Nocebo effects in the treatment of bipolar disorder: Results from an individual study participant level meta-analysis of the placebo arm of olanzapine clinical trials

Nocebo effects in the treatment of bipolar disorder: Results from an individual study participant level meta-analysis of the placebo arm of olanzapine clinical trials

This project will be conducted by the researchers during time paid by their employers. A/Prof Dodd is an employee of Barwon Health. Mohammadreza Mohebbi and Michael Berk are employees of Deakin University. Michael Berk currently holds a Senior Research Fellowship from the NHMRC (Australia).

Potential conflicts of interest will be disclosed when the research is presented and published.

The nocebo effect, when a harmless substance creates harmful effects in a person who takes it, is a clinically salient yet seldom studied phenomenon that may be associated with poorer treatment outcomes, perceived adverse events and treatment discontinuation. The covert presence of nocebo responders in clinical trials may contribute to outcome variance in both placebo and active treatment arms for important primary and secondary endpoints. Nocebo effects are thought to be driven by expectancy and conditioning.

In this study we will investigate variables associated with the emergence of adverse outcomes in placebo-treated participants in clinical trials of olanzapine for bipolar disorder. Nine suitable studies have been identified. Data from placebo treated study participants will be pooled and meta-analysed using established statistical techniques.

Placebo controlled clinical trials have become essential and are regarded as being the best method to provide evidence that a treatment is safe and effective. They are a cornerstone of drug development. They are also very expensive. The placebo is a key component of clinical trials. Although the placebo is inert and inactive, many study participants will respond to placebo treatment. This response may be a negative response, called a nocebo response. A strong placebo response is the most common reason for failure of clinical trials. With clinical trials having such an important role in drug development and being so expensive it is imperative that placebo and nocebo phenomena are better understood. This study will look specifically at the nocebo response. The aims is to investigate the prevalence and characteristics of the response, and also to see if study variables can be used to identify predictors of nocebo response.

[{ "PostingID": 2015, "Title": "LILLY-F1D-MC-HGEH", "Description": "Olanzapine Versus Placebo in the Treatment of Mania Associated with Bipolar I Disorder" },{ "PostingID": 2016, "Title": "LILLY-F1D-MC-HGHL", "Description": "Olanzapine Versus Placebo in the Prevention of Relapse in Bipolar Disorder" },{ "PostingID": 2089, "Title": "LILLY-F1D-JE-BMAC", "Description": "Placebo- and Haloperidol-Controlled Double-Blind Trial of Olanzapine in Patients with Manic or Mixed Episode of Bipolar I Disorder" },{ "PostingID": 2090, "Title": "LILLY-F1D-MC-HGFU", "Description": "Olanzapine Added to Mood
Stabilizers in the Treatment of Bipolar Disorder" },{ "PostingID": 2092, "Title": "LILLY-F1D-MC-HGGW", "Description": "Olanzapine Versus Placebo in the Treatment of Bipolar Disorder, Manic or Mixed" },{ "PostingID": 2093, "Title": "LILLY-F1D-MC-HGGY", "Description": "Placebo-Controlled Olanzapine Monotherapy in the Treatment of Bipolar I Depression" },{ "PostingID": 2096, "Title": "LILLY-F1D-MC-HGIU", "Description": "Olanzapine Versus Placebo in the Treatment of Mania in Adolescents With Bipolar I Disorder" },{ "PostingID": 2097, "Title": "LILLY-F1D-MC-HGKQ", "Description": "Olanzapine Versus Divalproex and Placebo in the Treatment of Mild to Moderate Mania Associated With Bipolar I Disorder" },{ "PostingID": 2098, "Title": "LILLY-F1D-MC-HGMP", "Description": "Efficacy and Safety of Olanzapine in the Treatment of Patients with Bipolar I Disorder, Depressed: A Randomized, Double-Blind Comparison with Placebo" }]

Dodd S, Walker AJ, Brnabic AJM, Hong N, Burns A, Berk M. Incidence and characteristics of the nocebo response from meta-analyses of the placebo arms of clinical trials of olanzapine for bipolar disorder.
Bipolar Disord. 2018;00:1-9.

https://doi.org/10.1111/bdi.12662