Assessment of adverse effects in clinical studies of antipsychotic medication: survey of methods used

Abstract

BackgroundClinical studies of antipsychotic medication are a primary source of data on the nature of, and relative liability for, adverse effects, relevant to prescribing decisions in clinical practice.AimsTo identify how safety and tolerability data were collected and reported in recent clinical studies of antipsychotics.MethodA survey was conducted of all 167 eligible studies published between 2002 and 2007 on the Cochrane Schizophrenia Group register.ResultsExtrapyramidal side-effects (EPS) and weight gain were most frequently assessed. A minority of reports addressed metabolic abnormalities, aversive subjective experiences and sexual dysfunction. Published rating scales were frequently used to evaluate EPS, but systematic methods were rarely applied to other treatment-emergent problems. The definition of individual adverse effects and the manner of reporting were inconsistent.ConclusionsThe way in which safety and tolerability data are collected and reported in clinical studies does not allow for fair and meaningful comparison of the relative risk profiles of individual antipsychotic drugs.

Assessing and Reporting the Adverse Effects of Antipsychotic Medication

“…The current findings are similar to Pope et al 22 whose review of 167 antipsychotic trials likewise found that EPS were assessed more frequently and systematically than other AEs. Given their debilitating and potentially irreversible nature, it is encouraging that motor disturbances were carefully reported across different designs.…”

“…This inconsistent assessment of non-neurological effects replicates the conclusions of existing surveys, 22,[50][51] despite concerns about the substantial impact of nonneurological AEs on factors like physical attractiveness, 52 feelings of reduced intelligence and creativity, 53 and social stigma and ridicule. 54 Furthermore, while sedation was generally well-reported, affective and non-sedative cognitive AEs were referred to far less frequently, despite patient testimony that subjective effects like dysphoria (e.g., feeling 'robotic', 'emotionally empty,' 53 ) are both common and distressing.…”

“…21 A review of safety and tolerability data from 167 antipsychotic trials likewise indicated numerous failings, primarily inconsistent measurement and inadequate or confusing reporting. 22 Other authors have provided detailed information on global AE domains (e.g. EPS 23 ), specific experiences (e.g.…”

“…weight gain, sexual dysfunctions, amenorrhoea, tardive dyskinesia). Assessment length was therefore coded as: 0= ≤ 12 weeks; 1= [13][14][15][16][17][18][19][20][21][22][23][24] weeks; 2= ≥ 25 weeks. If treatment duration was not provided, then timeframe was coded according to the length of the study.…”

Antipsychotic drugs and extrapyramidal side effects in first episode psychosis: a systematic review of head–head comparisons

“…This recommendation has been made previously (Hamer and Haddad 2007;Pope et al 2010). This would facilitate comparison of study results and inform clinical decisions about medication choice.…”