Do Over-the-Counter Antidepressants Actually Work?

Daniel Lieberman

Reviewed by Daniel Z. Lieberman, MD

Written by Taylor Trudon

Published 04/22/2022

Updated 11/15/2023

If you’re reading this, chances are, you’ve heard of antidepressants. But did you know there are over-the-counter “medications” you can buy that label themselves as antidepressants?

Before we get any further, we should note that over-the-counter antidepressants aren’t a real thing but rather an umbrella term for all kinds of supplements you can buy without a prescription.

Having said that, you can walk into your local pharmacy and pick up an over-the-counter (OTC) antidepressant alternative with the same ease you can pick up a bag of chips or a tube of toothpaste. You can even order these supplements online, just like buying a pair of sneakers.

Still, you might be wondering why someone would opt for over-the-counter medicine in lieu of actual antidepressants to treat their anxiety or depression in the first place? 

Like many things in life, it totally depends on the person. For some, accessing over-the-counter meds is simply more convenient because they don’t require a prescription. For others with more mild depression or moderate symptoms of depression, over-the-counter medication might seem like the better choice.

And if you decide to explore this route, it’s never a bad idea to speak with a healthcare provider.

In the meantime, this guide can help answer some initial questions you might have, including what over-the-counter antidepressants actually are (spoiler: they’re not the same as prescription medication), the most commonly used ones, how they work and what the medical community has to say about their effectiveness. 

Over-the-counter antidepressants explained

Before we take the plunge into the over-the-counter antidepressants pool, it’s helpful to first understand what exactly antidepressants do for depression and how they function differently from OTC options.

With an estimated 21 million U.S. adults experiencing at least one major depressive episode each year, antidepressants have proven to be both an effective and popular treatment. Symptoms of depression include feeling sad or hopeless, losing interest in activities you once enjoyed, insomnia and weight gain or loss.

Some people may experience short-term depression as a result of specific life circumstances, like the death of a loved one or losing a job. But for others, depression can last years.

Fortunately, taking antidepressants can help regulate your mood and reduce symptoms by targeting certain neurotransmitters, like serotonin, dopamine and norepinephrine. While anxiety is different from depression, this mental health disorder is often treated with antidepressants because the conditions have similar symptoms.

Our full antidepressants list goes over all the medications to consider if you’re interested in exploring your options.

It’s important to note that in order to get antidepressant medication, you must have a prescription from a healthcare provider.

While you don’t need a prescription to access over-the-counter medication, there’s a level of uncertainty that comes with it. For instance, what’s the correct dose to take? And how would that dose interact with other medications?

Some experts are averse to over-the-counter antidepressants because the evidence for their effectiveness is weak compared to prescription medications and active ingredients vary among brands and individual batches, producing unpredictable results.

Let us reiterate: Over-the-counter antidepressants aren’t technically a real thing but rather an umbrella term for various supplements that might be beneficial.

So yes, there are big differences between antidepressants and over-the-counter meds. However, some people definitely think they benefit from over-the-counter drugs.

Some of the most commonly used options are:

  • St. John’s wort

  • Omega-3 fatty acids

  • 5-HTP

  • Rhodiola rosea 

  • SAMe

  • Various vitamins and minerals

Let’s get to know each one better. 

St. John’s Wort

St. John’s wort is a plant that grows in the wild and has been used for centuries for mental health conditions. Popularly prescribed in Europe, it’s also sold as a dietary supplement in the U.S., where the requirements for selling supplements are less strict than the requirements for prescriptions and over-the-counter drugs with FDA approval. 

When it comes to treating depression, research tells us St. John’s wort isn’t consistently effective. A small study conducted in 2011 looked at both St. John’s wort and a prescription antidepressant and found that neither treated minor depression any better than a placebo.

We do know, however, that St. John’s wort limits the effectiveness of other prescription medications, including birth control pills and antidepressants. 

We also know that combining St. John’s wort with certain antidepressants may lead to a potentially life-threatening increase in serotonin, causing side effects like agitation, diarrhea, fast heartbeat, high blood pressure and hallucinations.

Additionally, there have been reports of worsening psychotic symptoms among people with bipolar disorder or schizophrenia.

The less intense side effects of St. John’s wort are more uncommon and minor, like upset stomach, dry mouth, headache, fatigue, dizziness, confusion and sexual dysfunction.

Omega-3 Fatty Acids

Omega-3s, also known as omega-3 fatty acids, are a kind of fat found in foods that are crucial for cells throughout the body. You might’ve heard of people taking omega-3 supplements, such as seafood and fish oil supplements, in the hopes of shinier, healthier hair — honestly, aren’t we all?

