Does Depression Severity Limit Treatment Options?

October 25, 2018

ORLANDO, Fla.—Mark Zimmerman, MD, addressed a pair of controversies in depression treatment at Psych Congress 2018: Are antidepressants only effective in patients with severe depression, and, in this population, does evidence suggest psychotherapy has little or no place in care?

In short, the answer to both questions is no, Dr. Zimmerman said.

    Mark Zimmerman, MD

“The efficacy of antidepressants does not seem to be limited to severely depressed patients,” said Dr. Zimmerman, director of outpatient psychiatry and the partial hospital program at Rhode Island Hospital and a psychiatry professor at the Brown University medical school in Providence, Rhode Island. “The efficacy of psychotherapy does not seem to be limited to mildly and moderately depressed patients.”

Behind both controversies, Dr. Zimmerman said, is an incomplete view of the literature.


What constitutes severe depression—severity in most illnesses, actually—differs across rating scales, treatment guides, and clinician viewpoints, Dr. Zimmerman pointed out.

“There is no clear consensus in how to conceptualize severity,” he explained. “And there’s no data in the literature as to how clinicians think about severity.”

The DSM-5, for example, categorizes depression severity based on the number of symptoms, a patient’s distress level, and the level of impairment experienced. Different rating scales, meanwhile, vary in content, instructions, and severity groupings.

As a result, patients with similar symptoms could fall into different severity groups depending on the measurements used. Severity as a construct is by no means clear-cut.


Uncertainty about the effectiveness of antidepressants in patients with mild or moderate depression was raised by a 2002 meta-analysis in The Journal of Clinical Pharmacology. Researchers analyzed 45 studies from the US Food and Drug Administration (FDA) database and used mean baseline scores on the Hamilton Depression Rating Scale rather than individual patient data.

They concluded the effects of antidepressants seemed to be more robust among patients with more severe depression. Still, the study advised that findings should be used to inform the design of future trials rather than be applied in clinical practice.

Controversy grew several years later, when a second meta-analysis of 35 FDA trials found that drug-placebo differences increased with depression severity.

“That’s when the popular press jumped,” Dr. Zimmerman said, with prominent stories appearing in Newsweek, Time, WebMD, and even Psychology Today casting doubt on the effect of antidepressants in most patients.

The degree of response the second meta-analysis generated, Dr. Zimmerman said, was partly due to the wording of author conclusions. Rather than suggesting findings may not be relevant to clinical practice, the study declared it found “little evidence to support the prescription of antidepressant medication to any but the most severely depressed patients.”

A 2010 JAMA study which analyzed individual patient data spanning 718 patients “put the nail in the coffin,” Dr. Zimmerman said. It concluded there was little evidence to show antidepressants offered any benefit for the majority of patients with less severe depression.

More recent large-scale pooled analyses, however, suggest effectiveness across severity groups. Dr. Zimmerman reviewed several, including a 2012 Archives of General Psychiatry study spanning more than 9,000 patients, a 2017 Journal of Clinical Psychopharmacology study that included more than 4,200 patients, and a 2016 study in the British Journal of Psychiatry that looked at data for more than 10,000 patients.

These pooled analysis studies suggest, Dr. Zimmerman explained, antidepressant “efficacy is not limited to a narrow band of severely depressed patients.”


The belief that psychotherapy alone is not beneficial for severe depression, which has worked its way into official treatment guideline recommendations, stems from a 1989 study in the Archives of General Psychiatry, Dr. Zimmerman explained. The research predated both selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors and involved just 200 or so patients, each of whom received treatment with one of four possible treatments (placebo, imipramine, cognitive behavioral therapy, or interpersonal therapy).

Since then, several meta-analyses and a pooled analysis have been published that suggest depression severity does not predict a poorer response to psychotherapy.

Consequently, “empirical support for treatment guidelines recommending medication as the first-line treatment for severe depression is limited,” Dr. Zimmerman said.

—Jolynn Tumolo


 “Severity and the treatment of depression: a review of two controversies.” Presented at Psych Congress 2018: Orlando, FL.; October 25, 2018.