Paul J. Perry

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.

Recombinant Human Erythropoietin Treatment in Pre-Dialysis Patients: A Double-Blind Placebo-Controlled Trial

STUDY OBJECTIVE To determine the efficacy and safety of recombinant human erythropoietin (r-HuEPO) in predialysis renal patients. DESIGN Randomized, double-blind, placebo-controlled trial for 8 weeks. SETTING Inpatient and outpatient facility in the Clinical Research Center of a university-based hospital. PATIENTS Fourteen adult subjects with renal insufficiency (mean serum creatinine, 473 mumol/L +/- 61 [6.2 +/- 0.8 mg/dL]) and anemia (mean hematocrit, 0.27 +/- 0.01). INTERVENTIONS Recombinant human erythropoietin, 50, 100, or 150 IU/kg body weight or placebo given intravenously three times per week. MEASUREMENTS AND MAIN RESULTS Subjects who received active r-HuEPO showed a dose-dependent rise in hematocrit; mean hematocrit increased 41% from 0.27 +/- 0.01 to 0.38 +/- 0.01. At the same time, erythrocyte mass rose 43% from 13.7 +/- 0.6 mL/kg in the baseline state to 19.6 +/- 1.0 mL/kg after treatment. Maximal oxygen consumption during exercise increased 9% from 16.0 mL/min.kg +/- 1.8 to 17.5 mL/min.kg +/- 1.9. CONCLUSIONS Recombinant human erythropoietin is effective and safe in ameliorating the anemia of pre-dialysis patients.

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.

Pharmacotherapy for major depression with melancholic features: relative efficacy of tricyclic versus selective serotonin reuptake inhibitor antidepressants

The effectiveness of tricyclic antidepressants (TCAs) and selective serotonin reuptake inhibitors (SSRIs) were contrasted in endogenous/melancholic depression. By reviewing Hamilton Depression Rating data from controlled trials, the data indicate that TCAs are consistently more effective than the SSRIs. Despite the wide use of SSRIs in the treatment of depression, it seems reasonable that clinicians subtype their depressed patients and treat melancholic patients first with a course of TCAs. For melancholic patients who have not responded to a SSRI, pharmacotherapeutic alternatives include (1) a TCA alone; (2) TCA augmentation of the SSRI, or (3) lithium augmentation of the SSRI.

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.

Psychosexual effects of three doses of testosterone cycling in normal men.

BACKGROUND Testosterone is receiving increased attention for contraceptive and therapeutic indications. The potential psychosexual side effects of testosterone therapy and withdrawal are unclear. METHODS Healthy men between the ages of 21 and 40 years were recruited via advertisement for a randomized, controlled, double-blind study of acute and withdrawal effects of three doses of testosterone. Two weeks of placebo injections were followed by one of three randomized weekly doses of testosterone cypionate (100 mg, 250 mg, or 500 mg) for the next 14 weeks. Twelve weeks of placebo injections followed during the withdrawal phase of the study. Psychosexual effects were monitored throughout the study. RESULTS All doses of testosterone demonstrated only minimal effects on measures of mood and behavior during acute and withdrawal phases for all study completers. There were no effects on psychosexual function. There was no evidence of a dose-dependent effect on any measure. One noncompleter on 500 mg of testosterone developed a brief syndrome with symptoms similar to an agitated and irritable mania. CONCLUSIONS Doses of testosterone up to five times physiologic replacement dose appear to have minimal risk of adverse psychosexual effects in the majority of normal men; however, beginning at around 500 mg per week of testosterone cypionate, a minority of normal men may experience significant adverse psychological effects. Because illicit anabolic steroid users may use larger doses of multiple drugs under less restrictive conditions, our study may significantly underestimate the psychological effect of steroid use in the community.

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.