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What are the most common depression medications?

Statistics show that SSRIs are the first-line option, with one Rx prescribed most often

Whether you need support during a short-term period of grief and loss or you live with long-term depression, your healthcare provider may recommend the use of an antidepressant. Medications like SSRIs, SNRIs, atypical antidepressants, TCAs, and MAOIs are primarily used to alleviate depression symptoms like sadness, hopelessness, difficulty concentrating, and loss of interest in activities you once enjoyed. But some antidepressants work for other conditions, too, including anxiety, insomnia, and fibromyalgia

In this guide, learn the most common antidepressants, how they work, how fast they relieve symptoms, and what conditions they treat best.

What is the most commonly prescribed antidepressant?

A 2021 research review reported that Zoloft (sertraline) is the most commonly prescribed antidepressant in recent years.

5 most common types of depression medications

There are several classes of depression medications to choose from. Effectiveness varies from person to person, so there is technically no “best” or “strongest” antidepressant, says Peter Zafirides, MD, a board-certified psychiatrist and founder of Central Ohio Behavioral Medicine in Columbus, Ohio. The right medication is the one that alleviates your symptoms with minimal side effects.

The following are the five most common types of antidepressants in the order they are most often prescribed.

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1. Selective serotonin reuptake inhibitors (SSRIs)

Selective serotonin reuptake inhibitors (SSRIs) are antidepressants that work by increasing brain levels of serotonin, a neurotransmitter—a type of chemical that acts as a messenger by carrying information from nerve cells in the brain to the nerve cells in the body. Serotonin plays a crucial role in mood and functions such as sleep, wound healing, and digestion.

SSRIs are the most common depression medication for depressive disorders, such as major depressive disorder (MDD), generalized anxiety disorder (GAD), bipolar disorder, and panic disorder, says Erika Gray, Pharm.D., chief medical officer and co-founder of Toolbox Genomics. Medications in this drug class include:

SSRIs are commonly used for mental health conditions due to their ease of use, efficacy, and limited side effect profile, says Dr. Zafirides. After starting treatment, the medications begin to work within two weeks but often take six to eight weeks to reach the full effect. 

2. Serotonin and norepinephrine reuptake inhibitors (SNRIs)

Serotonin and norepinephrine reuptake inhibitors (SNRIs) are a class of medications that are FDA approved to treat major depression. Some are also approved for anxiety disorders or fibromyalgia. These include: 

SNRIs impact the neurotransmitters norepinephrine, serotonin, and dopamine—chemicals that help regulate mood and affect the reward system, says Wendi D. Jones, Pharm.D., a pharmacist with AspenRx Health based in Washington, North Carolina. They work by increasing levels of dopamine in the brain and blocking the reabsorption of serotonin and norepinephrine, which then reduces depression symptoms.

Along with SSRIs, SNRIs are the most commonly prescribed antidepressants among other drug classes because they cause fewer side effects, cost less, and are effective for anxiety disorders, according to Dr. Gray. SNRI may be prescribed to patients who don’t tolerate SSRIs due to side effects like sexual problems and weight gain, Dr. Zafirides adds. Cymbalta, in particular, is considered a first-line treatment in patients who have depression and chronic neuropathic pain, says Dr. Gray. 

It can take six to eight weeks before SNRIs work to treat symptoms of depression.


3. Atypical antidepressants

Atypical antidepressants don’t fit into other antidepressant classes, and the mechanism of action for each drug is slightly different, says Dr. Jones. Wellbutrin, the most common one, works by increasing levels of norepinephrine and dopamine, she explains. 

Atypical antidepressants do have a critical thing in common—they work by impacting levels of one or more of the neurotransmitters dopamine, serotonin, or norepinephrine. 

Common atypical antidepressants include:

These antidepressants can take several weeks to work.

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4. Tricyclic antidepressants (TCAs)

Tricyclic antidepressants (TCAs) are a class of medications that are FDA approved to treat MDD. Because they were among the first antidepressants created, TCAs are considered “first-generation antidepressants.” They work by increasing brain levels of norepinephrine and serotonin to improve mood. Prescriptions in this category include:

In general, these medications are rarely used as a first-line treatment for depression because “second-generation” antidepressants like SSRIs have fewer side effects and are more effective. However, the tricyclic antidepressant clomipramine is considered the gold-standard treatment for obsessive-compulsive disorder (OCD). Tricyclic antidepressants typically begin to work in two to four weeks. One other drawback of tricyclics is that, if taken in excess, overdoses can be fatal. 

