SSRIs Effective in Patients With Nonsevere Depression

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Based on improved symptoms measured by the 6-item Hamilton Depression Rating Scale, SSRIs appear to be as effective in patients with nonsevere depression as in patients with severe depression.

Interpretation of depression scale scores may indicate inaccurately that selective serotonin reuptake inhibitors (SSRIs) are not as effective for nonsevere depression, according to research published in Lancet Psychiatry. This contradicts previous reports that antidepressants are only effective in patients with severe depression. Such studies typically use disputed measures of improvement and are based on group-level rather than on patient-level data.

An item-based, patient-level, post-hoc analysis included data from 8262 adult patients with major depressive disorder who participated in completed acute-phase, placebo-controlled, industry-sponsored, Hamilton Depression Rating Scale (HDRS)-based trials of the SSRIs citalopram, paroxetine, or sertraline. Patient-level data were examined through item-based post-hoc analyses, which illuminated the effect of baseline severity of depression on treatment response. Researchers used the HDRS-17 sum score to demonstrate an overall parameter for depressive symptoms, and then performed a repeat analysis of a modified population using unidimensional reports from the Bech subscale (HDRS-6), with the remaining 11 HDRS (non-HDRA-6) items providing outcome measures of SSRI treatment efficacy.

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The study group comprised 654 patients with nonsevere depression and 1377 with severe depression. Participants were treated with citalopram (n=744), paroxetine (n=2981), sertraline (n=1202), fluoxetine for the active-control group (n=754), or a placebo (n=2581).

On the HDRS-6 subscale, there was no difference between patients with severe or nonsevere depression with respect to SSRI-induced decrease in depressed mood and other symptoms. After excluding patients with extreme baseline values, a positive association was seen between severity and efficacy when looking at the HDRS-17 sum score. However, using the non-HDRA-6 sum score as an outcome measurement, a significant treatment response was seen in patients with severe depression, but no effect was seen in those with nonsevere depression. Results demonstrated that the majority of differences between these groups of patients was a result of these non-HDRA-6 symptoms.

The study was limited by its lack of data on the effect of SSRIs on mild depression as well as a lack of data on the relationship between depression severity and doses.

Previous interpretations of inefficacy of SSRIs in patients with nonsevere depression may be the result of statistical rather than pharmacologic issues. Researchers stated, “The present analysis does not support limiting antidepressant treatment to patients with severe depression.

“These observations highlight the importance of reconsidering how depression rating scales are used to define depression severity and to assess treatment response. They also underline the importance of interpreting results from group-level meta-analyses with due caution,” they concluded.


Hieronymus F, Lisinski A, Nilsson S, Eriksson E. Influence of baseline severity on the effects of SSRIs in depression: an item-based, patient-level analysis [published online July 11, 2019]. Lancet Psychiatry. doi:10.1016/S2215-0366(19)30216-0