Brian C. Lund

The Anticholinergic Drug Scale as a measure of drug-related anticholinergic burden: associations with serum anticholinergic activity.

Anticholinergic Drug Scale (ADS) scores were previously associated with serum anticholinergic activity (SAA) in a pilot study. To replicate these results, the association between ADS scores and SAA was determined using simple linear regression in subjects from a study of delirium in 201 long‐term care facility residents who were not included in the pilot study. Simple and multiple linear regression models were then used to determine whether the ADS could be modified to more effectively predict SAA in all 297 subjects. In the replication analysis, ADS scores were significantly associated with SAA (R 2 = .0947, P <.0001). In the modification analysis, each model significantly predicted SAA, including ADS scores (R 2 = .0741, P <.0001). The modifications examined did not appear useful in optimizing the ADS. This study replicated findings on the association of the ADS with SAA. Future work will determine whether the ADS is clinically useful for preventing anticholinergic adverse effects.

Risperidone versus clonidine in the treatment of children and adolescents with Tourette's syndrome.

OBJECTIVE To evaluate the efficacy and tolerability of risperidone in comparison with clonidine in the treatment of children and adolescents with Tourettes syndrome (TS). METHOD Following a 7- to 14-day single-blind, placebo lead-in, 21 subjects aged 7 to 17 years were randomly assigned to 8 weeks of double-blind treatment with clonidine or risperidone. Research scales evaluated tics and comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms. RESULTS Risperidone and clonidine appeared equally effective in the treatment of tics in an intent-to-treat analysis, as rated by the Yale Global Tic Severity Scale (YGTSS). Risperidone produced a mean reduction in the YGTSS of 21%; clonidine produced a 26% reduction. Among subjects with comorbid obsessive-compulsive symptoms, 63% of the risperidone group and 33% of the clonidine group responded to treatment (not significant). The most common adverse event seen with both treatments was sedation, which was mild to moderate in severity. Sedation subsequently resolved with continued administration of the medication or with a dose reduction. No clinically significant extrapyramidal symptoms were observed. CONCLUSIONS In this pilot study, risperidone demonstrated efficacy equivalent to clonidine in the treatment of tic symptoms in children and adolescents with TS. Further research is needed to clarify the role of atypical antipsychotics in TS and to delineate potential benefits for comorbid obsessive-compulsive and attention-deficit/hyperactivity symptoms.

Inappropriate Prescribing Predicts Adverse Drug Events in Older Adults

BACKGROUND Explicit measures of potentially inappropriate prescribing, such as the Beers criteria, have been associated with risk for adverse drug events (ADEs). However, no such link has been established for actual inappropriate prescribing using implicit measures. OBJECTIVE To determine whether an implicit measure of inappropriate prescribing can predict ADE risk. METHODS Patients were veterans aged 65 years and older who were seen in primary care clinics and participated in a randomized controlled trial of a pharmacist-physician collaborative intervention. Inappropriate prescribing was determined at baseline, using the 2003 Beers criteria as an explicit measure and the Medication Appropriateness Index (MAI) as an implicit measure. A modified MAI scoring approach was designed to target ADE risk and was used in addition to standard scoring. ADEs that occurred during the 3 months following baseline were assessed by patient interview and plausibility verification by blinded pharmacist review. Logistic regression analysis was used to determine whether inappropriate prescribing predicted risk for an ADE, controlling for potential confounding factors. RESULTS Of 236 patients, 34 (14.4%) experienced an ADE. Inappropriate prescribing was common at baseline, with 48.7% of patients receiving a Beers criteria drug and 98.7% of patients having an inappropriate rating on at least 1 MAI criterion. Modified MAI scoring, but not other measures of inappropriate prescribing, significantly predicted ADE risk. For every unit increase in modified MAI score (3.1 +/- 3.5; mean +/- SD), the adjusted 3-month odds of an ADE increased 13% (OR 1.13; 95% CI 1.02 to 1.26). For example, patients with a modified MAI score of 3, near the precise mean score of 3.1, were at a nearly 40% greater risk for an ADE compared with patients with a score of zero. CONCLUSIONS Implicit measurement of actual inappropriate prescribing predicted ADE risk, an important clinical outcome. This finding helps confirm the validity of prior studies that have relied on explicit measures to link potentially inappropriate prescribing to adverse health outcomes.