5. Monoamine oxidase inhibitors (MAOIs)

FDA approved to treat symptoms of depression, monoamine oxidase inhibitors (MAOIs) were the first class of antidepressants invented. Monoamine oxidase is an enzyme that clears the neurotransmitters norepinephrine, serotonin, and dopamine from the brain. MAOIs stop this process, making the chemicals available longer. They include:

According to Dr. Jones, MAOIs are rarely used today and are considered a last-line treatment for depressive disorders because other drugs are more effective and have fewer adverse effects. MAOIs such as selegiline are also used to treat Parkinson’s disease—by increasing dopamine in the brain, movement symptoms improve. 

MAOIs take about two to three weeks to take effect. 

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How does a healthcare provider choose the best antidepressant for you?

Healthcare providers consider several factors when prescribing an antidepressant. “One of the most important is if an individual has had previous response to an antidepressant,” Dr. Zafirides says. Other considerations include:

  • Does the patient have a first-degree relative who responded well to a particular antidepressant?
  • What are the risks of side effects?
  • What are the symptoms being treated?
  • What other medications is the patient taking? This is important for potential drug interactions.
  • Does the patient have other health conditions?
  • Is the individual pregnant or breastfeeding?

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Which antidepressant works the fastest?

In general, it is not unusual for people to start noticing an improvement in their mood within a couple of weeks, with maximum effect typically occurring between four to six weeks, says Dr. Zafirides. Often, the patient’s loved ones will notice positive changes in the patient’s mood before they do. 

He adds that you should see a quicker response from medications like Trintellix and Lexapro when starting at a therapeutic dose (the amount needed to treat a condition effectively). Other medicines require one to two dosage adjustments, so they take longer to achieve their full therapeutic effects. 

Which antidepressant is the hardest to come off of?

Never stop your antidepressant medications without speaking with your healthcare provider. Suddenly stopping an antidepressant can cause withdrawal symptoms, known as antidepressant discontinuation syndrome (ADS). Possible side effects of antidepressant withdrawal include dizziness, nausea, insomnia, fatigue, mood changes, and achiness. 

ADS can happen after abruptly stopping a medication you’ve taken for six weeks or more. Although it’s not dangerous, it can be uncomfortable—and symptoms of anxiety or depression may return. Because of that, you should work with your provider to taper the medication (slowly lower the doses) to minimize symptoms.

An antidepressant medication’s half-life (the time it takes for half of the drug’s active substance to leave the body) is an important indicator of whether or not you’re likely to experience withdrawal side effects. “For example, medications with a shorter half-life, like Paxil (paroxetine) and Effexor (venlafaxine), have a higher risk of withdrawal symptoms,” says Dr. Zafarides. MAOIs and tricyclic antidepressants also carry a high risk of withdrawal symptoms.

The bottom line: Antidepressants are one part of a treatment plan 

In treating depression, SSRIs are the most commonly prescribed class of drug—but Dr. Zacharides says that medication is one piece of the puzzle. “It’s crucial to pair it with therapy (such as psychotherapy or talk therapy), self-care, exercise, and a healthy routine. Mindfulness, yoga, or relaxation techniques can complement medication and improve overall well-being,” he says. 

Dr. Gray recommends the following lifestyle changes to complement antidepressant therapy:

  • Practice good sleep habits. Aim for seven to nine hours each night and wake up at the same time each day. 
  • Avoid alcohol or substance misuse. 
  • Stop smoking. Cigarettes and tobacco products are linked to depression and anxiety symptoms. 
  • Eat a healthy diet rich in fruits, vegetables, whole grains, fish, olive oil, antioxidants, and protein. Limit ultra-processed foods, refined grains, sugar, and high-fat dairy products.
  • Exercise. Engage in at least 150 minutes of moderate or 75 minutes of vigorous activity per week. 

If you feel that your antidepressant isn’t working as well as it should, speak with your provider about the best way to manage your mental health symptoms. If you experience severe depression or serious adverse effects, such as suicidal thoughts or mania, seek emergency medical attention. The Suicide and Crisis Lifeline is available 24/7 by dialing 988.

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