Depression Medications: A Complete Guide

If you have clinical depression, the right medication can help to relieve your symptoms, stabilize your mood and improve your quality of life. 

Not all people experience depression the same way. Depression can vary hugely in severity and type, from mild depression that comes and goes to severe, persistent depression that requires a more thorough treatment approach.

Because of this, there’s no “best” depression medication for everyone. For a variety of complex reasons, people with depression often respond better to some medications than to others. 

If you’re depressed and need treatment, it’s important to understand your options and discuss them with your healthcare provider.

Below, we’ve listed many common medications that are currently used to treat depression, with information on how each type of treatment works to improve symptoms. 

Medications for Depression: An Overview

Medications used to treat depression are known as antidepressants. They’re some of the most widely used medications in the world.

According to the American Psychological Association, in 2017 as many as 12.7 percent of people aged 12 and over in the United States used antidepressants.

Most antidepressants are thought to work by adjusting the quantity of certain chemicals in the brain and body called neurotransmitters. These chemicals are responsible for regulating a variety of biological functions in the body, including your mood.  

Antidepressant medications have been used since the 1950s. Over the years, researchers have developed a range of newer antidepressants that are more effective at improving depression symptoms and less likely to produce side effects. 

Today, most of the medications prescribed to treat depression belong to a class of drugs called selective serotonin reuptake inhibitors (SSRIs). Other common types of depression medications include: 

• serotonin and norepinephrine reuptake inhibitors (SNRIs)

• tricyclic antidepressants (TCAs)

• monoamine oxidase inhibitors (MAOIs)

• tetracyclic antidepressants (TeCAs)

• dopamine reuptake inhibitors (DRIs)

Although this list can look confusing, the way in which most antidepressants work in the body is relatively easy to understand.

Below, we’ve explained how these antidepressants work. We’ve also listed some of the most common medications within each class of depression treatments. 

Selective Serotonin Reuptake Inhibitors (SSRIs)

Selective serotonin reuptake inhibitors, or SSRIs, are the most common type of antidepressants prescribed in the United States.

SSRIs are used to treat a large range of psychiatric disorders. As well as being widely used as a treatment for depression, SSRIs are prescribed to treat panic disorders, posttraumatic stress disorder (PTSD), social anxiety disorder (SAD) and obsessive-compulsive disorder (OCD).

Certain SSRIs are also prescribed to treat conditions such as premenstrual dysphoric disorder and anorexia. 

If you’ve looked into depression medication before, you’ve probably already heard of some of the most common SSRIs.

Medications like Prozac® (fluoxetine), Zoloft® (sertraline), Paxil® (paroxetine) and Lexapro® (escitalopram) all belong to this class of medications. 

SSRIs were first approved in the 1980s. Compared to older antidepressants, most SSRIs are safer, easier to use and less likely to cause unpleasant side effects. This improved safety and convenience has made them most healthcare professionals’ first choice for treating depression. 

How SSRIs Work

SSRIs work by increasing the amount of serotonin in the brain. Serotonin is a neurotransmitter that’s responsible for a range of functions within the body. Experts believe that these functions include regulating mood, memory, social behavior, sleep and sexual desire, among others.

Low levels of serotonin are associated with mood disorders such as depression and anxiety. By blocking the reabsorption of serotonin by the brain, SSRIs can increase the amount of serotonin that’s active in your body at any time, helping to improve mood and treat depression. 

Fluoxetine (Prozac)

Fluoxetine, the active ingredient in Prozac, was the first SSRI to come onto the US market. Today, it’s one of the widely used prescription medications in the country.

Fluoxetine is usually prescribed to treat depression. However, it’s also used to treat obsessive compulsive disorder (OCD), panic disorder and eating disorders such as bulimia.

The starting dose of fluoxetine for depression is 20mg, taken daily. If you’ve been diagnosed with depression and have been prescribed fluoxetine, your healthcare provider may suggest a dosage of 20 to 60 mg depending on your symptoms, age and overall health. 

