What Is the Best, Most Effective Antidepressant for Me?

Written by Christina Aungst, PharmD | Reviewed by Alyssa Billingsley, PharmD

Key takeaways:

• All antidepressants are similarly effective for treating depression, but some cause more side effects than others.
• Selective serotonin reuptake inhibitors (SSRIs) are the most common type of antidepressant prescribed, but serotonin and norepinephrine reuptake inhibitors (SNRIs) and bupropion (Wellbutrin) are also popularly prescribed options.
• If you’re experiencing certain side effects from one type of antidepressant, switching to another may help relieve them.

Major depressive disorder — commonly referred to as depression — is characterized by symptoms such as loss of interest, low energy, sleep changes, trouble concentrating, and feelings of guilt or hopelessness that have been present for more than 2 weeks. It is often treated with antidepressants, with or without talk therapy.

Depression is one of the most common mental health conditions people experience. In 2017, over 17 million U.S. adults had at least one major depressive episode. Of those adults, 50% took medication to treat their depression.

If you or someone you care about is struggling with depression, you may have considered taking medication. But with so many antidepressants available, which ones are the most effective? Here, we’ll discuss the various medications available for treating depression and how your healthcare provider may decide which one to prescribe for you.

Who is at a greater risk for depression?

Depression can happen to anyone, but some groups have different risks than others. There are known healthcare disparities that historically underrepresented communities face — having less access to mental health services is one of them.

In the U.S., Black adults experience feelings of hopelessness, worthlessness, and sadness more often than white adults. But only a third of Black adults who need mental health treatment receive care.

Talking about mental health struggles can often carry a lot of social stigma. These feelings of shame or embarrassment can prevent a person from getting the help they need. A study from the National Mental Health Association (NMHA) found that 63% of Black adults believed that depression is a sign of personal weakness.

These beliefs combined with racial trauma and less access to healthcare put the Black community at a higher risk for many health problems. In fact, Black Americans are 20% more likely than the general population to have more serious mental health conditions.

We’re here to say you’re not alone. Knowing how to find the right therapist is an important step. Understanding the antidepressants that are often prescribed is important too. 

What are the best antidepressants? 

Over the years, studies have compared various antidepressants. After reviewing the available research, the American Psychiatric Association (APA) concluded that no one antidepressant was more effective at treating depression than others. Instead, antidepressants are typically recommended based on factors like their side effects, the cost, and whether you’ve responded favorably to a particular medication in the past.

Healthcare providers typically start most people on either a selective serotonin reuptake inhibitor (SSRI) or serotonin and norepinephrine reuptake inhibitor (SNRI). These medications are generally better tolerated than other antidepressants and can also treat other conditions that people sometimes experience along with depression, like anxiety.

But in the end, the best antidepressant is the one that provides you the most benefit with the fewest side effects. Everyone’s journey to finding the right depression treatment is unique.

What are the different types of antidepressants?

Antidepressants fall into one of five medication classes:

1. SSRIs
2. SNRIs
3. Atypical antidepressants
4. Tricyclic antidepressants (TCAs)
5. Monoamine oxidase inhibitors (MAOIs)

Below, we’ll briefly discuss some well-known antidepressants and which classes they belong to.

Please note: We will not be discussing the risks, warnings, and drug interactions for each type of antidepressant in this article. Please speak with your healthcare provider or pharmacist for more detailed information on your particular medication.

SSRIs

The five most well-known, FDA-approved SSRIs to treat depression are:

1. Citalopram (Celexa)
2. Escitalopram (Lexapro)
3. Fluoxetine (Prozac)
4. Paroxetine (Paxil)
5. Sertraline (Zoloft)

SSRIs are considered first-choice medications for treating depression. These medications are believed to work by raising the amount of serotonin, which is a hormone that helps regulate mood, in the brain. While effective for treating depression, they can take up to 6 weeks to kick in.

SNRIs

There are three well-known SNRIs that are FDA-approved to treat depression:

1. Desvenlafaxine (Pristiq)
2. Duloxetine (Cymbalta)
3. Venlafaxine (Effexor)

Another first-choice option, SNRIs work by raising brain levels of serotonin and norepinephrine, a hormone that helps boost alertness and focus. As with SSRIs, these medications can also take up to 6 weeks to start relieving symptoms.

