STAR*D: A Tale and Trail of Bias

Article excerpt

The 35-million-dollar Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study is the largest antidepressant effectiveness study ever conducted. STAR*D enrolled 4,041 depressed patients and provided them with exemplary free acute and continuing antidepressant care to maximize their likelihood of achieving and maintaining remission. Patients who failed to get adequate relief from their first antidepressant were provided with up to three additional trials of pharmacologically distinct treatments. This article identifies numerous instances of apparent bias in the conduct and reporting of outcomes from this study. In contrast to STAR*D's report of positive findings supporting antidepressants' effectiveness, only 108 of its 4,041 patients (2.7%) had an acute-care remission, and during the 12 months of continuing care, these patients neither relapsed nor dropped out. This article also discusses the roles of the American Journal of Psychiatry (AJP) and the National Institute of Mental Health (NIMH) in promoting the biased reporting of STAR*D's results.

Keywords: major depression; antidepressants; researcher bias; STAR*D

In the controlled clinical trials article describing STAR*D's methods, research design, and purpose, its authors state:

STAR*D uses a randomized, controlled design to evaluate both the theoretical principles and clinical beliefs that currently guide the management of treatment-resistant depression in terms of symptoms, function, satisfaction, side-effect burden, and health care utilization and cost estimates. Given the dearth of controlled data, results should have substantial public health and scientific significance, since they are obtained in representative participant groups/settings, using clinical management tools that can easily be applied in daily practice. (Rush, Fava, et al., 2004, p. 136)

To accomplish these objectives, STAR*D:

* Enrolled 4,041 real patients seeking care versus people responding to advertisements for depressed subjects as is common in industry-sponsored research.

* Included patients meeting a lower depression severity threshold than common in efficacy trials by requiring only a baseline Hamilton Rating Scale of Depression (HRSD) score of ≥14 versus ≥20 (e.g., see Davidson et al., 2002). This low symptom threshold, though, is similar to the many patients who are only mildly depressed when first prescribed antidepressants in routine clinical practice (Zimmerman, Mattia, & Posternak, 2002).

* Included depressed patients with comorbid medical and psychiatric conditions while only excluding those with a primary diagnosis of bipolar, psychotic, obsessive-compulsive, or eating disorders.

* Used "remission" versus "response" as the primary criterion of successful treatment.

* Provided 12 months of continuing care while monitoring the durability of treatment gains versus only reporting acute-care improvement.

STAR*D provided these 4,041 "real-world" depressed patients with exemplary free acute and continuing-care drug treatment while making extensive efforts to keep patients in treatment and maximize their likelihood of achieving and maintaining remission in a manner consistent with "the theoretical principles and clinical beliefs that currently guide the management of treatment-resistant depression." These efforts included:

* Providing a multistep educational program for patients and families throughout acute-care based on the neurochemical imbalance theory of depression that included "a glossy visual representation of the brain and neurotransmitters," consistently emphasizing that "depression is a disease, like diabetes or high blood pressure, and has not been caused by something the patient has or has not done. (Depression is an illness, not a personal weakness or character flaw.) The educator should emphasize that depression can be treated as effectively as other illnesses," and "explaining the basic principles of mechanism of action" for the patient's current antidepressant drug (O'Neal & Biggs, 2001, pp. …