When prescribed for depression, studies show that for people who respond to it, fluoxetine usually takes four to six weeks to start working.

Like other SSRIs, it can cause a range of side effects. Many of these side effects are common during the first few weeks of treatment but often resolve on their own over time. 

Our guide to fluoxetine (Prozac) goes into more detail on how fluoxetine works, its side effects and more. 

Sertraline (Zoloft)

Sertraline, the active ingredient in Zoloft, is another widely used SSRI. First approved in 1991, it’s the most common SSRI currently on the market, with tens of millions of prescriptions in the United States alone. 

Like other SSRIs, sertraline is prescribed to treat depression and a range of other conditions, such as obsessive compulsive disorder (OCD), panic disorder, posttraumatic stress disorder (PTSD), social anxiety disorder (SAD) and premenstrual dysphoric disorder (PMDD).

Sertraline is approved for daily use at a dosage of 25mg to 200 mg per day. As with other SSRIs, your healthcare provider may prescribe sertraline at a relatively low starting dosage and adjust it over time based on your symptoms. 

As a treatment for depression, sertraline can take from six to eight weeks or longer to work. It may cause a range of side effects, many of which are temporary and likely to disappear over several weeks of treatment.

Our guide to sertraline (Zoloft) explains how sertraline works, its side effects and other useful information about this medication in more detail. 

Escitalopram (Lexapro)

Escitalopram, the active ingredient in Lexapro, is a common SSRI that’s used to treat depression and generalized anxiety disorder (GAD).

Like fluoxetine and sertraline, escitalopram is a widely used prescription medication, also garnering millions of prescriptions in the United States. 

Studies, such as this 2018 review, have noted that escitalopram is one of the most effective and tolerable antidepressant medications. In addition to depression and GAD, escitalopram is also sometimes prescribed off-label help to relieve some premenstrual syndrome (PMS) symptoms. 

Escitalopram is intended for daily use. It’s typically prescribed at a dosage of 10mg, with a maximum recommended dosage of 20mg. 

Like other SSRIs, it usually takes about six to eight weeks for escitalopram to start working. The side effects of escitalopram are similar to other SSRIs, with many of the medication’s common side effects gradually passing on their own.

Paroxetine (Paxil)

Paroxetine, the active ingredient in Paxil, is another widely used SSRI. Although it’s slightly less commonly prescribed than fluoxetine, sertraline and escitalopram, it’s one of the most common prescription drugs in the United States, with millions of prescriptions written for it in the United States every year.

In addition to depression, paroxetine is prescribed to treat social anxiety disorder, panic disorder, OCD and premenstrual dysphoric disorder. 

Paroxetine may also be prescribed at a low dosage to treat symptoms of menopause, such as hot flashes. 

When used for depression, paroxetine is typically prescribed at a starting dosage of 20mg per day, with a maximum recommended dosage of 50mg. Like other SSRI medications, it’s designed for daily use. 

When prescribed for depression, it may take six to eight weeks for paroxetine to work. As with other SSRIs, paroxetine can cause a range of side effects, some of which can be very severe. One review of the literature suggests that paroxetine may be the least safe of the antidepressants..

Other Selective Serotonin Reuptake Inhibitors (SSRIs)

Several other SSRI medications are also available. Some of these, such as fluvoxamine (Luvox®) and citalopram (Celexa®) are used to treat depression, while others are typically prescribed for a variety of other conditions. Other SSRI medications include:

• Fluvoxamine (commonly sold as Luvox or Faverin®)

• Citalopram (commonly sold as Celexa or Cipramil®)

Serotonin–Norepinephrine Reuptake Inhibitors (SNRIs)

Serotonin–norepinephrine reuptake inhibitors, or SNRIs, are a newer class of antidepressants that were introduced in the 1990s. They work similarly to SSRIs and TCAs to change the levels of certain neurotransmitters responsible for regulating your mood and mental wellbeing.

