What is the most common antidepressant?

October 13, 2025 •

4 min read

Recent prescription data shows that sertraline (brand name Zoloft) is consistently ranked as the most prescribed individual medication in the United States, positioning it as a key answer to the question, 'What is the most common antidepressant?'. In general, Selective Serotonin Reuptake Inhibitors (SSRIs) are the most commonly prescribed class of antidepressant worldwide.

Quick Summary

Sertraline is currently the most commonly prescribed antidepressant, part of the widely used SSRI class. This article details sertraline and other common antidepressants, comparing their uses, mechanisms, and side effects.

Key Points

Sertraline is most common: In recent years, sertraline (Zoloft) has been the single most prescribed antidepressant in the U.S..
SSRIs are the most common class: Selective Serotonin Reuptake Inhibitors (SSRIs) like sertraline, fluoxetine, and escitalopram are the preferred first-line treatment for many mental health conditions.
Antidepressant effectiveness varies: The right medication depends on individual factors, and it can take several weeks to see the full effect.
Different classes exist: Beyond SSRIs, other classes like SNRIs (e.g., duloxetine), atypical antidepressants (e.g., trazodone), and older TCAs and MAOIs are available, with different mechanisms and side effects.
Trazodone is also highly prescribed: This atypical antidepressant, ranking high in prescription volume, is frequently used off-label for insomnia.
Side effects and tolerability differ: While SSRIs are generally well-tolerated, individual side effects vary by medication and person.
Always consult a doctor: Medication management, including starting or stopping an antidepressant, should be done under a healthcare provider's supervision.

Sertraline: The Most Prescribed Antidepressant

While Selective Serotonin Reuptake Inhibitors (SSRIs) represent the most frequently prescribed class of antidepressant, sertraline (commonly known by its brand name, Zoloft) is consistently identified as the single most prescribed antidepressant medication. Since its approval in 1991, sertraline's widespread use can be attributed to its effectiveness for a range of conditions and generally favorable side-effect profile compared to older options.

As an SSRI, sertraline works by increasing the levels of serotonin, a neurotransmitter that helps regulate mood, anxiety, and other cognitive functions, in the brain. By blocking the reabsorption of serotonin into presynaptic neurons, it ensures more of this chemical messenger is available to improve communication between nerve cells. This action helps to alleviate symptoms associated with depression and other mental health conditions.

Sertraline is FDA-approved to treat a variety of mental health conditions in addition to major depressive disorder (MDD), including:

Obsessive-compulsive disorder (OCD)
Panic disorder
Post-traumatic stress disorder (PTSD)
Social anxiety disorder (SAD)
Premenstrual dysphoric disorder (PMDD)

The Rise and Prevalence of SSRIs

SSRIs are the most common type of antidepressant prescribed today, largely because they are considered first-line treatment for many mental health disorders. Their popularity over older medications like TCAs and MAOIs is due to a better safety profile, fewer side effects, and lower potential for issues at higher doses. Besides sertraline, other well-known SSRIs are also widely prescribed and serve as effective first-line treatments for major depressive disorder:

Fluoxetine (Prozac): One of the oldest and most well-known SSRIs, it's notably the only one approved for depression in children by the FDA.
Escitalopram (Lexapro): Often praised for being well-tolerated with relatively few drug interactions.
Citalopram (Celexa): A closely related SSRI to escitalopram, also widely used for depression.
Paroxetine (Paxil): An effective SSRI, though it may be associated with a higher risk of weight gain compared to some other options.

Comparing Common Antidepressants

While sertraline is the most prescribed, selecting the right antidepressant is a highly individualized process determined by a healthcare provider based on symptom profile, side effect tolerance, and other factors. Here is a comparison of some of the most commonly used options:


