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Are SSRIs Effective Only for Severe Depression?

July 29, 2019

By Marilynn Larkin

NEW YORK—Selective serotonin reuptake inhibitors (SSRIs) may effectively treat non-severe depression, but the effect would not be apparent with the commonly used rating scale, researchers say.

"Reports claiming that antidepressants are effective only in patients with severe depression have affected treatment guidelines but these reports usually use a disputed measure of improvement, a decrease in the sum-score of the 17-item Hamilton Depression Rating Scale (HDRS-17), and are based on group-level rather than patient-level data," note Dr. Elias Eriksson of the University of Gothenburg and colleagues.

The team pooled data data from all completed, acute-phase, placebo-controlled, industry-sponsored, HDRS-based trials of the SSRIs citalopram, paroxetine, or sertraline in adult major depression.

They did post-hoc analyses to assess the effect of baseline severity of depression on the response to treatment as assessed with HDRS-17 sum score; a six-item subscale of the HDRS (HDRS-6) that includes depressed mood, guilt, work and interests, psychomotor retardation, psychic anxiety, and general somatic symptoms); and the remaining 11 HDRS items not included in the subscale (non-HDRS-6).

Patients were defined as having non-severe depression if they had a baseline HDRS-17 sum score of 18 points or less and as having severe depression if they had a score of 27 points or more.

As reported online July 11 in The Lancet Psychiatry, the team analyzed data from 8,262 patients enrolled in 28 placebo-controlled SSRI trials: 744 were treated with citalopram; 2,981 with paroxetine; 1,202 with sertraline; 754 with fluoxetine (active-control group); and 2,581 who received placebo.

A total of 654 patients had non-severe depression and 1,377 had severe depression. Patients with non-severe and severe depression did not differ with respect to the SSRI-induced decrease in depressed mood and other HDRS symptoms in the HDRS-6 subscale.

However, after exclusion of outliers at baseline, a positive association was seen between severity and efficacy when using the HDRS-17 sum score as the effect parameter. This result was largely due to a more pronounced response to treatment with respect to non-HDRS-6 items in patients with severe depression compared with those with non-severe depression, according to the authors.

"This outcome could be explained by non-HDRS-6 items, more so than HDRS-6 items, being more severe and prevalent at baseline in severe than in non-severe cases; hence, less room was left for improvement in these areas in patients with non-severe depression," the authors state.

"The use of an outcome measure that includes symptoms that rate low at baseline in patients with non-severe depression might result in the interpretation that SSRIs are ineffective in these patients," they continue. "With respect to alleviation of HDRS-6 items, SSRIs appear to be as effective in patients with non-severe depression as in those with severe depression."

Dr. Toshi Furukawa of Kyoto University, author of a related editorial, commented by email, "There has been much research into and controversy about the influence of baseline severity on the efficacy of antidepressants - some claiming smaller benefit for the milder forms of major depressive disorder, while others not replicating such tendencies."

"A recent report based on an extremely large dataset has confirmed the influence of baseline severity: the efficacy of antidepressants is smaller but is still there for the less severe patients," he told Reuters Health.

That report, presented at the 2018 American Society of Clinical Psychopharmacology meeting in Miami, found an average improvement of 2.4 points in the HDRS sum score among patients with a baseline severity of 30 points (severe depression) and 1.1 points among patients with a baseline severity of 17 points (mild depression).

"Whether this benefit is worth the costs and possible side effects of antidepressants awaits individual decisions," Dr. Furukawa said.

The current study, he added, "pointed out that such dependency of efficacy on baseline severity may be due to how you measure depression. Depression severity is usually measured by so-called core depression items and associated symptoms (sleep, gastrointestinal symptoms etc.)."

"If you focus on the core depression items, the improvement in depression was not dependent on the baseline severity," he said.

"This study opens up some fundamental questions," he noted in his editorial. "What is depression? How can we measure it most adequately and appropriately? And what do we mean to treat when we treat people with depression?"

Dr. Eriksson did not respond to requests for a comment.


Lancet Psychiatry 2019.

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