In addition to treating depression, certain SNRIs are prescribed to treat social anxiety disorder, panic disorder and generalized anxiety disorder. Some SNRIs may also be prescribed to treat chronic pain conditions such as fibromyalgia and neuropathic pain. 

Despite being newer than SSRIs, SNRIs are less widely prescribed. Some of the more common SNRI medications in the United States include Cymbalta® (duloxetine) and Effexor® (venlafaxine).

How SNRIs Work

Like SSRIs, SNRIs inhibit the reuptake of serotonin within your brain, increasing the amount of serotonin that’s active in your body at any one time. 

However, SNRIs also inhibit the reuptake or a neurotransmitter called norepinephrine, which is responsible for promoting and regulating alertness, arousal, focus and memory.

By increasing the amount of serotonin and norepinephrine in the brain, SNRIs may help to improve your mood and treat depression. 

Duloxetine (Cymbalta®)

Duloxetine, the active ingredient in Cymbalta, is an SNRI that’s prescribed to treat depression and generalized anxiety disorder. It’s also used as a treatment for some pain conditions, such as fibromyalgia, diabetic peripheral neuropathy and chronic musculoskeletal pain. 

It is currently one of the most widely used prescription medications in the United States.

Duloxetine comes in tablet form in strengths of 20mg, 30mg and 60mg. For depression, it’s prescribed at a typical starting dose of 40mg to 60mg per day, which may be increased to a maximum of 120mg a day depending on your symptoms.  

When prescribed for depression, duloxetine is quite a fast-acting medication, taking from two to four weeks to work. Most of the side effects of duloxetine are mild and temporary, although like other antidepressants, it can in rare cases cause more severe side effects. 

Venlafaxine (Effexor®)

Venlafaxine, the active ingredient in Effexor, is another common SNRI prescribed to millions of Americans every year.

Venlafaxine is prescribed to treat depression, as well as anxiety disorders such as generalized anxiety disorder, social anxiety disorder and panic disorder. It’s occasionally used off label as a treatment for neuropathic pain and certain menopause symptoms.

As a treatment for depression, venlafaxine typically starts to work in six to eight weeks. It comes in tablet form and is typically prescribed at a starting dose of 75mg, with a maximum safe dose of 225mg. 

However, it is sometimes prescribed at a starting dose of 37.5 for patients who want their bodies to adjust to the medication before increasing to the 75mg starting dose.

Like other SNRIs, venlafaxine can cause a range of common and severe side effects. Some of this medication’s common side effects are mild and temporary. 

Levomilnacipran (Fetzima®)

Levomilnacipran, the active ingredient in Fetzima, is a relatively new SNRI antidepressant that was approved in 2009 by the FDA. It’s currently approved as a treatment for Major Depressive Disorder.

As a relatively new medication, levomilnacipran may not be as commonly prescribed as duloxetine or many older antidepressants.

It’s also currently approved specifically for depression and is not typically prescribed to treat anxiety or chronic pain conditions.

Like other SNRIs, levomilnacipran comes in tablet form and is typically prescribed at a dosage of 40mg to 120mg per day. 

Other SNRIs

Several other SNRIs are also available, both to treat depression and as treatments for chronic pain and other conditions. Other SNRI medications include:

• Desvenlafaxine (commonly sold as Pristiq® and Khedezla®)

• Milnacipran (commonly sold as Savella®)

Others, such as milnacipran, are not approved for use as treatments for depression but may be prescribed off-label for this purpose.

Tricyclic Antidepressants (TCAs)

Tricyclic antidepressants, or TCAs, are an older class of medications used to treat depression and several other conditions. The first TCSs were developed in the 1950s, with many still in use today.

Healthcare professionals often prescribe TCAs  when newer antidepressants, such as SSRIs and SNRIs, aren’t effective. Some tricyclic antidepressants are used specifically for persistent depressive disorder (PDD) and treatment-resistant depression (TRD). 

