How do antidepressants work? New perspectives for refining future treatment approaches

Abstract

Most currently available antidepressants target monoamine neurotransmitter function. However, a purely neurotransmitter-based explanation for antidepressant drug action is challenged by the delayed clinical onset of most agents and the need to explain how neurochemical changes reverse the many different symptoms of depression. Novel approaches to understanding of antidepressant drug action include a focus on early changes in emotional and social processing and the role of neural plasticity. In this Review, we discuss the ways in which these two different theories reflect different or complementary approaches, and how they might be integrated to offer novel solutions for people with depression. We consider the predictions made by these mechanistic approaches for the stratification and development of new therapeutics for depression, and the next steps that need to be made to facilitate this translation of science to the clinic.

A role for activity‐dependent epigenetics in the development and treatment of major depressive disorder

“…105 Paradoxically, the intended neurochemical effects of typical antidepressants are measurable within days of treatment initiation. 104 This discrepancy suggests that, in addition to increasing levels of 5-hydroxytryptamine A novel theory of antidepressant function suggests that, selective serotonin reuptake inhibitors (SSRIs) create a window for change by increasing brain plasticity and leaving the patient highly susceptible to their environment. 106 Indeed, evidence suggests that environmental enrichment is necessary for the antidepressant-like effect of fluoxetine in mice, and that this effect is mediated through increased hippocampal BDNF and decreased corticosterone levels.…”

Understanding Peripartum Depression Through Neuroimaging: a Review of Structural and Functional Connectivity and Molecular Imaging Research

“…Monoamine oxidase A (MAO-A) metabolizes a variety of neurotransmitters such as serotonin and norepinephrine, both of which are implicated in depressive disorders outside of the peripartum period (80, 81). Moreover, alterations in MAO-A enzyme density has been reported in non-peripartum depressive disorders(82) and preclinical studies report a relationship between estrogen and MAO-A (83).…”

Transcranial Low-Level Laser Therapy for Depression and Alzheimer’s Disease

“…Serotonin is a messenger that produces pleasure and affects almost every aspect of brain activity from regulating emotion, energy, and memory to shaping life [38]. Therefore, antidepressants generally play a role by increasing brain serotonin [40]. In addition, dopamine is also an important neurotransmitter which is closely related to depression, mainly used to transmit excitement and happiness [40].…”

“…Therefore, antidepressants generally play a role by increasing brain serotonin [40]. In addition, dopamine is also an important neurotransmitter which is closely related to depression, mainly used to transmit excitement and happiness [40]. Both serotonin and dopamine levels in the TBI [26,27].…”

“…Depression, which is characterized by lack of energy, impaired concentration and fatigue, is believed to be closely related to mitochondrial dysfunction [40][41][42]. These clinical symptoms may be partly attributed to reduced synthesis of adenosine triphosphate (ATP) due to mitochondrial dysfunction [41][42][43].…”