Abstract
Background/Aims The purpose of this study was to develop a protocol using electronic medical records to identify cases of extreme weight gain (EWG) among adult users of atypical antipsychotics for future pharmacogenomics research.
Methods We used literature reviews and input from an expert panel to develop a working phenotype definition of EWG. We identified eligible antipsychotic users at Group Health and Geisinger Health System from 2004–2009 and extracted a standardized dataset, including: demographics, enrollment, vitals, pharmacy, inpatient and outpatient diagnoses and procedures, and laboratory measures. We then identified subjects with weight gain >7%, >15%, or >25% during an antipsychotic drug treatment episode. Visual inspection of the weight trajectory of each case was used to confirm weight gain during the drug treatment period. A standardized set of decision rules allowed for consistent application of the EWG phenotype across both sites.
Results We identified 43,639 adult users of antipsychotic medications with available weight measures both before and after initiating treatment. Among these, 3,113 (7.1%) had a documented increase in body weight of at least 7% after starting an atypical antipsychotic. To date we have reviewed the individual prescription histories and weight trajectories on a subset of 1,104 cases that had a documented increase in body weight of >15% or >25%. Among these, a total of 249 (23%) are considered to be “confirmed” cases, with valid weight measures that clearly indicate a change in weight at or above the 15% or 25% threshold. An additional 341 (30%) were categorized as “possible” cases and will require chart review and patient interview for confirmation. Most (~55%) of the confirmed EWG cases occurred among adults who were overweight or obese pre-treatment.
Conclusions In this large cohort of adult users of atypical antipsychotic medications from two integrated health plans, we find that 7.1% are suspected of experiencing weight gain of >7% after initiating treatment. This degree of weight gain has been suggested by other research as clinically meaningful and associated with increased risk of obesity-related comorbidities. We believe that this adverse event is both common and serious and warrants further genetic and clinical research.
