scholarly journals Treatment-Resistant Depression Revisited: A Glimmer of Hope

2021 ◽  
Vol 11 (2) ◽  
pp. 155
Author(s):  
Angelos Halaris ◽  
Emilie Sohl ◽  
Elizabeth A. Whitham
Keyword(s):  
Significant Risk ◽  
Treatment Resistance ◽  
Contributory Factor ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Test Procedures ◽  
Gonadal Dysfunction ◽  
Immune Biomarkers ◽  
Resistant Depression

Major Depressive Disorder (MDD) is a highly prevalent psychiatric disorder worldwide. It causes individual suffering, loss of productivity, increased health care costs and high suicide risk. Current pharmacologic interventions fail to produce at least partial response to approximately one third of these patients, and remission is obtained in approximately 30% of patients. This is known as Treatment-Resistant Depression (TRD). The burden of TRD exponentially increases the longer it persists, with a higher risk of impaired functional and social functioning, vast losses in quality of life and significant risk of somatic morbidity and suicidality. Different approaches have been suggested and utilized, but the results have not been encouraging. In this review article, we present new approaches to identify and correct potential causes of TRD, thereby reducing its prevalence and with it the overall burden of this disease entity. We will address potential contributory factors to TRD, most of which can be investigated in many laboratories as routine tests. We discuss endocrinological aberrations, notably, hypothalamic-pituitary-adrenal (HPA) axis dysregulation and thyroid and gonadal dysfunction. We address the role of Vitamin D in contributing to depression. Pharmacogenomic testing is being increasingly used to determine Single Nucleotide Polymorphisms in Cytochrome P450, Serotonin Transporter, COMT, folic acid conversion (MTHFR). As the role of immune system dysregulation is being recognized as potentially a major contributory factor to TRD, the measurement of C-reactive protein (CRP) and select immune biomarkers, where testing is available, can guide combination treatments with anti-inflammatory agents (e.g., selective COX-2 inhibitors) reversing treatment resistance. We focus on established and emerging test procedures, potential biomarkers and non-biologic assessments and interventions to apply personalized medicine to effectively manage treatment resistance in general and TRD specifically.

scholarly journals Treatment-Resistant Depression in Adolescents: Clinical Features and Measurement of Treatment Resistance

2020 ◽  
Vol 30 (4) ◽  
pp. 261-266 ◽  
Author(s):  
Jeffrey R. Strawn ◽  
Scott T. Aaronson ◽  
Ahmed Z. Elmaadawi ◽  
G. Randolph Schrodt ◽  
Richard C. Holbert ◽  
...  
Keyword(s):  
Clinical Features ◽  
Treatment Resistance ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

The Role of Transcranial Magnetic Stimulation in Treatment-Resistant Depression: A Review

2012 ◽  
Vol 18 (36) ◽  
pp. 5846-5852 ◽  
Author(s):  
Jonathan C. Lee ◽  
Daniel M. Blumberger ◽  
Paul B. Fitzgerald ◽  
Zafiris J. Daskalakis ◽  
Andrea J. Levinson
Keyword(s):  
Transcranial Magnetic Stimulation ◽  
Magnetic Stimulation ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

scholarly journals Role of the serotonergic system in subcallosal DBS for treatment-resistant depression

2021 ◽  
Author(s):  
A. Ghaderi ◽  
E.C. Brown ◽  
D.L. Clark ◽  
R. Ramasubbu ◽  
Z.H.T. Kiss ◽  
...  
Keyword(s):  
Serotonergic System ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression

An Update on Glutamatergic System in Suicidal Depression and on the Role of Esketamine

2020 ◽  
Vol 20 (7) ◽  
pp. 554-584 ◽  
Author(s):  
Domenico De Berardis ◽  
Carmine Tomasetti ◽  
Maurizio Pompili ◽  
Gianluca Serafini ◽  
Federica Vellante ◽  
...  
Keyword(s):  
Nmda Receptor ◽  
Depressive Symptomatology ◽  
Phase Iii ◽  
Glutamatergic Neurotransmission ◽  
Treatment Resistant Depression ◽  
Glutamatergic System ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Imminent Risk

