Psychopharmacol Bull
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Paroxetine controlled-release (CR) was developed with the objective of minimizing the occurrence and severity of selective serotonin reuptake inhibitor (SSRI)-associated adverse events, thereby improving clinical outcomes. Paroxetine CR delays the onset and controls the rate of absorption of medication. ⋯ Other studies have demonstrated the efficacy and tolerability of paroxetine CR in geriatric depression, panic disorder, and social anxiety disorder. The CR formulation of paroxetine appears to represent an effective pharmacokinetic approach to minimizing SSRI adverse events and thereby enhancing clinical outcomes.
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Major depression is recognized as a common, often chronic and recurrent illness that is associated with significant disability and comorbidity. The treatment of patients with major depressive disorder has advanced tremendously in the past decade as a result of the availability of effective and well-tolerated antidepressants. ⋯ Evidence for the efficacy and tolerability of anew controlled-release formulation of paroxetine also has been published. Findings from paroxetine clinical studies have added considerably to our knowledge and understanding of the treatment of major depressive disorder, particularly with regard to duration of treatment, the need for treating to full remission and with full doses, and treatment of patients with concurrent symptoms of anxiety.
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Modeling in animals is an invaluable tool in exploring the pathophysiology of human diseases and developing better therapies. Models can be generated using a variety of pharmacological, behavioral, and genetic approaches, but they all require extensive subsequent validation. Ideally, validation should be based on the following 3 axes: face validity (commonalties between the behavioral features of the model and of the human disorder being modeled), predictive validity (the specificity and degree to which drugs that are effective in humans have a corresponding effect in the model), and construct validity (a possible common mechanistic theory that can explain both the model and the human disorder being modeled). ⋯ New construct validity-driven models focusing on signaling pathways include models based on perturbations of G proteins, phosphoinositide signaling, and mitogen-activated protein (MAP) kinase cascades. These new models hold much promise in delineating the underlying pathophysiology of bipolar disorder and for the development of novel, improved therapeutics. Psychopharmacology Bulletin.