conclusion Vitamin D deficiency is very common in patients with diabetes. We found no significant association between vitamin D level and glycemic control in patients with diabetes after adjustment for control variables.