What’s the best antidepressant for me?

Types of antidepressants | Compare common antidepressants | Most effective antidepressant | Discontinuation syndrome | Side effects | Newest antidepressant | How to find the best antidepressant | Safety tips

The National Institute of Mental Health estimates that in 2019, about 19 million people—or 7.8% of the U.S. population—experienced at least one major depressive episode. There are several types of depression, but major depressive disorder is one of the most common.  

A major depressive episode is defined as having persistent feelings of sadness, loss of interest in usual activities, changes to appetite and sleep patterns, loss of energy, difficulty concentrating, and suicidal ideation for at least two weeks, per the American Psychiatric Association.

Despite the fact that so many adults, across all age groups, live with depression each year, there are still many hurdles to receiving proper treatment. One is finding the right antidepressant medication to treat your individualized symptoms: with seven classes of antidepressants and roughly two dozen common medications available, identifying the right drug for you can seem as hard as finding a needle in a haystack.

Thankfully, there are ways to narrow down your options with your healthcare provider to make the search less intimidating. Here are some strategies for honing in on the best antidepressant to meet your needs.

RELATED: Depression statistics

Types of antidepressants

When you hear the word antidepressant, your mind might immediately jump to drugs like Prozac and Zoloft. That makes sense; those drugs are selective serotonin reuptake inhibitors (SSRIs) and are some of the most commonly prescribed antidepressants in the U.S. 

But SSRIs aren’t the only type of antidepressant out there—and not everyone with depression needs to increase their levels of serotonin, a neurotransmitter (a.k.a chemical messenger) responsible for feelings of well-being.   

“Antidepressants target the neurotransmitters in your brain, increasing or decreasing activity in the brain circuits related to mood regulation,” says adult and geriatric psychiatrist David A. Merrill, MD, Ph.D., director of the Pacific Neuroscience Institute’s Pacific Brain Health Center at Providence Saint John’s Health Center in California. 

The neurotransmitters most commonly affected by antidepressants include serotonin, norepinephrine, and dopamine; different classes of antidepressants work on these different neurotransmitter systems.

There are seven types of antidepressants:

1. Selective serotonin reuptake inhibitors (SSRIs), including Prozac (fluoxetine), Paxil (paroxetine), Lexapro (escitalopram), Celexa (citalopram), Viibryd (vilazodone HCl), and Zoloft (sertraline)
2. Serotonin-norepinephrine reuptake inhibitors (SNRIs), including Cymbalta (duloxetine), Pristiq (desvenlafaxine), and Effexor XR (venlafaxine)
3. Atypical antidepressants, including Wellbutrin (bupropion), Desyrel (trazodone), and Remeron (mirtazapine)
4. Tricyclic antidepressants (TCAs), including amitriptyline, Tofranil (imipramine), and Pamelor (nortriptyline)
5. Monoamine oxidase inhibitors (MAOIs), including Marplan (isocarboxazid) and Nardil (phenelzine)
6. Norepinephrine and dopamine reuptake inhibitors (NDRIs), including dexmethylphenidate, and Wellbutrin (bupropion)
7. Serotonin antagonist and reuptake inhibitors (SARIs), including Oleptro (trazodone), and Brintellix (vortioxetine)

Although all of these antidepressants are prescribed by healthcare providers to treat different types of patients and different types of depression, SSRIs are used the most often as a first-line treatment, says Dr. Merrill, with some SSRIs prescribed far more frequently than others.

“Within the SSRIs, the most commonly used is Prozac because it has a lot of evidence [to support its use],” he explains, adding that Zoloft and Lexapro are also broadly prescribed.

RELATED: SSRIs vs. SNRIs: What’s the difference?

What’s the best antidepressant?

Let’s be clear: The best antidepressant for you is the one that you and your healthcare provider agree provides the most symptom relief with the least amount of side effects. Only you, in conjunction with your healthcare team, can decide what specific drug that is. 

However, there are some antidepressants prescribed more often than others to people within certain population groups—and certain factors, like age, gender, pregnancy, and overall health, can determine which group you fall into (and which different antidepressants might be worth trying first). 

Here are the most commonly prescribed antidepressants for the following groups of people:

The best antidepressants were chosen through a combination of expert interviews and popular data. SingleCare doesn’t endorse any particular drug over another.

What’s the most effective antidepressant?

There’s no single best antidepressant. Because everyone has a unique body chemistry, all antidepressants will work differently across the population of users. But some antidepressants have been shown to work more reliably and effectively for large groups of patients. 

