Relative Efficacy and Safety of Adjunctive CT-152 in Patients with Major Depressive Disorder: Systematic Review and Network Meta-Analysis

Background: The FDA recently authorized CT-152 as a prescription digital therapeutic adjunct to antidepressant (ADT) medications for patients with major depressive disorder (MDD).
Methods: A systematic literature review (SLR) was conducted using PubMed, Cochrane, and Embase to identify randomized controlled trials assessing adjunctive digital, pharmacological, and non-pharmacological treatments in MDD. The SLR followed PRISMA and HTA guidelines compliant two-review and a quality control process. Bayesian (base-case), and Frequentist random-effect (RE) and fixed-effect (FE) network meta-analyses (NMA) were employed to assess 6-week efficacy and safety, with sensitivity analyses (SA) addressing heterogeneity and outlier studies.
Results: Thirty studies assessing 12,830 patients were included. CT-152 demonstrated similar reduction in MADRS total scores compared to adjunctive ADTs (weighted mean difference, WMD, 0.97) and atypical antipsychotics (AAPs) (WMD, 0.22). CT-152 showed a similar reduction in CGI-S scores vs. AAPs (WMD, 0.01), ADTs (WMD, -0.33), and deprexis (WMD, -0.19). Remission and response rates, respectively, were similar for CT-152 vs. AAPs (rate ratio, RR, 0.90 and 1.04), ADTs (RR, 1.03 and 1.22), and cognitive behavioral therapies (CBT) (RR for remission:1.59). Additional analyses revealed a statistically superior safety profile for CT-152 compared to AAPs (odds ratio, OR, 0.32) and ADTs (OR, 0.37) for any treatment-emergent adverse events. The FE, SA and Frequentist approach results were broadly aligned with the base-case RE NMA.
Conclusion: CT-152 showed similar efficacy to adjunctive ADTs, AAPs, and CBT with a statistically superior safety profile than AAPs and ADTs. Consistent results from different NMA methods further establish CT-152 as a viable treatment for MDD