Table of ContentsView AllTable of ContentsHow They WorkCategorizationSSRIsSNRIsTCAsMAOIsAtypical AntidepressantsEffectivenessTreatment OptionsRisks and Considerations

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View All

Table of Contents

How They Work

Categorization

SSRIs

SNRIs

TCAs

MAOIs

Atypical Antidepressants

Effectiveness

Treatment Options

Risks and Considerations

Close

What is the most important information I should know about antidepressants?Different antidepressants have different potential side effects, both when taking the drug and stopping it, and these effects can range from mild to severe.If you experience serious side effects when taking or stopping an antidepressant, such as seizures or irregular heartbeat, seek immediate medical attention.

What is the most important information I should know about antidepressants?

Different antidepressants have different potential side effects, both when taking the drug and stopping it, and these effects can range from mild to severe.If you experience serious side effects when taking or stopping an antidepressant, such as seizures or irregular heartbeat, seek immediate medical attention.

Different types of antidepressants may be used to treatmental health conditions. There are five major types of antidepressants and several others that are less commonly used. The major types are:

While some may be considered preferred options, the drug selection can vary based on your symptoms, treatment history, and co-existingpsychological disorders. Keep reading to learn about each type of antidepressant, including how they work, their benefits and uses, and their potential side effects and risks.

How Antidepressants Work

There are three basic molecules, known chemically as monoamines, believed to be involved in mood regulation. These primarilyserve as neurotransmitters, which transmit nerve signals to their corresponding receptors in the brain.

In people with depression, the availability of these neurotransmitters in the brain is characteristically low. Antidepressants increase the availability of one or several of these neurotransmitters in different, distinctive ways.

How Antidepressants are Categorized

Antidepressants are grouped into classes based on how they affect the chemistry of the brain. While the antidepressants in a class will tend to have similar side effects andmechanisms of action, there are differences in their molecular structures, which can influence how well the drug is absorbed, disseminated, or tolerated in different people.

Of the five major types of antidepressants, SSRIs are the most commonly prescribed, particularly in first-line treatment.Other antidepressants may be used if these drugs fail or in cases of intractable depression, also referred to astreatment-resistant depression.

The Chemistry of Depression

Selective Serotonin Reuptake Inhibitors (SSRIs)

Potential SSRI Side EffectsSSRIs tend to have fewer side effects than older antidepressants but are still known to cause side effects such as dry mouth, gastrointestinal issues, sexual dysfunction, and irregular heart rhythm.

Potential SSRI Side Effects

SSRIs tend to have fewer side effects than older antidepressants but are still known to cause side effects such as dry mouth, gastrointestinal issues, sexual dysfunction, and irregular heart rhythm.

In addition to treating depression, SSRIs are also sometimes used to treatanxiety disorders,eating disorders,autism spectrum disorders, andpremenstrual dysmorphic disorder.They have also proved helpful during stroke recovery.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin and norepinephrine reuptake inhibitors(SNRIs) work in a similar way to SSRIs except that they inhibit the reuptake of both norepinephrine and serotonin. The first SNRI was FDA-approved in December of 1993.

Increasing norepinephrine levels in tandem with serotonin levels can be particularly useful for people withpsychomotor retardation(the slowing of physical movement and thought). Examples of SNRIs include:

SNRI Side EffectsCommon side effects of SNRIs include nausea, drowsiness, fatigue, constipation, and dry mouth.

SNRI Side Effects

Common side effects of SNRIs include nausea, drowsiness, fatigue, constipation, and dry mouth.

Some SNRIs, like Cymbalta, can also be used totreat chronic pain, a condition closely linked to the development of depression. They have also proven useful in treating generalized anxiety,post-traumatic stress disorder(PTSD),social anxiety disorder(SAD),panic disorder, and nerve pain associated with fibromyalgia.

Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants(TCAs) are an older class of drugs first designed in the 1950s.They were named after their chemical structure, which is composed of three interconnected rings of atoms.

TCAs work similarly to reuptake inhibitors in that they block the absorption of serotonin and norepinephrine into nerve cells, as well as another neurotransmitter known as acetylcholine (which helps regulate the movement of skeletal muscles). Examples of TCAs include:

Ludiomil (maprotiline) belongs to the same class of drugs. However, it is more appropriately described as a tetracyclic antidepressant (TeCA) due to its fourth atomic ring.

TCA Side EffectsCommon side effects of TCAs include constipation, dry mouth, blurry vision, drowsiness, dizziness, and weight gain. In some cases, irregular heartbeat, low blood pressure, and seizures can also occur.

