Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment.Many well-designed randomized controlled trials(RCTs)of depression have a high proportion ...Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment.Many well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to why.The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders.Methods This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo response.Monoaminergic genetic polymorphisms were also assessed.Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score.The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models.Results Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo response.An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy.Single nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple comparisons.Conclusion This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response.Several variables appeared to predict the placebo response.Such findings may encourage future trial designs which could dampen placebo response,improve assay sensitivity,and allow for treatment effects to be potentially more detectable.展开更多
基金funded by an Australian National Health and Medical Research Council project grant (No. APP1048222) and was co-sponsored by FITBio Ceuticals (who provided the trial product and placebo)supported by an NHMRC Fellowship (No. APP1125000)supported by a NHMRC Senior Principal Research Fellowship (No. 1059660 and 1156072)
文摘Objective The placebo response in depression studies is the change in symptoms amongst those who receive an inactive treatment.Many well-designed randomized controlled trials(RCTs)of depression have a high proportion of placebo responders,with little understanding as to why.The present study assesses characteristics associated with the placebo response in a nutraceutical trial with a large proportion of placebo responders.Methods This is a secondary analysis of a nutraceutical depression RCT which identified no overall treatment benefit relative to placebo(n=69 in placebo group).We investigated participant characteristics such as socio-demographics,clinical features,and recruitment methods,and their association with the placebo response.Monoaminergic genetic polymorphisms were also assessed.Placebo response was measured based on change in Montgomery-Asberg Depression Rating Scale score.The association of these hypothesis-driven variables of interest and the placebo response was examined using linear mixed effects models.Results Greater levels of education,particularly pursuing post-high school education,better self-reported general health,marriage/de facto,greater improvement in the first trial week,and more failed antidepressant therapies in the current depressive episode were associated with greater placebo response.An increased placebo response was not found in those recruited via social media nor in those with concomitant antidepressant therapy.Single nucleotide polymorphisms from the tryptophan hydroxylase 1(TPH1)gene(A779C and A218C)were weakly associated with greater placebo response,although the evidence was attenuated after accounting for multiple comparisons.Conclusion This is,to our knowledge,the first study within nutraceutical research for depression to assess the association between participant characteristics and variation in the placebo response.Several variables appeared to predict the placebo response.Such findings may encourage future trial designs which could dampen placebo response,improve assay sensitivity,and allow for treatment effects to be potentially more detectable.
