What Is The Most Effective Antidepressant?

When dealing with depression or anxiety disorders, finding the most effective treatment can be 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 reported using antidepressants in the past 30 days. But while antidepressants are a common treatment for certain mental health disorders, what is the best 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 (GAD), post-traumatic stress disorder (PTSD), and chronic (long-term) pain.

In some cases, antidepressants are used to treat bipolar disorder, but they’re typically used conservatively. This is due to the risk that they may worsen symptoms when used alone, particularly when it comes to older types of antidepressants, such as tricyclic antidepressants (TCAs). 

Although the exact mechanism is unknown, antidepressants are thought to work by affecting certain brain chemicals (or neurotransmitters) associated with major depression and other mental health disorders. Some examples of neurotransmitters that you may have heard of include serotonin, dopamine, and norepinephrine. 

Research suggests that the benefits of antidepressants increase with depression severity. That means that while they can be quite beneficial for people with severe depression, they may not have as much of an effect on mild to moderate depression.

Antidepressants are often used in combination with psychotherapy (talk therapy) to treat more severe depression and other mental health conditions.

There are several different types of antidepressants. Below, we’ll briefly explore each of the five major classes of antidepressants.

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

Selective serotonin reuptake inhibitors (SSRIs)

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

Some examples of SSRIs are:

• Citalopram (Celexa^®)

• Escitalopram (Lexapro^®)

• Fluoxetine (Prozac^®)

• Fluvoxamine (Luvox^®)

• Paroxetine (Paxil^®)

• Sertraline (Zoloft^®)

• Vilazodone (Viibryd^®)

Serotonin-norepinephrine reuptake inhibitors (SNRIs)

Serotonin-norepinephrine reuptake inhibitors (SNRIs) work to increase the activity of both serotonin and norepinephrine in the brain. Examples of SNRIs include:

• Desvenlafaxine (Pristiq^®)

• Duloxetine (Cymbalta^®)

• Levomilnacipran (Fetzima^®)

• Milnacipran (Savella^®, not approved as an antidepressant in the U.S.)

• Venlafaxine (Effexor^®)

Tricyclic antidepressants (TCAs)

An older class of antidepressants, tricyclic antidepressants (TCAs) work by increasing the activity of serotonin and norepinephrine in the brain.

There are many different types of TCAs. A few you may have heard of include:

• Amitriptyline

• Clomipramine

• Doxepin

• Imipramine

• Nortriptyline (Pamelor^®)

Monoamine oxidase inhibitors (MAOIs)

Monoamine oxidase inhibitors (MAOIs) are another older class of antidepressants. They prevent the breakdown of the neurotransmitters serotonin, norepinephrine, and dopamine by blocking the enzyme monoamine oxidase.

MAOIs are used for the treatment of panic disorder, social phobia, and depression, particularly with atypical features. A couple examples of MAOIs are phenelzine and tranylcypromine.

Atypical antidepressants

Some medications are referred to as atypical antidepressants because they don’t fall under the other classes of antidepressants. Bupropion (Wellbutrin^®) and mirtazapine (Remeron^®) are two examples of atypical antidepressants.

Of the atypical antidepressants, bupropion (Wellbutrin^®) is one of the most commonly prescribed. It also generally has a lower risk of some side effects associated with other antidepressants, such as weight gain and sexual problems.

Bupropion is approved by the Food and Drug Administration (FDA) for the treatment of major depressive disorder, seasonal affective disorder (SAD), and smoking cessation. However, it has several off-label uses as well.

Antidepressants are useful in relieving symptoms of depression as well as those of other mental health disorders. 

But what’s the best antidepressant?

There’s no one tried-and-true answer to this question. What makes the most effective antidepressant 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 individuals 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:

• Your specific diagnosis and symptoms

• Whether you’ve responded well to a particular antidepressant in the past

• The possible side effects of the antidepressant

• Any additional health conditions you have

• The other medications you’re taking

• Your personal preference related to factors like cost or possible side effects

Generally speaking, older antidepressants, such as TCAs and MAOIs, aren’t prescribed as often. However, they may still be used when other antidepressants aren’t effective.

Currently, most people are prescribed SSRIs or SNRIs. These two types of antidepressants are generally better tolerated and have an improved safety profile compared to older antidepressants.

One study found that 70 percent of people treated with antidepressants in the U.S. between 1996 and 2015 were taking SSRIs. Sertraline (Zoloft^®) and fluoxetine (Prozac^®) were the most popular SSRIs prescribed for depression in this study.

While some SSRIs continue to be commonly used treatment options, they’re not the only effective option.  

A 2018 study reviewed 522 clinical trials and looked at the effectiveness and tolerability for 21 antidepressants over an 8-week period.

The researchers noted that certain antidepressants were more effective than others:

Some people with treatment-resistant depression may find that MAOIs are effective. Treatment-resistant depression affects about 30% of people with major depressive disorder.

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

Different medications can also cause different side effects and risks in different individuals. That’s why it’s important to consider an antidepressant’s possible side effects as well as your underlying health conditions when selecting one.

Duloxetine (Cymbalta^®), 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.

It’s important to know that possible side effects can vary by the type of antidepressant. However, some common side effects associated with antidepressants may include:

• Feeling agitated, shaky or anxious

• Nausea

• Diarrhea

• Constipation

• Appetite changes

• Weight gain

• Dizziness

• Insomnia or drowsiness

• Headaches

• Dry mouth

• Sexual problems, like reduced sex drive and difficulty having an orgasm

• Changes in heart rhythm

• Suicidal thoughts

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

Before starting any new medication, you should receive medical advice by discussing the benefits and risks of the different types of antidepressants with your healthcare provider.

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 (talk therapy), such as cognitive-behavioral therapy (CBT).

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.