Transcript: 

Major Depressive Disorder, or MDD, is a common psychiatric disorder affecting millions of people worldwide. 

In fact, MDD is a leading cause of disability that impacts approximately 350 million people globally.  

According to a 2022 report from the National Institute of Mental Health, an estimated 21.0 million adults in the U.S. had at least one major depressive episode (MDE) in 2020.   

The prevalence of adults with an MDE was highest among individuals aged 18-25, representing 17% of the population.  

Antidepressants are common pharmacological interventions used to treat MDD.  Most antidepressants target the monoamines, dopamine, norepinephrine, and serotonin, which play integral roles in neuronal functions in the brain. 

Antidepressants can be divided into several subcategories based on their mechanism of action.  

Monoamine oxidase inhibitors (MAOIs) were first discovered in the 1950s. These work to stop the metabolic enzyme, monoamine oxidase, from breaking down the monoamines.  

Today, MAOIs are used less frequently because of potentially severe reactions with foods high in tyramine, which can cause critical increases in blood pressure. As a result, MAOI treatment typically involves dietary restrictions. Therefore, these are often reserved for when other antidepressant options have failed.  

This class is also used to treat agoraphobia, social phobia, bulimia, post-traumatic stress disorder, borderline personality disorder, and bipolar depression. 

Tricyclic antidepressants (TCAs) were also discovered in the 1950s and work to inhibit the reuptake of both serotonin and norepinephrine.  

Tricyclic antidepressants were named after their chemical structure, which includes three interconnected rings of atoms.  

In addition to blocking the absorption of serotonin and norepinephrine, TCAs block acetylcholine, another neurotransmitter with an important role in regulating the movement of skeletal muscles. This class of drugs is also used to treat chronic pain. 

Selective serotonin reuptake inhibitors (SSRIs) were first developed in the 1970s.  

SSRIs work to prevent the reuptake of serotonin from the synaptic cleft. 

In addition to treating MDD, this class of drugs can also be used to treat obsessive-compulsive disorder, generalized anxiety disorder, and eating disorders. They’ve also been shown to help during stroke recovery.  

Serotonin and norepinephrine reuptake inhibitors (SNRIs) prevent the reuptake of serotonin and norepinephrine. 

The first SNRI was FDA-approved in December 1993. 

Targeting both serotonin and norepinephrine mechanisms has shown to be specifically useful for people with a slowing of physical movement and thought, a condition called psychomotor retardation.  

A relatively new class of antidepressants, called atypical antidepressants, includes drugs that do not fit into the previous categories. These affect serotonin, norepinephrine, and dopamine levels in unique ways.  

These include serotonin antagonist and reuptake inhibitors (SARIs), noradrenergic antagonists, and others.    

Overall, each of these categories fight depressive symptoms by allowing monoaminergic neurotransmitters to remain in the synaptic environment and influence neurotransmission for a longer duration.   

Hundreds of studies have demonstrated the efficacy of individual antidepressants. One recent meta-analysis evaluated the efficacy of 21 commonly prescribed antidepressants. The results showed that each of the 21 antidepressants were significantly more effective than placebo in treating adults with major depressive disorder.  

Antidepressants do sometimes carry a spectrum of potential side effects. These include nausea, vomiting, problems sleeping, sexual problems, sweating, agitation, dry mouth, constipation, fatigue, dizziness, and/or blurred vision.  

It is important to note that some patients, particularly children and teens, taking antidepressants may be more likely to think about hurting or killing themselves when starting treatment or when a dose is changed.  

In addition to adverse events, some withdrawal symptoms can occur with the discontinuation of antidepressant medications.  

These symptoms are often mild and self-limiting. They can include dizziness, headache, sleep disturbances, and mood swings. Serious or prolonged withdrawal symptoms rarely occur.  

To avoid such discomforts, antidepressants should be tapered over a period of more than four weeks. 

Overall, antidepressants are effective treatment options for treating MDD. These operate through various mechanisms of action but predominantly target the monoamine class of neurotransmitters. 

Additional treatment options for MDD that target non-monoaminergic pathways are emerging.