RESUMEN
Background: Postpartum blues (PPB) is a frequent syndrome of sad mood, crying spells, anxiety, restlessness, reduced appetite, and irritability, typically peaking day 5 postpartum. When severe, it greatly increases risk for later postpartum depression. This trial compared a dietary supplement to placebo on PPB severity. The supplement was designed to counter downstream effects of elevated monoamine oxidase A level, implicated in causing PPB. Methods: Participants recruited by advertisement from the Toronto region completed procedures at CAMH, Canada and/or participants' homes. Oral supplement or identical appearing relatively inert placebo were administered in randomised, double-blind fashion. Supplement was blueberry juice and extract given four times between nighttime day 3 and morning day 5 postpartum; tryptophan 2 g nighttime day 4 postpartum, and tyrosine 10 g morning day 5 postpartum. On day 5, depressed mood induction procedure (MIP) and postpartum blues were assessed. All data is presented (NCT03296956 closed, clinicaltrials.gov). Findings: Between January 2019 and December 2022, participants took supplement (n = 51) or placebo (n = 52). There was no significant effect on primary outcome MIP on visual analogue scale for depressed mood (mean difference = -0.39 mm, 95% CI: -6.42 to 5.65 mm). Stein Maternity Blues scores, exploratory PPB measure, was lower in the active group (effect size 0.62; median, interquartile range (IQR): active 2.00 (IQR 1, 4); placebo 4.00 (IQR 1.5, 6); regression with general linear model, supplement effect, ß coefficient = -1.50 (95%: CI -2.60, -0.40), p = 0.008; effect of CES-D crying category before supplement, p = 0.03-0.00000023). Twenty-six and 40 different adverse events occurred within 25% and 42% of supplement and placebo cases respectively (Chi-Square, p = 0.06). Interpretation: The primary outcome was negative for effect on depressed mood induction, however the supplement moderately reduced PPB. Funding: CAMH/Exeltis.
RESUMEN
Gliosis is implicated in the pathophysiology of many neuropsychiatric diseases, including treatment-resistant major depressive disorder (TRD). Translocator protein total distribution volume (TSPO VT), a brain marker mainly reflective of gliosis in disease, can be measured using positron emission tomography (PET). Minocycline reduces gliosis and translocator protein binding in rodents, but this is not established in humans. Here, the ability of oral minocycline to reduce TSPO VT was assessed in TRD. To determine whether oral minocycline, as compared to placebo, can reduce prefrontal cortex (PFC), anterior cingulate cortex (ACC), and insula TSPO VT in TRD, twenty-one TRD participants underwent two [18F]FEPPA PET scans to measure TSPO VT. These were completed before and after either oral minocycline 100 mg bid or placebo which was administered in a randomized double-blinded fashion for 8 weeks. There was no significant difference between the minocycline and placebo groups on change in TSPO VT within the PFC, ACC, and insula (repeated measures ANOVA, effect of group interaction, PFC: F1,19 = 0.28, P = 0.60; ACC: F1,19 = 0.54, P = 0.47; insula F1,19 = 1.6, P = 0.22). Oral minocycline had no significant effect on TSPO VT which suggests that this dosage is insufficient to reduce gliosis in TRD. To target gliosis in TRD either alternative therapeutics or intravenous formulations of minocycline should be investigated. These results also suggest that across neuropsychiatric diseases in humans, it should be assumed that oral minocycline will not reduce TSPO VT or gliosis unless empirically demonstrated.