Do Over-the-Counter Antidepressants Actually Work?

Before we dive into the details, 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 tube of toothpaste. You can even order these supplements online. Still, you might be wondering why someone would opt for over-the-counter medicine in lieu of actual antidepressants to treat their anxiety disorder 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. Over-the-counter medication might also seem like the better choice for some people with mild depression, while moderate symptoms of depression or severe depression may require more comprehensive treatment.

Whatever route you decide to take, 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 common ones, how they work, and what the medical community has to say about their effectiveness.

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. Some symptoms of depression include:

• Feeling sad or hopeless

• Losing interest in activities you once enjoyed

• Insomnia

• 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, losing a job, or a breakup. 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. And while anxiety is different from depression, this mental health disorder is also often treated with antidepressants.

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 research for their effectiveness isn’t as strong as that of prescription medications. Also, 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. But 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 wild plant that’s been used for centuries to help treat mental health conditions. Popularly prescribed in Europe, it’s also sold as a dietary supplement in the U.S. 

Here, the requirements for selling supplements are less strict than those for prescriptions and over-the-counter drugs that need FDA approval. 

When it comes to treating depression, research suggests that St. John’s wort isn’t always effective. One small study looked at both St. John’s wort and a prescription antidepressant and found that neither treated minor depression any better than a placebo. 

This is a somewhat surprising result since the prescription antidepressant proved to be more effective than placebo for major depression in multiple other studies. It suggests that, overall, treatment may not be as effective for minor depression (depression with only mild symptoms) as it is for major depression.

St. John’s wort also limits the effectiveness of other prescription medications, including birth control pills and antidepressants. 

Combining St. John’s wort with certain antidepressants may also lead to a potentially life-threatening increase in serotonin (referred to as serotonin syndrome), causing side effects like:

• Agitation

• Diarrhea

• Fast heartbeat

• High blood pressure

• 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, such as:

• Upset stomach

• Dry mouth

• Headache

• Fatigue

• Dizziness

• Confusion

• 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, one review of 26 studies 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 symptoms.   

5-HTP

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 on the effectiveness of 5-HTP supplements. Based on one review of studies, 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 temps 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 Russian, Scandinavian, and other European communities to treat depression, anxiety, and fatigue. 

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

For example, one small, early clinical trial on people with stress-related burnout took 400 milligrams of rhodiola a day for 12 weeks. Participants reported improvements in symptoms associated with burnout, such as stress and depression. This suggests that rhodiola might be able 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 in studies. 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.

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

SAMe

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 isn’t conclusive. Still, one 2020 review found that when taken alongside prescribed antidepressants, using SAMe can have positive results.

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 vitamins and minerals 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:

• Selective serotonin reuptake inhibitors (SSRIs)

• Serotonin-norepinephrine reuptake inhibitors (SNRIs)

• Monoamine oxidase inhibitors (MAOIs)

• Tricyclic antidepressants (TCAs)

• Atypical antidepressants

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.

At the end of the day, we can’t make any concrete conclusions about the effectiveness of over-the-counter antidepressants. Some supplements have promising research suggesting they might reduce depressive symptoms, while others need to be more thoroughly researched.

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

• Getting help from a therapist online or in person. 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 your healthcare provider or a psychiatrist. Based on your symptoms, a mental healthcare provider can make a diagnosis and help you develop a treatment plan, which may include medication on its own or in combination with talk therapy (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.

You’ve already taken the first step by exploring your options.

If you think you might be a good fit for antidepressants, you can access support by setting up a consultation on our online psychiatry platform.