TCA Side Effects

Common side effects of TCAs include constipation, dry mouth, blurry vision, drowsiness, dizziness, and weight gain. In some cases, irregular heartbeat, low blood pressure, and seizures can also occur.

In addition to their use in depression, tricyclic antidepressants can help treat chronic pain.They were also once commonly used inchildren with attention deficit hyperactivity disorder(ADHD) but have since been replaced with more effective drug agents with fewer side effects.

Monoamine Oxidase Inhibitors (MAOIs)

One of the first types of antidepressants developed wasmonoamine oxidase inhibitors(MAOIs). This antidepressant class, first discovered in the 1950s,inhibits the action of an enzyme called monoamine oxidase, whose role is to break down monoamines. By blocking this effect, more neurotransmitters are available for mood regulation.

Examples of MAOIs include:

MAOI Side EffectsMAOIs are less commonly used due to potentially severe reactions withfoods high in tyramine, potentially triggering critical increases in blood pressure. To avoid this, MAOI treatment usually involves dietary restrictions. Other side effects include nausea, dizziness, drowsiness, dry mouth, and insomnia.

MAOI Side Effects

MAOIs are less commonly used due to potentially severe reactions withfoods high in tyramine, potentially triggering critical increases in blood pressure. To avoid this, MAOI treatment usually involves dietary restrictions. Other side effects include nausea, dizziness, drowsiness, dry mouth, and insomnia.

Despite the risks, MAOIs have proven useful in treating agoraphobia, social phobia, bulimia, PTSD,borderline personality disorder, and bipolar depression. Even so, its use is usually reserved for when other antidepressant options have failed.

There are also other fairly new types of antidepressants that do not fit into any of the above-listed categories. Broadly described as atypical antidepressants, they affect serotonin, norepinephrine, and dopamine levels in unique ways.

Examples include:

Atypical Antidepressant Side Effects

Over-the-Counter Antidepressants

Antidepressant Effectiveness

Antidepressants are effective in treating depression, although individual responses may vary. One 2018 review of 21 different types of antidepressants found that all of these medications were more effective at treating depression than placebo.However, a 2020 meta-analysis concluded that for many people, the treatment effects of antidepressants were relatively small.

So which type of antidepressant is the most effective? According to the 2018 review, the five most effective antidepressants that people were least likely to stop taking were:

In general, SSRIs are the most commonly prescribed, primarily because they are effective, well-tolerated, and produce relatively few side effects. Wellbutrin and SNRIs also typically have fewer side effects and good efficacy.

All types of antidepressants take a few weeks to begin working. For many people, this means it may take up to eight weeks to feel the full effects of an antidepressant medication.

Choosing the Right Antidepressant

There are several factors that go intochoosing the right antidepressant. Chief among them is tolerability. Because many different types of antidepressants are equally effective in treating depression, a greater emphasis is placed on prescribing the drugs with the fewest short- and long-term side effects.

This is especially true with nausea andweight gain. Both of these effects can impact a person’s quality of life and lead to the premature discontinuation of treatment.

Antidepressants are most effective whenused in conjunction with psychotherapy, self-help strategies, social support, and the treatment of co-existing conditions (such as chronic pain, anxiety, bipolar disorder, and personality disorders).

Natural Antidepressants

In addition to the different types of prescription antidepressants, some people opt to trynatural antidepressant options. Options include herbs and supplements that may have a beneficial effect on mood, such asSt. John’s wort. Some people may find that alternative therapies such as brain stimulation therapy and acupuncture can be helpful.

Even natural options can have side effects, may come with risks, and can interact with other medications you are taking. Always talk to your healthcare provider before trying a natural antidepressant.

Lifestyle modifications can also play an important role in depression treatment and augment medication and therapy. Exercise, nutrition, social support, andspending time in natureare just a few things you can do to feel better.

How to Switch to a New Antidepressant Safely

Antidepressant Risks and Considerations

Antidepressants are sometimes used in combination with other drugs to treat a variety of conditions. In some cases, the combined use of drugs that both exert serotonergic action can lead toserotonin syndrome. This is the toxic accumulation of serotonin that can trigger a cascade of potentially dangerous physical and psychiatric symptoms.

To avoid this, always advise your physician about any and all drugs you are taking, including prescription drugs, over-the-counter medication, nutritional supplements, or herbal remedies.

Antidepressants should only be used as prescribed and may take up to eight weeks before the benefits are fully felt. It is important never to stop, interrupt, decrease, or increase doses without first speaking with your physician.

