Research suggests that individuals experiencing depression exhibit decreased levels of gamma-aminobutyric acid (GABA) in both plasma and cerebrospinal fluid (CSF), along with a reduction in GABAergic interneurons. Zuranolone, a neurosteroid, functions by modulating the extrasynaptic GABA receptor (GABAA), thereby addressing, and resolving the imbalances in brain networks associated with depression.
The meta-analysis, published in the current issue of eClinicalMedicine, explored the effectiveness and safety of zuranolone as a treatment for major depressive disorder (MDD). The systematic review and meta-analysis were conducted using a random-effects model to calculate effect sizes based on standardized mean differences (SMDs) and odds ratios (ORs) with 95% confidence intervals (CIs). The primary outcome was the improvement in depressive symptoms, while secondary outcomes included response and remission rates of depression, improvement in anxiety symptoms, incidence of dropouts, and any side effects. Subgroup analyses were conducted for general MDD and postpartum-onset MDD, and a dose-response meta-analysis was performed to estimate the relationship between zuranolone and outcomes.
Lin and colleagues identified 603 studies from the database, of which only seven randomized controlled trials were examined. These studies encompassed 1789 participants (72% females) with a mean age of 38.7 years. All studies included a cohort of MDD patients who received zuranolone in daily doses of 20 to 50 mg per day.
The researchers noted that zuranolone yielded a reduction in depressive symptoms (SMD = −0.37, 95% CIs = −0.51 to −0.23), an increase in response rate (OR = 2.06, 95% CIs = 1.48–2.85), and remission rate (OR = 2.04, 95% CIs = 1.38–3.02). Anxiety symptoms also exhibited improvement (SMD = −0.26, 95% CIs = −0.39 to −0.14). In addition, patients treated with zuranolone reported more side effects compared to the control group. The dropout rate, however, did not show a significant difference between the two groups (OR = 1.13, 95% CIs = 0.85–1.49). According to the dose-response meta-analysis, zuranolone demonstrated effective improvements in depression and anxiety with increasing doses, up to a maximum daily dose of 30 mg. Beyond this threshold, an increase in the incidence of side effects was noted. Subgroup analyses indicated that zuranolone exhibited greater efficacy in treating postpartum-onset MDD than general MDD, although the difference did not reach statistical significance.
Another recent study by Parikh et al. also reported a significant improvement in depressive symptoms among patients with major depressive disorders using zuranolone.
The researchers concluded that zuranolone effectively alleviates depression and anxiety, acknowledging the potential risk of adverse effects. With a balance between therapeutic efficacy and side effects, a daily dose of 30 mg appears to be the optimal choice. Further research is warranted to ascertain whether zuranolone is more efficacious against postpartum depression than general MDD.
References
- Lin YW, Tu YK, Hung KC, Liang CS, Tseng PT, Lin PY, et al. Efficacy and safety of zuranolone in major depressive disorder: a meta-analysis of factor effect and dose-response analyses. eClinicalMedicine [Internet]. 2023 Dec 1 [cited 2023 Nov 21];66.
- Parikh SV, Aaronson ST, Mathew SJ, Alva G, DeBattista C, Kanes S, et al. Efficacy and safety of zuranolone co-initiated with an antidepressant in adults with major depressive disorder: results from the phase 3 CORAL study. Neuropsychopharmacol. 2023 Oct 24;1–9.