Placebo response in antipsychotic trials of patients with acute mania

Placebo Response and Its Predictors in Attention Deficit Hyperactivity Disorder: A Meta-Analysis and Comparison of Meta-Regression and MetaForest

“…Because ADHD is more frequently diagnosed and treated in the United States than in the rest of the world and research is also more prevalent in this country, expectations regarding the efficacy of pharmacological treatment may also be higher, resulting in higher placebo response. Nevertheless, it must be stressed that some studies on disorders other than ADHD have found placebo response to be lower in the United States ( Mallinckrodt et al, 2010 ; Welten et al, 2015 ; Leucht et al, 2018 , 2019 ), and other studies have found no effect of location on placebo response ( Bridge et al, 2009 ; Agid et al, 2013 ). Altogether, these results suggest that the true effect of location might be small or near zero and, for this reason, some studies find a positive, others a negative, and others a null effect.…”

“…Placebo response has been documented in other psychiatric disorders such as depression ( Undurraga and Baldessarini, 2012 ), acute schizophrenia ( Leucht et al, 2018 ), stable schizophrenia ( Fraguas et al, 2019 ), bipolar mania ( Yildiz et al, 2011 ; Welten et al, 2015 ), bipolar depression ( Bridge et al, 2009 ; Nierenberg et al, 2015 ), and obsessive compulsive disorder ( Ackerman and Greenland, 2002 ; Kotzalidis et al, 2018 ). Unlike mania, depression, and acute schizophrenia, where severity of symptoms change over a short period of time, ADHD is a relatively stable condition and the reduction of ADHD symptoms during the clinical trial is less likely to be due to the natural course of the disorder.…”

“…An increase of placebo response has been documented before by Khan et al (2017) in a meta-analysis of 17 clinical trials of ADHD medications approved by the US Food and Drug Administration between 2000 and 2009 as well as in other fields of psychiatry such as schizophrenia ( Agid et al, 2013 ; Leucht et al, 2018 ), depression ( Walsh et al, 2002 ; Papakostas and Fava, 2009 ; Undurraga and Baldessarini, 2012 ), obsessive compulsive disorder ( Ackerman and Greenland, 2002 ; Kotzalidis et al, 2018 ), and bipolar disorder ( Sysko and Walsh, 2007 ). Changes over time in baseline severity ( Bridge et al, 2009 ; Nierenberg et al, 2015 ; Cohen et al, 2018 ), number of study centers ( Bridge et al, 2009 ; Yildiz et al, 2011 ; Undurraga and Baldessarini, 2012 ; Agid et al, 2013 ; Leucht et al, 2018 ; Fraguas et al, 2019 ), sex ( Yildiz et al, 2011 ; Welten et al, 2015 ), study quality ( Agid et al, 2013 ), and type of drug ( Agid et al, 2013 ) have frequently been alluded to as an explanation for this time-related increase of placebo response in psychiatry. These covariates do not seem to confound the moderating effect of publication date in our study because none of them were found to be associated with placebo response in any analysis.…”

“…Comprehensive analysis of placebo response and the factors influencing placebo response in RPCCTs has been conducted for schizophrenia, depression, and mania ( Walsh et al, 2002 ; Khan et al, 2003 ; Papakostas and Fava, 2009 ; Yildiz et al, 2011 ; Undurraga and Baldessarini, 2012 ; Nierenberg et al, 2015 ; Welten et al, 2015 ; Leucht et al, 2018 ; Fraguas et al, 2019 ). In contrast, few studies have investigated placebo response in attention deficit hyperactivity disorder (ADHD) ( Newcorn et al, 2009 ; Waschbusch et al, 2009 ; Waxmonsky et al, 2011 ; Buitelaar et al, 2012 ; Khan et al, 2017 ; Cohen et al, 2018 ; Ben-Sheetrit et al, 2020 ).…”

Should the demonstration of improved patient outcome be necessary to overhaul diagnostic approaches?: Comment on Bach and Tracy (2022).

“…The nonspecific aspects of treatment underlying the placebo response include the expectation of benefit, support from a clinician showing concern and attention, and symptom resolution due to the natural history of the disorder. For mood and anxiety disorders, recent meta-analyses have found placebo response rates of 35% to 40% for major depressive disorder (Papakostas et al, 2016), 30% to 40% for bipolar depression (Bartoli et al, 2018; Papakostas et al, 2016), 30% for bipolar mania (Bartoli et al, 2018; Welten et al 2015), 45% to 50% for panic disorder (Zhang et al, 2020), 40–50% for generalized anxiety disorder (Li et al, 2017), and 35% to 40% for social anxiety disorder (Li et al, 2020). Appreciable placebo response rates have even been found for patients who are considered treatment resistant.…”