scholarly journals Chronic, treatment-resistant depression and right fronto-striatal atrophy

2002 ◽  
Vol 180 (5) ◽  
pp. 434-440 ◽  
Author(s):  
P. J. Shah ◽  
M. F. Glabus ◽  
G. M. Goodwin ◽  
K. P. Ebmeier
Keyword(s):  
Magnetic Resonance ◽  
Treatment Resistance ◽  
Volumetric Analysis ◽  
Magnetic Resonance Images ◽  
Severe Illness ◽  
Cumulative Number ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Resistant Depression ◽  
Mri Changes

BackgroundTreatment-resistant depression (TRD) is relatively common but its neurobiological basis is poorly understood. Fronto-striatal structural brain changes have been reported in patients with depression but their association with treatment resistance and chronicity has not been established.MethodMagnetic resonance images of 20 patients with TRD were compared with images of 20recovered patients and 20 healthy controls. Images were compared using a voxel-based analysis (VBA) method; the results were validated by conventional volumetric analysis. The clinical associations of magnetic resonance imaging (MRI) changes with illness duration and severity were examined by VBA.ResultsOnly the TRD group exhibited right fronto-striatal atrophy, and subtle MRI changes in the left hippocampus on VBA. Atrophy was confirmed on volumetric analysis, the degree correlating with the cumulative number of electroconvulsive therapy (ECT) treatments received, suggesting an acquired deficit.ConclusionsThis is the first study to demonstrate fronto-striatal atrophy in patients with depression with poor outcome; the atrophy is more marked in those with more severe illness.

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

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 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.

scholarly journals The Role of Inflammatory Proteins in Anti-Glucocorticoid Therapy for Treatment-Resistant Depression

2021 ◽  
Vol 10 (4) ◽  
pp. 784
Author(s):  
Rebecca Strawbridge ◽  
Alzbeta Jamieson ◽  
John Hodsoll ◽  
Ian Nicol Ferrier ◽  
Richard Hamish McAllister-Williams ◽  
...  
Keyword(s):  
Clinical Outcomes ◽  
Mediation Effect ◽  
Severe Illness ◽  
Control Group ◽  
Treatment Resistant Depression ◽  
Treatment Resistant ◽  
Primary Analysis ◽  
Double Blind ◽  
Inflammatory Proteins ◽  
Resistant Depression

Background: Optimising treatments for patients with treatment-resistant depression (TRD) is key to reducing the burden of this severe illness. The anti-glucocorticoid medication metyrapone has mixed evidence supporting a role as a possible augmentation treatment in TRD. The degree of treatment resistance in depression has been associated prospectively and retrospectively with elevated inflammation, and inflammatory activity may influence responses to antidepressant treatments. Aims: To investigate whether levels of pro-inflammatory cytokines are associated with clinical outcomes to metyrapone or placebo. Methods: A double-blind RCT randomised patients with TRD to 3 weeks of placebo or metyrapone augmentation to ongoing serotonergic antidepressants. No benefit of metyrapone was reported in the primary analysis. The current study assessed levels of pro-inflammatory proteins interleukin-6 (IL-6), tumour necrosis factor (TNFα), c-reactive protein (CRP) and interleukin-10 (IL-10) before randomisation and after treatment as potential moderators and/or mediators of clinical outcomes. Results: The three pro-inflammatory proteins (but not IL-10) were elevated in this sample of patients with TRD compared to a non-affected control group. High pre-treatment IL-6 levels predicted a poorer response in the trial overall but did not moderate response to metyrapone versus placebo. Changes in IL-6 indirectly mediated depression outcome, with metyrapone increasing IL-6 levels and IL-6 increase associated with a poorer outcome on depression. Other inflammatory proteins did not mediate or moderate treatment outcomes. Interpretation: Metyrapone is hypothesised to have a therapeutic effect in depression on the basis of inhibiting the synthesis of cortisol. In this study, metyrapone did not reduce cortisol, possibly due to glucocorticoid system overcompensation). The mediation effect of IL-6 may support this and perhaps help to indicate why the treatment was not effective.