A 2018 study in The Lancet asserts that, based on extensive reviews of published studies, the antidepressants Lexapro, Paxil, Zoloft, and Remeron performed better than many other antidepressants, including popular drugs like Prozac, Luvox, and Desyrel. 

It should be noted, though, that the study wasn’t able to look at how well these antidepressants work alongside other treatments, like therapy, or the side effects they may cause. (In other words, a drug that technically works to treat your depression may still not be feasible for you if it causes disruptive or serious side effects.)

It’s also important to note that most antidepressants take a long time to show their full effectiveness. “Despite brain changes happening quickly, the mood changes can take a couple of months with most of the broadly prescribed antidepressants,” says Dr. Merrill, adding that it can take anywhere from six to eight weeks, or even 12 weeks for older adults. 

While two or three months is a long time to wait to see if your antidepressant is truly helping you, it may not be necessary to wait quite so long if you aren’t feeling any improvement at all. “Many times, if patients are going to benefit [from a specific drug], they’ll start feeling improvement within two weeks; if you’re not, it might be worth considering moving on more rapidly, depending on how severe your depression is,” Dr. Merrill says.

Which is the hardest antidepressant to come off of?

Some antidepressants, particularly SSRIs and SNRIs, can cause a condition called “discontinuation syndrome” when therapeutic use is abruptly stopped; Dr. Merrill says this occurs because of the way the brain and body respond to the loss of serotonin support.

Per Harvard Health, typical symptoms of discontinuation syndrome include:

• Gastrointestinal upset
• Difficulty sleeping
• Flu-like symptoms
• Sweating and flushing
• Dizziness
• Hyperarousal
• Anxiety
• Agitation or irritability

While any SSRI or SNRI can cause discontinuation syndrome, the SNRI Effexor (venlafaxine) can be one of the trickiest to wean off, says psychiatrist and sleep medicine specialist Alex Dimitriu, MD, founder of Menlo Park Psychiatry & Sleep Medicine.

“Venlafaxine is an excellent medication, but missed doses can give people ‘brain zaps’ and quick feelings of vertigo, which I’ve called ‘vestibular jitters,’” Dr. Dimitriu explains. “These go away, fortunately, but it can make it hard to stop venlafaxine in particular.” 

Dr. Merrill notes that Paxil is similarly difficult to discontinue, to the point where people will often put up with a lot of side effects simply to avoid having to stop its use. There are ways to make this process easier, though, so you don’t have to either suffer from discontinuation syndrome or stay on a drug in spite of your desire to wean off.

“Prozac has a longer half-life [than some of these other drugs], so it can be used as a bridging drug,” Dr. Merrill says. “We can transition off shorter-acting antidepressants into Prozac until your mood remains stable and we can get you off [the short-acting drug completely].”

Which antidepressants have the mildest side effects?

In general, SSRIs are considered the most well-tolerated antidepressants, per the Mayo Clinic; they typically have fewer side effects than other types and can be safely used at higher doses. Common side effects of SSRIs include sexual dysfunction, weight gain, trouble sleeping, drowsiness, dizziness, and nausea. SNRIs are also considered fairly safe, though Dr. Dimitriu says they can sometimes cause insomnia and elevate your blood pressure.

Atypical antidepressants all come with a common side effect profile, which includes dry mouth, headaches, dizziness, nausea, and fatigue. Tricyclic antidepressants are an older class and often carry more side effects: They have what Dr. Merrill calls a strong “cross-reactivity” with other drugs, a high instance of anticholinergic effects like blurred vision, sudden drops in blood pressure, and confusion, and can result more easily in toxicity than other antidepressants.

MAOIs can be complicated because they inhibit the metabolic response to an enzyme called tyramine, which causes them to potentially interact with a significant number of foods and drugs containing tyramine. As tyramine levels in the body rise, people can experience headaches, heart problems, nausea, and visual disturbances. It can be more challenging to take these drugs safely, but they do work well for some people.

Finally, it’s important to know that starting any new antidepressant can lead to increased suicidal thoughts; while these are considered rare adverse events, they are still possible, especially in children and adolescents taking antidepressants. 

It’s difficult for researchers to assess the risk of suicide related to antidepressants since there are so many factors to account for. However, one 2015 study in The BMJ found that MAOIs, atypical antidepressants, and SNRIs were more likely to result in suicide or self harm than SSRIs and tricyclic antidepressants, with the highest risks found with Remeron (mirtazapine), Effexor (venlafaxine), and Desyrel (trazodone). 

