(1) To investigate if gut microbiota can be a predictor of remission in geriatric depression and to identify features of the gut microbiota that is associated with remission. (2) To determine if changes in gut microbiota occur with remission in geriatric depression.

Secondary analysis of a parent randomized placebo-controlled trial (NCT02466958).

Los Angeles, CA, USA (2016-2018)

Seventeen subjects with major depressive disorder, over 60 years of age, 41.2% female.

Levomilacipran (LVM) or placebo.

Remission was defined by Hamilton Depression Rating Scale score of 6 or less at 12 weeks. 16S-ribosomal RNA sequencing based fecal microbiota composition and diversity were measured at baseline and 12 weeks. Differences in fecal microbiota were evaluated between remitters and non-remitters as well as between baseline and post-treatment samples. LVM and placebo groups were combined in all the analyses.

Baseline microbiota showed no community level α-diversity or β-diversity differences between remitters and non-remitters. At the individual taxa level, a random forest classifier created with nine genera from the baseline microbiota was highly accurate in predicting remission (AUC = .857). Of these, baseline enrichment of Faecalibacterium, Agathobacter and Roseburia relative to a reference frame was associated with treatment outcome of remission. Differential abundance analysis revealed significant genus level changes from baseline to post-treatment in remitters, but not in non-remitters.

This is the first study demonstrating fecal microbiota as a potential predictor of treatment response in geriatric depression. Our findings need to be confirmed in larger prospective studies.

Post hoc analyses were conducted to evaluate the efficacy of levomilnacipran extended-release (ER) in subgroups of patients with major depressive disorder (MDD).

Data were pooled from 5 completed Phase II/III studies. Patients were categorized by sex, age, MDD duration, recurrence of MDD, current episode duration, number of prior episodes, and baseline Montgomery–Åsberg Depression Rating Scale (MADRS) score. Efficacy was evaluated by MADRS least squares (LS) mean change from baseline, response (MADRS improvement ≥50%), and remission (MADRS ≤10).

In the pooled population, treatment with levomilnacipran ER versus placebo resulted in greater improvement in MADRS score (−15.8 versus −12.9; LS mean difference, −2.9; P < .001) and higher response rates (44.7% versus 34.5%; P < .001). Comparable treatment effects were found in most subgroups. Remission rates in the overall population were higher for levomilnacipran ER versus placebo (27.7% versus 21.5%; P < .05); notably high remission rates were seen in patients with baseline MADRS score < 30 (48.8% versus 28.9%; P < .001).

Clinically meaningful improvements in depressive symptoms were found across subgroups, including statistically significant outcomes for both response and remission.

Levomilnacipran ER was efficacious across a wide range of MDD patients, including men and women, ages 18–78, with varying histories and symptom severity.