Antidepressants should be used with extreme caution in children, teens, and younger adults. In 2007, the FDA issued a black box warning about the increased risk of suicidal thoughts and actions in people under 24 on antidepressants of any type.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.For more mental health resources, see ourNational Helpline Database.

If you are having suicidal thoughts, contact theNational Suicide Prevention Lifelineat988for support and assistance from a trained counselor. If you or a loved one are in immediate danger, call 911.

For more mental health resources, see ourNational Helpline Database.

Antidepressants should only be used in children, teens, and younger adults when absolutely needed and only after weighing the potential benefits of treatment against the potential risks.

How Real Is the Risk of Suicide With Antidepressants?

20 SourcesVerywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Institute for Quality and Efficiency in Health Care.Depression: Learn more — How effective are antidepressants?NIH MedlinePlus Magazine.Commonly prescribed antidepressants and how they work. National Library of Medicine.Bremshey S, Groß J, Renken K, Masseck OA.The role of serotonin in depression—A historical roundup and future directions.J Neurochem. 2024. doi:10.1111.jnc.16097Fasipe O.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arc Med Heal Sci.2018:6(1):81-94. doi:10.4103/amhs.amhs_7_18.Edinoff AN, Akuly HA, Hanna TA, et al.Selective serotonin reuptake inhibitors and adverse effects: A narrative review.Neurol Int. 2021;13(3):387-401. doi:10.3390/neurolint13030038Lin DJ, Finklestein SP, Cramer SC.New directions in treatments targeting stroke recovery.Stroke. 2018;49:3107-3114. doi:10.1161/STROKEAHA.118.021359Sansone RA, Sansone LA.Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison.Innov Clin Neurosci. 2014;11(3-4):37-42.Cleveland Clinic.Beyond depression: Other uses for tricyclic antidepressants.Cleveland Clinic.Tricyclic antidepressants.Beal BR, Wallace MS.An overview of pharmacologic management of chronic pain.Med Clin. 2015;100(1):65-79. doi:10.1016/j.mcna.2015.08.006Singh J.Pharmacotherapeutic options for attention deficit hyperactivity disorder (ADHD).Int J Res Med Sci. 2017;5(11):4677-4682. doi:10.18203/2320-6012.ijrms20170001O’Connor AD, Mills KC.Monoamine oxidase inhibitors.Crit Care Toxicol. 2016:1-18. doi:10.1007/978-3-319-20790-2_28-2Cleveland Clinic.MAOIs (Monoamine oxidase inhibitors).Cipriani A, Furukawa TA, Salanti G, et al.Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.Lancet. 2018;391(10128):1357-1366. doi:10.1016/S0140-6736(17)32802-7Hengartner MP, Jakobsen JC, Sørensen A, Plöderl M.Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg Depression Rating Scale, the gold standard clinician rating scale: A meta-analysis of randomised placebo-controlled trials.PLoS One. 2020;15(2):e0229381. doi:10.1371/journal.pone.0229381Marasine NR, Sankhi S, Lamichhane R, Marasini NR, Dangi NB.Use of antidepressants among patients diagnosed with depression: A scoping review.Biomed Res Int. 2021;2021:6699028. doi:10.1155/2021/6699028Arterburn D, Sofer T, Boudreau DM, et al.Long-Term Weight Change after Initiating Second-Generation Antidepressants.J Clin Med.2016;5(4) doi:10.3390/jcm5040048National Institute of Mental Health.Depression.Cleveland Clinic.Serotonin syndrome.Friedman RA.Antidepressants' black-box warning–10 years later.N Engl J Med.2014;371(18):1666-8. doi:10.1056/NEJMp1408480Additional ReadingHillhouse, T. and Porter, J.A brief history of the development of antidepressant drugs: From monoamines to glutamate.Exp Clin Psychopharmacol.2015;23(1):1-21. DOI: 10.1037/a0038550.

