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Tarazi, Frank

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Tarazi

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Tarazi, Frank
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    Gene–Environment Interaction in Major Depression: Focus on Experience-Dependent Biological Systems
    (Frontiers Media S.A., 2015) Lopizzo, Nicola; Bocchio Chiavetto, Luisella; Cattane, Nadia; Plazzotta, Giona; Tarazi, Frank; Pariante, Carmine M.; Riva, Marco A.; Cattaneo, Annamaria
    Major depressive disorder (MDD) is a multifactorial and polygenic disorder, where multiple and partially overlapping sets of susceptibility genes interact each other and with the environment, predisposing individuals to the development of the illness. Thus, MDD results from a complex interplay of vulnerability genes and environmental factors that act cumulatively throughout individual’s lifetime. Among these environmental factors, stressful life experiences, especially those occurring early in life, have been suggested to exert a crucial impact on brain development, leading to permanent functional changes that may contribute to lifelong risk for mental health outcomes. In this review, we will discuss how genetic variants (polymorphisms, SNPs) within genes operating in neurobiological systems that mediate stress response and synaptic plasticity, can impact, by themselves, the vulnerability risk for MDD; we will also consider how this MDD risk can be further modulated when gene × environment interaction is taken into account. Finally, we will discuss the role of epigenetic mechanisms, and in particular of DNA methylation and miRNAs expression changes, in mediating the effect of the stress on the vulnerability risk to develop MDD. Taken together, we aim to underlie the role of genetic and epigenetic processes involved in stress- and neuroplasticity-related biological systems on the development of MDD after exposure to early life stress, thereby building the basis for future research and clinical interventions.
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    The Preclinical and Clinical Effects of Vilazodone for the Treatment of Major Depressive Disorder
    (Taylor & Francis, 2016) Sahli, Zeyad T.; Banerjee, Pradeep; Tarazi, Frank
    ABSTRACT Introduction:: Major depressive disorder (MDD) is the leading cause of disability worldwide, and according to the STAR*D trial, only 33% of patients with MDD responded to initial drug therapy. Augmentation of the leading class of antidepressant treatment, selective serotonin reuptake inhibitors (SSRIs), with the 5-HT1A receptor agonist buspirone has been shown to be effective in treating patients that do not respond to initial SSRI therapy. This suggests that newer treatments may improve the clinical picture of MDD. The US Food and Drug Administration (FDA) approved the antidepressant drug vilazodone (EMD 68843), a novel SSRI and 5-HT1A receptor partial agonist. Vilazodone has a half-life between 20–24 hours, reaches peak plasma concentrations at 3.7–5.3 hours, and is primarily metabolized by the hepatic CYP450 3A4 enzyme system. Areas covered: The authors review the preclinical and clinical profile of vilazodone. The roles of serotonin, the 5-HT1A receptor, and current pharmacotherapy approaches for MDD are briefly reviewed. Next, the preclinical pharmacological, behavioral, and physiological effects of vilazodone are presented, followed by the pharmacokinetic properties and metabolism of vilazodone in humans. Last, a brief summary of the main efficacy, safety, and tolerability outcomes of clinical trials of vilazodone is provided. Expert opinion: Vilazodone has shown efficacy versus placebo in improving depression symptoms in several double-blind, placebo-controlled trials. The long-term safety and tolerability of vilazodone treatment has also been established. Further studies are needed that directly compare patients treated with an SSRI (both with and without an adjunctive 5-HT1A partial agonist) versus patients treated with vilaozodone.