Researchers analyze inclusion/exclusion criteria used in antidepressant efficacy studies

Mark Zimmerman, M.D., a clinical researcher at Rhode Island Hospital, and his team analyzed the criteria used in antidepressant efficacy studies (AETs) and learned that the inclusion/exclusion criteria for AETs have narrowed over the past five years so that the most patients are excluded. The research was published today in Mayo Clinic Proceedings.

"The inclusion/exclusion criteria for AETs have narrowed over the past five years, thereby suggesting that AETs may be even less generalizable than they were previously," said Zimmerman, director of outpatient psychiatry and the partial hospital program at Rhode Island Hospital and director of the Rhode Island Methods to Improve Diagnostic Assessment and Services (MIDAS) project, a study that integrated researchers' assessment tools and procedures into a hospital-affiliated outpatient practice.

"More than a decade ago, our clinical research group raised concerns about the generalizability of AETs and suggested that the majority of patients seen in routine clinical practice would not qualify for an AET," Zimmerman added. "These results were replicated multiple times. We therefore wondered if drug companies changed how they recruited patients into studies. In fact, they have, but in an unexpected way. The more recent AETs are even less generalizable than the prior studies, which themselves excluded most depressed patients from drug company-sponsored treatment studies."

Zimmerman examined 170 placebo-controlled AETs published during the past 20 years, 56 of which were published during the past five years. The more recent studies were significantly more likely to: 1)exclude patients with comorbid Axis I disorders and personality disorders; 2)exclude patients because the episode duration was too long or too short; and 3)exclude patients who met diagnostic criteria for major depression but did not score high enough on a rating scale.

"For severely ill patients, such as those who express suicidal thoughts, it makes ethical sense to exclude them from a study where they may receive placebos," said Zimmerman. "However, excluding patients with co-morbid psychiatric disorders has become more frequent, and patients with any comorbid Axis I disorder are twice as likely to be excluded in recent studies. This is important because the majority of depressed patients have another psychiatric diagnosis. The exclusion of depressed patients who score too low on rating scales is the most concerning. This would exclude approximately half of the patients seen in clinical practice. In addition, studies have shown that antidepressants do not work as well for less severely depressed patients. Thus, drug companies seem to be stacking the deck to demonstrate that their products work, even though they might work only for a narrow segment of depressed patients."

The National Institute of Mental Health estimates that nearly one in five Americans suffers from mental illnesses as defined in the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders.