RETRACTED: Double‐blind, randomized, placebo‐controlled pilot study of the phosphodiesterase‐3 inhibitor cilostazol as an adjunctive to antidepressants in patients with major depressive disorder

Abstract

Aims: Cilostazol (CLS) has shown antidepressant effect in cardiovascular patients, post-stroke depression, and animal models through its neurotrophic and antiinflammatory activities. Consequently, we aimed to investigate its safety and efficacy in patients with MDD by conducting double-blind, randomized, placebo-controlled pilot study. Methods: 80 participants with MDD (DSM-IV criteria) and Hamilton DepressionRating Scale (HDRS) score >20 were treated with CLS 50 mg or placebo twice daily plus escitalopram (ESC) 20 mg once daily for six weeks. Patients were evaluated by HDRS scores (weeks 0, 2, 4, and 6). Serum levels of CREB1, BDNF, 5-HT, TNFα, NF-κB, and FAM19A5 were assessed pre-and post-treatment.Results: Co-administration of CLS had markedly decreased HDRS score at all-time points compared to the placebo group (p < 0.001). Early improvement, response, and remission rates after 6 weeks were significantly higher in the CLS group (90%, 90%, 80%, respectively) than in the placebo group (25%, 65%, 50% respectively) (p < 0.001). Moreover, the CLS group was superior to the placebo group in modulation of the measured neurotrophic and inflammatory biomarkers. Conclusion:CLS is safe and effective short-term adjunctive therapy in patients with MDD with no other comorbid conditions.Trial registration ID:NCT04069819.

White Matter Alterations in Depressive Disorder

“…According to the research of Khadivi et al., the HAMD score decreased significantly more in MDD patients treated with cilostazol and sertraline for six weeks than in those treated with sertraline alone, and the safety was no difference ( 89 ). When Cilostazol combined with escitalopram, similar results were obtained ( 90 ). A case report found that cilostazol was used intensively to treat a patient with intractable depression complicated by WMH.…”

Cilostazol as adjunctive therapy in treatment of children with autism spectrum disorders: a double-blind and placebo-controlled randomized trial

“…Moreover, all of the side effects showed a mild, transient nature without needing urgent medical attention. These findings were in line with those reported in other trials of cilostazol add-on therapies in schizophrenia and major depressive disorder settings (Rezaei et al , 2017; Abdallah et al , 2021). Furthermore, as mentioned previously, cilostazol is primarily prescribed for its antiplatelet and vasodilation effects to improve claudication.…”

“…Beneficial therapeutic outcomes of cilostazol adjuvant therapy have been reported for schizophrenia (Rezaei et al , 2017), major depressive disorder (Abdallah et al , 2021), and Alzheimer’s disease (Tai et al , 2017). However, studying cilostazol application in ASD management has been limited to a single animal study.…”

Microglia Involves in the Immune Inflammatory Response of Poststroke Depression: A Review of Evidence

“…Studies have suggested that brain injury during stroke stimulates the body to produce a rapid immune regulatory response. The peripheral immune system recruits inflammation-related cells and develops inflammation-related factors, which migrate to the brain injury area through the damaged blood-brain barrier for immune regulation [72][73][74][75]. The imbalance of homeostasis in the inflammatory state alters the endocrine function of nerve cells.…”