20 Sources

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.Institute for Quality and Efficiency in Health Care.Depression: Learn more — How effective are antidepressants?NIH MedlinePlus Magazine.Commonly prescribed antidepressants and how they work. National Library of Medicine.Bremshey S, Groß J, Renken K, Masseck OA.The role of serotonin in depression—A historical roundup and future directions.J Neurochem. 2024. doi:10.1111.jnc.16097Fasipe O.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arc Med Heal Sci.2018:6(1):81-94. doi:10.4103/amhs.amhs_7_18.Edinoff AN, Akuly HA, Hanna TA, et al.Selective serotonin reuptake inhibitors and adverse effects: A narrative review.Neurol Int. 2021;13(3):387-401. doi:10.3390/neurolint13030038Lin DJ, Finklestein SP, Cramer SC.New directions in treatments targeting stroke recovery.Stroke. 2018;49:3107-3114. doi:10.1161/STROKEAHA.118.021359Sansone RA, Sansone LA.Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison.Innov Clin Neurosci. 2014;11(3-4):37-42.Cleveland Clinic.Beyond depression: Other uses for tricyclic antidepressants.Cleveland Clinic.Tricyclic antidepressants.Beal BR, Wallace MS.An overview of pharmacologic management of chronic pain.Med Clin. 2015;100(1):65-79. doi:10.1016/j.mcna.2015.08.006Singh J.Pharmacotherapeutic options for attention deficit hyperactivity disorder (ADHD).Int J Res Med Sci. 2017;5(11):4677-4682. doi:10.18203/2320-6012.ijrms20170001O’Connor AD, Mills KC.Monoamine oxidase inhibitors.Crit Care Toxicol. 2016:1-18. doi:10.1007/978-3-319-20790-2_28-2Cleveland Clinic.MAOIs (Monoamine oxidase inhibitors).Cipriani A, Furukawa TA, Salanti G, et al.Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.Lancet. 2018;391(10128):1357-1366. doi:10.1016/S0140-6736(17)32802-7Hengartner MP, Jakobsen JC, Sørensen A, Plöderl M.Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg Depression Rating Scale, the gold standard clinician rating scale: A meta-analysis of randomised placebo-controlled trials.PLoS One. 2020;15(2):e0229381. doi:10.1371/journal.pone.0229381Marasine NR, Sankhi S, Lamichhane R, Marasini NR, Dangi NB.Use of antidepressants among patients diagnosed with depression: A scoping review.Biomed Res Int. 2021;2021:6699028. doi:10.1155/2021/6699028Arterburn D, Sofer T, Boudreau DM, et al.Long-Term Weight Change after Initiating Second-Generation Antidepressants.J Clin Med.2016;5(4) doi:10.3390/jcm5040048National Institute of Mental Health.Depression.Cleveland Clinic.Serotonin syndrome.Friedman RA.Antidepressants' black-box warning–10 years later.N Engl J Med.2014;371(18):1666-8. doi:10.1056/NEJMp1408480Additional ReadingHillhouse, T. and Porter, J.A brief history of the development of antidepressant drugs: From monoamines to glutamate.Exp Clin Psychopharmacol.2015;23(1):1-21. DOI: 10.1037/a0038550.

Verywell Mind uses only high-quality sources, including peer-reviewed studies, to support the facts within our articles. Read oureditorial processto learn more about how we fact-check and keep our content accurate, reliable, and trustworthy.

Institute for Quality and Efficiency in Health Care.Depression: Learn more — How effective are antidepressants?NIH MedlinePlus Magazine.Commonly prescribed antidepressants and how they work. National Library of Medicine.Bremshey S, Groß J, Renken K, Masseck OA.The role of serotonin in depression—A historical roundup and future directions.J Neurochem. 2024. doi:10.1111.jnc.16097Fasipe O.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arc Med Heal Sci.2018:6(1):81-94. doi:10.4103/amhs.amhs_7_18.Edinoff AN, Akuly HA, Hanna TA, et al.Selective serotonin reuptake inhibitors and adverse effects: A narrative review.Neurol Int. 2021;13(3):387-401. doi:10.3390/neurolint13030038Lin DJ, Finklestein SP, Cramer SC.New directions in treatments targeting stroke recovery.Stroke. 2018;49:3107-3114. doi:10.1161/STROKEAHA.118.021359Sansone RA, Sansone LA.Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison.Innov Clin Neurosci. 2014;11(3-4):37-42.Cleveland Clinic.Beyond depression: Other uses for tricyclic antidepressants.Cleveland Clinic.Tricyclic antidepressants.Beal BR, Wallace MS.An overview of pharmacologic management of chronic pain.Med Clin. 2015;100(1):65-79. doi:10.1016/j.mcna.2015.08.006Singh J.Pharmacotherapeutic options for attention deficit hyperactivity disorder (ADHD).Int J Res Med Sci. 2017;5(11):4677-4682. doi:10.18203/2320-6012.ijrms20170001O’Connor AD, Mills KC.Monoamine oxidase inhibitors.Crit Care Toxicol. 2016:1-18. doi:10.1007/978-3-319-20790-2_28-2Cleveland Clinic.MAOIs (Monoamine oxidase inhibitors).Cipriani A, Furukawa TA, Salanti G, et al.Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.Lancet. 2018;391(10128):1357-1366. doi:10.1016/S0140-6736(17)32802-7Hengartner MP, Jakobsen JC, Sørensen A, Plöderl M.Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg Depression Rating Scale, the gold standard clinician rating scale: A meta-analysis of randomised placebo-controlled trials.PLoS One. 2020;15(2):e0229381. doi:10.1371/journal.pone.0229381Marasine NR, Sankhi S, Lamichhane R, Marasini NR, Dangi NB.Use of antidepressants among patients diagnosed with depression: A scoping review.Biomed Res Int. 2021;2021:6699028. doi:10.1155/2021/6699028Arterburn D, Sofer T, Boudreau DM, et al.Long-Term Weight Change after Initiating Second-Generation Antidepressants.J Clin Med.2016;5(4) doi:10.3390/jcm5040048National Institute of Mental Health.Depression.Cleveland Clinic.Serotonin syndrome.Friedman RA.Antidepressants' black-box warning–10 years later.N Engl J Med.2014;371(18):1666-8. doi:10.1056/NEJMp1408480

