Newsletter No. 3, 2008 www.psychopharmbulletin.com Volume 41 • Number 3 • 2008

Psychopharmacology BULLETIN Newsletter

the advance newsletter of Psychopharmacology BULLETIN
Summary—Index of This Issue On-Press

Cocaine is a Major Risk Factor for Antipsychotic Induced Akathisia, Parkinsonism and Dyskinesia

abstract ~ Objective: To assess the relative contribution of different drugs of abuse to extrapyramidal side effects (EPS) of antipsychotic drugs. Method: 106 consecutively contacted or admitted male patients in the Psychiatric Center of Surinam (PCS) with schizophrenia or a related disorder were included. Prevalence and severity of EPS were measured with the Unified Parkinson’s Disease Rating Scale (UPDRS), the Abnormal Involuntary Movement rating Scale (AIMS), the Barnes Akathisia Rating Scale (BARS) and the Dystonia rating scale. Recent use of cigarettes, cannabis, alcohol, and cocaine were assessed. Standard multiple regression analyses were used to evaluate the relative contribution of above-mentioned drugs of abuse controlled for milligrams haloperidol equivalent a day and use of anticholinergic medication. Results: Recent cocaine use was significantly associated with severity of dyskinesia (p 5 0.001), parkinsonism (p 5 0.007), and akathisia (p , 0.001) (n 5 106). Conclusions: Recent cocaine use is a major risk factor for antipsychotic induced EPS.
Arija Maat, Annemarie Fouwels, Lieuwe de Haan, Psychopharmacology Bulletin. 2008;41(3):5–10.

The Efficacy and Tolerability of Once-Daily Extended Release Quetiapine Fumarate in Hospitalized Patients with Acute Schizophrenia: A 6-Week Randomized, Double-Blind, Placebo-Controlled Study

abstract ~ Objectives: This study aimed to demonstrate efficacy of once-daily extended release quetiapine fumarate (quetiapine XR) versus placebo in patients with acute schizophrenia. Methods: In this 6-week, randomized, double-blind study (5077IL/0041) patients were randomized to receive quetiapine XR (300, 600, or 800 mg/day), quetia- pine fumarate immediate release (quetiapine IR) [300 or 600 mg/day], or placebo. Primary endpoint was change from baseline in the Positive and Negative Syndrome Scale (PANSS) total score at Day 42. Secondary variables included PANSS response rate at Day 42 ($30% decrease in PANSS total score from baseline) and Clinical Global Impressions Severity (CGI-S) and Improvement (CGI-I) ratings. Safety assessments included adverse event (AE) reporting and laboratory measures. Results: Of 532 patients randomized, 222 (41.7%) completed the study. Improvements in PANSS total scores from baseline to Day 42 across treatment groups were: quetiapine XR 300 mg/day 25.01, 600 mg/day 213.01 and 800 mg/day 211.17, quetiapine IR 300 mg/day 29.42 and 600 mg/day 26.97, and placebo 25.19; the difference in change was statistically significant only for quetiapine XR 600 mg/day (p 5 0.033). There were no statistically significant differences between active treatment groups and placebo for PANSS response rates. Several post hoc analyses were conducted to explain the study efficacy outcome but these were inconclusive. Quetiapine XR was generally well tolerated with the majority of AEs being mild or moderate in intensity and no unexpected AEs. Conclusions: Superior efficacy of quetiapine XR versus placebo in patients with schizophrenia was demonstrated for quetiapine XR 600 mg/day. The safety and tolerability profile of quetiapine XR was similar to that of quetiapine IR.
Jean-Pierre Lindenmayer, David Brown, Sherry Liu, Martin Brecher, and Didier Meulien, on behalf of the Study 41 inv,estigators, Psychopharmacology Bulletin. 2008;41(3):11-35.

A Major Change of Prescribing Pattern in Absence of Adequate Evidence: Benzodiazepines Versus Newer Antidepressants in Anxiety Disorders

abstract ~ We performed a systematic review of controlled trials on anxiety disorders treatment (generalized anxiety disorder, panic disorder, social phobia and post traumatic stress disorder) published from 1980 to 2006, and identified trials comparing the efficacy of benzodiazepines (BZD) with that of antidepressants, in particular comparisons between BZD and newer antidepressants. Among 969 publications, 274 double-blind randomized controlled studies remained after using our exclusion criteria. These studies comprised altogether 439 comparisons. There were in total 23 comparisons of antidepressants versus BZD. Among these, 22 compared the efficacy of older antidepressants versus BZD, whereas only 1 concerned the comparison of a newer antidepressant versus BZD. It showed comparable efficacy between venlafaxine and diazepam in the treatment of generalized anxiety disorder. Our study shows that the major change of prescribing pattern from BZD to newer antidepressants in anxiety disorders has occurred in absence of comparative data of high level of proof.
Patricia Berney, Demian Halperin, Rodrigo Tango, Isabelle Daeniker-Dayer, Pierre Schulz, Psychopharmacology Bulletin. 2008;41(3):39–47.