Feature	Sertraline (Zoloft)	Fluoxetine (Prozac)	Escitalopram (Lexapro)
Drug Class	SSRI	SSRI	SSRI
Primary Uses	Depression, OCD, Panic Disorder, PTSD, SAD, PMDD	Depression, OCD, Bulimia Nervosa, Panic Disorder, PMDD	Depression, Generalized Anxiety Disorder (GAD)
Common Side Effects	Nausea, diarrhea, headaches, insomnia, sexual dysfunction	Nausea, insomnia, tiredness, anxiety, sexual dysfunction	Nausea, insomnia, sexual dysfunction, sweating, fatigue
Effectiveness	High, similar to other SSRIs. May be faster-acting than others in some cases.	High, similar to other SSRIs. Long half-life means it remains in the system longer.	High, comparable to other SSRIs. Some find it has fewer side effects.
Potential Issues	May cause gastrointestinal issues; caution with high doses in patients with liver impairment.	Potential for increased anxiety or insomnia; requires close monitoring in children and young adults.	Associated with a risk of QT prolongation at high doses, especially in older adults.
Weight Impact	Generally doesn't cause significant weight gain, though impact can vary.	Less likely to cause weight gain and may even cause initial weight loss.	Can cause appetite changes and potential weight changes.

Other Significant Antidepressant Classes

While SSRIs lead the pack, other classes of antidepressants play a critical role, particularly for patients who do not respond well to SSRIs or require different symptom management.

Serotonin and Norepinephrine Reuptake Inhibitors (SNRIs): This class affects both serotonin and norepinephrine neurotransmitters. Common examples include duloxetine (Cymbalta) and venlafaxine (Effexor XR). SNRIs can be effective for individuals with depression and pain-related symptoms.
Atypical Antidepressants: This is a diverse group of medications that do not fit into other categories and have unique mechanisms of action. A key player in this group is trazodone, which is the second most prescribed antidepressant overall, largely due to its frequent off-label use as a sleep aid. Other examples include bupropion (Wellbutrin), which primarily affects dopamine and norepinephrine and is associated with a lower risk of sexual side effects.
Older Generations (TCAs and MAOIs): Tricyclic antidepressants (TCAs) and monoamine oxidase inhibitors (MAOIs) are older drugs with a higher risk of significant side effects and drug interactions. They are typically reserved for patients whose depression has not responded to other treatments.

The Importance of Personalized Treatment

Ultimately, there is no single "best" antidepressant for everyone. The most appropriate medication depends on an individual's specific symptoms, medical history, other medications they take, and personal preferences regarding side effects. The decision to start, change, or stop an antidepressant should always be made in consultation with a qualified healthcare provider. It often takes time and patience to find the most effective treatment, sometimes requiring adjustments to dosage or a switch to a different medication. For comprehensive resources on mental health medications and conditions, one can consult organizations like the National Alliance on Mental Illness (NAMI).

Conclusion

Based on recent prescription data, sertraline is the most common antidepressant prescribed. However, it is just one of many options available within the broader and most commonly prescribed class of antidepressants, the SSRIs. The field of pharmacology offers a diverse arsenal of medications, each with its own benefits and side-effect profile. Successful treatment relies on a collaborative approach between the patient and a healthcare team to find the medication that provides the most benefit with the fewest side effects, emphasizing that personalized care is crucial for positive mental health outcomes.

Frequently Asked Questions

SSRIs are often the first choice because they are generally effective, have fewer bothersome side effects compared to older antidepressants like TCAs and MAOIs, and are less likely to cause problems at higher doses.

Both are effective SSRIs, but studies show minor differences in tolerability and side effect profiles. Fluoxetine has a longer half-life, meaning it stays in the body longer. Some studies suggest fluoxetine might cause more insomnia and anxiety than sertraline.

For most antidepressants, including sertraline, it typically takes 4 to 6 weeks for the medication to reach its full effect and for you to feel the maximum benefit.

No, you should not stop taking your antidepressant suddenly without talking to your doctor. Abruptly stopping can cause withdrawal symptoms. Your doctor will likely recommend a gradual reduction in dosage to minimize any adverse effects.

Common side effects of SSRIs can include nausea, insomnia, headache, diarrhea, and sexual dysfunction. These side effects are often mild and may decrease over the first couple of weeks of treatment.

Sertraline has demonstrated high effectiveness, comparable to other SSRIs. The "most effective" antidepressant is subjective and depends on individual response, symptom presentation, and tolerability of side effects.

Trazodone is an atypical antidepressant that is also widely used off-label as a sleep aid due to its sedative properties. This frequent use for insomnia, in addition to depression, contributes to its high prescription volume.