For patients battling severe depression, antidepressant medications are still the best option for treatment, but these drugs may offer little benefit to patients suffering from milder forms of depression, according to a new analysis published this week in the Journal of the American Medical Association. The review, which analyzed data from six previously published placebo-controlled trials that included patients with a broad range of depression severity, suggests that previous research highlighting the benefits of antidepressants may not accurately reflect how medications impact patients with less severe cases of depression. In fact, the researchers conclude that, “…the efficacy of [antidepressant medication] treatment for depression varies considerably as a function of symptom severity,” and, more specifically, that while the true effects of antidepressant drugs were considerable for patients with “very severe symptoms”—such as those that characterize major depressive disorder—for those with mild, moderate or even some severe symptoms, the true benefits of antidepressants over placebo were “nonexistent to negligible.”
So, how does these findings line up with the thousands of studies that have shown a benefit of antidepressants over placebo? The researchers say that too often the entry requirements for study participants limit studies to people with very severe depression, but that those findings are then generalized to a broader range of patients. That is, as defined by the American Psychiatric Association’s Handbook of Psychiatric Measures, the scale used to assess depression severity—the Hamilton Depression Rating Scale (HDRS)—indicates that patients with an initial score of 8–13 suffer from mild depression, 14-18, moderate depression, 19-22, severe depression, and 23 or higher, very severe depression. Yet, in their analysis of studies, the team of researchers point out a recent review of 35 studies, in which only 1 had an average baseline HDRS scores lower than 23. Yet, according to another recent study, the vast majority of people actually taking antidepressants—71%—have HDRS scores lower than 22.
In this latest analysis, led by researchers at the University of Pennsylvania, researchers analyzed six studies, including 434 patients with baseline HDRS scores ranging from 10 to 39, who were taking either the tricyclic antidepressant imipramine (Tofranil) or the selective serotonin re-uptake inhibitor paroxetine (Paxil). While the researchers say that they expected to see some correlation between depression severity and the success of drug intervention, they were surprised by how little effect antidepressant medications had on mild and even moderate symptoms as compared with the most severe cases. As they write:
“What makes our findings surprising is the high level of depression symptom severity that appears to be required for clinically meaningful drug/placebo differences to emerge, particularly given the evidence that the majority of patients receiving [antidepressant medications] in clinical practice present with scores below these levels.”
The authors did not wholly dismiss any potential benefit of antidepressants for some patients with mild or moderate depression, but suggested that this evidence underscores the need to try other forms of treatment before relying on medications. As Dr. Robert J. DeRubeis, a psychologist at the University of Pennsylvania and one of the study’s authors, told the New York Times:
“The message for patients with mild to moderate depression is, ‘Look, medications are always an option, but there’s little evidence that they add to other efforts to shake the depression — whether it’s exercise, seeing the doctor, reading about the disorder or going for psychotherapy.’ ”