Understanding the Real-World Prescription Patterns and Impact of Atypical Antipsychotic Augmentation Timing on Healthcare Cost in Adult Major Depressive Disorder in the United States: A Systematic Literature Review

This work was supported by Otsuka Pharmaceutical Development & Commercialization, Inc. Princeton, NJ, USA and Lundbeck LLC. DH and SKare employees of Otsuka Pharmaceutical Development & Commercialization Inc., Princeton, NJ, USA. BT is an employee of Lundbeck LLC, Deerfield, IL, USA. FA is an employee of H. Lundbeck A/S, Copenhagen, Denmark. BS and SA are employees of Pharmacoevidence, SAS Nagar, India, which was funded by Otsuka Pharmaceutical Development & Commercialization, Inc. Princeton, NJ, USA to conduct this analysis To improve the low remission rate with antidepressants (ADT) and reduce healthcare costs, healthcare providers benefit from an improved understanding of adherence to guidelines, disease course, and atypical antipsychotics (AAPs) usage in major depressive disorder (MDD). This systematic literature review (SLR) examines real-world prescription patterns and the impact of AAP augmentation timing on healthcare costs. US-specific studies meeting the eligibility criteria were identified through searches in biomedical databases (Embase®, MEDLINE®, CENTRAL®, and PsycINFO®). The SLR followed the standard methodology for reviews outlined in the Cochrane Handbook and PRISMA guidelines. The SLR included seven treatment guidelines (TGs) and 46 studies of treatment patterns (TPs). TP studies were aligned with TGs, reporting higher utilization of SSRIs (range 17.3% to 100%)/SNRIs (6.8% to 40.7%) as initial treatment. TGs recommended AAP augmentation for inadequate responders to prior ≥1L ADT. Real-world prescription patterns of AAP augmentation ranged from 0.70% to 100% with aripiprazole (3.4% to 53.4%) and quetiapine (2.3% to 52.6%), the most utilized AAPs. Seven studies reported the impact of AAP augmentation timing on healthcare costs. Early initiators (Time-to-augmentation 6 months), primarily due to reduced hospitalization rates. TGs were generally aligned with observed TPs, recommending SSRIs/SNRIs as first-line MDD treatment and AAP augmentation for inadequate ADT response. Early augmentation with AAPs was associated with cost savings. However, guidelines lack clear guidance for early AAP augmentation guidance, despite real-world studies indicating its substantial use after initial ADT failure, likely due to outdated guidelines.