Study Supports Raising SSRI Doses in Patients Who Do Not Respond to Low-Dose Treatment

Using a higher dose of selective serotonin reuptake inhibitors (SSRIs) for major depressive disorder appears to be associated with an increased likelihood of response, according to a meta-analysis published today in AJP in Advance. This benefit, which is somewhat offset by decreased tolerability of SSRIs at high doses, appears to plateau at about 50 mg of fluoxetine (250 mg imipramine-equivalent dose).

A team of researchers in the United States and London searched PubMed for randomized, placebo-controlled trials that examined the efficacy of SSRIs for treating adults with major depressive disorder and assessed improvement in depression severity at multiple time points. Additional data were collected on treatment response and all-cause and side effect-related discontinuation. All medication doses were transformed into imipramine-equivalent doses.

Based on an analysis of 40 studies involving 10,039 participants, the investigators found a statistically significant positive association between SSRI dose and measured efficacy of SSRIs in reducing depression severity, with the greatest measured efficacy of SSRIs observed in the dosing range of 200–250 imipramine equivalents. The analysis also revealed that higher doses of SSRIs were associated with an increased likelihood of dropouts due to side effects but a decreased likelihood of all-cause dropout, which the authors noted “is likely attributable to their greater efficacy.”

“Our meta-analysis provides evidence to support clinical guidelines that recommend raising SSRI dose in adults with major depressive disorder who do not respond to SSRI medications at or below the lower end of the therapeutic dose range,” the study authors wrote.

For related information, see the Psychiatric News article “Study to Answer What Comes Next When MDD Patients Don’t Respond.”

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