If you start taking a new antidepressant and notice an increase in thoughts related to suicide or death, reach out to a healthcare professional or trusted friend or family member as soon as possible. You can also contact the National Suicide Prevention Lifeline at 1-800-273-8255 or text GO to 741741 for immediate help.

What’s the newest antidepressant on the market?

SSRIs and SNRIs are newer antidepressants among the five major classes, and 

vortioxetine, or Trintellix, is one of the more recent SSRIs to come on the market, says Dr. Dimitriu. Approved by the FDA for treating major depressive disorder in 2013, it works a bit differently than other SSRIs by directly interacting with serotonin receptors. 

“It touts lower sexual side effects and possibly improved cognition as its features,” Dr. Dimitriu explains. “These benefits have seen mixed results in clinical practice, [but] for people who have not responded to the older SSRIs, Trintellix may offer hope.”

RELATED: Trintellix side effects

How to find the best antidepressant for you

If you’re ready to start finding the right antidepressant for you, here are four basic steps you should take to ensure the process moves as seamlessly and quickly as possible.

1. Talk to a healthcare professional

It can be your PCP, your gynecologist, your therapist—it doesn’t matter who you talk to, just that you find a healthcare professional you’re comfortable with. If they can’t personally prescribe an antidepressant, most providers will happily refer you to someone who can or work with that healthcare provider to coordinate your care. 

2. Identify your target symptoms

As you can see, different symptoms, types of depression, and co-existing factors like age and gender can determine which antidepressant might be the best fit. It’s important to know what areas you, personally, need the most help with or want to see the most improvement in. Dr. Merrill says these are called “target symptoms of depression,” and they include things like energy, appetite, concentration, and sleep.

If you struggle with energy and motivation, for example, Dr. Dimitriu says a combination drug that targets more than just serotonin may be particularly helpful: “Adding the norepinephrine piece to the SSRI helps with energy and motivation, [and] bupropion, which is a dopamine and norepinephrine reuptake inhibitor, is also good.”

RELATED: What to expect from a depression screening

3. Consider pharmacogenomic testing

One of the most fascinating medical advances in recent history is pharmacogenomic testing, which helps you identify how your body will metabolize a drug and how your brain will respond to it, says Dr. Merrill. 

Using this testing (which involves a simple blood draw or saliva swab) can make it easier for your healthcare provider to tell which antidepressants you might have a hard time metabolizing. This is important information, because if your body can’t metabolize a drug the way it’s supposed to, it will likely either not work well or cause troublesome side effects. With testing, you might be able to identify more quickly the class of drugs that will benefit you rather than going through months of ineffective drug trials.

“If you’ve failed with one or more antidepressants, it could be reasonable to do a pharmacogenomic test to see which one you’re most likely to tolerate,” advises Dr. Merrill.

4. Discuss all depression treatment options

Unfortunately, the best antidepressant for you won’t completely cure or eliminate your depression—it’s a whole body condition that affects every part of your life, and it’s important to use antidepressants as only part of a comprehensive treatment plan.

“Sleep and exercise are essential to getting better; as a sleep specialist, we have had extraordinary breakthroughs by getting people to sleep better,” says Dr. Dimitriu. “[You have] to meet your medicine halfway…[as the saying goes], you cannot push the gas pedal if there is no gas in the tank.”

It’s also recommended to receive some type of therapy in addition to taking medication, such as psychotherapy. While drugs can alter your neurochemistry, says Dr. Merrill, they can’t change your life circumstances. You will see better results if you can address the origin of your depression and work to heal or resolve the things that contribute to it. A good therapist can assist with that, as can increasing your social support network.

“There are no silver bullets—antidepressants aren’t going to work in isolation even under the best of circumstances,” Dr. Merrill asserts. “They are modulators of the responses to what’s going on in our lives, and it really takes an all-around holistic approach [to feel better].”

RELATED: How to get therapy without insurance

How to take antidepressants safely

Once you find the right antidepressant for you, it’s important to always take it safely. Remember to:

• Take the medication every day—don’t skip doses.
• Avoid drug interactions (ask your doctor or pharmacist what foods, medications, or supplements you should avoid while taking your antidepressant).
• Don’t stop taking the medication suddenly; talk to your healthcare provider about safely discontinuing use.
• Make note or keep a diary of side effects so you can share them with your provider.
• Avoid excessive alcohol use while taking antidepressant drugs.

Above all else, be patient—it may take several months for the medication to be fully effective, so as long as you’re seeing some improvement after a few weeks, try to stay the course for a bit rather than switching medications too frequently. If you still feel your medication isn’t helping, however, please reach out to a healthcare professional for assistance.