Certain TCAs are also used to treat anxiety, obsessive-compulsive disorder, insomnia, eating disorders and a diverse variety of other conditions. 

Tricyclic antidepressants are often effective at treating depression. However, they’re also more likely to cause certain side effects than newer SSRI and SNRI medications. These side effects can include drowsiness, blurred vision and fluid retention among others. 

Some tricyclic antidepressants may also contribute to cardiovascular side effects, such as heart arrhythmias and high blood pressure.

To avoid these, your healthcare provider may require that you undergo occasional tests if you’re prescribed this type of antidepressant. 

Tricyclic antidepressants may also be more likely than the newer medications to interact with other prescription medications and alcohol. 

How Tricyclic Antidepressants Work

Tricyclic antidepressants inhibit the neurotransmitters serotonin and norepinephrine from being reabsorbed by the brain’s nerve cells. This increases the level of serotonin and norepinephrine in the brain, helping to improve and better regulate mood in people with depression. 

Certain tricyclic antidepressants may also have antihistamine effects, which can contribute to feelings of drowsiness. For example, doxepin, a tricyclic antidepressant, is also used at a low dose as a prescription sleeping pill. 

Amitriptyline

Amitriptyline is a tricyclic antidepressant. It’s used as a treatment for depression, particularly when other medications aren’t effective. It’s also used to treat certain forms of chronic and neuropathic pain.

Despite being used more commonly as an alternative prescription treatment, it still garners several million prescriptions per year in the US. Today, amitriptyline is a generic drug that isn’t available as a brand name medication. 

Like other tricyclic antidepressants, amitriptyline is more likely to cause certain side effects than newer medications. Amitriptyline is one of the depression medications most commonly linked to weight gain. 

Due to its age and side effect profile, amitriptyline isn’t commonly used as a first-line treatment for depression. However, your healthcare provider may prescribe this medication if you don’t experience any improvements from newer depression medications, such as SSRIs or SNRIs. 

Doxepin

Doxepin is another tricyclic antidepressant. It’s used to treat depression, anxiety disorders and, in topical form, skin conditions such as hives and atopic dermatitis. It’s also used at a low dose as a sleeping pill to treat acute and chronic insomnia.

Like other tricyclic antidepressants, doxepin is an older medication that was first approved  in the 1960s. Although it’s rarely used as a first-line treatment for depression today, it may be used if you have depression that isn’t responsive to newer treatments.

Other Tricyclic Antidepressants

Numerous other tricyclic antidepressants are still available and in use today. Due to their risk of side effects, many of these medications are only used as depression treatments if other, newer medications are ineffective. Other tricyclic antidepressants include:

• Amoxapine

• Clomipramine 

• Desipramine

• Imipramine

• Nortriptyline

• Protriptyline 

• Trimipramine 

Monoamine Oxidase Inhibitors (MAOIs)

Monoamine oxidase inhibitors, or MAOIs, are another older class of antidepressants. The first MAOIs were developed in the 1950s. MAOIs were widely used to treat depression throughout the 1950s, 60s and 70s. 

In addition to depression, some MAOI medications are also prescribed to treat social anxiety disorder, panic disorder, agoraphobia, posttraumatic stress disorder and Parkinson’s disease. 

Although MAOIs are effective at treating depression, they’re less likely to be prescribed today than newer antidepressants due to their risk of causing side effects and interactions. In some cases, these side effects and interactions can be severe and life-threatening.

Because of their side effect profile and interaction risk, MAOIs have largely been replaced by newer antidepressants. However, your healthcare provider may still prescribe an MAOI if other depression medications aren’t effective. 

How MAOIs Work

MAOIs work by inhibiting the effects of monoamine oxidase, an enzyme that’s produced by the body to break down the neurotransmitters serotonin, norepinephrine and dopamine. 

