Perhaps the most recognizable among them is Prozac (fluoxetine). It’s still the best option for many people, but since it was approved by the Food and Drug Administration (FDA) in 1987, Prozac has been joined by a variety of other antidepressant medications. If you’re considering taking an antidepressant, understanding how the most popular ones work can help you and your healthcare provider decide which might work best for you and when you should take it.

What Is Depression Medication?

Depression medications, also referred to as antidepressants, are prescription medications that help manage depressive symptoms. These symptoms can vary, but include feeling “empty,” increased irritability, having a loss of energy, and a loss of interest in activities that one used to enjoy. In the 1950s, the antihypertensive drug reserpine was found to increase depression in some patients, mainly by depleting their levels of serotonin and catecholamines. This established the connection between some neurotransmitters and depression, also prompting the development of medications that increase these chemical substances.

How Do Antidepressants Work?

There are five major classes of antidepressants, and they all work in different ways:

Selective serotonin reuptake inhibitors (SSRIs)Serotonin and norepinephrine reuptake inhibitors (SNRIs)Tricyclic antidepressants (TCAs)Monoamine oxidase inhibitors (MAOIs)Atypical antidepressants

But the one thing all of these antidepressant medications have in common is that they increase the availability of monoamine neurotransmitters in the brain. In people with depression, the availability of these monoamine neurotransmitters in the brain is characteristically low. Antidepressants work by preventing the reuptake of one or more of these neurotransmitters, thereby increasing their availability.

Types of Depression Medication

Taking a more in-depth look at the top antidepressant medications can increase your understanding of how this mental health condition is treated with the use of prescription drugs. SSRIs, SNRIs, TCAs, MAOIs, and atypical antidepressants are part of this list of common depression medications.

SSRIs

Prozac belongs to a class of antidepressants called selective serotonin reuptake inhibitors (SSRIs). SSRIs do exactly what the name describes: They prevent ​the reuptake of serotonin, making more of the chemical available. In other words, SSRIs relieve depression by boosting low levels of serotonin in the brain. Some of the most commonly prescribed SSRIs include:

Prozac (fluoxetine): Prozac is still one of the most popular SSRIs in the United States. It’s one of the only that the FDA has approved for children and teenagers. The 2017 antidepressant use study found that a little over 11% of respondents reported taking Prozac for depression. Celexa (citalopram): Studies show that Celexa works as well as other SSRIs and has similar side effects. One important thing to know about this antidepressant is that taking high doses of it has been associated with a rare heart rhythm problem. An estimated 14% of antidepressant use study respondents reported that they were taking this medication. Zoloft (sertraline): Zoloft is highly effective, although some people find that it is more likely than other SSRIs to cause diarrhea. Zoloft is the most common depression medication; nearly 17% of those surveyed in the 2017 antidepressant use study reported that they had taken this medication. Paxil (paroxetine): You might be more likely to have sexual side effects if you choose Paxil over other antidepressants. It’s also linked to increased sweating. While paroxetine did not make the list of the 10 most commonly prescribed psychiatric drugs, it remains a good choice for some people. Lexapro (escitalopram): Along with Prozac, Lexapro is one of the only SSRIs approved by the FDA for teens. Around 8% of those surveyed reported that they had taken Lexapro.

Most SSRIs are similar in regard to how well they work, although there may be subtle differences that can make one a better choice for you. It takes a while for SSRIs to build up in the body enough to have an effect on symptoms. Because of this, it can take several weeks or even months of trial and error to find the particular drug and dosage that will do you the most good.

SNRIs

Other common antidepressants belong to a class of drugs called serotonin and norepinephrine reuptake inhibitors (SNRIs). These depression medications inhibit the reuptake of two neurotransmitters: serotonin and norepinephrine. The SNRIs that are available are:

Cymbalta (duloxetine) Effexor (venlafaxine) Fetzima (levomilnacipran) Pristiq (desvenlafaxine) Savella (milnacipran) Strattera (atomoxetine) Ultram (tramadol)

While Strattera is an SNRI, it is used as a non-stimulant medication to treat ADHD, not depression or anxiety. One of the most commonly prescribed SNRIs is Effexor (venlafaxine), which is as effective as other antidepressants in treating depression but does have a higher rate of causing nausea and vomiting, and may increase blood pressure and heart rate. The SNRI Cymbalta (duloxetine) can also increase blood pressure, but the bigger concern with this drug is that, in some people, it can lead to liver failure; so, if you have any sort of liver disease, it could be a dangerous choice for you. The same is true if you drink a lot of alcohol. In the 2017 study on psychiatric drugs, Cymbalta was the most commonly prescribed SNRI drug, with 7% of respondents reporting that they had taken it.

TCAs

Tricyclic antidepressants (TCAs) were among the first antidepressants. While they have been largely replaced by SSRIs, SNRIs, and other antidepressants, TCAs can still be a good option in cases where people have not responded to other types of antidepressant drugs. Types of tricyclics that are available include:

Asendin (amoxapine) Elavil (amitriptyline) Norpramin (desipramine) Pamelor (nortriptyline) Silenor (doxepin) Surmontil (trimipramine) Tofranil (imipramine) Vivactil (protriptyline)

Tricyclics work by blocking the absorption of serotonin and norepinephrine. By preventing the reuptake of those neurotransmitters, it increases serotonin and norepinephrine levels in the brain, which can help to improve mood and relieve depression.  No TCA medication made the top 10 list of the most commonly prescribed psychiatric drugs.

