Adverse Effect Assessment Methods in Clinical Trials of Psychotropic Medications: Implications for Social Workers' Role in Medication Monitoring (WITHDRAWN)

BACKGROUND and PURPOSE: Psychotropic medications are among the most widely used class of prescription drugs, with notably rapid expansion in use among children and adolescents. Currently, an estimated 6% of youth in the general population and 11.7% of youth involved in the child welfare system take at least one psychotropic drug. With such common use, the efficacy and safety of drug treatment should be central to determinations of individual and system-level practice effectiveness. However, while efficacy of psychotropic drugs is featured and highlighted in clinical trial research, the identification and reporting of adverse effects and harms is often neglected or under-reported. The present study examines types of adverse effect assessment methods used in clinical trials of three popular psychotropic drugs and investigates whether methods changed over time to be responsive to safety concerns emerging after marketing approval. This research holds important implications for developing social workers’ roles in medication monitoring.   

METHODS: Industry-funded published trials of atomoxetine (Strattera), duloxetine (Cymbalta), and olanzapine (Zyprexa) were retrieved from PubMed for the time period close to the drugs’ original marketing approval (1996-2004; n=33) and then several years post-approval (2009-2014; n=40). Verbatim adverse effect assessment methods and numbers of words describing efficacy and safety assessment were extracted by two coders. Results are presented using descriptive statistics.  

RESULTS: A total of 25,125 patients were enrolled across all 73 studies, with median study length of 8 to 12 weeks. Closest to drug approval (1996-2004), 77.8% of atomoxetine trials used open-ended questioning only, 50% of duloxetine trials used spontaneous self-report or clinician observation only, and 66.7% of olanzapine trials used a scale (primarily for extrapyramidal symptoms) and one former method. Open-ended questioning and spontaneous self-report assessment methods are known to underestimate the frequency of adverse effects. Recent studies (2009-2014) showed less rigor and transparency: 35.3% of atomoxetine and 64.7% of duloxetine studies reported no adverse effect assessment method and 50% of olanzapine studies no longer used scales. A large proportion (42.5%) of recently published clinical drug trials thus failed to report any method for identifying or assessing adverse effects, demonstrating a greater degree of neglect of possible drug harms than early trials conducted for marketing approval.  Overall, the mean number of words describing efficacy assessment increased from 202 to 309 but decreased from 83 to 63 for safety.

CONCLUSIONS and IMPLICATIONS: Trial methodology for assessing psychotropic drug safety remains an underdeveloped area with major public health implications. Social workers should understand the limits of what is known about psychotropic medications and adopt practice roles that emphasize medication monitoring for possible undetected adverse effects and harms. Social workers are positioned to adopt a more intensive role in medication monitoring due to greater involvement with multiple aspects of clients’ lives, often including contact with clients’ families, schools, workplaces, and other natural settings where medications’ effects can be observed. Simple checklists for treatment-emergent effects of medications on clients’ mood, behavior, and body can be implemented to more quickly identify possible medication-related concerns and ensure the safety of medicated clients.