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: 7.05). 09/2011; 37(1):77-101. DOI: 10.1038/npp.2011.198
Source: PubMed


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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    • "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). "

    • "Increased levels of reactive oxygen species (ROS) and reactive nitrogen species (NS) including peroxide (Maes et al., 2010) and nitric oxide (NO) (Dhir and Kulkarni, 2011; Suzuki et al., 2001) have been reported to be associated with mood disorders. Accordingly, O&NS mechanisms have been proposed as targets for novel drugs intended for mood disorders (Li et al., 2012; Lee et al., 2013). "
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    • "It is conceivable that these contrasting results are due to different levels of system xc-inhibition (acute and partial with sulfasalazine, versus chronic and complete in xCT −/− mice), or the species of animals used. At the same time, however, sulfasalazine is known to have poor blood–brain barrier permeability in intact animals (Liu et al., 2012), and peripheral and central off-target effects, such as anti-inflammatory properties (inhibition of nuclear factor kappa B, see (Wahl et al., 1998)) and blockade of NMDA receptors (Ryu et al., 2003), that could influence acute effects on behavior. Future studies will be of particular importance evaluating acute versus chronic modulation of system xc-and its relation to emotional behavior. "
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