13
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Pharmacological approaches to the challenge of treatment-resistant depression Translated title: Aproximaciones farmacológicas para el desafío de la depresión resistente al tratamiento Translated title: La dépression résistante au traitement: ses enjeux, son traitement

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Although monoaminergic antidepressants revolutionized the treatment of Major Depressive Disorder (MDD) over a half-century ago, approximately one third of depressed patients experience treatment-resistant depression (TRD). Such patients account for a disproportionately large burden of disease, as evidenced by increased disability, cost, human suffering, and suicide. This review addresses the definition, causes, evaluation, and treatment of unipolar TRD, as well as the major treatment strategies, including optimization, augmentation, combination, and switch therapies. Evidence for these options, as outlined in this review, is mainly focused on large-scale trials or meta-analyses. Finally, we briefly review emerging targets for antidepressant drug discovery and the novel effects of rapidly acting antidepressants, with a focus on ketamine.

          Translated abstract

          Aunque hace más de medio siglo los antidepresivos monoaminérgicos revolucionaron el tratamiento del Trastorno Depresivo Mayor (TDM), alrededor de un tercio de los pacientes con este cuadro presentan una depresión resistente al tratamiento (DRT). Tales pacientes representan una parte desproportionadamente alta del costo de la enfermedad, lo que se evidencia en el aumento de la discapacidad, el sufrimiento humano y el suicidio. Esta revisión está orientada a la definición, causas, evaluación y tratamiento del TDM unipolar, así como a las principales estrategias terapéuticas, incluyendo la optimización, aumento, combinación y cambio de tratamientos. La evidencia para estas opciones, como se describe en esta revisión, está focalizada printipalmente en ensayos de gran escala o meta-análisis. Por último, se revisan brevemente los blancos que están emergiendo para el descubrimiento de antidepresivos y los nuevos efectos de los antidepresivos de acción rápida, con el foco en la ketamina.

          Translated abstract

          Les antidépresseurs monoaminergiques ont révolutionné le traitement de l'épisode dépressif caractérisé (majeur) (EDM) il y a une cinquantaine d'années, mais environ un tiers des patients déprimés ont une dépression résistante au traitement (DRT). Ces patients représentent un fardeau important et disproportionné de la maladie, comme le prouve l'augmentation du handicap, des coûts, de la souffrance humaine et des suicides. Cet article s'intéresse à la définition, aux causes, à l'évaluation et au traitement de la DRT unipolaire, ainsi qu'aux principales stratégies thérapeutiques, dont les traitements d'optimisation, d'augmentation, d'association et de substitution. L'article souligne que ces solutions se fondent principalement sur des essais à grande échelle ou des métaanalyses. Enfin, nous revoyons brièvement la découverte de nouvelles cibles des médicaments antidépresseurs et les nouveaux effets des antidépresseurs d'action rapide, avec pour objectif principal la kétamine.

          Related collections

          Most cited references 138

          • Record: found
          • Abstract: found
          • Article: not found

          Acute and longer-term outcomes in depressed outpatients requiring one or several treatment steps: a STAR*D report.

          This report describes the participants and compares the acute and longer-term treatment outcomes associated with each of four successive steps in the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) trial. A broadly representative adult outpatient sample with nonpsychotic major depressive disorder received one (N=3,671) to four (N=123) successive acute treatment steps. Those not achieving remission with or unable to tolerate a treatment step were encouraged to move to the next step. Those with an acceptable benefit, preferably symptom remission, from any particular step could enter a 12-month naturalistic follow-up phase. A score of or=11 (HRSD(17)>or=14) defined relapse. The QIDS-SR(16) remission rates were 36.8%, 30.6%, 13.7%, and 13.0% for the first, second, third, and fourth acute treatment steps, respectively. The overall cumulative remission rate was 67%. Overall, those who required more treatment steps had higher relapse rates during the naturalistic follow-up phase. In addition, lower relapse rates were found among participants who were in remission at follow-up entry than for those who were not after the first three treatment steps. When more treatment steps are required, lower acute remission rates (especially in the third and fourth treatment steps) and higher relapse rates during the follow-up phase are to be expected. Studies to identify the best multistep treatment sequences for individual patients and the development of more broadly effective treatments are needed.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Antidepressant effects of ketamine in depressed patients.

            A growing body of preclinical research suggests that brain glutamate systems may be involved in the pathophysiology of major depression and the mechanism of action of antidepressants. This is the first placebo-controlled, double-blinded trial to assess the treatment effects of a single dose of an N-methyl-D-aspartate (NMDA) receptor antagonist in patients with depression. Seven subjects with major depression completed 2 test days that involved intravenous treatment with ketamine hydrochloride (.5 mg/kg) or saline solutions under randomized, double-blind conditions. Subjects with depression evidenced significant improvement in depressive symptoms within 72 hours after ketamine but not placebo infusion (i.e., mean 25-item Hamilton Depression Rating Scale scores decreased by 14 +/- SD 10 points vs. 0 +/- 12 points, respectively during active and sham treatment). These results suggest a potential role for NMDA receptor-modulating drugs in the treatment of depression.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial.

              Ketamine, a glutamate N-methyl-d-aspartate (NMDA) receptor antagonist, has shown rapid antidepressant effects, but small study groups and inadequate control conditions in prior studies have precluded a definitive conclusion. The authors evaluated the rapid antidepressant efficacy of ketamine in a large group of patients with treatment-resistant major depression. This was a two-site, parallel-arm, randomized controlled trial of a single infusion of ketamine compared to an active placebo control condition, the anesthetic midazolam. Patients with treatment-resistant major depression experiencing a major depressive episode were randomly assigned under double-blind conditions to receive a single intravenous infusion of ketamine or midazolam in a 2:1 ratio (N=73). The primary outcome was change in depression severity 24 hours after drug administration, as assessed by the Montgomery-Åsberg Depression Rating Scale (MADRS). The ketamine group had greater improvement in the MADRS score than the midazolam group 24 hours after treatment. After adjustment for baseline scores and site, the MADRS score was lower in the ketamine group than in the midazolam group by 7.95 points (95% confidence interval [CI], 3.20 to 12.71). The likelihood of response at 24 hours was greater with ketamine than with midazolam (odds ratio, 2.18; 95% CI, 1.21 to 4.14), with response rates of 64% and 28%, respectively. Ketamine demonstrated rapid antidepressant effects in an optimized study design, further supporting NMDA receptor modulation as a novel mechanism for accelerated improvement in severe and chronic forms of depression. More information on response durability and safety is required before implementation in clinical practice.
                Bookmark

                Author and article information

                Contributors
                Journal
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues Clin Neurosci
                Dialogues in Clinical Neuroscience
                Les Laboratoires Servier (France )
                1294-8322
                1958-5969
                June 2015
                June 2015
                : 17
                : 2
                : 111-126
                Affiliations
                Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
                Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
                Department of Psychiatry, Massachusetts General Hospital, Boston, Massachusetts, USA
                Author notes
                Article
                4518696
                Copyright: © 2015 Institut la Conférence Hippocrate - Servier Research Group

                This is an open-access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by-nc-nd/3.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                Categories
                State of the Art

                Comments

                Comment on this article