The Phosphodiesterase 3 Inhibitor Cilostazol as an Adjunct to Antidepressants in Major Depressive Disorder Patients
The Phosphodiesterase 3 Inhibitor Cilostazol as an Adjunct to Antidepressants in Major Depressive Disorder Patients
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.
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.
Inclusion Criteria:

 -  Eighty adult outpatients with the Diagnostic and Statistical Manual of Mental
 Disorders-IV (DSM-IV) diagnosis of MDD based on a MINI Neuropsychiatric Interview
 (MINI) (American Psychiatric Association., 2000; Sheehan et al., 1998), without
 psychotic features and a total 17 item HAM-D score of at least 20 with item 1
 (depressed mood) scored 2 or greater were eligible (Hamilton, 1960).

 -  Patients were requested to be free of all the psychotropic and anti-inflammatory
 medications for at least 4 weeks before participating in the study.

 Exclusion Criteria:

 -  Patients with bipolar I or bipolar II disorder

 -  Patients with personality disorders

 -  Patients with eating disorders

 -  Patients with substance dependence or abuse

 -  Patients with concurrent active medical condition

 -  Patients with history of seizures

 -  Patients with history of receiving Electroconvulsive therapy (ECT)

 -  Patients with inflammatory disorders

 -  Patients with allergy or contraindications to the used medications

 -  Patients with finally pregnant or lactating females

 -  Cardiovascular disorders

 -  Severe renal impairment: creatinine clearance of ≤ 25 ml/min

 -  Moderate or severe hepatic impairment