What Is The Most Effective Antidepressant?

Kristin Hall

Reviewed by Kristin Hall, FNP

Written by Rachel Sacks

Published 09/12/2022

Updated 09/13/2022

When dealing with major depression or anxiety disorders, finding the most effective treatment feels like a step in the right direction. Antidepressants are a common medication prescribed to treat certain mental health disorders. Antidepressant drugs are so common that between 2015 and 2018, over 13 percent of U.S. adults used antidepressants daily. But while antidepressants are a common treatment for certain mental health disorders, what is the most effective antidepressant?

We’ll go over what antidepressants are and answer whether there is one medication that is the most effective antidepressant.

Antidepressant medications are used to treat major depressive disorder as well as obsessive-compulsive disorder (OCD), generalized anxiety disorder, post-traumatic stress disorder (PTSD) and chronic (long-term) pain.

In some cases, antidepressants are used to treat bipolar disorder, although they’re used conservatively due to risks.

Although the exact mechanism is unknown, antidepressants are thought to work by affecting certain brain chemicals (or neurotransmitters) associated with major depression, such as serotonin, dopamine and norepinephrine. If you're curious about what antidepressants feel like, we've covered that in our guide.

Research suggests that antidepressants can be helpful for people with chronic, moderate or severe depression and may not have as much of an effect on symptoms of mild depression.

Antidepressants mainly treat depression symptoms so they are often used in combination with psychotherapy to treat more severe depression and other mental health conditions.

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The five major classes of antidepressants are:

  • Selective serotonin reuptake inhibitors (SSRIs).SSRIs are the most commonly prescribed antidepressant. They increase the amount of serotonin in your brain by preventing the brain from reabsorbing the neurotransmitter.

  • Serotonin-norepinephrine reuptake inhibitors (SNRIs). These antidepressants work to increase levels of both serotonin and norepinephrine in the brain. Like other antidepressants, SNRIs can cause side effects.

  • Tricyclic antidepressants (TCAs). An older class of antidepressants, TCAs work by increasing certain neurotransmitters in the brain, including serotonin and norepinephrine.

  • Monoamine oxidase inhibitors (MAOIs). Monoamine oxidase inhibitors are another older class of antidepressants. They increase the neurotransmitters serotonin, norepinephrine, dopamine and tyramine by blocking the enzyme monoamine oxidase, which breaks down those neurotransmitters. MAOIs are used for the treatment of panic disorder, social phobia and depression with atypical features.

  • Atypical antidepressants. Some medications are referred to as atypical antidepressants because they don’t fall under the other classes of antidepressants.

Our full list of antidepressants goes into more detail on all the types of antidepressants, their side effects, and more.

Antidepressants are useful in relieving depression symptoms and other mental disorders.

But what is the most effective antidepressant?

That depends on a variety of factors such as symptoms, severity, other existing health conditions and more. Similar to many other medications, certain antidepressants may work for some and not as well for others.

After reviewing multiple studies on various antidepressants, the American Psychiatric Association found that no one antidepressant was more effective at treating depression than others.

A healthcare provider or mental health professional will typically prescribe an antidepressant based on factors like its side effects, cost and whether you’ve responded well to a particular medication in the past.

Many people start taking SSRIs or SNRIs, as these two types of antidepressants are generally better tolerated and effective at managing symptoms of depression and other conditions.

Older medications, such as tricyclic antidepressants and monoamine oxidase inhibitors, aren’t prescribed as often due to more side effects compared to newer antidepressants.

Many people still use tricyclic antidepressants though when other treatments aren’t effective.

One study found that 70 percent of people treated with antidepressants in the U.S. between 1996 and 2015 were taking SSRIs.

Fluoxetine (Prozac®) was one of the most popular SSRIs in the U.S., with a little over 11 percent of respondents taking fluoxetine for depression.

While some SSRIs remain commonly used treatment options, other studies have found different antidepressants to be effective, too.

A review of 21 antidepressants found that five antidepressants were more effective over eight weeks of treatment:

Other types of antidepressants were found to be as effective and popular as SSRIs.

Monoamine oxidase inhibitors are not typically recommended for most people with depression due to their risks of serious side effects, necessary dietary restrictions and many medication interactions.

Although some people with treatment-resistant depression — depression that doesn’t improve with other antidepressants — may find MAOIs effective. Those diagnosed with Parkinson's disease and multiple system atrophy could also benefit from taking MAOIs.

Of the atypical antidepressants, bupropion (Wellbutrin®) is one of the most commonly prescribed. Bupropion generally has a lower risk of side effects and is just as effective as other antidepressants at treating anxiety associated with depression.

However, different medications can cause different side effects and risks in different individuals.

Duloxetine, for example, can increase blood pressure and lead to liver failure in some people. So if you have any sort of liver disease, that particular antidepressant could be a dangerous choice for you.

Common side effects of SSRIs and SNRIs can include:

  • Feeling agitated, shaky or anxious

  • Indigestion and stomach aches

  • Diarrhea or constipation

  • Loss of appetite

  • Dizziness

  • Insomnia or feeling very sleepy

  • Headaches

  • Reduced sex drive

  • Weight gain

Side effects tend to be mild and go away as your body adjusts to the medication.

Before starting any new medication, you should discuss the benefits and risks with your healthcare provider.

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In the end, the most effective antidepressant is the one that gives you the most benefits with the fewest side effects. Everyone’s journey to finding the right antidepressant and overall treatment is unique.

The best treatment for depression and anxiety is a combination of antidepressant medication and psychotherapy, such as cognitive-behavioral therapy.

Talk to your healthcare provider about treatment if you’re struggling with major depression, anxiety, or another mental health disorder. Mental health treatment is the result of a healthcare provider’s professional opinion of the best course of treatment for you. 

An easy way to start is by completing a consultation with a licensed psychiatry provider online.

You can also learn more about what to expect from healthcare providers in our guide on how to get antidepressants.

Taking the next step, however big or small, is the best thing you can do for your mental health.

18 Sources

Hims & Hers has strict sourcing guidelines to ensure our content is accurate and current. We rely on peer-reviewed studies, academic research institutions, and medical associations. We strive to use primary sources and refrain from using tertiary references.

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This article is for informational purposes only and does not constitute medical advice. The information contained herein is not a substitute for and should never be relied upon for professional medical advice. Always talk to your doctor about the risks and benefits of any treatment. Learn more about our editorial standards here.

Kristin Hall, FNP

Kristin Hall is a board-certified Family Nurse Practitioner with decades of experience in clinical practice and leadership. 

She has an extensive background in Family Medicine as both a front-line healthcare provider and clinical leader through her work as a primary care provider, retail health clinician and as Principal Investigator with the NIH

Certified through the American Nurses Credentialing Center, she brings her expertise in Family Medicine into your home by helping people improve their health and actively participate in their own healthcare. 

Kristin is a St. Louis native and earned her master’s degree in Nursing from St. Louis University, and is also a member of the American Academy of Nurse Practitioners. You can find Kristin on LinkedIn for more information.

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