Treatment Resistant Depression: A Clinical Perspective*

1988 ◽  
Vol 33 (9) ◽  
pp. 788-792 ◽  
Author(s):  
G. William Macewan ◽  
Ronald A. Remick
Keyword(s):  
Bipolar Disorder ◽  
Treatment Resistance ◽  
Treatment Resistant Depression ◽  
Clinical Perspective ◽  
Recurrent Depression ◽  
Treatment Resistant ◽  
Pharmacological Interventions ◽  
Axis Ii ◽  
Symptom Remission ◽  
Resistant Depression

One hundred and fourteen patients with a diagnosis of “treatment resistant depression” (TRD) were assessed and treated at a Mood Disorders Clinic. Diagnostically, 52 (45.6%) subjects met criteria for bipolar disorder, 49 (42.9%) for recurrent depression, and 13 (11.4%) patients did not fulfill diagnostic criteria for affective disorder which explained their treatment resistance. With appropriate, individualized treatment, 59 of 98 (60.2%) patients had complete symptom remission based on clinical and psychometric ratings (initial Ham-D 26.7, final Ham-D 5.9). Eighteen of 98 patients had partial remission (final Ham-D 15.9) with vigorous pharmacological interventions, and 8 subjects exhibited “absolute” TRD (final Ham-D 23.4). The results suggest the value of specialized mood disorder services. The partial and absolute TRD's were more likely to be older, received more Axis II diagnoses, and had previous histories of drug or alcohol abuse.

scholarly journals Esketamine and rapastinel, but not imipramine, have antidepressant-like effect in a treatment-resistant animal model of depression

2019 ◽  
Vol 31 (05) ◽  
pp. 258-265 ◽  
Author(s):  
Vitor Silva Pereira ◽  
Sâmia R.L. Joca ◽  
Brian H. Harvey ◽  
Betina Elfving ◽  
Gregers Wegener
Keyword(s):  
Forced Swim Test ◽  
Treatment Options ◽  
Treatment Resistance ◽  
Repeated Treatment ◽  
Treatment Resistant Depression ◽  
Sprague Dawley ◽  
Treatment Resistant ◽  
Sprague Dawley Rats ◽  
Animal Model Of Depression ◽  
Resistant Depression

AbstractObjectives:Treatment-resistance to antidepressants is a major problem in the pharmacotherapy of major depressive disorder (MDD). Unfortunately, only a few animal models are suitable for studying treatment-resistant depression, among them repeated treatment with Adrenocorticotropic hormone (ACTH) appears to be useful to mimic treatment-resistance to monoaminergic antidepressants. Therefore, the present work aimed to investigate the effectiveness of s-ketamine and rapastinel (formerly GLYX13), modulators of the glutamatergic N-methyl-D-aspartate receptor in ACTH-treated animals.Methods:Naïve male Sprague Dawley rats were subjected to repeated subcutaneous injections with ACTH (100 µg/0.1 ml/rat/day) for 14 days and drug treatment on the test day (open field and forced swim test) with imipramine, s-ketamine or rapastinel. In addition, assessment of plasma levels of corticosterone and ACTH was carried out.Results:We found that rats repeatedly treated with ACTH for 14 days responded to single injections with s-ketamine (15 mg/kg) and rapastinel (10 mg/kg), but failed to respond to imipramine (15 mg/kg). In the plasma, the levels of corticosterone and ACTH were increased after 14 days of daily treatment with ACTH, independently of the treatment.Conclusion:The present data confirm development of a resistance to treatment following chronic ACTH administration. In addition, the study confirms the possible effectiveness of s-ketamine and rapastinel as treatment options in treatment-resistant depression. Moreover, it highlights the importance of the glutamatergic system in the neurobiology of depression. Further studies are necessary to evaluate how repeated treatment with ACTH leads to a depressed condition resistant to monoaminergic antidepressants.

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