Carol Ott

The cognitive impact of anticholinergics:a clinical review

Context: The cognitive side effects of medications with anticholinergic activity have been documented among older adults in a variety of clinical settings. However, there has been no systematic confirmation that acute or chronic prescribing of such medications lead to transient or permanent adverse cognitive outcomes. Objective: Evaluate the existing evidence regarding the effects of anticholinergic medications on cognition in older adults. Data sources: We searched the MEDLINE, OVID, and CINAHL databases from January, 1966 to January, 2008 for eligible studies. Study selection: Studies were included if the anticholinergic activity was systematically measured and correlated with standard measurements of cognitive performance. Studies were excluded if they reported case studies, case series, editorials, and review articles. Data extraction: We extracted the method used to determine anticholinergic activity of medications and its association with cognitive outcomes. Results: Twenty-seven studies met our inclusion criteria. Serum anticholinergic assay was the main method used to determine anticholinergic activity. All but two studies found an association between the anticholinergic activity of medications and either delirium, cognitive impairment or dementia. Conclusions: Medications with anticholinergic activity negatively affect the cognitive performance of older adults. Recognizing the anticholinergic activity of certain medications may represent a potential tool to improve cognition.

Adherence, Persistence of Use, and Costs Associated With Second-Generation Antipsychotics for Bipolar Disorder

OBJECTIVE A retrospective study using Medicaid claims identified patients with bipolar disorder for whom oral second-generation antipsychotics were prescribed and compared rates of adherence, persistence of use, and costs across five groups of patients taking aripiprazole, olanzapine, quetiapine, risperidone, or ziprasidone. METHODS Medicaid claims data for 2,446 bipolar patients were analyzed from eight states. The 18-month observation period included the six months before and the 12 months after the index prescription date. Adherence was defined as a medication possession ratio >80%. Persistence of use was measured by the number of days of medication therapy before a 30-day gap. Mental health-related prescription costs, total prescription costs, total mental health-related costs, and total costs were assessed. Ziprasidone was the comparator. RESULTS Clinically recommended doses of second-generation antipsychotic medications were prescribed for 45% of the patients (N = 1,102). Of these, 58% (N = 642 of 1,102) were adherent with the prescribed medication, with no significant differences between medication groups. Median time to nonpersistence of use averaged 96 days. Patients taking olanzapine were about 35% more likely than patients taking ziprasidone to discontinue taking their medication (hazard ratio = 1.34, 95% confidence interval = 1.02-1.76, p = .04). Mental health-related prescription costs and total prescription costs were lower for risperidone than ziprasidone. No statistically significant differences were found between the groups for all mental health-related costs or total costs. CONCLUSIONS Among patients in a sizeable Medicaid cohort for whom a second-generation antipsychotic medication was prescribed, less than half had a clinically recommended dose, and less than two-thirds with a clinically recommended dose were adherent to the medication, confirming that many patients with bipolar disorder do not receive clinically recommended doses of second-generation antipsychotics.

Valproic Acid—Induced Hyperammonemia in a Patient With Schizoaffective Disorder

Valproic acid is used in psychiatry as a mood stabilizer and can be very effective in reducing symptoms of agitation. Valproic acid may cause hyperammonemia through carnitine deficiency created by its inhibition of mitochondrial enzymes in the urea cycle. Clinical presentation of hyperammonemia usually involves lethargy and somnolence, which may also be noted with therapeutic serum concentration during valproic acid therapy. The diagnosis of hyperammonemia is often overlooked due to a clinical presentation that may include normal liver enzyme tests and serum valproate levels that are within the therapeutic range. Treatment modalities may include discontinuation of valproic acid therapy, lactulose, naloxone, and hemodialysis. Carnitine supplementation, for both prevention and acute treatment of hyperammonemia, has been anecdotally reported and may be considered. This article illustrates a case of an adult male with schizoaffective disorder who was treated with valproic acid and subsequently developed hyperammonemia, despite therapeutic valproic acid serum levels and normal liver enzyme tests. Possible causes of hyperammonemia and current treatment options will be described, as well as suggestions for monitoring for this adverse event in the clinical setting.

Extent of use of long-acting injectable antipsychotics in children and adolescents within Indiana Medicaid

Introduction: Oral formulations of the antipsychotics aripiprazole, asenapine, lurasidone, olanzapine, paliperidone, quetiapine, and risperidone are indicated for use in pediatrics for several diagnoses. Long-acting injectable (LAI) antipsychotics are of interest in this special population because they may be used due to convenience and desire to improve adherence, despite limited support in the literature. The primary intent of this study is to provide descriptive information on the use of paliperidone palmitate, risperidone microspheres, aripiprazole extended-release injection, and olanzapine pamoate in pediatric patients within Indiana Medicaid. Methods: This study was a retrospective database analysis, which retrieved information from Indiana Medicaid over a 2-year timeframe spanning from July 1, 2012, through June 30, 2014. The study included the prescription medications filled for all children and adolescents within Indiana Medicaid who received the LAI antipsychotics paliperidone palmitate, risperidone microspheres, aripiprazole extended-release injection, and olanzapine pamoate. Results: From July 1, 2012, through June 30, 2014, 150 Indiana Medicaid patients younger than 18 years old were prescribed a LAI atypical antipsychotic. A total of 1013 LAI atypical antipsychotic doses were billed to Indiana Medicaid during the study period for pediatric patients. Paliperidone palmitate was billed most frequently. Discussion: Long-acting injectable atypical antipsychotics are being prescribed for children and adolescents within Indiana Medicaid, despite minimal clinical evidence supporting use. There is a need for further research in this area to increase generalizability of results and aid in implementation of policies to prevent inappropriate use of LAI antipsychotics in children and adolescents.

Evaluation of adherence and persistence with oral versus long-acting injectable antipsychotics in patients with early psychosis

Introduction: Despite the theory that long-acting injectable (LAI) antipsychotics should be more likely to improve adherence, reduce gaps in therapy, and prevent relapse compared with oral antipsychotics, there is little published evidence on this issue, specifically in patients with early psychosis. Methods: Patients with a new diagnosis for a psychotic disorder between July 1, 2013, and August 31, 2014, were retrospectively evaluated during a 12-month duration. The primary outcomes were adherence and persistence. Adherence was determined by proportion of days with medication, and persistence was defined as zero gaps in medication therapy. The secondary outcome was the number of times a psychiatric acute care service was used. Patients were divided into 3 groups based on their antipsychotic prescription history: oral only, LAI only, or both formulations at separate times throughout the study period. Results: Forty-seven patients met inclusion criteria. The average proportions of days with medication were 32%, 76%, and 75% for the oral, LAI, and both formulations groups, respectively (P < .001). For medication persistence, there were 32 patients (91%), 3 patients (75%), and 5 patients (63%) with at least 1 gap in therapy for the oral, LAI, and both formulations groups, respectively (P = .098). For acute care services, there was a median number of zero acute care visits for each of the 3 groups (P = .179). A post hoc subgroup analysis found medication adherence to be statistically different between the oral and LAI groups. Discussion: Long-acting injectable antipsychotics were associated with better adherence compared with oral antipsychotics in patients with early psychosis.