Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials

Eman Ali; Fakhar Latif; Yusra Mashkoor; Ayesha Sheikh; Amna Iqbal; Rabia Owais; Jawad Ahmed; Sadiq Naveed; Abdul Moeed; Irfan Ullah; Sanila Mughal

doi:10.1016/j.ajp.2024.104005

Role of adjunctive cariprazine for treatment-resistant depression in patients with major depressive disorder: A systematic review and meta-analysis of randomized controlled trials

Asian J Psychiatr. 2024 Mar 11:95:104005. doi: 10.1016/j.ajp.2024.104005. Online ahead of print.

Authors

Affiliations

¹ Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan.
² Psychiatry Program Director at Eastern Connecticut Health Network, CT, USA; Associate Professor of Psychiatry, University of Connecticut, CT, USA; Associate Professor of Psychiatry, Frank H. Netter School of Medicine at Quinnipiac University, CT, USA; Fellow, Infant, Parent Mental Health, University of Massachusetts, Boston, USA.
³ Kabir Medical College, Gandhara University, Peshawar, Pakistan.
⁴ Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan. Electronic address: sanilamughal2@gmail.com.

PMID: 38513509
DOI: 10.1016/j.ajp.2024.104005

Abstract

Introduction: Cariprazine is an orally active dopamine D3-preferring D3/D2 receptor and serotonin 5-HT1A receptor partial agonist, being considered as a treatment for refractory MDD. Therefore, we aim to perform the first meta-analysis of current literature, to collate changes in depression from baseline and assess tolerability of adjunctive cariprazine in MDD populace.

Methods: PubMed, Embase, Google Scholar, ClinicalTrials.Gov, and Cochrane Library were searched from inception till 1st September 2023. RCTs of adult patients with refractory MDD under adjunctive cariprazine vs. placebo were included. Primary outcomes included improvement in MADRS, CGI-S, and HAM-D 17 scores. Secondary outcomes included treatment-emergent adverse events. The statistical analysis was performed using generic inverse variance with random-effects model. The overall risk ratios (RR) were calculated for dichotomous outcomes.

Results: A total of five RCTs were analysed, enrolling 2013 participants (cariprazine: 959 participants, Placebo: 1054). Supplementation of ADT with cariprazine demonstrated a significant improvement in MADRAS, CGI-S and HAMD-17 scores from baseline (LSMD: -1.88, 95% CI [-2.94, -0.83], p=0.0005), (LSMD: -0.18, 95% CI [-0.29, -0.07], p=0.002), and (LSMD: -0.96, 95% CI [-1.70, -0.21], p=0.01) respectively. Treatment with adjunctive cariprazine therapy demonstrated significantly increased incidence of akathisia, nausea, dizziness, fatigue, restlessness, somnolence, and tremors when compared with placebo.

Conclusion: Our meta-analysis provides evidence supporting the efficacy of adjunctive cariprazine in patients with refractory MDD. However, it is essential to consider the safety profile of cariprazine, particularly the increased risk of adverse events. The vigilant monitoring and management of these side effects should be integrated into clinical practice to minimize discontinuation rates and optimize patient outcomes.

Keywords: Cariprazine; Depression scores; Dopamine receptor agonist; Major Depressive Disorder; Randomized Controlled Trials; Tolerability.

Publication types

Review