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

Journal: Asian journal of psychiatry

Volume: 95

Issue: 

Year of Publication: 

Affiliated Institutions:  Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan. 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. Kabir Medical College, Gandhara University, Peshawar, Pakistan. Department of Internal Medicine, Dow University of Health Sciences, Karachi, Pakistan. Electronic address: sanilamughal@gmail.com.

Abstract summary 

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.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.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.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.

Authors & Co-authors:  Ali Latif Mashkoor Sheikh Iqbal Owais Ahmed Naveed Moeed Ullah Mughal

Study Outcome 

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Statistics
Citations : 
Authors :  11
Identifiers
Doi : 10.1016/j.ajp.2024.104005
SSN : 1876-2026
Study Population
Male,Female
Mesh Terms
Other Terms
Cariprazine;Depression scores;Dopamine receptor agonist;Major Depressive Disorder;Randomized Controlled Trials;Tolerability
Study Design
Study Approach
Country of Study
Publication Country
Netherlands