Weight gain associated with the −759C/T polymorphism of the 5HT2C receptor and olanzapine

Weight gain from atypical antipsychotic use has become a significant problem. Recent reports have liked the −759 polymorphism of the 5HT2C receptor and obesity as well as weight gain from chlorpromazine, risperidone, and clozapine.

Anabolic steroids: a review for the clinician.

AbstractThe number of athletes self-administering ergogenic pharmacological agents to increase their competitive edge continues to be a problem. Most athletes using anabolic steroids (AS) have acquired a crude pharmacological database regarding these drugs. Their opinions regarding steroids have been derived from their subjective experiences and anecdotal information. For this reason, traditional warnings regarding the lack of efficacy and potential dangers of steroid misuse are disregarded. A common widely held opinion among bodybuilders is that the anabolic steroid experts are the athletic gurus who for years have utilised themselves as the experimental participants and then dispensed their empirical findings. This review will address the common anabolic steroid misconceptions held by many of today’s athletes by providing an evaluation of the scientific literature related to AS in athletic performance.

Olanzapine plasma concentrations and clinical response : Acute phase results of the North American Olanzapine Trial

Olanzapine is an atypical antipsychotic that is effective in the treatment of schizophrenia. Olanzapine plasma concentrations ≥ 9.3 ng/mL (24 hours postdose) have been identified as a predictor of clinical response in acutely ill patients with schizophrenia. The authors report a receiver operating characteristic (ROC) curve analysis of 12-hour olanzapine concentrations and treatment response from the North American Double-Blind Olanzapine Trial. After a 4- to 7-day placebo lead-in, patients meeting DSM-III-R criteria for schizophrenia were randomly assigned to receive olanzapine, haloperidol, or placebo. Patients who were randomly assigned to receive olanzapine were given daily doses ranging from 2.5 to 17.5 mg/day for up to 6 weeks. Blood samples for the determination of olanzapine plasma concentrations were obtained between 10 and 16 hours (11.7 ± 1.7 hours) after the last dose was administered. Therapeutic response data and olanzapine concentrations used for analysis were obtained from the endpoint visit for each patient if the patient had been receiving a fixed olanzapine dose for at least the last 2 weeks of the study. Plasma concentrations from previous visits were used if endpoint concentrations were invalid. Response was defined as a ≥ 20% reduction in Brief Psychiatric Rating Scale (BPRS) scores and a Clinical Global Impression (CGI) Severity scale score of ≤ 3 or a final BPRS score of ≤ 35. The final ROC analysis included data from 84 patients and suggested an olanzapine concentration ≥ 2 3.2 ng/mL to be a predictor of therapeutic response. Fifty-two percent of patients with 12-hour olanzapine concentrations ≥ 23.2 ng/mL responded, whereas only 25% of patients with concentrations <23.2 ng/mL responded. Furthermore, an olanzapine concentration ≥ 23.2 ng/mL was a predictor of response in the Scale for the Assessment of Negative Symptoms (≥ 20% decrease and endpoint CGI ≤ 3). Olanzapine concentrations were found to be a function of olanzapine dose (in milligrams per day) and gender such that prospective olanzapine dosing is feasible. A 12-hour olanzapine plasma concentration of >23.2 ng/mL was a predictor of therapeutic response in acutely ill patients with schizophrenia. Males required a higher olanzapine dose to reach this threshold concentration than their female counterparts.

The concurrent use of anticholinergics and cholinesterase inhibitors: Rare event or common practice?

Objectives: To measure the prevalence of anticholinergic use cross‐sectionally in patients receiving cholinesterase inhibitors and to describe change in use of anticholinergics upon inception of cholinesterase inhibitor treatment.

Anabolic steroid use in weightlifters and bodybuilders: an internet survey of drug utilization.

