Contribution of spontaneous improvement to placebo response in depression: A meta-analytic review
Section snippets
Background and objectives
Scientific and popular interest in placebo effects has been rising due to increased recognition of their therapeutic effectiveness in the treatment of some illnesses, such as Major Depressive Disorder (MDD). Placebo response in acute randomized controlled trials (RCTs) of antidepressant medications for MDD averages 30% (Walsh et al., 2002), and meta-analyses suggest that placebo treatment conditions may duplicate 50–75% of the improvement observed with active treatment (Kirsch and Sapirstein,
Search strategy and selection criteria
PubMed and PsycINFO were searched to identify prospective clinical studies contrasting psychotherapy to a wait-list control condition in adults with depression. To capture all available psychotherapy studies, we used the search terms “psychotherapy” OR the specific names of all known psychotherapy modalities (e.g., cognitive behavior therapy, behavior therapy, interpersonal therapy, psychodynamic psychotherapy, etc.), which we compiled by referencing standard textbooks of psychiatry (Sadock and
Characteristics of included studies and participants
Ten trials met the study's inclusion and exclusion criteria (Arean et al., 1993; Bolton et al., 2003; Clarke et al., 1999; Cohen et al., 2010; Diamond et al., 2002; Mufson et al., 1999; Nezu, 1986, Nezu and Perri, 1989; O'Leary and Beach, 1990; Wright et al., 2005). As shown in Table 1, the 10 trials had a mean sample size of 32.3 ± 51.6 patients, duration of 10.0 ± 3.7 weeks, and dropout rate of 18.6% ± 17.1%. The 340 participants assigned to wait-list control conditions across these 10 trials
Discussion
Consistent with the hypothesis of this meta-analysis, patients with MDD randomized to wait-list control conditions experienced symptomatic improvement. The magnitude of this improvement corresponds to a medium effect size of approximately 0.5, which was significantly different from zero (p < 0.001). Left untreated, patients with MDD may expect an improvement on average of approximately 4 HRSD points based upon the passage of time alone.
For the purpose of comparison, prior meta-analyses of
Conflict of interest
Dr. Rutherford, Ms. Mori, Dr. Sneed, and Ms. Pimontel report no disclosures or potential conflicts of interest. Dr. Roose reports serving on a Data and Safety Monitoring Board for Medtronics, Inc.
Role of the funding source
This study was supported by a Hope for Depression Research Grant (BRR) as well as National Institute of Mental Health grants K23 MH085236 (BRR), K23 MH075006 (JRS), and R21 MH087774 (JRS).
Contributors
Dr. Rutherford designed the study and drafted the manuscript. Ms. Mori assisted with the literature review and data extraction. Dr. Sneed, Dr. Roose, and Ms. Pimontel assisted with the statistical analyses and revision of the manuscript. All authors contributed to and have approved the final manuscript.
Acknowledgments
This work was supported by a National Institute of Mental Health grants K23 MH085236 (BRR), K23 MH075006 (JRS), R21 MH087774 (JRS), T32 MH15144 (SPR), and a Hope for Depression Research Foundation (BRR). Dr. Rutherford, Ms. Mori, Dr. Sneed, and Ms. Pimontel have no disclosures to report. Dr. Roose reports serving on a Data and Safety Monitoring Board for Medtronics, Inc. This paper has not been previously presented.
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2019, Journal of Affective DisordersCitation Excerpt :In part, this may be due to lowered expectations for therapy effectiveness (Elliott and Brown, 2002), as assignment to waitlist control may have been experienced as demoralising, or to the symptom improvement among participants reassessed at the post-control period. Research suggests individuals with MDD assigned to waitlist control report 33% of the improvement occurring in the active treatment arm (Rutherford et al., 2012). Despite this, a three-quarters of a standard deviation improvement in overall depression still represents a considerable change.
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2018, International Review of NeurobiologyCitation Excerpt :In antidepressant trials, the natural history of the disease accounted for 24% of the overall treatment effect (Kirsch & Sapirstein, 1998). Similarly, in a more recent meta-analysis of patients with major depression, the improvement of patients in the wait-list group was compared with that observed in the placebo and active treatment groups; thus, patients in wait-list control conditions experience approximately 33% of the improvement occurring with medication treatment and 40% of the improvement seen with placebo administration (Rutherford, Mori, Sneed, Pimontel, & Roose, 2012; Rutherford & Roose, 2013). In a Cochrane review of 37 RCTs with three-armed trials, Krogsbøll, Hróbjartsson, and Gøtzsche (2009) investigated to which extent spontaneous remission contributes to the observed symptom change in different clinical conditions.
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