Journal of the American Academy of Child & Adolescent Psychiatry
New researchDeconstructing Pediatric Depression Trials: An Analysis of the Effects of Expectancy and Therapeutic Contact
Section snippets
Search Strategy and Selection Criteria
A Medline search was conducted to identify clinical studies of antidepressants in children and adolescents with depressive disorders. The search strategy comprising depression or depressive disorder or major depressive disorder or dysthymia and antidepressant or the class and individual generic name of all antidepressants approved by the Food and Drug Administration returned 55,353 results (Figure 1). These results were limited to English-language articles, age group 18 years or younger, and
Characteristics of Included Studies and Participants
Nine open studies, 18 placebo-controlled trials, and four comparator trials met the study's inclusion and exclusion criteria (Table 1).25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55 As presented in Table 2, these included nine medication monotherapy conditions enrolling 228 participants in the open studies, five medication monotherapy conditions enrolling 325 participants in the comparator studies, and 19 medication
Discussion
This meta-analysis examined 31 studies of antidepressant medication for depressive disorders in children and adolescents across open, placebo-controlled, and active comparator study designs. Consistent with the study hypotheses, open studies of antidepressant medications were associated with a significantly higher medication response rate compared with placebo-controlled and comparator RCTs. Contrary to the hypotheses, response rates to antidepressant medication did not differ significantly
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Factors associated with placebo response in depression trials: A systematic review of published meta-analyses (1990–2017)
2018, Neurology Psychiatry and Brain ResearchCitation Excerpt :Ten studies were excluded from further consideration because of not fulfilling the selection criteria for pooled analysis and/or quality of underlying study results. The examination of the reference lists of the remaining 18 studies yielded an additional 40 studies, resulting in a total of 58 studies included in the current systematic review (Fig. 1) (Bridge, Birmaher, Iyengar, Barbe, & Brent, 2009; Brown, Johnson, & Chen, 1992; Brunoni, Lopes, Kaptchuk, & Fregni, 2009; Dodd, Berk, Kelin, Mancini, & Schacht, 2013; Dunlop et al., 2012; Entsuah & Vinall, 2007; Entsuah, Shaffer, & Zhang, 2002; Evans, Sills, Wunderlich, & McDonald, 2004; Faries et al., 2000; Fountoulakis & Möller, 2011; Fountoulakis, Veroniki, Siamouli, & Moller, 2013; Fournier et al., 2010; Furukawa et al., 2016; Gibbons, Hur, Brown, Davis, & Mann, 2012; Greenberg, Fisher, & Riter, 1995; Hunter, Cook, & Leuchter, 2010; Iovieno & Papakostas, 2012; Iovieno, Tedeschini, Ameral, Rigatelli, & Papakostas, 2011; Iovieno, Tedeschini, Levkovitz, Ameral, & Papakostas, 2012; Khan, Bhat, Faucett, Kolts, & Brown, 2011; Khan et al., 2010; Khan, Brodhead, Kolts, & Brown, 2005; Khan, Faucett, & Brown, 2014a; Khan, Faucett, & Brown, 2014b; Khan, Khan, Walens, Kolts, & Giller, 2003; Khan et al., 2004; Khan, Leventhal, Khan, & Brown, 2002; Khan, Schwartz, Kolts, Ridgway, & Lineberry, 2007; Khin, Chen, Yang, Yang, & Laughren, 2011; Kirsch et al., 2008; Klemp, Tvete, Gåsemyr, Natvig, & Aursnes, 2011; Lam & Andersen, 2006; Lee, Walker, Jakul, & Sexton, 2004; Locher et al., 2015; Mallinckrodt, Meyers, Prakash, Faries, & Detke, 2007; Mancini et al., 2014; Melander, Salmonson, Abadie, & van Zwieten-Boot, 2008; Montgomery & Kasper, 2007; Nelson, Delucchi, & Schneider, 2013; Nelson et al., 2012; Papakostas, Fan, & Tedeschini, 2012; Papakostas & Fava, 2009; Posternak & Zimmerman, 2007; Quitkin et al., 2002; Rabinowitz et al., 2016; Rief et al., 2009; Rutherford et al., 2013; Rutherford et al., 2011; Rutherford, Tandler, Brown, Sneed, & Roose, 2014; Sinyor et al., 2010; Stein, Baldwin, Dolberg, Despiegel, & Bandelow, 2006; Stolk, ten Berg, Hemels, & Einarson, 2003; Tedeschini et al., 2011; Thase et al., 2007; Trivedi & Rush, 1994; Turner, Matthews, Linardatos, Tell, & Rosenthal, 2008; Undurraga & Baldessarini, 2012; Walsh, Seidman, Sysko, & Gould, 2002). The vast majority of identified meta-analyses (75%) were published between 2005 and 2015.
A Machine Learning Approach to Identifying Placebo Responders in Late-Life Depression Trials
2018, American Journal of Geriatric PsychiatryUnsolved, Forgotten, and Ignored Features of the Placebo Response in Medicine
2017, Clinical TherapeuticsCitation Excerpt :This may especially be true for treatments of children because the PR in children was frequently associated with parents’ characteristics and their perception of the clinical situation and communication with the treating doctor.26 Furthermore, the placebo by proxy effect could explain why many of the predictors of PEs in adults are not effective in children, for example, the amount of time children spent with medical staff.27 However, this concept that our social environment (families, relatives, friends, peers) contributes to treatment outcomes is not new but is almost completely ignored when it comes to PRs.
Placebo effects in psychiatry: Mediators and moderators
2015, The Lancet PsychiatryClinic visits in late-life depression trials: Effects on signal detection and therapeutic outcome
2014, American Journal of Geriatric PsychiatryCitation Excerpt :One study design feature implicated as a contributor to increased placebo response and reduced drug–placebo differences is the intensity of supportive care provided in an antidepressant trial. In adolescents with depression, a greater number of visits during the acute treatment period has been associated with significantly increased placebo response but not medication response.7 Similarly, an analysis of antidepressant clinical trials enrolling adults aged 18–65 years found a cumulative and positive therapeutic effect of additional follow-up visits on placebo response, but the effect of this increased therapeutic contact was approximately 50% less in the medication groups.8
Pain and placebo in pediatrics: A comprehensive review of laboratory and clinical findings
2014, PainCitation Excerpt :In clinical practice, pediatricians could learn from our understandings of the impact of their interactions with their young patients and their parents. Although interactions with physicians could affect placebo and clinical outcomes, children and adolescents may not be able to fully understand the meaning and significance of the information being provided to them by the physician, and physicians may believe that these patients will not be able to comprehend the information being provided [62]. This indicates the need for physicians to vary and match their verbal and nonverbal communication strategies with patients of younger age and their parents to optimize the potential for positive health outcomes.
This work was supported by National Institute of Mental Health grants K23 MH085236 (B.R.R.), K23 MH075006 (J.R.S.), R21 MH087774 (J.R.S.), MH36197 (B.S.P.), and K02-74677 (B.S.P.), a Hope for Depression Research Foundation grant (B.R.R.), and a National Alliance for Research on Schizophrenia and Depression Young Investigator Award (B.R.R.).
Disclosure: Dr. Roose has served on a Data and Safety Monitoring Board for Medtronics, Inc. Drs. Rutherford, Sneed, Rindskopf, and Peterson and Ms. Tandler report no biomedical financial interests or potential conflicts of interest.