Institute for Quality and Efficiency in Health Care.Depression: Learn more — How effective are antidepressants?

NIH MedlinePlus Magazine.Commonly prescribed antidepressants and how they work. National Library of Medicine.

Bremshey S, Groß J, Renken K, Masseck OA.The role of serotonin in depression—A historical roundup and future directions.J Neurochem. 2024. doi:10.1111.jnc.16097

Fasipe O.Neuropharmacological classification of antidepressant agents based on their mechanisms of action.Arc Med Heal Sci.2018:6(1):81-94. doi:10.4103/amhs.amhs_7_18.

Edinoff AN, Akuly HA, Hanna TA, et al.Selective serotonin reuptake inhibitors and adverse effects: A narrative review.Neurol Int. 2021;13(3):387-401. doi:10.3390/neurolint13030038

Lin DJ, Finklestein SP, Cramer SC.New directions in treatments targeting stroke recovery.Stroke. 2018;49:3107-3114. doi:10.1161/STROKEAHA.118.021359

Sansone RA, Sansone LA.Serotonin norepinephrine reuptake inhibitors: a pharmacological comparison.Innov Clin Neurosci. 2014;11(3-4):37-42.

Cleveland Clinic.Beyond depression: Other uses for tricyclic antidepressants.

Cleveland Clinic.Tricyclic antidepressants.

Beal BR, Wallace MS.An overview of pharmacologic management of chronic pain.Med Clin. 2015;100(1):65-79. doi:10.1016/j.mcna.2015.08.006

Singh J.Pharmacotherapeutic options for attention deficit hyperactivity disorder (ADHD).Int J Res Med Sci. 2017;5(11):4677-4682. doi:10.18203/2320-6012.ijrms20170001

O’Connor AD, Mills KC.Monoamine oxidase inhibitors.Crit Care Toxicol. 2016:1-18. doi:10.1007/978-3-319-20790-2_28-2

Cleveland Clinic.MAOIs (Monoamine oxidase inhibitors).

Cipriani A, Furukawa TA, Salanti G, et al.Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis.Lancet. 2018;391(10128):1357-1366. doi:10.1016/S0140-6736(17)32802-7

Hengartner MP, Jakobsen JC, Sørensen A, Plöderl M.Efficacy of new-generation antidepressants assessed with the Montgomery-Asberg Depression Rating Scale, the gold standard clinician rating scale: A meta-analysis of randomised placebo-controlled trials.PLoS One. 2020;15(2):e0229381. doi:10.1371/journal.pone.0229381

Marasine NR, Sankhi S, Lamichhane R, Marasini NR, Dangi NB.Use of antidepressants among patients diagnosed with depression: A scoping review.Biomed Res Int. 2021;2021:6699028. doi:10.1155/2021/6699028

Arterburn D, Sofer T, Boudreau DM, et al.Long-Term Weight Change after Initiating Second-Generation Antidepressants.J Clin Med.2016;5(4) doi:10.3390/jcm5040048

National Institute of Mental Health.Depression.

Cleveland Clinic.Serotonin syndrome.

Friedman RA.Antidepressants' black-box warning–10 years later.N Engl J Med.2014;371(18):1666-8. doi:10.1056/NEJMp1408480

Hillhouse, T. and Porter, J.A brief history of the development of antidepressant drugs: From monoamines to glutamate.Exp Clin Psychopharmacol.2015;23(1):1-21. DOI: 10.1037/a0038550.

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