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      Treatment-Resistant Depression in Primary Care Across Canada

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          Abstract

          Objective:

          Treatment-resistant depression (TRD) represents a considerable global health concern. The goal of the InSight study was to investigate the prevalence of TRD and to evaluate its clinical characterization and management, compared with nonresistant depression, in primary care centres.

          Methods:

          Physicians completed a case report on a consecutive series of patients with major depressive disorder ( n = 1212), which captured patient demographics and comorbidity, as well as current and past medication.

          Results:

          Using failure to respond to at least 2 antidepressants (ADs) from different classes as the definition of TRD, the overall prevalence was 21.7%. There were no differences in prevalence between men and women or among ethnicities. Patients with TRD had longer episode duration, were more likely to receive polypharmacy (for example, psychotropic, lipid-lowering, and antiinflammatory agents), and reported more AD related side effects. Higher rates of disability and comorbidity (axes I to III) were associated with treatment resistance. Obesity and being overweight were also associated with treatment resistance. While the selection and sequencing of pharmacotherapy by family physicians in this sample was in line with recommendations from evidence-based treatment guidelines, the wait time to make a change in treatment was 6 to 8 weeks in both groups, which exceeds guideline recommendations.

          Conclusions:

          These real-world data demonstrate the high prevalence of TRD in primary care settings, and underscore the substantial burden of illness associated with TRD.

          Translated abstract

          Objectif :

          La dépression réfractaire au traitement (DRT) représente un problème de santé considérable sur le plan mondial. Le but de l’étude InSight était de rechercher la prévalence de la DRT et d’en évaluer la caractérisation et la gestion cliniques, comparativement à la dépression non réfractaire, dans les centres de soins primaires.

          Méthodes :

          Les médecins ont procédé à une étude de cas sur une série consécutive de patients souffrant de trouble dépressif majeur ( n = 1212), qui comprenait les données démographiques et les comorbidités des patients, ainsi que leurs médicaments présents et passés.

          Résultats :

          En utilisant la non réponse à au moins 2 antidépresseurs (AD) de différentes classes comme définition de la DRT, la prévalence globale était de 21,7 %. Il n’y avait pas de différence de prévalence entre hommes et femmes ou entre groupes ethniques. Les patients souffrant de DRT avaient des épisodes de plus longue durée, étaient plus susceptibles de recevoir une polypharmacie (par exemple, des agents psychotropes, des hypolipidémiants, et antiinflammatoires), et déclaraient plus d’effets secondaires liés aux AD. Des taux élevés d’invalidité et de comorbidité (axes I à III) étaient associés à la résistance au traitement. L’obésité et l’embonpoint étaient aussi associés à la résistance au traitement. Même si la sélection et la séquence de la pharmacothérapie par les médecins de famille dans cet échantillon étaient conformes aux recommandations des lignes directrices basées sur les données probantes du traitement, le temps d’attente pour effectuer un changement de traitement était de 6 à 8 semaines dans les 2 groupes, ce qui excède les recommandations des lignes directrices.

          Conclusions :

          Ces données en milieu réel démontrent la prévalence élevée de la DRT dans les soins de première ligne, et soulignent le fardeau substantiel de la maladie associé à la DRT.

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          Most cited references58

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          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.
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            Global burden of depressive disorders in the year 2000.

            The initial Global Burden of Disease study found that depression was the fourth leading cause of disease burden, accounting for 3.7% of total disability adjusted life years (DALYs) in the world in 1990. To present the new estimates of depression burden for the year 2000. DALYs for depressive disorders in each world region were calculated, based on new estimates of mortality, prevalence, incidence, average age at onset, duration and disability severity. Depression is the fourth leading cause of disease burden, accounting for 4.4% of total DALYs in the year 2000, and it causes the largest amount of non-fatal burden, accounting for almost 12% of all total years lived with disability worldwide. These data on the burden of depression worldwide represent a major public health problem that affects patients and society.
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              Canadian Network for Mood and Anxiety Treatments (CANMAT) clinical guidelines for the management of major depressive disorder in adults. III. Pharmacotherapy.

              In 2001, the Canadian Psychiatric Association and the Canadian Network for Mood and Anxiety Treatments (CANMAT) partnered to produce evidence-based clinical guidelines for the treatment of depressive disorders. A revision of these guidelines was undertaken by CANMAT in 2008-2009 to reflect advances in the field. The CANMAT guidelines are based on a question-answer format to enhance accessibility to clinicians. An evidence-based format was used with updated systematic reviews of the literature and recommendations were graded according to Level of Evidence using pre-defined criteria. Lines of Treatment were identified based on criteria that included Levels of Evidence and expert clinical support. This section on "Pharmacotherapy" is one of 5 guideline articles. Despite emerging data on efficacy and tolerability differences amongst newer antidepressants, variability in patient response precludes identification of specific first choice medications for all patients. All second-generation antidepressants have Level 1 evidence to support efficacy and tolerability and most are considered first-line treatments for MDD. First-generation tricyclic and monoamine oxidase inhibitor antidepressants are not the focus of these guidelines but generally are considered second- or third-line treatments. For inadequate or incomplete response, there is Level 1 evidence for switching strategies and for add-on strategies including lithium and atypical antipsychotics. Most of the evidence is based on trials for registration and may not reflect real-world effectiveness. Second-generation antidepressants are safe, effective and well tolerated treatments for MDD in adults. Evidence-based switching and add-on strategies can be used to optimize response in MDD that is inadequately responsive to monotherapy.
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                Author and article information

                Journal
                Can J Psychiatry
                Can J Psychiatry
                Canadian Journal of Psychiatry. Revue Canadienne de Psychiatrie
                The Canadian Psychiatric Association
                0706-7437
                1497-0015
                July 2014
                : 59
                : 7
                : 349-357
                Affiliations
                [1 ]Student, Departments of Pharmaceutical Sciences and Neuroscience, University of Toronto, Toronto, Ontario; Clinical Research Coordinator, Department of Psychiatry, University Health Network, Toronto, Ontario.
                [2 ]Chief Operating Officer and Chief Financial Officer, Canadian Heart Research Centre, Toronto, Ontario.
                [3 ]Statistician, Canadian Heart Research Centre, Toronto, Ontario.
                [4 ]Project Manager, Department of Psychiatry, University Health Network, Toronto, Ontario.
                [5 ]Director of Primary Care Initiatives, Canadian Heart Research Centre, Toronto, Ontario.
                [6 ]Psychiatrist, Department of Psychiatry, University Health Network, Toronto, Ontario; Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario; Professsor, Department of Pharmacology, University of Toronto, Toronto, Ontario.
                [7 ]Psychiatrist, Department of Psychiatry, University Health Network, Toronto, Ontario; Professor, Department of Psychiatry, University of Toronto, Toronto, Ontario; Professor, Institute of Medical Sciences, University of Toronto, toronto, Ontario.
                Author notes
                Correspondence: Department of Psychiatry, University Health Network, Room 222, Eaton North Wing, 8th Floor, 200 Elizabeth Street, Toronto, ON M5G 2C4; sidney.kennedy@ 123456uhn.ca .
                Article
                cjp-2014-vol59-july-349-357
                10.1177/070674371405900702
                4086317
                25007419
                7ec5cd83-f674-456f-ba76-1e113ee5f7c6
                © 2014 Canadian Psychiatric Association

                This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution license ( http://creativecommons.org/licenses/by/3.0/).

                History
                : September 2013
                : January 2014
                : January 2014
                Categories
                Original Research

                treatment-resistant depression,prevalence,risk factors,primary care

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