Premium
Incidence and characteristics of the nocebo response from meta‐analyses of the placebo arms of clinical trials of olanzapine for bipolar disorder
Author(s) -
Dodd Seetal,
Walker Adam J,
Brnabic Alan J M,
Hong Nancy,
Burns Amber,
Berk Michael
Publication year - 2019
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12662
Subject(s) - nocebo effect , nocebo , placebo , medicine , olanzapine , adverse effect , clinical trial , psychology , clinical psychology , psychiatry , physical therapy , schizophrenia (object oriented programming) , alternative medicine , pathology
Objectives In the clinical setting, the nocebo phenomenon is where clinical worsening or adverse events occur as a response to a treatment, in a situation in which conditioning from previous treatment exposure and/or expectations of sickness or symptoms lead to sickness and symptoms in a conditioned or expectant individual. The nocebo response may thus be a confounder in clinical treatment and clinical research. There is a need to know how to predict if an individual is likely to be a nocebo responder, and how significant and commonplace the nocebo effect might be. Methods An analysis was conducted on nine placebo‐controlled, randomized clinical trials of olanzapine for the treatment of bipolar disorder using data from placebo‐treated study participants only. Data were analysed to identify participant or study characteristics associated with a nocebo event, defined as any treatment‐emergent adverse event ( TEAE ) or an increase in score from baseline to endpoint for primary measures of clinical symptoms. Results A total of 1185 participants were randomized to placebo, of whom 806 (68%) reported a TEAE . Hamilton Depression Rating Scale ( HDRS ) data were only available for 649 placebo‐treated participants, of whom 321 (49.5%) demonstrated worsening. Nocebo events were significantly associated with: not being treatment‐naïve, younger age, being located in the USA , being a participant in an earlier study, and being classified as obese compared with normal weight. Conclusions A pattern to identify nocebo responders did not emerge, although some prognostic variables were associated with a greater probability of nocebo response. There was some evidence to support the role of expectancy as a cause of nocebo reactions.