By inhibiting the effects of monoamine oxidase, MAOI antidepressants can increase the levels of serotonin, norepinephrine and dopamine in the brain. 

In addition to its role in regulating levels of these neurotransmitters, monoamine oxidase also breaks down tyramine, a chemical that regulates blood pressure. 

This is where one of the potential dangers of MAOIs comes from. If you’re prescribed a MAOI and eat a food that’s high in tyramine — such as certain cheeses, cured meats or sauces — it’s possible for your body’s tyramine levels to increase rapidly, significantly raising your blood pressure. 

If you’re prescribed a MAOI, make sure that your healthcare provider gives you a list of medications and high tyramine foods to avoid. 

List of Monoamine Oxidase Inhibitors (MAOIs)

There are more than 20 different MAOI medications, including numerous older medications that are no longer prescribed. MAOIs approved by the FDA to treat depression include:

• Isocarboxazid (Marplan®)

• Phenelzine (Nardil®)

• Selegiline (Emsam®)

• Tranylcypromine (Parnate®)

Tetracyclic Antidepressants (TeCAs)

Tetracyclic antidepressants, or TeCAs, are another older class of antidepressants. Introduced in the 1970s, tetracyclic antidepressants are similar to tricyclic antidepressants. 

Like tricyclic antidepressants, tetracyclic antidepressants were widely prescribed throughout the 20th century. Although they’re less commonly prescribed today, they’re still occasionally used to treat cases of depression that don’t respond to other treatments.

Of the tetracyclic antidepressants, mirtazapine (Remeron®) is by far the most widely used. 

Certain tetracyclic antidepressants may also be used to treat anxiety disorders, panic disorder, posttraumatic stress disorder, obsessive-compulsive disorder, schizophrenia and insomnia. 

How Tetracyclic Antidepressants (TeCAs) Work

Tetracyclic antidepressants work similarly to tricyclic antidepressants, by inhibiting the reuptake of the neurotransmitters serotonin and noradrenaline. By elevating serotonin and noradrenaline levels in the brain, TeCAs can improve mood and treat depression or anxiety. 

List of Tetracyclic Antidepressants (TeCAs)

Most tetracyclic antidepressants are prescribed to treat depression. However, some are used almost exclusively to treat non-depression conditions. Tetracyclic antidepressants approved by the FDA to treat depression includeMaprotiline (Ludiomil®)

Dopamine Reuptake Inhibitors and Norepinephrine–Dopamine Reuptake Inhibitor (DRIs and NDRIs)

Dopamine reuptake inhibitors, or DRIs, are a class of medications that work by increasing the amount of dopamine, a neurotransmitter responsible for regulating reward, attention, memory and motivation, in the brain. 

DRIs are used to treat a variety of conditions, including attention-deficit hyperactivity disorder (ADHD), narcolepsy, lethargy and as smoking cessation treatments. Some DRIs may also be used to treat depression. 

Norepinephrine–dopamine reuptake inhibitor, or NDRIs, inhibit the reuptake of norepinephrine as well as dopamine, increasing levels of both of these neurotransmitters in the brain.  

Some NDRIs, such as are prescribed to treat depression and as drugs for quitting smoking. 

Other Depression Medications

In addition to the medications listed above, some other medications may be prescribed alone or in combination with other drugs to treat depression. 

These include 5-HT receptor antagonists, atypical antidepressants and even natural treatments for depression. Often, these medications are prescribed as add-on treatments to be used with a conventional antidepressant. 

In Conclusion

A diverse range of medications are available to treat depression. Depending on your symptoms, use of other medications and general health, your healthcare provider may prescribe a common medication such as an SSRI or SNRI, or recommend a different type of antidepressant. 

If you’re prescribed any type of medication for depression, it’s important that you closely follow your healthcare provider’s instructions. If you have any questions about your medication, talk to your healthcare provider before making any changes to your routine.