 

Developing and Testing Adaptive Treatment Strategies Using Substance-Induced Psychosis
as an Example

Abstract ~ Decisions concerning treatment changes pervade the management of chronic psychiatric disorders that resist definitive cure, yet empirical evidence for the comparative clinical effectiveness of treatment strategies remains underdeveloped. In this paper we exploit the example of psychosis following substance use to illustrate some new developments in clinical trials design that can provide the most solid evidence base for defining successful strategies. The intent is to explore the strengths and limitations of the methodological approach through a meaningful clinical example, with an emphasis on concepts and issues. Both methodology and clinical science are overviewed.
Ree Dawson, Alan I. Green, Robert E. Drake, Thomas H. McGlashan, Bella Schanzer, Philip W. Lavori Psychopharmacology Bulletin. 2008;41(3):51–67.

Psychometric Evaluation of a Patient-Rated Troubling Symptom Scale for Generalized Anxiety Disorder Clinical Trials

ABSTRACT ~ Background: The majority of clinical outcome assessments developed for generalized anxiety disorder (GAD) may not efficiently and sensitively reflect heterogeneous symptom clusters from a patient perspective. The Patient-Rated Troubling Symptoms Scale for Anxiety (PaRTS-A) instrument was developed to provide an individualized assessment of patient relevant GAD symptoms. Objective: The objective of this analysis was to evaluate the psychometric characteristics of the PaRTS-A. Methods: Data were taken from a 6-week clinical trial evaluating the efficacy of adjunctive risperidone therapy in GAD patients undergoing standard treatment. Patients completed the PaRTS-A, the Quality of Life Enjoyment and Satisfaction Questionnaire (Q-LES-Q), and the Sheehan Disability Scale (SDS) as well as impressions of improvement. Physicians completed the Hamilton Anxiety Rating Scale (HAM-A). A instrument characteristics were assessed through statistical tests of reliability, reproducibility, construct and discriminant validity, and responsiveness. Results: In the item response theory (IRT) analysis, the PaRTS-A items fit into a single construct of anxiety. Internal consistency reliability exceeded 0.70. The PaRTS-A total score was moderately correlated with the Q-LES-Q and the SDS. The PaRTS-A distinguished between patients with high and low HAM-A scores (p,0.001). The PaRTS-A was responsive to changes in clinical status and the minimal important difference was identified. Conclusion: The PaRTS-A provides a unique patient-rated assessment of anxiety symptoms. The instrument may provide clinicians with useful information regarding patient’s self-rated anxiety disorder symptoms and the hierarchy of symptoms that they considered most troubling. Our analysis suggests that the PaRTS-A is an internally consistent, valid, and responsive instrument that may be a beneficial adjunct to other instruments in clinical trials.
Gahan J. Pandina, Dennis A. Revicki, Leah Kleinman, Ibrahim Turkoz, Jasmanda Wu, Ramy Mahmoud, Georges M. Gharabawi, Psychopharmacology Bulletin. 2008;41(3):68–90.

Placebo Response in Depression: A Perspective for Clinical Practice

abstract ~ Practicing clinicians appreciate that depression is not an easy disorder to treat and manage. Despite the plethora of new treatments—both pharmacological and non pharmacological—that has flooded the market in the past years, we are still nowhere close to obtaining full symptom relief for all patients and eradicating the morbidity and mortality associated with depression.

In this context, recent methodological research, concentrating on the effectiveness of antidepressants has raised doubts about their therapeutic index. Because of obtuseness of the methodology and biased interpretations, we are submitting this perspective to clinicians so that they can appreciate some of the deficits of the recent research publications. For the practicing clinician, the best available data suggest that clinically depressed patients warrant treatment and the most robust available body of data (published and unpublished) would favor the use of antidepressants.
Arif Khan, Shirin Khan, Psychopharmacology Bulletin. 2008;41(3):91–98.