Related Experiment Video
Updated: May 13, 2026
04:29
Vagus Nerve Stimulation As an Adjunctive Neurostimulation Tool in Treatment-resistant Depression
Published on: January 7, 2019
Serotonin and beyond: therapeutics for major depression
Pierre Blier1, Mostafa El Mansari
1Institute of Mental Health Research, University of Ottawa, Ottawa, Ontario, Canada. pierre.blier@theroyal.ca
Summary
Major depressive disorder (MDD) treatments leverage the serotonin (5-HT) system. Combining antidepressants with complementary actions on 5-HT, norepinephrine (NE), and dopamine (DA) systems can significantly improve remission rates in treatment-resistant MDD.
Area of Science:
- Neuroscience
- Psychiatry
- Pharmacology
Background:
- The serotonin (5-HT) system is implicated in major depressive disorder (MDD) pathogenesis and antidepressant treatment efficacy.
- Antidepressant strategies consistently enhance 5-HT transmission in animal models.
- Norepinephrine (NE) and dopamine (DA) also play roles in antidepressant mechanisms.
Purpose of the Study:
- To explore the role of monoaminergic systems (5-HT, NE, DA) in MDD treatment.
- To understand how functional connectivity between these systems impacts treatment resistance.
- To evaluate novel augmentation strategies for MDD.
Main Methods:
- Review of existing literature on antidepressant mechanisms.
- Analysis of studies investigating the impact of selective serotonin reuptake inhibitors (SSRIs) on NE and DA activity.
- Examination of proof-of-concept studies on augmentation strategies in treatment-resistant MDD.
Main Results:
- SSRI-induced 5-HT enhancement may dampen NE and DA neuron activity, potentially contributing to low remission rates.
- Functional connectivity between 5-HT, NE, and DA systems is crucial for understanding treatment-resistant MDD.
- Antidepressants with complementary monoaminergic actions can double remission rates in clinical trials.
Conclusions:
- Understanding the interplay between 5-HT, NE, and DA systems is key to improving MDD treatment outcomes.
- Augmentation strategies targeting multiple monoaminergic systems show promise for treatment-resistant MDD.
- Novel MDD treatments continue to involve modulation of monoaminergic systems.
Related Concept Videos
01:23Antidepressant Drugs: MAOIs and Other Agents
Atypical antidepressants, including bupropion (Wellbutrin), mirtazapine (Remeron), nefazodone (Serzone), trazodone (Desyrel), and vilazodone (Viibryd), offer unique mechanisms of action. Bupropion weakly inhibits dopamine and norepinephrine reuptake, aiding depression treatment and smoking cessation, with a low risk of sexual dysfunction. Mirtazapine enhances serotonin and norepinephrine neurotransmission, leading to sedation, increased appetite, and weight gain. As a result, it helps treat...
01:25Antidepressant Drugs: Overview
Antidepressant drugs are a class of medications primarily used for treating various mood disorders, including major depression, anxiety disorders, and other related conditions. These medicines work by modulating the neurotransmitter balance within the brain, alleviating depressive symptoms. Antidepressants can be broadly categorized into several groups according to their mechanism of action and chemical structure: Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine...
01:28Antidepressant Drugs: Tricyclics, SSRIs, and SNRIs
Tricyclic Antidepressants (TCAs), including Desipramine (Norpramin), Imipramine (Tofranil), Clomipramine (Anafranil), and Amitriptyline (Elavil), inhibit serotonin and norepinephrine reuptake and also block other receptors. They are used for depression, pain conditions, and insomnia. Common adverse effects include anticholinergic effects, sedation, orthostatic hypotension, and weight gain. They have a narrow therapeutic window and so require plasma-level monitoring. Abrupt discontinuation can...
01:18Depression: Overview
Depression is a prevalent mental illness marked by persistent sadness and lack of interest in previously enjoyable activities. It can take several forms, including major depression, persistent depressive disorder, and bipolar I and II disorders. Symptoms range from emotional changes like chronic worry to physical changes like sleep disturbances and suicidal thoughts. From a neurobiological perspective, depression is believed to be triggered by abnormalities in the brain's prefrontal cortex,...
01:28Drug Therapy
The advent of drug therapy has profoundly shaped modern mental health care, providing targeted treatments for a range of psychological disorders. Psychotherapeutic drugs, classified into antianxiety, antidepressant, and antipsychotic medications, address symptoms across anxiety disorders, mood disorders, and schizophrenia. While these medications have transformed patient outcomes, they require careful management due to their potential side effects and limitations.
Antianxiety Medications
Antianxiety Medications
01:21G-protein Coupled Receptors
G-protein coupled receptors are ligand binding receptors that indirectly affect changes in the cell. The actual receptor is a single polypeptide that transverses the cell membrane seven times creating intracellular and extracellular loops. The extracellular loops create a ligand specific pocket which binds to neurotransmitters or hormones. The intracellular loops holds onto the G-protein.