Purpose:Dietary supplements and ergogenic agents, including anabolic steroids, are common components of present-day bodybuilder and weightlifter training regimens. Prior reports of anabolic steroid use suggest polypharmacy and high doses of injectable agents. Hypothesis:To provide an updated description of anabolic steroid regimens employed by weightlifters and bodybuilders and to determine the extent to which anabolic steroid-associated behaviors are consistent with substance dependence. Study Design:Web-based survey. Methods:Links to the Web-based survey instrument were established from leading bodybuilding and fitness web pages. The questionnaire included demographic information, anabolic drug use history, adverse effects, information sources, and steroid use behavior consistent with criteria for a substance dependence disorder. Results:A total of 207 subjects provided a detailed anabolic steroid drug history. Steroid regimens included a mean of 3.1 agents, involved cycles ranging from 5 to 10 weeks, and often included doses 5 to 29 times greater than physiologic replacement doses. Behavior consistent with a substance dependence disorder was endorsed by 33% of respondents. Conclusions:These findings suggest that anabolic steroid use among weightlifters and bodybuilders continues, generally involving multiple steroids and additional dietary supplementary agents. The adverse effects, polypharmacy, large dosages, and risk of substance abuse are all major health care concerns that require further study. Clinical Relevance:The survey findings provide sports medicine practitioners a reasonable estimate of the expected drug history among bodybuilders and weightlifters for the use of performance-enhancing agents.

Evaluation of the Iowa Medicaid pharmaceutical case management program.

OBJECTIVE To test the effect of pharmaceutical case management (PCM) on medication safety and health care utilization. DESIGN Prospective cohort design with 9-month follow-up period (enrollment from October 1, 2000, through July 1, 2001, with follow-up through July 1, 2002). SETTING Iowa Medicaid program. PARTICIPANTS 2,211 noninstitutionalized, continuously eligible Iowa Medicaid patients taking four or more chronic medications including at least one agent commonly used in at least 1 of 12 specific diseases who were cared for by pharmacists in 117 pharmacies. INTERVENTIONS Reimbursement for PCM services (initial patient assessment, written recommendations to physician, follow-up assessments and communication of progress and new problems to physician). MAIN OUTCOME MEASURES Use of high-risk medications, Medication Appropriateness Index (MAI) score, health care utilization. RESULTS Pharmacists in 114 pharmacies had eligible patients during at least one quarter during the study period; 28 pharmacies were classified as high intensity based on the number of PCM patients they managed. A total of 524 of the eligible patients received 1,599 PCM services; 90% of claims were filed by pharmacists, and the remainder by physicians. Nearly one half (46.1%) of medications and 92.1% of patients had at least one medication problem before PCM. By closeout, the percentage of medications with problems decreased in 8 of 10 MAI domains for those who received PCM. Compared with baseline, mean MAI score improved significantly from 9.4 to 8.3 among PCM recipients (P < .001). Percentage of PCM recipients using high-risk medications decreased significantly compared with PCM eligibles who did not receive the service. In the 28 pharmacies that adopted the new service most intensely, patients had a significant decrease in high-risk medication use, compared with patients of low-intensity pharmacies (P < .001). No difference was observed between PCM recipients and PCM eligibles who did not receive PCM in health care utilization or charges, even after including reimbursements for PCM. CONCLUSION Medication safety problems were prevalent in this high-risk population. The PCM program improved medication safety during a 9-month follow-up period.

Bupropion SR vs. Methylphenidate vs. Placebo for Attention Deficit Hyperactivity Disorder in Adults

Despite the increasing recognition of attention-deficit hyperactivity disorder (ADHD) in adults, there are few controlled trials demonstrating the effectiveness of pharmacological treatments, particularly with nonstimulants. One controlled trial found bupropion SR more effective than placebo in the treatment of ADHD adults. We conducted a controlled study to contrast the effectiveness of bupropion SR and methylphenidate to placebo in ADHD adults. A randomized, double-blind, parallel design was used in this study. Following a 7-day placebo lead-in, 30 ADHD (DSM-IV) subjects (18–60 years old) were randomized to bupropion, methylphenidate, or placebo for 7 weeks. Methylphenidate was titrated over 1 week to a maximum dose of 0.9 mg/kg/d divided into 3 doses while bupropion was titrated over 2 weeks to a maximum dose of 200 mg A.M. and 100 mg P.M. Response rates based on Clinical Global Impression improvement ratings in patients receiving bupropion, methylphenidate, and placebo were 64, 50, and 27%, respectively. The difference in response rates between active treatment and placebo was not statistically significant (p = 0.14). Neuropsychological testing demonstrated trends favoring drug treatment on measures of immediate recall and verbal fluency. While bupropion SR may be a viable clinical alternative for adults with ADHD, further investigation is needed.