MAOIs

Monoamine oxidase inhibitors (MAOIs) were the first type of medication developed to treat depression. They have been largely replaced by newer antidepressants that are safer and have fewer side effects, but there are still several MAOIs available. Some of the most commonly prescribed MAOIs include:

Emsam (selegiline)Marplan (isocarboxazid)Nardil (phenelzine)Parnate (tranylcypromine)

MAOIs work by inhibiting monoamine oxidase, an enzyme that breaks down serotonin, dopamine, and norepinephrine, which are all neurotransmitters that control mood. This results in higher levels of these chemicals in the brain which helps improve mood and reduce anxiety. MAOIs are rarely prescribed given the significant risk associated with eating certain foods containing tyramine, which can cause a hypertensive crisis.

Atypical Antidepressants

Atypical antidepressants are those that don’t fit into any of the other classes. Doctors often prescribe them if other antidepressants either don’t work or cause unbearable side effects. Common atypical antidepressants include:

Desyrel (trazodone) Wellbutrin (bupropion) Remeron (mirtazapine) Trintellix (vortioxetine)

Each of these atypical antidepressants influences different neurotransmitters in different ways. Some target dopamine, for example, while others serotonin or norepinephrine. Still others target a combination of the three. As a result, they have different side effects compared to other antidepressants. For example, compared to other antidepressants, Desyrel is less likely to cause symptoms such as sexual dysfunction, insomnia, or anxiety. Of the atypical antidepressants, Wellbutrin is one of the most commonly prescribed. It works by acting on the neurotransmitter dopamine affecting energy levels, motivation, and attention. It has a lower risk of sexual and gastrointestinal side effects. In fact, some doctors prescribe Wellbutrin along with another SSRI to help counter low libido.

Effectiveness of Depression Medication

In a study involving 180 people using antidepressants long-term, 89.4% indicated that medication improved their depression. Additionally, 53.9% of the subjects said that their quality of life had “greatly improved” while taking antidepressants. The medications taken in this study included citalopram, venlafaxine, paroxetine, fluoxetine, loxamine, and nortriptyline. Another piece of research looked at 522 different trials and found that “all antidepressants were more effective than placebo” for individuals with major depressive disorder (MDD). Also known as clinical depression, MDD involves having at least five depressive symptoms every day for at least two weeks, among other diagnostic criteria.

Uses for Depression Medication

Depression medications are used to help reduce depression symptoms. While these symptoms can vary from one person to another, they may include:

Change in appetite Feeling low or “empty” Irritability or anxiousness Lack of energy Physical aches and pain Reduced interest in activities Sleep issues Thoughts of suicide Trouble concentrating

Taking Depression Medication

There is no one-size-fits-all depression medication. Your healthcare provider can help find the best medication for you, along with finding the proper dosage. Finding the best antidepressant for you depends on a variety of factors, such as: For more mental health resources, see our National Helpline Database.

How well you tolerate the antidepressant (your side effects)Potential drug interactions (if you’re taking other medicines or supplements)The medication’s effectiveness (whether it works for you)Your depression types and symptoms (how depression appears for you)

It generally takes four to eight weeks for these medicines to work, though you may notice positive changes related to sleeping and eating, for instance, before seeing improvements in your mood. While many people take antidepressants for six to 12 months, your length of use may be longer. When taking antidepressants, avoiding drugs and alcohol is important. Your provider may also suggest that you engage in psychotherapy along with taking medications to provide a greater treatment effect. Never stop the use of antidepressant medications without consulting with your healthcare provider as this can cause a relapse in your symptoms. Also, talk with your provider if you’re having trouble with your medicine’s side effects. Lowering the dosage or switching medicines may help ease these effects.

Common Side Effects of Antidepressants

Antidepressants can improve the symptoms of depression, but, like all medications, they can also cause side effects. The frequency and severity of these side effects vary depending on the class of medication you’re taking. Common side effects of antidepressants include:

ConstipationDrowsinessNauseaSexual dysfunctionSleep disturbancesWeight gain

Antidepressants may also increase the risk of suicidal thinking and behavior (suicidality), especially during the first few months of treatment, or when your dose is increased or decreased. Teens and young adults are especially at risk and should be monitored closely. Side effects tend to be mild and go away as your body adjusts to the medication. If your side effects are severe or last for longer than a few weeks, your prescribing doctor may adjust your dosage or recommend a different antidepressant. If and when you and a doctor decide to stop your medication, it’s important to wean off most antidepressants slowly. If you suddenly stop taking an antidepressant medication, you can experience withdrawal symptoms, such as mood swings, dizziness, flu-like symptoms, and headaches.

Natural Depression Treatment Options

Prescription medications aren’t the only options for treating depression. Some researchers also suggest that there are a few natural products that can be helpful for reducing depressive symptoms. According to a 2022 article published in Evidence-Based Complementary and Alternative Medicine, natural depression treatment options may include:

Tetragonia tetragonioides, also known as New Zealand spinach Supplemental mixtures that include various Chinese or Korean herbs and plants, such as Xiao Yao San, Chaihu-Shugan-San, and So-Ochim-Tang-Gamibang Traditional Chinese medicines, like acupuncture

Other studies report that, for some people, St. John’s wort is as effective as SSRIs for treating depression. Positive results have also been found for omega-3 fatty acids, vitamin D, S-adenosylmethionine (SAMe), and methylfolate. Ng QX, Venkatanarayanan N, Ho CYX. Clinical use of Hypericum perforatum (St John’s wort) in depression: A meta-analysis. J Affect Disord. 2017;210:211-21. doi:10.1016/j.jad.2016.12.048