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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.

      63,741 Monthly downloads/views I 2.989 Impact Factor I 4.5 CiteScore I 1.09 Source Normalized Impact per Paper (SNIP) I 0.744 Scimago Journal & Country Rank (SJR)

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      Management of Treatment-Resistant Depression: Challenges and Strategies

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          Abstract

          Treatment-resistant depression (TRD) is a subset of Major Depressive Disorder which does not respond to traditional and first-line therapeutic options. There are several definitions and staging models of TRD and a consensus for each has not yet been established. However, in common for each model is the inadequate response to at least 2 trials of antidepressant pharmacotherapy. In this review, a comprehensive analysis of existing literature regarding the challenges and management of TRD has been compiled. A PubMed search was performed to assemble meta-analyses, trials and reviews on the topic of TRD. First, we address the confounds in the definitions and staging models of TRD, and subsequently the difficulties inherent in assessing the illness. Pharmacological augmentation strategies including lithium, triiodothyronine and second-generation antipsychotics are reviewed, as is switching of antidepressant class. Somatic therapies, including several modalities of brain stimulation (electroconvulsive therapy, repetitive transcranial magnetic stimulation, magnetic seizure therapy and deep brain stimulation) are detailed, psychotherapeutic strategies and subsequently novel therapeutics including ketamine, psilocybin, anti-inflammatories and new directions are reviewed in this manuscript. Our review of the evidence suggests that further large-scale work is necessary to understand the appropriate treatment pathways for TRD and to prescribe effective therapeutic options for patients suffering from TRD.

          Most cited references118

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          The Inventory of Depressive Symptomatology (IDS): psychometric properties.

          A Rush, C Gullion, M. Basco … (1996)
          The psychometric properties of the 28- and 30-item versions of the Inventory of Depressive Symptomatology, Clinician-Rated (IDS-C) and Self-Report (IDS-SR) are reported in a total of 434 (28-item) and 337 (30-item) adult out-patients with current major depressive disorder and 118 adult euthymic subjects (15 remitted depressed and 103 normal controls). Cronbach's alpha ranged from 0.92 to 0.94 for the total sample and from 0.76 to 0.82 for those with current depression. Item total correlations, as well as several tests of concurrent and discriminant validity are reported. Factor analysis revealed three dimensions (cognitive/mood, anxiety/arousal and vegetative) for each scale. Analysis of sensitivity to change in symptom severity in an open-label trial of fluoxetine (N = 58) showed that the IDS-C and IDS-SR were highly related to the 17-item Hamilton Rating Scale for Depression. Given the more complete item coverage, satisfactory psychometric properties, and high correlations with the above standard ratings, the 30-item IDS-C and IDS-SR can be used to evaluate depressive symptom severity. The availability of similar item content for clinician-rated and self-reported versions allows more direct evaluations of these two perspectives.
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            Efficacy and safety of transcranial magnetic stimulation in the acute treatment of major depression: a multisite randomized controlled trial.

            John P. O’Reardon, H Solvason, Philip G Janicak … (2007)
            We tested whether transcranial magnetic stimulation (TMS) over the left dorsolateral prefrontal cortex (DLPFC) is effective and safe in the acute treatment of major depression. In a double-blind, multisite study, 301 medication-free patients with major depression who had not benefited from prior treatment were randomized to active (n = 155) or sham TMS (n = 146) conditions. Sessions were conducted five times per week with TMS at 10 pulses/sec, 120% of motor threshold, 3000 pulses/session, for 4-6 weeks. Primary outcome was the symptom score change as assessed at week 4 with the Montgomery-Asberg Depression Rating Scale (MADRS). Secondary outcomes included changes on the 17- and 24-item Hamilton Depression Rating Scale (HAMD) and response and remission rates with the MADRS and HAMD. Active TMS was significantly superior to sham TMS on the MADRS at week 4 (with a post hoc correction for inequality in symptom severity between groups at baseline), as well as on the HAMD17 and HAMD24 scales at weeks 4 and 6. Response rates were significantly higher with active TMS on all three scales at weeks 4 and 6. Remission rates were approximately twofold higher with active TMS at week 6 and significant on the MADRS and HAMD24 scales (but not the HAMD17 scale). Active TMS was well tolerated with a low dropout rate for adverse events (4.5%) that were generally mild and limited to transient scalp discomfort or pain. Transcranial magnetic stimulation was effective in treating major depression with minimal side effects reported. It offers clinicians a novel alternative for the treatment of this disorder.
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              Daily left prefrontal transcranial magnetic stimulation therapy for major depressive disorder: a sham-controlled randomized trial.

