Understanding the Classes: How are Antidepressants Classified?

October 12, 2025 •

4 min read

Antidepressant consumption is rising globally, with a mean increase across 30 OECD countries from 52.42 daily doses per 1,000 people in 2010 to 69.5 in 2020 [1.4.2]. Understanding how are antidepressants classified is key to comprehending their role in managing depression and other conditions.

Quick Summary

Antidepressants are categorized by their chemical structure and how they affect neurotransmitters in the brain. Major classes include SSRIs, SNRIs, TCAs, MAOIs, and atypical antidepressants, each with unique mechanisms and side effect profiles.

Key Points

Primary Classification: Antidepressants are primarily classified by their mechanism of action, which is how they affect neurotransmitters like serotonin and norepinephrine in the brain [1.2.2].
SSRIs as First-Line: Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed class due to their favorable side effect profile compared to older drugs [1.2.4, 1.3.5].
Dual-Action Agents: Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) and Tricyclic Antidepressants (TCAs) work by increasing both serotonin and norepinephrine levels [1.2.1].
Older Classes with Restrictions: Monoamine Oxidase Inhibitors (MAOIs) are an older class that is highly effective but requires strict dietary restrictions to prevent dangerous side effects [1.3.5, 1.6.5].
Atypical Antidepressants: This is a diverse group of drugs that don't fit into other categories, each with a unique mechanism of action, such as affecting dopamine or working on different receptors [1.2.1, 1.5.2].
Individualized Treatment: The choice of antidepressant depends on many factors, including the patient's specific symptoms, other medical conditions, and potential for side effects [1.7.2].
Side Effect Profiles Differ: Each class has a distinct side effect profile; for example, TCAs can cause dry mouth and constipation, while SSRIs are more associated with sexual dysfunction and nausea [1.3.1, 1.3.2].

The Pharmacological Blueprint of Mood Regulation

Antidepressants are a cornerstone of treatment for major depressive disorder and other conditions like anxiety disorders and chronic pain [1.3.2, 1.7.2]. Their classification is primarily based on their pharmacological mechanism of action—specifically, how they interact with neurotransmitters in the brain [1.2.2]. Neurotransmitters are chemical messengers that brain cells use to communicate, and medications aim to adjust the levels of key ones like serotonin, norepinephrine, and dopamine to improve mood and relieve symptoms of depression [1.2.2, 1.6.1].

Historically, the first antidepressants were Tricyclic Antidepressants (TCAs) and Monoamine Oxidase Inhibitors (MAOIs) [1.2.5]. While effective, these older medications often came with a significant number of side effects due to their broad action on various receptors in the body [1.2.4, 1.3.4]. This led to the development of more targeted agents, starting with Selective Serotonin Reuptake Inhibitors (SSRIs), which have a more refined mechanism and are generally better tolerated [1.2.4]. A healthcare provider selects a medication based on a patient's specific symptoms, other health conditions, potential side effects, and even what has worked for a close relative [1.7.2].

Selective Serotonin Reuptake Inhibitors (SSRIs)

SSRIs are often the first-line treatment for depression because they are effective and typically have fewer and milder side effects than older drug classes [1.3.2, 1.3.5].

Mechanism of Action: SSRIs work by blocking the reabsorption (reuptake) of serotonin into neurons. This makes more serotonin available in the synapse (the space between neurons), enhancing its ability to transmit messages related to mood [1.6.1].
Common Examples: Fluoxetine (Prozac), Sertraline (Zoloft), Citalopram (Celexa), Escitalopram (Lexapro), and Paroxetine (Paxil) [1.3.2].
Side Effects: Common side effects can include nausea, headache, insomnia, sexual dysfunction, and weight gain [1.3.1, 1.3.2].

Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs)

SNRIs are similar to SSRIs but have a dual-action mechanism.

Mechanism of Action: They increase levels of both serotonin and norepinephrine by inhibiting their reuptake [1.2.1, 1.6.1]. Norepinephrine is involved in alertness and stress response.
Common Examples: Venlafaxine (Effexor), Duloxetine (Cymbalta), Desvenlafaxine (Pristiq), and Levomilnacipran (Fetzima) [1.3.2].
Side Effects: Side effects are similar to SSRIs and may also include increased blood pressure, especially at higher doses [1.3.2].

Tricyclic Antidepressants (TCAs)

TCAs are an older class of antidepressants and are generally prescribed less frequently now due to a higher side effect burden [1.3.2, 1.3.4]. However, they can be very effective for some individuals, particularly when newer agents fail [1.3.2].

Mechanism of Action: Like SNRIs, TCAs block the reuptake of serotonin and norepinephrine, but they are less selective and also affect other neurotransmitter systems, leading to more side effects [1.2.1, 1.6.1].
Common Examples: Amitriptyline (Elavil), Imipramine (Tofranil), and Nortriptyline (Aventyl) [1.3.2].
Side Effects: Include dry mouth, blurred vision, constipation, sedation, weight gain, and potential heart rhythm abnormalities [1.3.1, 1.3.2].

