Treatment-Resistant Depression Revisited: A Glimmer of Hope

Abstract

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.

Treatment-Resistant Depression in Poland—Epidemiology and Treatment

“…Major depressive disorder (MDD) is one of the most prevalent psychiatric disorders worldwide, especially in high-income regions [1][2][3][4][5]. It causes individual suffering, a loss of productivity and increased health care costs; it is also associated with a high suicide risk [2]. As such, MDD represents a major economic and medical burden for societies [1].…”

“…Over the last 60 years, several antidepressant drugs (ADs) have been developed that can be effective in treating MDD. Although treatment leads to significant improvement in several patients, up to 30% of them fail to achieve remission [1,2,4,10]. Even after sequential treatments, 10-20% of depressive patients remain significantly symptomatic [4].…”

Frequency of Vitamin D Deficiency in Patients of Asthma

“…Vitamin D is a key component of the immune system and its deficiency has been reported in inflammatory bowel disease, rheumatoid arthritis, celiac disease, clinical depression, encephalomyelitis, sepsis, and most recently in patients with COVID-19 pneumonia [7][8][9][10]. The prevalence of vitamin D deficiency is high in Pakistan and does not demonstrate significant seasonal disparity for gender, comorbid, or age; it is a phenomenon consistently observed by health care workers throughout the year [11,12].…”

Neuroimmunology and (Epi)Genetics in Depressive Disorders

“…Despite the fact that depressive disorders are a serious brain dysfunction, their etiopathogenesis is not yet fully understood. Only 60–70% of patients suffering from Major Depressive Disorders (MDD) respond to the standard antidepressant treatment, which means that Treatment Resistant Depression (TRD) can be as prevalent as 1/3 of patients with clinical depression [ 1 ]. Hence, it is essential to continue searching for possible pathological mechanisms and potential contributory factors to TRD in order to find new, effective and safe therapies.…”

“…Dysregulation of the immune system is recognized as one of the most important contributory factors to TRD [ 1 ]. No wonder, then, that a serious question arises: whether specific interventions such as dietary modification can influence “psychoneuroimmunity” to help fight mood disorders.…”