Cortical thickness increases with levomilnacipran treatment in a pilot randomised double‐blind placebo‐controlled trial in late‐life depression

Abstract

Background Late‐life depression (LLD) is associated with significant medical comorbidity, cognitive impairment, and suboptimal treatment response compared to depression experienced earlier in life. Levomilnacipran (LVM) is a novel antidepressant the effects of which on neuroplasticity have not yet been investigated. We investigated the effect of LVM on cortical thickness in a pilot randomised placebo‐controlled trial in LLD. Methods Twenty‐nine adults (≥ 60 years) with major depression (48.3% female; mean age = 71.5 ± 5.8 years; mean education = 16.0 ± 1.7 years) were randomised to either LVM or placebo for 12 weeks. T1‐weighted images were acquired at baseline and 12 weeks. Thirteen subjects (six LVM and seven placebo) completed the study. Group differences in cortical thickness change across the study period were evaluated, with age and total intracranial volume included as covariates. Results Dropout rates did not differ significantly between groups. The LVM group had significantly more side effects, but no serious adverse events were reported. Lower LVM dose (≤ 40 mg) was better tolerated than higher doses (80–120 mg). Additionally, the LVM group showed a larger increase in cortical thickness in the right postcentral gyrus (primary somatosensory), supramarginal gyrus (sensory association region), and lateral occipital cortex (visual cortex) compared to the placebo group and greater reductions in the left insula. Conclusions LVM may be less tolerable by older adults with depression and the effects on cortical thickness across sensory and sensory association regions may be related to the experience of side effects. Larger studies are necessary to evaluate treatment efficacy, tolerability, and neural effects of LVM in LLD.

Cortical Thickness Predicts Response Following 2 Weeks of SSRI Regimen in First-Episode, Drug-Naive Major Depressive Disorder: An MRI Study

“…A longitudinal study found that after 8 weeks of antidepressant treatment, the remitter patients with MDD (n = 19) at baseline had a lower thickness in the right insula and right rostral middle frontal gyrus than non-remitters (n = 23); moreover, following treatment, the thickening degree of the cortex in the majority of brain regions in the remitter group was greater than that in the non-remitter group. Several studies noted increased cortical thickness following the amelioration of symptoms for those with mental health disorders (59)(60)(61)(62)(63). Kornig et al found that the more severe the depression symptoms, the lower cortical thickness of the right insula is; however, there was no difference in severity of symptoms between the responder and non-responder groups at baseline in our study (64).…”

Gut Microbiome Diversity and Abundance Correlate with Gray Matter Volume (GMV) in Older Adults with Depression

“…Participants were recruited from geriatric ambulatory care settings (UCLA Geriatric Medicine-Psychiatry clinics) and from local advertisements to participate in the parent clinical trial of levomilnacipran for geriatric depression (NCT 02466958) that was previously reported elsewhere [ 27 , 49 ]. Of 29 randomized patients, 16 older adults (37.5% female; mean age, 70.6 (SD = 5.7) years; Table 1 ) completed both MRI and stool sample collection and were included in this report.…”

“…Depressive symptom severity was assessed using the Hamilton Depression Rating Scale (HAMD-24) [ 51 , 52 ] and the Montgomery–Åsberg Depression Rating Scale (MADRS) [ 53 ]. Exclusion criteria and recruitment have previously been described in more detail [ 49 ]. This study was approved by the UCLA Institutional Review Board.…”

Mental depression: Relation to different disease status, newer treatments and its association with COVID-19 pandemic (Review)

“…a recent study demonstrated that levomilnacipran in older patients with depression has lower tolerability than in older adults with depression. levomilnacipran requires to be more deeply studied to analyze its efficacy and tolerability in patients with depression (140).…”