Atypical antidepressants

This group includes antidepressants that don’t fit into other medication classes. Commonly prescribed atypical antidepressants are these three:

1. Bupropion (Wellbutrin)
2. Mirtazapine (Remeron)
3. Trazodone (Desyrel)

The ways these types of antidepressants work aren’t fully understood. Bupropion and mirtazapine are similarly effective to SSRIs and SNRIs and are considered first-choice options for treating depression. Trazodone may be preferred if a person has both depression and trouble sleeping.

TCAs

There are several TCAs available, but four commonly used options are:

1. Amitriptyline
2. Desipramine (Norpramin)
3. Doxepin 
4. Nortriptyline (Pamelor)

TCAs treat depression by raising levels of serotonin and norepinephrine in the brain. While some studies suggest they may be more effective for certain people with severe depression, they have a greater risk of side effects. Because they aren’t as well-tolerated as previously listed antidepressants, healthcare providers often prescribe them after you’ve tried other medications first.

MAOIs

MAOIs are typically avoided for most people with depression due to their risks of serious side effects, necessary dietary restrictions, and numerous medication interactions. However, studies have shown they can be effective for treatment-resistant depression — meaning other antidepressants aren’t working.

How does a healthcare provider decide which antidepressant is best for you?

If you have successfully taken an antidepressant in the past, this is always a good place to start. You are more likely to experience benefits from a medication that has worked before. But if you’ve never taken medication for depression before, healthcare providers often look at the likelihood of side effects when choosing a medication.

Newer antidepressants, such as SSRIs and SNRIs, tend to be better tolerated than older antidepressants. SNRIs may be preferred over SSRIs if you also have a chronic pain condition, as SNRIs can also help with symptoms of that condition.

Sexual problems, like erectile dysfunction, tend to be more common with SSRIs and SNRIs than other antidepressants. If sexual side effects happen, bupropion (Wellbutrin) may be a better option, as these side effects are very uncommon with this medication. Bupropion can also be added to your medication regimen if your current antidepressant is working well for your depression.

As mentioned earlier, if you have both depression and insomnia (trouble sleeping), trazodone is a possible choice. This medication tends to cause a lot of drowsiness, so a healthcare provider may try to use this side effect as a method of helping you sleep better.

Which class of antidepressant is the most commonly prescribed?

SSRIs are the most commonly prescribed class of antidepressants. This is because they are effective for treating depression, generally well-tolerated, inexpensive, and safe to use long term. SNRIs and bupropion are also common choices for similar reasons.

Which antidepressant works the fastest?

Unfortunately, all antidepressants take a few weeks to kick in. How fast an antidepressant starts working varies widely from person to person. Generally speaking, you can expect to experience some effects between 4 and 6 weeks after starting your medication. If you don’t feel any change after 8 weeks of starting an antidepressant, contact your healthcare provider to let them know it’s not working.

Which antidepressant is the hardest to come off of?

One downside of SSRIs and SNRIs is that they can be difficult to come off of. This is because these medications can cause withdrawal symptoms if your dose is lowered too quickly. Be sure to follow your healthcare provider’s instructions about how you should lower your dose.

Withdrawal symptoms from these antidepressants may include:

• Flu-like symptoms
• Insomnia
• Nausea
• Headaches
• “Pins-and-needles” sensations
• “Electric shock-like” sensations

If you experience these symptoms when trying to come off your antidepressant, let your healthcare provider know. But keep in mind that these symptoms are temporary and should resolve within 1 to 2 weeks.

The bottom line

Depression is a common mental health condition that can be treated with a variety of medications. SSRIs, SNRIs, and bupropion are some of the most commonly prescribed antidepressants, but studies suggest that all antidepressants are similarly effective.

Because of this, healthcare providers typically select an antidepressant based on its possible side effects or its abilities to treat other health conditions you have. Depression treatments should be personalized based on your needs and your response to medication. Be sure to let your healthcare provider know how you are feeling after starting an antidepressant so, if necessary, they can make any adjustments in your antidepressant regimen.