Why Antidepressants Fail to Work in Some People

medication

here are many factors that can affect the provision of effective pharmacotherapy for depressed patients depending on the functional changes that result from depression as the condition progresses, environmental factors such as childhood maltreatment, disease episodes, previous life events, and different treatment schedules that remain unidentified and thus reduce the likelihood of detecting response biomarkers that might be necessary for proper diagnosis of the condition and hence treatment. Other factors such as pregnancy, age, sex, and genetic components can affect effective treatment and management of depression.

Major depression is widely recognized as the second leading cause of neuropsychiatric disability worldwide. However, only one-third of patients with depression benefit from the antidepressants being prescribed for them. There have even been situations where intervention with multi-class regimen has not provided optimal therapy have not provided beneficial therapy. It is a fundamental problem that the outcomes of individual antidepressant treatments are still highly unpredictable. Patient-specific factors have been identified due to the influence of genes. However, there are other determinants that influence the outcome of antidepressant therapy. For instance, in clinical studies, discovery of biomarkers for antidepressant response is hampered by confounding factors such as the heterogeneity of the disease phenotype and additional environmental factors, e.g., previous life events and different schedules of psychopharmacological treatment, which reduce the power to detect true response biomarkers. The researchers stressed the fact that a “one size fits all” approach is not effective or efficient in the treatment of the major depressive disorder (MDD) even though it would be ideal for tailoring available treatments to individual patients

Recently, a team of scientists led by Marianne Müller and her colleagues from the University Medical Center Mainz and the Max Planck Institute of Psychiatry, both in Germany, conducted the new research that showed that the major reason why antidepressants work for many people, but between 30 and 50% of depressed people while in the rest of the population antidepressants don’t work might be as a result of a cluster of anti-depressant response associated genes as predicted by a mouse model. Their finding was then validated via a cohort of depressed patients from our collaborators from Emory University, Atlanta. The scientists discovered that certain genes are responsible for altered drug response in specific population subgroups. The results of their finding showed that the treatment response in mice could predict the outcome in a human cohort with an accuracy of 76 percent.

The study was conducted using a mouse model. They were able to discover that the glucocorticoid receptor (GR) — and GR sensitivity in particular — as playing a pivotal role in shaping a person’s response to treatment with antidepressants. The GR helps to fine-tune the stress hormone system. According to medicalnewstoday , the researchers  wrote, “intriguingly, we finally show that GR-regulated genes are significantly enriched in this cluster of antidepressant-response genes, pointing to the involvement of GR sensitivity as a potential key mechanism in shaping transcriptional changes and clinical response to antidepressant treatment.”

The need to tailor drug therapy to individual patients has been the primary goal of pharmacogenomics and advances in the field of molecular biology and genetics has enabled the identification of several genes that may alter drug response in specific population subgroups. It is hoped that further studies will allow the adequate provision of beneficial therapy that will meet the need for a wide range of individuals living with depression.