What is the Best Medication for Depression?

Summary: The best medication for depression is the one that works for you. You learn which is best for you through a collaborative process with your mental health treatment providers, including your psychiatrist, psychotherapist, and/or counselor.

Key Points:

• Medication for depression – called antidepressant medication or antidepressants – is a standard, first-line treatment for major depressive disorder (MDD).
• In most cases, medication is part of a comprehensive, holistic approach to treatment, which includes medication, psychotherapy, lifestyle changes, and various types of complementary support.
• Factors unique to you – identified in a complete biopsychosocial evaluation – determine the best medication for depression for your specific needs.

Depression and Medication for Depression: You Are Not Alone

When you receive a diagnosis for major depressive disorder (MDD) and research the best medication for depression, you may feel isolated and alone.

That’s okay, and it’s not uncommon.

But you are not alone.

And we have the data to support that statement.

Here are the most recent facts on the prevalence of major depressive disorder (MDD) and use of depression medication among adults in the U.S., published by the Centers for Disease Control (CDC)/National Center for Health Statistics (NCHS):

Prevalence of Depression Diagnosis and Prevalence of Medication for Depression: 2023

Diagnosis of MDD:

• Total: 13.1%
• By gender:
  • Female: 16.0%
  • Male: 10.2%
• By age group:
  • 12-19: 19.2%
  • 20-39: 16.6%
  • 40-59: 10.8%
  • 60+: 8.7%

Use of prescription medication for MDD:

• Total: 11.4%
• By gender:
  • Females: 15.3%
  • Males: 7.4%
• By race/ethnicity:
  • White: 14.3%
  • Black: 7.7%
  • American Indian/Alaska Native: 6.9%
  • Hispanic: 6.7%
  • Asian: 3.4%
• By age group:
  • 18-44: 10.7%
  • 45-64: 12.1%
  • 65-74: 12.4%
  • 75+: 11.3%

We include this data to remind you that millions of people in the U.S. This data tells us that almost 20 million adults in the U.S. have major depressive disorder, and close to 15 million take antidepressant medication.

We hope that helps you make the best choice for you as you navigate your diagnosis of depression. In the rest of this article, we’ll outline the basic process for finding an effective medication for depression for you.

Finding the Best Medication for Depression: How it Works

We’ll start with the good news: antidepressant medication is safe and effective and can help you manage your symptoms and live a full and fulfilling life. In some cases, antidepressant medication, in combination with therapy, lifestyle changes, and various support – peer groups, stress management, mediation, and others – can result in full remission of depressive symptoms.

However, you may need to try more than one type of antidepressant, and more than one dosage, before finding the best medication for you. You may also need to try a second medication to help, amplify, or improve the results of the first, which is called antidepressant combination therapy.

The process for finding the best medication works like this:

• You receive a full psychiatric evaluation, called a biopsychosocial evaluation, and receive a diagnosis for MDD.
• You review treatment options with your provider, which may include antidepressant medication.
• Your provider reviews your evaluation, considers your needs and goals, and makes a recommendation for an antidepressant.

Your provider decides what medication to recommend based on the following seven factors:

1. The details of your diagnosis.

• The best medication for you depends on the specifics of how your depression presents. Presentation – i.e. how it looks/appears in you – includes the following:
  • The primary symptoms you experience. Different people report symptoms in different combinations, with some more dominant than others. For instance, one person may feel intense sadness every day, while another person may feel angry and irritable every day, and another may feel tired every day. Or they may experience some combination of all three, while feeling one more intensely than the others.
  • The severity of your depression. Assessing clinicians will determine whether your depression is mild, moderate, or severe.
  • Any specifiers. Specifiers attached to and MDD diagnosis may include MDD with:
    • Anxious distress
    • Psychotic features
    • Seasonal onset
    • Peripartum onset

2. Your medical history.

• When prescribing the best medication for depression for you, your prescribing psychiatrist will carefully review your medical history to identify any possible impact on your current condition and potential treatment plan.

3. Treatment history.

• Your psychiatric medication and mental health history matter when considering a medication for depression. Your prescribing clinician will review your treatment history for other mental health diagnoses and any related medications. If you’ve tried medication for depression without success, they’ll likely recommend a different medication, or possibly a different dosage of the same medication.

4. Family history with medication for depression.

• If a specific medication worked well for a close relative such as a parent or a sibling, that increases the likelihood – based on shared genetic factors – that it may work well for you, too.

5, Current medical/medication/health status.

