A renewed, ethical defense of placebo-controlled trials of new treatments for major depression and anxiety disorders

Abstract

The use of placebo as a control condition in clinical trials of major depressive disorder and anxiety disorders continues to be an area of ethical concern. Typically, opponents of placebo controls argue that they violate the beneficent-based, “best proven diagnostic and therapeutic method” that the original Helsinki Declaration of 1964 famously asserted participants are owed. A more consequentialist, oppositional argument is that participants receiving placebo might suffer enormously by being deprived of their usual medication(s). Nevertheless, recent findings of potential for suicidality in young people treated with antidepressants, along with meta-analyses suggesting that antidepressants add no significant clinical benefit over placebos, warrant a re-evaluation of the arguments against placebo. Furthermore, the nature of placebo treatment in short-term clinical trials is often not well understood, and lack of understanding can foster opposition to it. This paper will show how scientific justifications for placebo use are morally relevant. The fundamental ethical importance of placebo controls is discussed in relation to several aspects of clinical trials, including detection of adverse events, accurate assessment of clinical benefit, advancing understanding of the heterogeneity of depression and anxiety disorders and respecting informed consent requirements. Prohibiting the use of placebo controls is morally concerning in that such prohibitions allow for the possibility of serious adverse public health consequences. Moral worries that research participants receiving placebo are being unduly jeopardised will be shown to be exaggerated, especially in relation to the net benefits for end-users to be gained from the quality of data resulting from using placebo controls.

The investigator and the IRB: A survey of depression and schizophrenia researchers

“…Both the fields of schizophrenia and depression research have debated the ethicality of placebo-controlled trials (Dunlop & Banja, 2009; Fischer, 2006; Charney et al, 2002; Laughren, 2001; Weijer, 1999; Carpenter et al, 1997) and a similar percentage of respondents from these groups believed a placebo-controlled trial would be unethical (30% in the schizophrenia group, 26% in the depression group). The largest differences between groups, as with the prisoner scenario, was in the greater percentages of schizophrenia researchers who thought a placebo-controlled study would be too difficult to implement or would not be approved by the IRB.…”

The Use of Placebo and the Right of Autonomy

“…Hence, the revision of the Helsinki Declaration is justified. Furthermore, according to Dunlop and Banja, regarding the patients of major depression and anxiety disorder, "the currently existing drugs help approximately one-third of patients achieve remission and another third to achieve a good response (that falls short of a full remission of symptoms)" [3]. Given that placebos have no side-effects, they are the best proven treatment for about one-third of these patients.…”

“…For example, if both the study drug and the established drug have a side-effect that is also a symptom of the disease in question, the researcher does not know how much the new drug contributes to the symptom [3]. Banning placebo-controlled studies will deprive the potential end-users, which include the participants, of a better drug.…”

Enhancing Informed Consent in Clinical Trials and Exploring Resistances to Disclosing Adverse Clinical Trial Results

“…We believe that opponents of placebo controls often exaggerate the harms that might befall trial participants (Dunlop and Banja, 2009). Consider that while it might seem cruel to subject, say, persons with anxiety or depression to a placebo and risk inviting the persistence of their symptoms, it is quite likely that they had already been experiencing those symptoms for some time prior to their enrolling in a trial.…”