However, some take omega-3s because they think it helps their depression. So far, studies have shown mixed results as to whether this is accurate. 

For instance, a 2015 evaluation of 26 studies that included more than 1,400 people concluded that if there is an effect, it may be too small to make any real impact.

On the other hand, other studies have suggested that omega-3s used with standard antidepressants produce the best results. There’s also a review of scientific evidence suggesting omega-3s might alleviate mild to moderate depression.

The bottom line? You probably shouldn’t exclusively rely on omega-3s (or any supplement, for that matter) to “cure” your depression. Still, consuming omega-3-rich foods (check out our full list of foods that help fight depression) and supplements may have a positive effect on reducing your systems.   


5-what? 5-HTP, or 5-hydroxytryptophan (phew, that’s a mouthful), is a chemical byproduct of an amino acid known as L-tryptophan — something your body naturally produces.

Dairy products, red meat, poultry and eggs all contain L-tryptophan. So when you chomp down something like a juicy steak, your body organically converts the 5-HTP it absorbs into serotonin. And since serotonin is associated with regulating your mood and feelings of happiness, some believe 5-HTP can be used as a natural mood stabilizer to help with depression.

Similar to most supplements, the jury’s still out in terms of the effectiveness of 5-HTP supplements. Based on a 2019 review, though, researchers found that if taken alongside certain prescribed antidepressants, 5-HTP supplements may potentially boost the effectiveness of those antidepressants.

Rhodiola Rosea

Rhodiola rosea is an herb that comes from Rhodiola, a plant found in Europe and South Asian countries with cold regions and high altitudes. It’s considered an adaptogen, a natural substance believed to help with stress management.

This “arctic” or “golden” root has been used for centuries by Russians, Scandinavians and other Europeans to treat depression, anxiety and fatigue. 

How effective is Rhodiola? As you might’ve already guessed, some research points towards its benefits.

For instance, a 2017 study involving 118 people with stress-related burnout took 400 milligrams of rhodiola a day for 12 weeks. Participants showed improved symptoms associated with burnout, like stress and depression. While it was only the first clinical trial, this outcome indicates there’s potential for rhodiola to help some people better deal with stress during difficult times. It’s important to note, however, that there was no comparison condition in this study. Everybody got rhodiola. That’s a problem. Sometimes, being in a study promotes hope, which is sometimes the real reason people get better. That’s known as the placebo effect. The best studies compare the treatment being studied to a placebo to make sure the treatment is really effective.

Perhaps unsurprisingly, some medical community members believe more in-depth research is required in order to prove this herbal supplement can provide substantial health benefits.


Like 5-HTP, SAMe is a chemical naturally found in the body. Short for S-adenosyl-L-methionine, SAMe is made from an amino acid called methionine, and it helps regulate neurotransmitters.

When it comes to depression — which SAMe has been studied for the most extensively, along with osteoarthritis and liver diseases — the research wasn’t conclusive. However, a 2020 review did find that when taken alongside prescribed antidepressants, using SAMe can have positive results.

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Vitamins and Minerals

Even if you’ve never heard of 5-HTP or SAMe (which is totally fair), there’s a good chance you’re familiar with regular ol’ vitamins and minerals — even if it’s the gummy ones from when you were a kid.

Vitamins are nutrients all bodies need to properly function. And research shows that deficiencies in certain vitamins and minerals can be linked to mental health conditions, like depression.

Here are a few V&Ms your body needs to be its best self: 

  • Vitamin D. Vitamin D is a big one. It’s especially important for bone growth, cell growth, managing inflammation and immune function. A lack of vitamin D puts people more at risk for developing depression, as one study shows. While you can definitely take supplements to help curb this, getting outside and soaking up the sunshine can help enormously too.

  • Zinc. Zinc is heavily involved in your body’s cellular metabolism. It can be found in foods like oysters, red meat and poultry. Research suggests that deficiencies in zinc play a role in depression among people and animals.

  • Magnesium. When it comes to essential functions like nerve signaling, muscle regeneration, protein synthesis and blood sugar regulation, your magnesium levels are where it’s at. It has other benefits too. Research conducted by the University of Adelaide Press found that magnesium supplements can make a substantial difference in your mood if you’re struggling with depression.

  • Probiotics. You might have heard probiotics referred to as “good” bacteria. Probiotics are live microorganisms naturally found in fermented foods, like yogurt and sourdough bread. Not only do they help get rid of “bad” bacteria like those that cause infection, but new research suggests probiotic supplements may also be effective for reducing depression symptoms when used with other depression treatments.

