How "blind" are double-blind studies?

Margraf, Jürgen; Ehlers, Anke; Roth, Walton T.; Clark, Duncan B.; Sheikh, Javaid I.; Agras, W. Stewart; Taylor, C. Barr

doi:10.1037/0022-006x.59.1.184

Cited by 108 publications

(61 citation statements)

References 7 publications

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“…Most controlled drug studies utilize inert placebos which can ‘unblind’ studies because clinician or patient raters may be able to tell who is receiving the active medication by detecting side effects [14, 27, 28, 29]. Guessing the correct condition may result in disparate expectations for positive results, thereby affecting outcome ratings or even outcome itself.…”

Section: Belief No 1: Antidepressants Are Conclusively More Effectivmentioning

confidence: 99%

Raising Questions about Antidepressants

Antonuccio

Danton

DeNelsky

et al. 1999

Psychother Psychosom

104

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Antidepressant medication has apparently become the most popular treatment for depression in the USA. Several beliefs about the efficacy of antidepressant medications prevail among mental health professionals and the public. This paper explores relevant research data and raises questions about these beliefs. Many of the common beliefs about these medications are not adequately supported by scientific data. The following issues are raised: (1) industry-funded research studies which result in negative findings sometimes do not get published; (2) placebo washout procedures may bias results in some studies; (3) there are serious questions about the integrity of the double-blind procedure; (4) the ‘true’ antidepressant drug effect in adults appears to be relatively small; (5) there is minimal evidence of antidepressant efficacy in children; (6) side effects are fairly common even with the newer antidepressants; (7) combining medications raises the risk for more serious complications; (8) all antidepressants can cause withdrawal symptoms; (9) genetic influences on unipolar depression appear to be weaker than environmental influences; (10) biochemical theories of depression are as yet unproven; (11) biological markers specific for depression have been elusive; (12) dosage and plasma levels of antidepressants have been minimally related to treatment outcome; (13) preliminary evidence suggests that patients who improve with cognitive-behavioral psychotherapy show similar biological changes as those who respond to medication, and (14) the evidence suggests that psychological interventions are at least as effective as pharmacotherapy in treating depression, even if severe, especially when patient-rated measures are used and long-term follow-up is considered.

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Section: Belief No 1: Antidepressants Are Conclusively More Effectivmentioning

confidence: 99%

Raising Questions about Antidepressants

Antonuccio

Danton

DeNelsky

et al. 1999

Psychother Psychosom

104

View full text Add to dashboard Cite

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“…In many trials that have taken this precaution, blinding was not actually achieved in that participants and/or assessors guessed the participants’ treatment allocation better than chance [1, 2]. This often raises concerns regarding the validity of the trials’ results.…”

Section: Introductionmentioning

confidence: 99%

Expectancy in Double-Blind Placebo-Controlled Trials: An Example from Alcohol Dependence

Colagiuri¹,

Morley

Boakes³

et al. 2009

Psychother Psychosom

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Background: Double-blind placebo-controlled trials are intended to control for the impact of expectancy on outcomes. Whether they always achieve this is, however, questionable. Methods: Reanalysis of a clinical trial of naltrexone and acamprosate for alcohol dependence investigated this issue further. In this trial, 169 alcohol-dependent patients received naltrexone, acamprosate or placebo for 12 weeks. In addition to being assessed on various indices of alcohol dependence, they were asked whether they believed they received active medication or placebo. Results: While there were no differences in outcomes between treatment groups, those who believed they had been taking active medication consumed fewer alcoholic drinks and reported less alcohol dependence and cravings. That is, irrespective of actual treatment, perceived medication allocation predicted health outcomes. Conclusions: These results highlight the differences between treatment administration in clinical trials and standard medical practice, a discrepancy that may sometimes decrease the validity of these types of trials.

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“…When interpreting these results in terms of clinical significance, one should consider the fact that many of the included trials comprised treatment arms with suboptimal dosage; the presented ESs, similar to those obtained in most metaanalyses regarding antidepressants, are hence lower than one may expect when using adequate doses. 18 The fact that the presence of side effects might compromise the integrity of the double-blind procedure in both raters [20][21][22][23] and patients, 3,[24][25][26] and that the resulting unblinding may introduce a bias favoring the active drug, has been discussed since long. During the '60s and '70s, when most antidepressants displayed easily recognizable anticholinergic side effects, attempts were made to explore this possibility by comparing antidepressants with so-called active placebos, that is, drugs exerting no antidepressant effect but being anticholinergic.…”

Section: Discussionmentioning

confidence: 99%

Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression

et al. 2017

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It has been suggested that the superiority of antidepressants over placebo in controlled trials is merely a consequence of side effects enhancing the expectation of improvement by making the patient realize that he/she is not on placebo. We explored this hypothesis in a patient-level post hoc-analysis including all industry-sponsored, Food and Drug Administration-registered placebocontrolled trials of citalopram or paroxetine in adult major depression that used the Hamilton Depression Rating Scale (HDRS) and included a week 6 symptom assessment (n = 15). The primary analyses, which compared completers on active treatment without early adverse events to completers on placebo (with or without adverse events) with respect to reduction in the HDRS depressed mood item showed larger symptom reduction in patients given active treatment, the effect sizes being 0.48 for citalopram and 0.33 for paroxetine. In actively treated subjects reporting early adverse events, who also outperformed those given placebo, the severity of the adverse events did not predict response. Several sensitivity analyses, for example, including (i) those using change of the sum of all HDRS-17 items as effect parameter, (ii) those excluding all subjects with adverse events (that is, also those on placebo) and (iii) those based on the intention-to-treat population, were all in line with the primary analyses. The finding that both paroxetine and citalopram are clearly superior to placebo also when not producing adverse events, as well as the lack of association between adverse event severity and response, argue against the theory that antidepressants outperform placebo solely or largely because of their side effects.

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How "blind" are double-blind studies?

Cited by 108 publications

References 7 publications

Raising Questions about Antidepressants

Raising Questions about Antidepressants

Expectancy in Double-Blind Placebo-Controlled Trials: An Example from Alcohol Dependence

Efficacy of selective serotonin reuptake inhibitors in the absence of side effects: a mega-analysis of citalopram and paroxetine in adult depression

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