A new study revealed that research studies for new antidepressant medications do not evaluate the effectiveness of the drugs on the general population.
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 so much over the past five years that most patients are excluded.
In other words, the results of the trials may not be applicable to most of us.
Dr. Zimmerman explained why the research was needed:
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.
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.
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.
Dr. Zimmerman examined 170 placebo-controlled studies 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:
- exclude patients with co-morbid Axis I disorders and personality disorders;
- exclude patients because the episode duration was too long or too short;
- exclude patients who met diagnostic criteria for major depression but did not score high enough on a rating scale.
In a public release, Dr. Zimmerman elaborated on the findings:
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.
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 research was published earlier this week in Mayo Clinic Proceedings.