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Key considerations in the pharmacological management of treatment-resistant depression.

ABSTRACT: Introduction: Treatment-resistant depression (TRD) is a complex, multifactorial, and biologically heterogeneous disorder with debilitating outcomes. Understanding individual reasons why patients do not respond to treatment is necessary for improving clinical recommendations regarding medication regimens, augmentation strategies, and alternative treatments.Areas covered: This manuscript reviews evidence-based treatment strategies for the clinical management of TRD. Current developments in the field and potential future recommendations for personalized treatment of TRD are also discussed.Expert opinion: Treatment guidelines for TRD are limited by the heterogeneous nature of the disorder. Furthermore, current strategies reflect this heterogeneity by emphasizing disease characteristics as well as drug trial response or failure. Developing robust biomarkers that could one day be integrated into clinical practice has the potential to advance specific treatment targets and ultimately improve treatment and remission outcomes.

SUBMITTER: Yavi M

PROVIDER: S-EPMC8648908 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

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Key considerations in the pharmacological management of treatment-resistant depression.

Yavi Mani M Henter Ioline D ID Park Lawrence T LT Zarate Carlos C

Expert opinion on pharmacotherapy 20210721 17

<b>Introduction:</b> Treatment-resistant depression (TRD) is a complex, multifactorial, and biologically heterogeneous disorder with debilitating outcomes. Understanding individual reasons why patients do not respond to treatment is necessary for improving clinical recommendations regarding medication regimens, augmentation strategies, and alternative treatments.<b>Areas covered:</b> This manuscript reviews evidence-based treatment strategies for the clinical management of TRD. Current developme ...[more]

PMID: 34252320

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Project description:BackgroundTreatment-resistant depression (TRD) in major depressive disorder (MDD) is defined as the failure of two or more antidepressants. Few studies have characterized the natural history and treatment patterns of these patients. This study aims to identify the natural history of disease and treatment trajectories for patients with TRD.MethodsA retrospective longitudinal study used claims data linked to electronic health records (EHRs) from January 1, 2017, to October 31, 2021. Inclusion criteria were age ≥ 18 years, ≥ 1 MDD diagnosis, no antidepressant use at baseline, and an index date within 90 days of MDD diagnosis. Exclusions included psychiatric disorders other than MDD. TRD patients were defined as receiving third-line antidepressant treatment within two years of first-line initiation. Second- and third-line antidepressant treatment was defined as a switch to or addition of a different antidepressant with an adequate dose/duration or initiation of an augmentation treatment.ResultsOut of 301,821 individuals with MDD using antidepressants or augmentation medications during the study, 2,409 incident TRD patients were selected out of 50,374 meeting the criteria. The median time to TRD (time from first to third line index date) was 11.5 months, and the TRD episode duration was 10.8 months. Initial treatment was predominantly antidepressant monotherapy, declining from 91.0% in the first line to 39.4% in the third line. Combination therapy including antidepressants and augmentation medications increased over lines, reaching 55.6% in the third line. During the TRD episode, SSRIs were the most prescribed antidepressants with the longest duration of use. Cognitive-behavioral therapy was used by 53.5% of TRD patients, while other nonpharmacological therapies were rarely used. Treatment trajectories varied by age, sex, and anxiety.ConclusionsThis study identified contemporary treatment patterns in TRD patients, with combination therapy and augmentation medications increasingly used, highlighting the need for precision treatment based on individual trajectories.

Project description:BackgroundDepression in older adults is often undertreated. A 2011 systematic review of treatments for treatment-resistant depression (TRD) in older adults identified one placebo-controlled randomised controlled trial (RCT). We aimed to update this review, synthesising evidence for the effectiveness of treatments for TRD in older people.MethodsWe systematically searched electronic databases (PubMed, Cochrane, Web of Science) from 9 January 2011 through 10 December 2023 (updating our search on 7 January 2024 for RCTs investigating TRD therapies in adults aged ≥55 years, defining treatment resistance as ≥1 unsuccessful treatment. We assessed bias with the Cochrane Risk of Bias (RoB) 2 tool, meta-analysed remission rates and evaluated evidence using GRADE (Grading of Recommendations Assessment, Development, and Evaluation) criteria.Results14 studies (11 newly identified, 3 from previous review) involving 1196 participants (mean age 65.0, male/female 548/648) met the inclusion criteria; 10 were placebo controlled and 4 were rated as low RoB. The pooled proportion of participants in intervention arms remitting was 0.35 (17 arms; 95% CI=0.26; 0.45). Relative to placebo, intervention participants were more likely to remit (9 studies; OR 2.42 (95% CI=1.49; 3.92)). Relative to controls, remission rates favoured ketamine (n=3; OR 2.91 (1.11; 7.65)), with a trend towards transcranial magnetic stimulation (TMS) (n=3; 1.99 (0.71; 5.61)), and in single placebo-controlled studies, selegiline, aripiprazole augmentation, pharmacogenetic-guided prescribing (PGP) and cognitive remediation favoured interventions.ConclusionsWe identified weak evidence that ketamine therapy and aripiprazole augmentation, and very weak evidence that TMS, PGP and cognitive remediation increased remission. Lack of evidence regarding routinely prescribed antidepressants and psychosocial treatments is problematic, requiring clinicians to extend evidence from younger populations.Prospero registration numberCRD42023494513.

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Key considerations in the pharmacological management of treatment-resistant depression.

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Key considerations in the pharmacological management of treatment-resistant depression.

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