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      Neuropsychiatric Disease and Treatment (submit here)

      This international, peer-reviewed Open Access journal by Dove Medical Press focuses on all aspects of neuropsychiatric and neurological disorders. Sign up for email alerts here.

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      Agomelatine and its therapeutic potential in the depressed patient

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          Abstract

          Despite advances in understanding potential disease mechanisms and in developing novel therapeutic approaches to the treatment of major depressive disorder, the disease continues to carry an enormous personal, social, and economic burden. Agomelatine represents an important opportunity to advance the treatment of depression. It is a melatonergic (MT 1 and MT 2) agonist and serotonergic (5HT 2C) antagonist. Evidence from animal models of depression, complements emerging clinical data. In a dose range of 25–50 mg daily, agomelatine is an effective antidepressant with a very favorable side-effect profile. In particular, sleep restorative action in the absence of sedation and minimal effect on sexual function suggests that agomelatine represents a worthwhile treatment alternative for patients with major depressive disorder.

          Most cited references65

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          A new depression scale designed to be sensitive to change

          The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inner-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.
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            A neurotrophic model for stress-related mood disorders.

            There is a growing body of evidence demonstrating that stress decreases the expression of brain-derived neurotrophic factor (BDNF) in limbic structures that control mood and that antidepressant treatment reverses or blocks the effects of stress. Decreased levels of BDNF, as well as other neurotrophic factors, could contribute to the atrophy of certain limbic structures, including the hippocampus and prefrontal cortex that has been observed in depressed subjects. Conversely, the neurotrophic actions of antidepressants could reverse neuronal atrophy and cell loss and thereby contribute to the therapeutic actions of these treatments. This review provides a critical examination of the neurotrophic hypothesis of depression that has evolved from this work, including analysis of preclinical cellular (adult neurogenesis) and behavioral models of depression and antidepressant actions, as well as clinical neuroimaging and postmortem studies. Although there are some limitations, the results of these studies are consistent with the hypothesis that decreased expression of BDNF and possibly other growth factors contributes to depression and that upregulation of BDNF plays a role in the actions of antidepressant treatment.
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              Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice.

              Selective serotonin reuptake inhibitors (SSRIs) are widely used to treat depression, but the rates, timing, and baseline predictors of remission in "real world" patients are not established. The authors' primary objectives in this study were to evaluate the effectiveness of citalopram, an SSRI, using measurement-based care in actual practice, and to identify predictors of symptom remission in outpatients with major depressive disorder. This clinical study included outpatients with major depressive disorder who were treated in 23 psychiatric and 18 primary care "real world" settings. The patients received flexible doses of citalopram prescribed by clinicians for up to 14 weeks. The clinicians were assisted by a clinical research coordinator in the application of measurement-based care, which included the routine measurement of symptoms and side effects at each treatment visit and the use of a treatment manual that described when and how to modify medication doses based on these measures. Remission was defined as an exit score of or=50% in baseline QIDS-SR score. Nearly 80% of the 2,876 outpatients in the analyzed sample had chronic or recurrent major depression; most also had a number of comorbid general medical and psychiatric conditions. The mean exit citalopram dose was 41.8 mg/day. Remission rates were 28% (HAM-D) and 33% (QIDS-SR). The response rate was 47% (QIDS-SR). Patients in primary and psychiatric care settings did not differ in remission or response rates. A substantial portion of participants who achieved either response or remission at study exit did so at or after 8 weeks of treatment. Participants who were Caucasian, female, employed, or had higher levels of education or income had higher HAM-D remission rates; longer index episodes, more concurrent psychiatric disorders (especially anxiety disorders or drug abuse), more general medical disorders, and lower baseline function and quality of life were associated with lower HAM-D remission rates. The response and remission rates in this highly generalizable sample with substantial axis I and axis III comorbidity closely resemble those seen in 8-week efficacy trials. The systematic use of easily implemented measurement-based care procedures may have assisted in achieving these results.

                Author and article information

                Journal
                Neuropsychiatr Dis Treat
                Neuropsychiatric Disease and Treatment
                Neuropsychiatric Disease and Treatment
                Dove Medical Press
                1176-6328
                1178-2021
                August 2007
                : 3
                : 4
                : 423-428
                Affiliations
                University Health Network, University of Toronto, Canada
                Author notes
                Correspondence: Sidney H Kennedy, University Health Network, 200 Elizabeth, St, EN8-222, Toronto, ON M5G 2C4, Canada, Tel +1 416 340 3888, Fax +1 416 340 4198, Email sidney.kennedy@ 123456uhn.on.ca
                Article
                ndt-3-423
                2655086
                19300571
                5af7b62e-a087-4801-b05d-fa77222e4ec4
                © 2007 Dove Medical Press Limited. All rights reserved
                History
                Categories
                Expert Opinion

                Neurology
                agomelatine,tolerability,antidepressant,major depressive disorder,efficacy
                Neurology
                agomelatine, tolerability, antidepressant, major depressive disorder, efficacy

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