              Mark S. George, Sarah Lisanby, David Avery … (2010)
              Daily left prefrontal repetitive transcranial magnetic stimulation (rTMS) has been studied as a potential treatment for depression, but previous work had mixed outcomes and did not adequately mask sham conditions. To test whether daily left prefrontal rTMS safely and effectively treats major depressive disorder. Prospective, multisite, randomized, active sham-controlled (1:1 randomization), duration-adaptive design with 3 weeks of daily weekday treatment (fixed-dose phase) followed by continued blinded treatment for up to another 3 weeks in improvers. Four US university hospital clinics. Approximately 860 outpatients were screened, yielding 199 antidepressant drug-free patients with unipolar nonpsychotic major depressive disorder. We delivered rTMS to the left prefrontal cortex at 120% motor threshold (10 Hz, 4-second train duration, and 26-second intertrain interval) for 37.5 minutes (3000 pulses per session) using a figure-eight solid-core coil. Sham rTMS used a similar coil with a metal insert blocking the magnetic field and scalp electrodes that delivered matched somatosensory sensations. In the intention-to-treat sample (n = 190), remission rates were compared for the 2 treatment arms using logistic regression and controlling for site, treatment resistance, age, and duration of the current depressive episode. Patients, treaters, and raters were effectively masked. Minimal adverse effects did not differ by treatment arm, with an 88% retention rate (90% sham and 86% active). Primary efficacy analysis revealed a significant effect of treatment on the proportion of remitters (14.1% active rTMS and 5.1% sham) (P = .02). The odds of attaining remission were 4.2 times greater with active rTMS than with sham (95% confidence interval, 1.32-13.24). The number needed to treat was 12. Most remitters had low antidepressant treatment resistance. Almost 30% of patients remitted in the open-label follow-up (30.2% originally active and 29.6% sham). Daily left prefrontal rTMS as monotherapy produced statistically significant and clinically meaningful antidepressant therapeutic effects greater than sham. clinicaltrials.gov Identifier: NCT00149838.
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                Author and article information

                Journal
                Journal ID (nlm-ta): Neuropsychiatr Dis Treat
                Journal ID (iso-abbrev): Neuropsychiatr Dis Treat
                Journal ID (publisher-id): NDT
                Journal ID (pmc): neurodist
                Title: Neuropsychiatric Disease and Treatment
                Publisher: Dove
                ISSN (Print): 1176-6328
                ISSN (Electronic): 1178-2021
                Publication date (Electronic): 21 January 2020
                Publication date Collection: 2020
                Volume: 16
                Pages: 221-234
                Affiliations
                [1 ]Centre for Addiction and Mental Health , Toronto, Ontario, Canada
                [2 ]Department of Psychiatry, University of Toronto , Toronto, Ontario, Canada
                Author notes
                Correspondence: Daniel M Blumberger Centre for Addiction and Mental Health , 1001 Queen Street West, Unit 4-1, Toronto, OntarioM6J1H4, CanadaTel +1 416 535-8501Fax +1 416 583-1358 Email daniel.blumberger@camh.ca
                Author information
                http://orcid.org/0000-0002-7450-4434
                Article
                Publisher ID: 198774
                DOI: 10.2147/NDT.S198774
                PMC ID: 6982454
                PubMed ID: 32021216
                SO-VID: 9c98399b-d3bd-453d-b835-535c1c41e3f7
                Copyright © © 2020 Voineskos et al.
                License:

                This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License ( http://creativecommons.org/licenses/by-nc/3.0/). By accessing the work you hereby accept the Terms. Non-commercial uses of the work are permitted without any further permission from Dove Medical Press Limited, provided the work is properly attributed. For permission for commercial use of this work, please see paragraphs 4.2 and 5 of our Terms ( https://www.dovepress.com/terms.php).

                History
                Date received : 11 October 2019
                Date accepted : 07 January 2020
                Page count
                References: 149, Pages: 14
                Categories
                Subject: Review

                ScienceOpen disciplines: Neurology
                Keywords: treatment resistant depression,major depressive disorder,pharmacotherapy,psychotherapy,brain stimulation,novel therapies
                Data availability:
                ScienceOpen disciplines: Neurology
                Keywords: treatment resistant depression, major depressive disorder, pharmacotherapy, psychotherapy, brain stimulation, novel therapies

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