Definitions and Predictors of Treatment‐resistant Depression

Souery, Daniel; Pitchot, William; Kasper, Siegfried; Montgomery, Stuart

doi:10.1002/9781118556719.ch1

Cited by 7 publications

(9 citation statements)

References 34 publications

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“…In particular, the allele G (reverse compliment) of rs10508649 in PIP4K2A may increase resistance to antidepressant treatment and be at the same time protective against recurrent manic or mixed episodes. These data suggest interesting avenues for the study of the pathogenesis of mania and its possible connections with the pathogenesis of treatment-resistant depression (McIntyre et al, 2014). It is known that antidepressant drugs are not suitable in treatment of bipolar disorder, because they do not provide the desired response; moreover, evidence from clinical practice suggests that antidepressants may precipitate manic symptoms (Hirschfeld, 2014).…”

Section: Cross-disorder Aspects Of Mania and Antidepressant Therapeutmentioning

confidence: 99%

NRG1, PIP4K2A, and HTR2C as Potential Candidate Biomarker Genes for Several Clinical Subphenotypes of Depression and Bipolar Disorder

et al. 2020

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Genetic Associations for Subphenotypes of Mood Disorders Bioinformatic functional annotation of associated variants revealed possible impact for transcriptional regulation of PIP4K2A. In addition, the allele A of rs2248440 (HTR2C) may be a prognostic biomarker of depression severity. This allele decreases expression of the neighboring immune system gene IL13RA2 in the putamen according to the GTEx portal. The variant rs2248440 is near rs6318 (previously associated with depression and effects of psychotropic drugs) that is an eQTL for the same gene and tissue. Finally, the study points to several protein interactions relevant in the pathogenesis of mood disorders. Functional studies using cellular or animal models are warranted to support these results.

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Section: Cross-disorder Aspects Of Mania and Antidepressant Therapeutmentioning

confidence: 99%

NRG1, PIP4K2A, and HTR2C as Potential Candidate Biomarker Genes for Several Clinical Subphenotypes of Depression and Bipolar Disorder

et al. 2020

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“…Clinical variables that can distinguish patients with TRD from treatment responding MDD patients include psychiatric co-morbidities (e.g., anxiety and panic disorder and social phobia), personality disorder, suicidality, psychosis, substance abuse and dependence, early age at onset, higher numbers of hospitalizations and recurrent episodes. A range of co-morbid medical conditions, notably, endocrinopathies, cardiovascular disease, neurological diseases and vitamin deficiencies, may also contribute to TRD [ 8 ]. With respect to the doctor–patient relationship, failure to conduct in-depth assessment of the patient’s depression and the possible developmental and environmental factors that are likely to be contributory, hurried evaluations by the clinician, failure to follow evidence-based guidelines for MDD diagnosis and treatment, use of ineffective doses of antidepressant agents and failure to incorporate psychotherapy can easily lead to labeling the patient’s condition as “pseudoresistance” [ 9 ].…”

Section: Introductionmentioning

confidence: 99%

Treatment-Resistant Depression Revisited: A Glimmer of Hope

Halaris

Sohl

Whitham

2021

JPM

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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.

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“…Previous studies that aimed to subtype antidepressant treatment response in MDD can be classified into three types: phenotypic, endophenotypic, and genotypic levels [3]. At the phenotypic level, several factors have been consistently recognized to be associated with treatment response, such as disease course, gender, age, and psychiatric comorbidity [4]; however, there were no robust conclusions at the endophenotypic and genotypic levels [5,6]. Since endophenotypic and genotypic studies require reliable phenotypes, inadequate validity of the phenotyping of treatment response to antidepressants may explain the inconsistent findings [7].…”

Section: Introductionmentioning

confidence: 99%

“…Although the MSM showed promise in predicting the risk and duration of a depressive episode during a follow-up period [12], recent literature suggests the inclusion of additional parameters to enhance the validity of measuring the level of treatment difficulty of MDD [4,13]. For example, the use of sedatives, psychodynamic psychotherapy, physical and psychiatric comorbidities, and medication adherence may also influence the evaluation of antidepressant treatment response.…”

Section: Introductionmentioning

confidence: 99%

Quantifying the level of difficulty to treat major depressive disorder with antidepressants: Treatment Resistance to Antidepressants Evaluation Scale

Liu¹,

Kuo²,

Lu³

et al. 2020

PLoS ONE

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Background The present study aimed to develop a new scale to evaluate the level of difficulty in treating major depressive disorder with antidepressants based on the lifetime treatment profile. Methods In addition to evaluating the difficulty of treatment with antidepressants (A subscale), the Treatment Resistance to Antidepressants Evaluation Scale (TRADES) is comprised of a subscale to account for the attributes that compromise the efficacy of treatment (B subscale). One hundred and six participants aged 18 to 65 years with remitted major depressive disorder were enrolled. Eligible cases were those with at least 2 years from disease onset until the scoring date of the TRADES (the index date), with a complete treatment record. Various psychosocial and clinical features, such as neuroticism, harm avoidance, and utilization of psychiatric services, were used to validate the TRADES. Results The mean duration of the course before and after the index date were 5.5 ± 3.5 and 3.1 ± 1.7 years, respectively. In a multiple regression analysis, the final total scores of the TRADES independently correlated with higher levels of neuroticism and harm avoidance. Total scores were also associated with a higher utilization of psychiatric outpatient and admission services before the index date. Furthermore, it is thought that total scores could predict a higher

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Definitions and Predictors of Treatment‐resistant Depression

Cited by 7 publications

References 34 publications

NRG1, PIP4K2A, and HTR2C as Potential Candidate Biomarker Genes for Several Clinical Subphenotypes of Depression and Bipolar Disorder

NRG1, PIP4K2A, and HTR2C as Potential Candidate Biomarker Genes for Several Clinical Subphenotypes of Depression and Bipolar Disorder

Treatment-Resistant Depression Revisited: A Glimmer of Hope

Quantifying the level of difficulty to treat major depressive disorder with antidepressants: Treatment Resistance to Antidepressants Evaluation Scale

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