Curious about your vitamin and mineral levels? Getting bloodwork done is an effective tool for actually determining if you need to increase them. That said, it’s always worth consulting with your healthcare provider for any kind of medical advice.

If you’d like to read up on additional natural remedies for treating depression in the meantime, you can check out our more detailed guide. 

One of the most critical differences between prescription antidepressants and over-the-counter medication is that they’re held to different standards.

The supplements we just went over don’t have the same requirements as drugs approved by the FDA (U.S. Food and Drug Administration), like Fluoxetine (Prozac®) or Sertraline (Zoloft®).

On the one hand, this makes over-the-counter medications more easily accessible. But on the other, you don’t know exactly what you’re getting, how much you should take or how it’ll interact with other medications. 

In contrast, we have significantly more evidence and understanding when it comes to prescription antidepressants, which are often considered a first-line treatment for depression.

Some of the most commonly used medications are:

While antidepressants are not addictive, other medications like benzodiazepines (used primarily to treat anxiety and panic disorders) have a high risk of dependency. If you have concerns about using any medication, your healthcare provider can help. 

To get antidepressant drugs, your primary care provider has to write you a prescription. The cost will depend on factors like what your insurance covers, but you can also access affordable antidepressants without insurance.

Alternatively, you can get medication by connecting with a qualified psychiatric provider online. Telehealth primary care can help you get depression medication online as well — no doctor’s trip necessary.

Have more questions about antidepressants? Check out our complete depression medications guide for a rundown on how each medication works.

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At the end of the day, it’s impossible to make any concrete conclusions about the effectiveness of over-the-counter antidepressants. Some supplements have promising evidence of potentially reducing depressive symptoms, while others need to be more sufficiently researched.

What is concrete, however, is that there are ways to find support beyond medication — over-the-counter or not. This includes:

  • Getting help online. If you’re struggling and want to open up to someone, a licensed therapist is always a great option. With the help of private online therapy sessions, you can access professional help from wherever is most convenient for you — be it on your couch at home or while on vacation. Anonymous support groups can also be a powerful form of support.

  • Talking to a mental healthcare professional. Based on your symptoms, a mental healthcare provider can make a diagnosis and help you develop a treatment plan, which may include medication, counseling and/or psychotherapy.

  • Practicing self-care. If you’re going through it, prioritizing your well-being by practicing self-care is crucial. For some, it might be breaking a sweat at the gym (exercise is a fantastic stress-reliever). For others, it could be doing mindfulness exercises like meditation, which can help lower cortisol levels.

Explore your options, and find the support you need today.

Related Articles

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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.

Daniel Z. Lieberman, MD

Dr. Daniel Z. Lieberman is the senior vice president of mental health at Hims & Hers and of psychiatry and behavioral sciences at George Washington University. Prior to joining Hims & Hers, Dr. Lieberman spent over 25 years as a full time academic, receiving multiple awards for teaching and research. While at George Washington, he served as the chairman of the university’s Institutional Review Board and the vice chair of the Department of Psychiatry and Behavioral Sciences.

Dr. Lieberman’s has focused on , , , and to increase access to scientifically-proven treatments. He served as the principal investigator at George Washington University for dozens of FDA trials of new medications and developed online programs to help people with , , and . In recognition of his contributions to the field of psychiatry, in 2015, Dr. Lieberman was designated a distinguished fellow of the American Psychiatric Association. He is board certified in psychiatry and addiction psychiatry by the American Board of Psychiatry and Neurology.

As an expert in mental health, Dr. Lieberman has provided insight on psychiatric topics for the U.S. Department of Health and Human Services, U.S. Department of Commerce, and Office of Drug & Alcohol Policy.

Dr. Lieberman studied the Great Books at St. John’s College and attended medical school at New York University, where he also completed his psychiatry residency. He is the coauthor of the international bestseller , which has been translated into more than 20 languages and was selected as one of the “Must-Read Brain Books of 2018” by Forbes. He is also the author of . He has been on and to discuss the role of the in human behavior, , and .


  • 1992: M.D., New York University School of Medicine

  • 1985: B.A., St. John’s College, Annapolis, Maryland

Selected Appointments

  • 2022–Present: Clinical Professor, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2013–2022: Vice Chair for Clinical Affairs, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2010–2022: Professor, George Washington University Department of Psychiatry and Behavioral Sciences

  • 2008–2017: Chairman, George Washington University Institutional Review Board

Selected Awards & Honors

  • 2022: Distinguished Life Fellow, American Psychiatric Association

  • 2008–2020: Washingtonian Top Doctor award

  • 2005: Caron Foundation Research Award


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