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A Guide to Over-The-Counter Antidepressants

Kristin Hall, FNP

Reviewed by Kristin Hall, FNP

Written by Our Editorial Team

Published 11/23/2021

Updated 11/24/2021

You might be familiar with prescription antidepressants, but did you know there are some over-the-counter medications that also bill themselves as being antidepressants? 

It’s true. Often used for mild to moderate depression, over-the-counter antidepressants can be bought online or at your local pharmacy. 

And while there’s no replacement for taking time to speak with a professional, we thought it would be useful to compile a list of some of the more popular over-the-counter antidepressants.

Read on to find out what the scientific community has to say about some of the popular over-the-counter antidepressants.

What Is Depression? 

Before diving into over-the-counter antidepressants, it helps to have a bit of background information on depression. 

Depression affects many people in the United States. In fact, according to the 2019 National Survey on Drug Use and Health more than 19 million adults in America experienced at least one major depressive episode during the previous year.

Symptoms of a depressive disorder include persistently feeling sad and/or hopeless, losing interest in things you used to find pleasure in, having a hard time sleeping and changes in appetite.

This mental illness is often connected to low levels or certain neurotransmitters — these transfer information between your neurons. 

Neurotransmitters that have been connected to depression include serotonin, dopamine, norepinephrine and more.

Prescription antidepressants work by addressing these low levels of neurotransmitters. 

Popular Over-The-Counter Antidepressants

That said, over-the-counter antidepressants are much different. They may share some similarities, but there’s a reason over-the-counter drugs are sold without prescriptions. That said, here are some of the more well known options out there. 

St. John’s Wort

This plant has been used for centuries to treat various ailments. It’s sold as an herbal supplement in the United States and is also used in Europe to treat depression.

So, does it work? The research is mixed. A 2009 review of studies found that St. John’s wort may be better than a placebo in treating depression. 

However, another small study done in 2011 looked at both St. John’s wort and a prescription antidepressant and found neither treated minor depression any better than a placebo.

St. John’s wort may be sold over the counter, but it’s not without potential dangers. Taking it along with certain prescription antidepressants can lead to dangerously high levels of serotonin (a condition called Serotonin Syndrome). 

It may also increase psychotic episodes in people with bipolar disorder. Finally, it can negatively interact with other medications.

Omega-3 Fatty Acids 

You may know that Omega-3s are touted as being able to boost hair and skin health. But some believe they can also help with depression — and there is some limited research to support this.

A review of scientific evidence found that omega-3s might alleviate mild to moderate depression.

Other studies have suggested that omega-3s used alongside standard antidepressants have the best outcome.


Nope, that’s not just a string of characters — it stands for 5-hydroxytryptophan, which is an amino acid your body produces that can be converted to serotonin. Because of this, some think it can help with depression.

More research is needed, but a 2019 review did suggest taking a 5-HTP supplement along with certain prescribed antidepressants can boost the effectiveness of those antidepressants.


This is another thing your body naturally produces. It’s full name is S-adenosyl-L-methionine and it plays a role in the regulation of neurotransmitters. 

A review of studies found that SAMe supplements may help symptoms of depression when used with standard antidepressants.

Other Ways to Treat Depression 

By now, perhaps you’ve gathered that while there is some research that tentatively supports the effectiveness of over-the-counter antidepressants, they aren’t a sure fire way to treat depression. 

It bears repeating: none of the over-the-counter antidepressants you read about above should replace an actual visit with your mental healthcare provider, and also shouldn’t be taken without their supervision or guidance.

That said, the below options are more commonly recommended to address depression by mental health professionals. 

Prescription Antidepressants 

Remember how we said that low levels of certain neurotransmitters may be behind depression? Prescription antidepressants increase levels of specific neurotransmitters to address depression symptoms. 

When taken properly under the supervision of your healthcare professional, they can begin to reduce symptoms of depression within four to eight weeks.

There are a number of different types of antidepressants, including:  

  • Selective serotonin reuptake inhibitors (SSRIs)

  • Serotonin–norepinephrine reuptake inhibitors (SNRIs)

  • Tricyclic antidepressants (TCAs)

  • Atypical antidepressants 

Bupropion (sold as the brand name Wellbutrin®) is the most well known of the last category mentioned above.

You can learn more about these medications in our Full List of Antidepressants guide.

Cognitive Behavioral Therapy (CBT)

Studies have found that CBT can help people deal with depression. 

In CBT, people work with a therapist to identify issues related to their depression and come up with what they’d like to see change. 

People then work together with their mental healthcare provider to figure out patterns you may be stuck in and figure out ways to address and change them.

Finding a therapist you feel comfortable with is an important component. You should feel free to interview a few before you settle on one. 

It’s also possible that a mental health professional will suggest both therapy for depression and prescription antidepressants in your treatment of depression. 

The Verdict About Over-The-Counter Antidepressants 

The truth is that research is inconclusive as to whether over-the-counter antidepressants are effective for moderate or mild depression.

Some of the more popular over-the-counter antidepressants (like St. John’s wort, omega-3 fatty acids, 5-HTP and SAMe) have some evidence to support that they could be effective, but way more studies need to be carried out before you should go running to your local pharmacy.

Over-the-counter antidepressants can also interact poorly with other medications you may take, so you should never take something without consulting with a healthcare professional.

Other treatments for depression include prescription medications and therapy, and those will likely be your best bet in addressing your mental health issues — for the time being, anyway.

Before embarking on any sort of treatment for depression, you should speak to a mental health professional. 

They’ll be able to assess your depression and go over your options. You’ll also be able to ask them questions — like what common side effects of different medications are or how long before you may notice a difference in how you’re feeling.

16 Sources

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Editorial Standards

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. See a mistake? Let us know at [email protected]!

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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