Depressive disorders: Treatment failures and poor prognosis over the last 50 years

Abstract

Depression like many diseases is pleiotropic but unlike cancer and Alzheimer's disease for example, is still largely stigmatized and falls into the dark shadows of human illness. The failure of depression to be in the spotlight for successful treatment options is inherent in the complexity of the disease(s), flawed clinical diagnosis, overgeneralization of the illness, inadequate and biased clinical trial design, restrictive and biased inclusion/exclusion criteria, lack of approved/robust biomarkers, expensive imaging technology along with few advances in neurobiological hypotheses in decades. Clinical trial studies summitted to the regulatory agencies ( FDA / EMA ) for approval, have continually failed to show significant differences between active and placebo. For decades, we have acknowledged this failure, despite vigorous debated by all stakeholders to provide adequate answers to this escalating problem, with only a few new antidepressants approved in the last 20 years with equivocal efficacy, little improvement in side effects or onset of efficacy. It is also clear that funding and initiatives for mental illness lags far behind other life‐treating diseases. Thus, it is no surprise we have not achieved much success in the last 50 years in treating depression, but we are accountable for the many failures and suboptimal treatment. This review will therefore critically address where we have failed and how future advances in medical science offers a glimmer of light for the patient and aid our future understanding of the neurobiology and pathophysiology of the disease, enabling transformative therapies for the treatment of depressive disorders.

The Potential Role of Dysfunctions in Neuron-Microglia Communication in the Pathogenesis of Brain Disorders

“…Depression has been reported as the leading cause of disability in terms of total years lost due to the impairments it generates [ 212 ]. According to the WHO estimations [ 213 ], the disease affects more than 300 million people worldwide.…”

Analysis of Differentially Expressed Genes in the Dentate Gyrus and Anterior Cingulate Cortex in a Mouse Model of Depression

“…The World Health Organization predicts that depression will become the main cause of human disability and one of the main disease burdens. At present, although some antidepressant drugs have been successfully used in the clinic, they are effective in only 30%-40% of patients with depression and often have various side effects [ 2 ]. These antidepressants are based on different hypotheses regarding the etiology of depression, such as monoamine dysfunction, neurogenesis, the corticotrophin-releasing factor (CRF) receptor, ketamine, and the N-methyl-D-aspartate (NMDA) receptor.…”

Visual Depression Diagnosis From Face Based on Various Classification Algorithms

“…Suicide-related outcomes (suicidal ideas, plans and attempts, and deaths by suicide) increased among young-adults ages 18 to 25 between 2009 and 2017, with smaller and less consistent increases among adults ages 26 and over. A successful cure for depressive disorders was obtained in most cases [2]. Furthermore, a shortage of funding and proficient health suppliers is a significant barrier to the successful detection of depression [1].…”