Original articleA meta-analysis of sleep changes associated with placebo in hypnotic clinical trials
Introduction
The symptoms of many different psychological disorders improve during administration of placebo in the context of controlled clinical trials of psychotropic medication. This phenomenon is commonly termed ‘the placebo effect’, but it is unclear to what extent the change in symptom severity is due to the expectant hopefulness in consumption of the placebo, or whether the change is attributable to the passage of time, or non-specific effects of participation in a research project. In the interest of linguistic precision, we will use the term ‘placebo effect’ only to refer to the patient's expectation associated with placebo ingestion, and will use the more general term ‘effects associated with placebo’ (EAP) to describe the sum of all factors leading to symptom change during placebo administration. Also, although the term placebo has been applied to non-pharmaceutical, psychological interventions such as quasi-desensitization, this paper will define placebo as an inert substance designed for ingestion unless otherwise specified.
Although EAP have been described for most psychiatric disorders, including even more severe disorders such as bipolar disorders and schizophrenia [1], [2], there is surprisingly little information about EAP during insomnia treatment. If EAP exist at all, then it seems likely that EAP would occur during clinical trials for primary insomnia, given that the overall level of psychopathology is by definition less than that seen in psychiatric disorders [3], and less severe disorders might be more susceptible to EAP [4].
Conclusions are mixed regarding whether there are EAP associated with insomnia, with some authors deducing that EAP do exist, [5], [6], [7], [8] and others take the opposing view [9], [10], [11], [12]. Resolution to this issue is not trivial, as administration of placebo in clinical trials has both economic and ethical implications. We sought to address this question through combining the information provided in several clinical studies using meta-analytic techniques. Our goal is not to establish the clinical significance of placebo, but rather to establish whether there is any change associated with placebo that might serve to guide the design of future clinical trials.
Section snippets
Strategy
Inspection of recently published hypnotic clinical trials reveals that many study designs include up to 4 weeks of treatment, and that changes in key outcome variables are typically reported for the end of each week of treatment. The possible number of outcome variables is large including subjective sleep latency (SL), subjective wake after sleep onset (WASO), subjective number of awakenings, subjective total sleep time (TST), polysomnographic (PSG) SL, PSG WASO, PSG TST, PSG sleep stages, PSG
Results
Our combined search strategy produced 402 candidate papers, and the abstract of each paper was read to ascertain qualification for the meta-analysis. The full paper was inspected if the abstract did not clarify the qualifications for analysis. Many studies prior to 1990 were eliminated on the basis of reporting only qualitative outcomes (i.e. changes in SL reported as ‘better’, ‘worse’, or ‘no change’) or failure to use a parallel group design. Papers from 1990 through 2000 were more likely to
Discussion
Our selection strategy identified only a small number of eligible papers. Many candidate papers with otherwise excellent designs were excluded because the data of interest were not reported, or were reported only in figures. The small number of eligible papers had a profound effect on our original ambition of examining EAP for four variables at four follow-up time points. Instead, we presented findings for only three variables at one time point.
Our results found statistically significant EAP
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