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Purpose/background: Zuranolone is a positive allosteric modulator of both synaptic and extrasynaptic γ-aminobutyric acid type A receptors and a neuroactive steroid approved as an oral, once-daily, 14-day treatment course for adults with postpartum depression in the United States. This study assessed zuranolone transfer into breast milk., Methods/procedures: Healthy, nonpregnant, lactating adult female participants received once-daily 30 mg zuranolone from day (D)1 through D5 in this phase 1 open-label study. The relative infant dose (RID; weight-adjusted proportion of the maternal dose in breast milk over 24 hours) for 30 mg zuranolone was assessed at D5. An RID for 50 mg zuranolone was estimated using a simulation approach across a range of infant ages and weights., Findings/results: Of 15 enrolled participants (mean age, 30.1 years), 14 completed the study. The mean RID for 30 mg zuranolone at D5 was 0.357%; the mean steady-state milk volume over D3 to D5 decreased from baseline by 8.3%. Overall unbound zuranolone in plasma was low (≤0.49%). Plasma concentrations peaked at D5 before decreasing in a biexponential manner. There was strong concordance between the temporal profiles of zuranolone concentrations in plasma and breast milk. The estimated mean RID for 50 mg zuranolone based on a milk intake of 200 mL/kg per day was 0.984%. All treatment-emergent adverse events reported by participants were mild, the most common being dizziness (n = 3)., Implications/conclusions: Zuranolone transfer into the breast milk of healthy, nonpregnant, lactating adult female participants was low; the estimated RID for 50 mg zuranolone was <1%, well below the <10% threshold generally considered compatible with breastfeeding., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objective: Evaluate clinical characteristics, comorbidity burden, major depressive disorder (MDD)-related healthcare resource utilization (HCRU), medication burden, and antidepressant treatment (ADT) patterns among older adults with MDD with and without selected comorbidities., Methods: Using Komodo's Healthcare Map claims data (1/1/2016-9/30/2022), patients with MDD (≥65 years) treated with ADTs were assessed 24 months preceding (baseline) and 12 months following (follow-up) first observed ADT prescription fill (index). Patients were separated into cohorts of those with ≥1 of 5 selected comorbidities and those without. Clinical characteristics, comorbidities, and MDD-related HCRU were assessed during baseline; treatment patterns were assessed during follow-up. Baseline and follow-up all-cause and comorbidity-specific medication burdens (mean prescription claims/month) were determined., Results: Among the total cohort ( N  = 417,643), 97.1% had ≥1 of 5 selected comorbidities: hypertension (80.3%), hyperlipidemia (75.4%), diabetes (54.2%), anxiety disorder (39.0%), and chronic obstructive pulmonary disorder (19.5%). Baseline and follow-up all-cause medication burdens per month were 3.8 and 4.5 for patients with selected comorbidities and 1.7 and 2.3 for those without. During baseline, most patients (96.0% with selected comorbidities, 96.2% without) had ≥1 outpatient visit, and a numerically higher percentage of those with vs. without selected comorbidities had MDD-related emergency room (13.9% vs. 6.0%) and inpatient (13.5% vs. 4.1%) visits. The majority of both cohorts (61.0% with selected comorbidities, 59.5% without) underwent treatment pattern changes., Conclusion: This study highlights the medication burden and ADT patterns in older adults with MDD, assessing these outcomes among patients with and without comorbidities. Numerically higher medication burdens among those with selected comorbidities suggests future studies could investigate the impact of comorbidities on MDD-related care.