Major Depressive Disorder Treatments: Medications and Other Options

Clinical depression, also called major depressive disorder or depression, is one of the most common mental health conditions in the world. When you have depression, it can affect your life in many different ways, including your physical health, your close relationships, and your job. Fortunately, treatment can help.

Let’s take a closer look at the many treatments for major depressive disorder. 

What is major depressive disorder (MDD)?

Depression is a mental health condition where you feel numb, empty, and sad most of the time. It can also make you less interested in your normal activities and take a toll at work, at home, and in your relationships. 

What medications are used for major depressive disorder treatment?

There are many medications that can help with depression. These typically include antidepressant medication, mood stabilizers, and atypical antipsychotics. You and your healthcare professional will work together to find the right medication — or combination of medications — for your unique symptoms. 

Here are some of the options. 

What type of therapy is used for major depressive disorder treatment?

Therapy can be an essential part of treatment for major depression, too — either on its own or together with medication. Sometimes, therapy may help within just a few weeks. Or, it can take longer, depending on your situation. 

There are different types of therapy that can help to treat depression, including:

• Cognitive behavioral therapy (CBT)

• Interpersonal therapy (IPT)

• Psychodynamic psychotherapy

• Supportive therapy

• Mindfulness-based cognitive therapy (MBCT)

When it comes to a therapist, it’s important to find the right fit for you. There are various ways to find a therapist, such as searching online or asking for recommendations. You can do therapy online over video, too. 

In some cases, therapy may include other people. For example, family or couples therapy can often be helpful, especially if depression has affected your relationships. And group therapy can be a great way to connect with other people going through similar experiences. 

What treatments are available for treatment-resistant depression?

Treatment-resistant depression (TRD) is when your depression symptoms don’t go away completely, even after you’ve tried at least two different medications. And it’s pretty common, too. In fact, TRD may happen in as many as 1 in 3 people with depression. 

But having TRD doesn’t mean you’re out of options. It just means you might have to try a different type of treatment to get relief. 

Here are some of the treatments that can help if you have TRD: 

• Switching to a new antidepressant: Changing to a different type of antidepressant can help some people with TRD. 

• Adding on a second or third medication: This could mean adding another antidepressant or an antipsychotic medication. Thyroid hormone and lithium are options for some people, too. 

• Adding on therapy: If medications haven’t worked on their own, adding on therapy can sometimes get results. 

• Trying brain stimulation therapies: These are medical procedures that stimulate your brain. Examples include transcranial magnetic stimulation (TMS) and electroconvulsive therapy (ECT). 

• Using esketamine and ketamine: Esketamine (Spravato) is an FDA-approved nasal spray for treating TRD. Ketamine is a similar medication that’s often used off-label to treat depression, including TRD. 

• Taking olanzapine / fluoxetine (Symbyax): Symbyax is a combination medication made of two medications: olanzapine and fluoxetine. It’s also FDA-approved for treating TRD. 

There are also new treatments that may grow in use over time, such as psilocybin (commonly known as “magic mushrooms”). This is a psychedelic compound that shows some promising benefits in treating depression, including TRD. But, for now, it’s still considered experimental. 

What supplements can help for major depressive disorder?

Some over-the-counter (OTC) supplements may help with depression. These include: 

• St. John’s wort: This is an herb that may be effective for depression. But it has side effects. And it can interfere with other medications you’re taking. It can also be risky to mix with some prescription medications, including certain antidepressants. 

• Omega-3 fatty acids: These are “good fats” that are important for brain health. There’s some evidence that taking omega-3 may help with depression.

• L-methylfolate or folic acid: L-methylfolate is the active form of folic acid, a type of vitamin B. It’s not clear how well folic acid works on its own for depression, but it may be helpful as an add-on to antidepressants. 

So far, there’s not enough evidence that any of these supplements work better than medications and therapy. And, remember, it’s always a good idea to talk with your healthcare team before taking a new supplement. OTC supplements may have side effects or could interact with your other medications. 

What lifestyle changes might help treat major depressive disorder?

There are some important lifestyle changes and daily habits that can help you manage depression symptoms. These include: 

• Exercise: Exercise can help reduce depression symptoms, especially when combined with medication or therapy. Exercise doesn’t have to be complicated. Even simple things can help, like a short walk around the block or playing basketball in your driveway.

• Healthy diet: A nutritious diet full of fruits and vegetables may help with depressive symptoms. It’s especially important to get enough vitamins and minerals, including vitamin B12, folate, and magnesium.

• Sleep: Many people with depression have trouble sleeping. Getting enough good-quality sleep can help your other depression symptoms get better, too. If you need help, your healthcare team can work with you to figure out ways to get better sleep. 

• Mind-body therapies: Mind-body activities — like yoga, tai chi, and meditation — can also be helpful for people with depression. They’re also good for other things that can go hand-in-hand with depression, like pain, stress, and anxiety. 

• Light therapy: Sitting in front of a special bright light box can help with some types of depression, especially seasonal affective disorder.

Can depression be cured?

It’s hard to say. Technically, depression isn’t an illness that can be cured. But, fortunately, many people do fully recover from major depression — especially with treatment. 

When it comes to depression, recovery is different for everyone. It depends on many things, including:

• Your symptoms

• Your family history

• Whether you’ve had an episode of depression before

• Your overall mental and physical health

• Your resources and social support

For some people, depression will go away and never come back. But for other people, symptom episodes will come and go over time. In fact, at least 1 out of every 2 people will have another episode of depression sometime in their life. And the more episodes you have, the more likely it is you’ll have another one in the future. 

Where can you find help for major depressive disorder treatment?

If you think you might have depression, it’s a good idea to talk with your healthcare team. You can start with your primary care provider. They might be able to get you started on medication, or they might provide a referral to a qualified mental health professional. 

If you don’t have a primary care provider, or aren’t sure where to start, ask friends and family for recommendations. If you’re covered by health insurance, you can also use your plan’s healthcare professional directory to look for a specialist in your area.

You can also start your search for mental health professionals online. And the National Alliance on Mental Illness (NAMI) has a helpline you can call at 1-800-950-NAMI (6264).

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Written by:

Christina Palmer, MD

Christina Palmer, MD, is a board-certified family physician with a focus on chronic care management, women’s health, and mental health. She’s the co-author of the book, “Open Heart: When Open-Heart Surgery Becomes Your Best Option”.

Edited by:

Sophie Vergnaud, MD

Sophie Vergnaud, MD, is the Senior Medical Director for GoodRx Health. A pulmonologist and hospitalist, she practiced and taught clinical medicine at hospitals in London for a decade before entering a career in health education and technology.

Reviewed by:

Sarah Gupta, MD

Sarah Gupta, MD, is a licensed physician with a special interest in mental health, sex and gender, eating disorders, and the human microbiome. She is currently board certified by the American Board of Psychiatry and Neurology.

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