• Your provider will review any current diseases, illnesses, or medications that may interact with any medication for depression they may prescribe.

6. Pregnancy/breastfeeding.

• If you’re currently pregnant or breastfeeding, your provider will consider any impact medication for depression may have in utero or during infancy.

7. Side effects.

• Your provider will review the known side effects of each possible medication with you.
• In collaboration with them, you review the risks and benefits of each medication and make an educated decision about what’s best for you.

That’s how the process works. It’s designed to ensure you get the most out of your treatment plan by emphasizing communication and collaboration between provider and patient. To make the best decision, you need the best available information – and all of it – in order to weigh the pros and cons of each medication for you and your life right now.

Next, we’ll review the types of antidepressants and antidepressant medication your treatment provider might recommend.

The Types of Antidepressants in Use Today

Mental health providers think of antidepressants in four general categories:

1. First generation/older antidepressants.

Tricyclic (TC) and monoamine oxidase inhibitors (MAOI) are associated with uncomfortable side effects and are only used in special circumstances today.

2. Second generation antidepressants.

Selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). These are the most commonly prescribed antidepressants. They’re safe, effective, and while they do have side effects, they’re not as uncomfortable/discouraging as those associated with first generation antidepressants.

• Selective serotonin reuptake inhibitors (SSRI). SSRIs prevent the reabsorption of serotonin – a neurotransmitter associated with happiness/positive mood – by brain cells. SSRIs include medications with brand names Zoloft, Prozac, Luvox, Paxil, Lexapro, and Celexa.
• Serotonin-norepinephrine reuptake inhibitors (SNRI). SNRIs prevent the reabsorption of serotonin and norepinephrine by brain cells. While higher levels of serotonin can improve mood, higher levels of norepinephrine can improve energy and motivation. SNRIs include medications with brand names Effexor, Pristiq, Fetzima, Cymbalta, and Savella, among others.

3. Atypical antidepressants.

These antidepressants are similar to first- and second-generation antidepressants, but target a wider range of chemicals in the brain than first- and second-generation antidepressants.

• Atypical antidepressants include medications with brand names Trazadone, Bupropion, and Vortioxetine, among others.

4. New/psychedelic medications.

These medications are derivatives of an anesthetic called ketamine, which increases the amount of glutamate in the brain. This increases and facilitates new connections between brain cells, which can help reduce symptoms of depression. Ketamine and its derivatives are fast-acting, and most often prescribed to people with treatment-resistant depression (TRD). People who try at least two courses of standard antidepressants with unsatisfactory results meet criteria for TRD. Types of psychedelic antidepressant medication include:

• Ketamine increases receptors for neurotransmitters involved with mood and neuroplasticity. Evidence shows these changes can lead to rapid relief of depressive symptoms. Patients receive ketamine either orally or through an intravenous drip (IV) in an outpatient setting, under direct medical supervision/observation.
• Esketamine is a ketamine derivative, and acts on the same brain cells and neurotransmitters as ketamine. While patients receive ketamine orally or intravenously, esketamine is delivered through a nasal powder – in the same manner as a nasal spray for allergies – in an outpatient setting, under direct medical supervision/observation.

Of those antidepressant medication, second-generation antidepressants are the most common. For millions of people, they’re the best medication for depression. Whether they’re the best for you depends on the details of your disorder, your unique needs, and your long-term treatment goals.

What Antidepressants are the Most Commonly Prescribed?

The 5 most commonly prescribed antidepressant medications include:

1. Zoloft
2. Trazadone
3. Prozac
4. Cymbalta
5. Lexapro

There are SSRIs, SNRIs, and atypical antidepressants on that list. If you start an antidepressant and don’t feel the benefits right away, don’t worry. In most cases, these medications take a week or two to begin working, and in some cases, may take as long as two months.

If you wait, and your medication is still not working, then the best thing to do is talk to your provider about changing your dosage, trying a supporting medication to amplify the effect of the first, trying a different medication in the same class, or trying one of the new, faster acting medications for depression such as ketamine or esketamine.

In any case, we encourage you to stay optimistic. Finding the best medication for depression is a process that can go quickly – some patients experience excellent results with their first medication – or can take several months. However, even patients with severe, treatment-resistant depression can find the right combination of medication, therapy, and lifestyle changes that work for them.

There’s hope for everyone and anyone with depression. The sooner you start the treatment process, the sooner you’ll know what works for you. When you find the medication that works for you, you increase your chances of reaching your treatment goals, and living the life you envision for yourself.