Article

Review of Pharmacological Treatment in Mood Disorders and Future Directions for Drug Development

Department of Psychiatry and Behavioral Neuroscience, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology (Impact Factor: 7.83). 09/2011; 37(1):77-101. DOI: 10.1038/npp.2011.198
Source: PubMed

ABSTRACT After a series of serendipitous discoveries of pharmacological treatments for mania and depression several decades ago, relatively little progress has been made for novel hypothesis-driven drug development in mood disorders. Multifactorial etiologies of, and lack of a full understanding of, the core neurobiology of these conditions clearly have contributed to these development challenges. There are, however, relatively novel targets that have raised opportunities for progress in the field, such as glutamate and cholinergic receptor modulators, circadian regulators, and enzyme inhibitors, for alternative treatment. This review will discuss these promising new treatments in mood disorders, the underlying mechanisms of action, and critical issues of their clinical application. For these new treatments to be successful in clinical practice, it is also important to design innovative clinical trials that identify the specific actions of new drugs, and, ideally, to develop biomarkers for monitoring individualized treatment response. It is predicted that future drug development will identify new agents targeting the molecular mechanisms involved in the pathophysiology of mood disorders.

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Available from: Richard C Shelton, Aug 20, 2014
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    • "Newly developed approaches are allowing basic scientists to formulate a circuit-level understanding of dimensions of depression-like behavior (Russo and Nestler, 2013). There is also increased understanding of interactions between the monoaminergic and glutamatergic systems and of mechanisms of neuroplasticity, cellular resilience and synaptic plasticity (Li et al., 2012; Prins et al., 2011; Russo and Nestler, 2013). A growing body of evidence implicates glutamate system dysregulation as a key pathophysiological feature of mood disorders, thereby making the glutamate system a prime target for innovative treatments (Der-Avakian and Markou, 2012; Lapidus et al., 2013; Russo and Nestler, 2013; Stahl, 2013). "
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    Journal of Psychopharmacology 10/2014; 29(5). DOI:10.1177/0269881114553252 · 2.81 Impact Factor
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    • "ADs are generally classified according to their primary pharmacological targets. The first developed ADs were monoamine oxidase inhibitors (MAOi) and tricyclic (TCA) and tetracyclic agents (Li et al, 2012). Second-generation ADs include the selective serotonin reuptake inhibitors (SSRIs), still the most prescribed ADs worldwide, and norepinephrine and serotonin reuptake inhibitors (NSRIs). "
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    Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology 07/2014; 40(2). DOI:10.1038/npp.2014.176 · 7.83 Impact Factor
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    • "Valproic acid (VPA) and lithium chloride (LiCl) are two mood-stabilizing drugs used to treat patients with bipolar disorder (Kazantsev and Thompson 2008; Li et al. 2012). It has been reported that the major pharmacological actions of VPA are to inhibit histone deacetylase (HDAC) and glycogen synthase kinase-3 (GSK-3) activities (Phiel et al. 2001; Werstuck et al. 2004), while LiCl is the inhibitor of GSK-3 (Stambolic et al. 1996; Zhang et al. 2003). "
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