The Phosphodiesterase-3 Inhibitor Cilostazol as an Adjunctive to Antidepressants in Patients With Major Depressive Disorder.
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Study type: Interventional

Summary: 
      Cilostazol is a PDE 3 inhibitor, which showed as decrease in HAM-D scores in post-stroke
      depression through inhibition of neurodegeneration in the primary lesion and secondary
      extrafocal sites and through promotion of neurogenesis. These beneficial effects on
      post-stroke depression may be involved in activation of CREB/BDNF signaling.The aim of the
      current study is to evaluate the potential adjunct antidepressant effect of cilostazol in
      adult patients with MDD. Furthermore, we will assess the relationship between HAM-D score and
      BDNF as well as their role as a therapeutic targets of MDD.
    

Detailed description: 
      Cilostazol produces various powerful pleiotropic effects via restoration of intracellular
      second messenger cyclic adenosine monophosphate (cAMP). Treatment with cilostazol against
      cerebral ischemic injury ameliorates negative effects of cerebral hypoperfusion through the
      PDE3- cAMP signaling cascade with subsequent activation of inducible transcription factor
      cAMP response element-binding protein (CREB), suggesting the importance of the CREB signaling
      pathway.

      Activation of CREB promotes the gene expression of neuroprotective molecules that activate
      subsequent anti-apoptotic pathways with the gene expression of brain-derived neurotrophic
      factor (BDNF). BDNF also regulates neurogenesis, proliferation, and survival of neural stem
      or progenitor cells, as well as neuronal survival. In addition, CREB and BDNF signaling play
      an important role in the pathophysiology of major depressive disorder .

      Psychopharmacotherapy with antidepressants or mood stabilizers provides an effective
      treatment for depression after stroke, but alternative therapy by activation of CREB and BDNF
      signaling may exert beneficial effects on various aspects of negative mood. Drugs that
      activate CREB and BDNF signaling may provide a potential therapeutic approach for treatment
      of poststroke depression via neural cell survival and proliferation of neural progenitor
      cells.

      The aim of the current study is to evaluate the potential adjunct antidepressant effect of
      cilostazol in adult patients with MDD. Furthermore, we will assess the relationship between
      HAM-D score and BDNF as well as their role as a therapeutic targets of MDD.
    

Intervention name(s): Cilostazol 50 MG Oral Tablet; Escitalopram; Placebo
Intervention type(s): Drug; Drug; Drug
Intervention description(s): Escitalopram,Selective serotonin reuptake inhibitor- Cilostazol, a selective phosphodiesterase 3 (PDE3) inhibitor, acts as an antiplatelet agent and has been widely approved for treatment of intermittent claudication with peripheral arterial disease and for secondary prevention of ischemic stroke.; Escitalopram 20 mg tablet once daily for 6 week; placebo
Intervention MeSH terms: Cilostazol; Escitalopram
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary purpose: Treatment