Background: A research on mood disorder pathophysiology has hypothesized abnormalities in glutamatergic neurotransmission, by suggesting further investigation on glutamatergic N-methyl-Daspartate (NMDA) receptor modulators in treating Major Depressive Disorder (MDD). Esketamine (ESK), an NMDA receptor antagonist able to modulate glutamatergic neurotransmission has been recently developed as an intranasal formulation for treatment-resistant depression (TRD) and for rapid reduction of depressive symptomatology, including suicidal ideation in MDD patients at imminent risk for suicide. Objective: The present study aims at investigating recent clinical findings on research on the role of the glutamatergic system and ESK in treating suicidal depression in MDD and TRD. Methods: A systematic review was here carried out on PubMed/Medline, Scopus and the database on U.S. N.I.H. Clinical Trials (https://clinicaltrials.gov) and the European Medical Agency (EMA) (https://clinicaltrialsregister.eu) from inception until October 2019. Results: Intravenous infusion of ESK is reported to elicit rapid-acting and sustained antidepressant activity in refractory patients with MDD and TRD. In phase II studies, intranasal ESK demonstrated a rapid onset and a persistent efficacy in patients with TRD as well as in MDD patients at imminent risk for suicide. However, some data discrepancies have emerged in phase III studies. Conclusion: The U.S. Food and Drug Administration (FDA) granted fast track and Breakthrough Therapy Designation to Janssen Pharmaceuticals®, Inc. for intranasal ESK in 2013 for treatment-resistant depression (TRD) and in 2016 for the treatment of MDD with an imminent risk of suicide. However, further studies should be implemented to investigate the long-term efficacy and safety of intranasal ESK.

Deep Brain Stimulation for Treatment Resistant Depression: The Role of the Ventral Capsule/Ventral Striatum

2010 ◽  
Vol 40 (10) ◽  
pp. 477-484 ◽  
Author(s):  
Cristina Cusin ◽  
Karleyton C. Evans ◽  
Linda L. Carpenter ◽  
Benjamin D. Greenberg ◽  
Donald A. Malone ◽  
...  
Keyword(s):  
Deep Brain Stimulation ◽  
Brain Stimulation ◽  
Ventral Striatum ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Deep Brain

scholarly journals Early labor force exits in patients with treatment-resistant depression: an assessment of work years lost in a Danish nationwide register-based cohort study

2020 ◽  
Vol 10 ◽  
pp. 204512532097379
Author(s):  
Kathrine Bang Madsen ◽  
Liselotte Vogdrup Petersen ◽  
Oleguer Plana-Ripoll ◽  
Katherine L. Musliner ◽  
Jean-Christophe Philippe Debost ◽  
...  
Keyword(s):  
Labor Force ◽  
Disability Pension ◽  
Cox Regression ◽  
Age Groups ◽  
Treatment Resistance ◽  
Total Sample ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Somatic Comorbidity ◽  
Resistant Depression

Background: Depression is one of the leading causes of premature workforce exit in many Western countries, but little is known about the extent to which treatment-resistance reduces number of work-years. We compared the risk of premature workforce exit among patients with treatment-resistant depression (TRD) relative to non-TRD patients and estimated work years lost (WYL) before scheduled retirement age. Methods: The study population, identified in the Danish National Prescription Registry, included all individuals born and living in Denmark who redeemed their first antidepressant (AD) prescription for depression at age 18–60 years between 2005 and 2012. TRD was defined as failure to respond to at least two different treatment trials. Premature workforce exit was measured using disability pension records. We used Cox regression to estimate the hazard ratio (HR) for premature workforce exit in TRD relative to non-TRD patients, adjusting for calendar year, psychiatric and somatic comorbidity, and educational level. Differences in WYL in patients with TRD and all depression patients were estimated through a competing risks model. Results: Out of the total sample of patients with depression ( N = 129,945), 7478 (5.75%) were classified as having TRD. During follow up, 17% of patients with TRD and 8% of non-TRD patients received disability pension, resulting in a greater than three-fold larger risk of premature workforce exit [adjusted HR (aHR) 3.23 95% confidence interval (CI) 3.05–3.43]. The TRD group lost on average six work-years (95% CI 5.64–6.47) more than the total sample due to early labor force exit. The association between TRD and age at premature workforce exit was inversely U-shaped; the hazard rate of premature workforce exit for patients with TRD compared with non-TRD patients was highest in the age groups 31–35, 36–40, and 41–45 years. Conclusion: Patients with TRD constitute a small group within depression patients, but contribute disproportionally to societal costs due to premature workforce exit at a young age.

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