Monoamine Oxidase Inhibitors (MAOIs)

MAOIs are the oldest class of antidepressants and are used infrequently today because of their potential for serious side effects and necessary dietary restrictions [1.6.5]. They are typically reserved for treatment-resistant depression [1.3.5].

Mechanism of Action: MAOIs work by blocking the action of monoamine oxidase, an enzyme that breaks down neurotransmitters like serotonin, norepinephrine, and dopamine [1.6.1, 1.6.5]. This increases the levels of these chemicals in the brain.
Common Examples: Phenelzine (Nardil), Tranylcypromine (Parnate), and Isocarboxazid (Marplan) [1.8.3].
Side Effects: MAOIs can cause a dangerous spike in blood pressure when combined with certain foods high in tyramine (like aged cheeses and cured meats) or some medications [1.3.5, 1.8.3]. Other side effects include dizziness, dry mouth, and insomnia [1.6.5].

Atypical Antidepressants

This is a broad category for medications that don't fit neatly into the other classes [1.2.1]. Each works differently.

Mechanism of Action: Varies by drug. For example, Bupropion (Wellbutrin) inhibits the reuptake of dopamine and norepinephrine [1.5.2]. Mirtazapine (Remeron) enhances serotonin and norepinephrine release through a different pathway [1.5.2].
Common Examples: Bupropion (Wellbutrin), Mirtazapine (Remeron), Trazodone, Vilazodone (Viibryd), and Vortioxetine (Trintellix) [1.5.3].
Side Effects: These are unique to each medication. Bupropion, for instance, has a lower risk of sexual side effects but may increase anxiety for some [1.5.5, 1.7.2]. Trazodone is often used for insomnia due to its sedative effects [1.5.3, 1.10.3].

Comparison of Major Antidepressant Classes


Class	Mechanism of Action	Common Examples	Common Side Effects
SSRIs	Selectively blocks serotonin reuptake [1.6.1].	Fluoxetine, Sertraline, Citalopram [1.3.2].	Nausea, headache, sexual dysfunction, insomnia [1.3.1, 1.3.2].
SNRIs	Blocks reuptake of both serotonin and norepinephrine [1.6.1].	Venlafaxine, Duloxetine, Desvenlafaxine [1.3.2].	Similar to SSRIs, plus potential for increased blood pressure [1.3.2].
TCAs	Blocks reuptake of serotonin and norepinephrine; less selective [1.6.1].	Amitriptyline, Imipramine, Nortriptyline [1.3.2].	Dry mouth, constipation, sedation, blurred vision, cardiac effects [1.3.2].
MAOIs	Inhibits the monoamine oxidase enzyme, increasing serotonin, norepinephrine, and dopamine [1.6.5].	Phenelzine, Tranylcypromine [1.8.3].	Dietary restrictions required to avoid hypertensive crisis; dizziness, insomnia [1.3.5, 1.6.5].
Atypicals	Various unique mechanisms [1.5.2].	Bupropion, Mirtazapine, Trazodone [1.5.3].	Varies widely; e.g., lower sexual side effects (Bupropion), sedation (Mirtazapine, Trazodone) [1.5.5].

Conclusion

The classification of antidepressants is rooted in their neurochemical mechanisms. From the broad-acting MAOIs and TCAs to the highly selective SSRIs and the dual-action SNRIs, each class offers a different approach to modulating brain chemistry. The existence of atypical antidepressants further expands the toolkit, providing alternatives with unique profiles for patients who may not respond to or tolerate first-line agents. The choice of an antidepressant is a highly individualized decision made in collaboration with a healthcare provider, balancing efficacy against the potential for side effects to find the best fit for the patient's needs [1.7.3, 1.7.4].

For more information, one authoritative resource is the National Institute of Mental Health (NIMH).

The National Institute of Mental Health (NIMH)

Frequently Asked Questions

The main classes are Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs), Tricyclic Antidepressants (TCAs), Monoamine Oxidase Inhibitors (MAOIs), and Atypical Antidepressants [1.2.1, 1.2.3].

SSRIs are typically the first choice because they have a better side effect profile and are generally better tolerated than older classes like TCAs and MAOIs [1.2.4, 1.3.2].

SSRIs work by increasing only serotonin levels, while SNRIs increase the levels of both serotonin and norepinephrine in the brain [1.6.1, 1.6.2].

MAOIs are rarely used today because they can cause severe reactions, such as dangerously high blood pressure, if taken with certain foods (containing tyramine) or other medications [1.3.5, 1.8.3].

A healthcare provider chooses an antidepressant based on factors like the patient's specific symptoms, other health conditions they have, potential side effects, other medications being taken, and even whether a close relative responded well to a particular drug [1.7.1, 1.7.2].

Atypical antidepressants are a group of medications that don't fit into the other major classifications. Each one works in a unique way to affect brain chemistry, such as bupropion, which primarily affects dopamine and norepinephrine [1.2.1, 1.5.2].

You should never stop taking an antidepressant suddenly. Always talk to your healthcare provider first. They will create a plan to slowly reduce the dose (tapering) to help prevent unpleasant discontinuation symptoms [1.10.1, 1.10.3].