Feelings of sadness are common human emotions. When more severe symptoms like lack of energy and hopelessness develop in multiple areas of a person’s life along with persistent sadness over at least two weeks, they may be experiencing a condition known as major depressive disorder (MDD). MDD is sometimes also referred to as clinical depression. Fortunately, with early identification, diagnosis and a treatment plan that can include a combination of medication, psychotherapy and healthy lifestyle choices, many people with depression can and do get better.
Some will only experience one depressive episode in their lifetime, but for most, the episodes recur. Without treatment, episodes may last a few months to several years.
About 15.5% of U.S. adults experience major depressive disorder in a given year. People of all ages and all racial, ethnic and socioeconomic backgrounds experience depression, but it does appear to be more prevalent in some groups than others.
Causes
Depression does not have a single cause. Symptoms can begin to appear following a life crisis, physical illness or something else—but they can also occur for no reason at all. Researchers have identified several factors that can contribute to depression:
Trauma. When people experience trauma at an early age, it can cause changes in how our brains respond to fear and stress. These changes may lead to depression.
Genetics. Mood disorders, such as depression, tend to run in families.
Life circumstances. Changes in relationships, financial status, living situation and loss of loved ones can influence whether someone develops symptoms of depression.
Brain changes. There is still much that we don’t know, but imaging studies have shown that the frontal lobe of the brain becomes less active when a person is depressed. Depression is also associated with changes in how the pituitary gland and hypothalamus respond to hormone stimulation.
Other medical conditions. People who have a history of sleep disturbances, medical illness, chronic pain, anxiety and attention-deficit hyperactivity disorder (ADHD) are more likely to develop depression. Some medical syndromes (like hypothyroidism) can mimic depressive disorder. Some medications can also cause symptoms of depression.
Drug and alcohol misuse. Adults with a substance use disorder are at significantly higher risk for experiencing a major depressive episode. Co-occurring disorders require coordinated treatment for both conditions, as alcohol can worsen depressive symptoms.
Personal Perspectives on Major Depressive Disorder
In this 2-part podcast series, NAMI Chief Medical Officer Dr. Ken Duckworth guides discussions on major depressive disorder that offer insights from individuals, family members and mental health professionals. Read the transcript. Note: Content includes discussions on topics such as suicide attempts and may be triggering.
Reviewed and updated June 2025
A diagnosis of major depressive disorder requires two weeks of depressed mood or loss of interest in daily activities plus at least 5 of these symptoms that cause a decrease in the person’s functioning. The symptoms include:
Changes in sleep
Changes in appetite
Lack of concentration
Loss of energy
Lack of interest in activities
Hopelessness or guilty thoughts
Physical aches and pains or feeling slowed down or agitated
Suicidal thoughts
It can be difficult to recognize these symptoms in ourselves, and many find it helpful to use a screening tool such as the PHQ-9, Patient Health Questionnaire. Many treatment professionals will ask people to complete a PHQ-9 as part of a regular health screening. It can help identify the potential presence and severity of depression. Consider talking with your treatment professional about a screening or look for one online that you can take in your own time.
Reviewed and updated June 2025
Major depressive disorder (MDD) is a common but serious mental health condition. Diagnosis is based on a thorough evaluation by a trained medical or mental health professional—such as a primary care doctor, psychiatrist, psychologist, or licensed therapist. There is no single test, like a blood test or brain scan, that can confirm depression. Instead, diagnosis relies on a careful review of symptoms, medical history, and how daily life is being affected.
Diagnostic Criteria
According to the Diagnostic and Statistical Manual of Mental Disorders (DSM-5-TR), to be diagnosed with MDD, a person must experience at least 5 of the symptoms mentioned above most of the day, nearly every day, for at least two weeks, and one of the symptoms must be either depressed mood or loss of interest or pleasure in most activities. These symptoms must cause significant distress or interfere with everyday life—such as work, school, or relationships—and cannot be explained by another medical condition, medication side effect, or substance use.
The Role of the Medical and Psychiatric Evaluation
Diagnosing depression involves more than just checking symptoms off a list. A healthcare provider will typically:
Ask about mood and behavior changes, and how long they’ve been happening
Explore personal history, including past episodes of depression, family history of mental illness, and life stressors
Consider medical causes, such as thyroid issues, side effects of other medications, substance use, vitamin deficiencies, or hormonal changes that can mimic or worsen depression
Use screening tools like the PHQ-9 (Patient Health Questionnaire) to assess severity
Using Screening Tools to Assess Severity
Screening tools, such as the PHQ-9 or the Beck Depression Inventory, are short questionnaires that ask about a person’s recent experiences with symptoms of depression. These tools help providers not only detect whether someone is likely experiencing depression, but also measure how severe the symptoms are—ranging from mild to moderate to severe. This information helps guide treatment decisions, such as whether therapy, medication, or a combination of approaches is most appropriate. Providers may also repeat the screening over time to track progress and adjust treatment plans as needed.
If the person has experienced manic or hypomanic episodes (periods of extremely elevated mood or energy), the diagnosis may instead be bipolar disorder, which requires a different treatment approach. A family history of bipolar disorder should also inform treatment options.
Importance of Early Diagnosis
Early recognition and diagnosis of depression can make a major difference. It helps people access the support and treatment they need—whether that’s therapy, medication, lifestyle changes, or a combination of these. Without diagnosis and care, depression can persist for months or years and increase the risk of other health problems, including suicide.
Reviewed and updated June 2025
Although major depressive disorder can be a challenging illness, it often responds to treatment. The key is to get a thorough evaluation and treatment plan. Safety planning is important for people who have thoughts of self-harm and/or suicide. After an assessment rules out medical and other possible causes, a person-centered treatment plan can include any one or a combination of the following:
Psychotherapy including cognitive behavioral therapy, family-focused therapy and interpersonal therapy
Medications including antidepressants, mood stabilizers and antipsychotic medications
Exercise can help with prevention and mild-to-moderate symptoms
Brain stimulation therapies can be used if psychotherapy and/or medication are not effective. These include electroconvulsive therapy (ECT) for depressive disorder with psychosis or repetitive transcranial magnetic stimulation (rTMS) for severe depression.
Light therapy, which requires specific kinds of light that can help with the seasonal dimension of depression for some people. These devices are not FDA approved.
Complementary and alternative approaches including acupuncture, meditation, faith and nutrition can be part of a comprehensive treatment plan
Innovative treatments for depression including ketamine and esketamine (Spravato)
Many treatment options are available for depression, but how well treatment works depends on the type of depression, its severity and the person themselves. For most people, a combination of psychotherapy and medication gives better results than either alone, but this is something to review with your mental health care provider.
Psychotherapy
Psychotherapy (or talk therapy) has an excellent track record of helping people with depressive disorder. While some types of psychotherapies have been researched more than others, many can be helpful and effective. A good relationship with a therapist can help improve outcomes.
Many clinicians are trained in more than one kind of psychotherapy, and it’s important to ask your clinician what kind of psychotherapy they practice and how it can help you. A few examples include:
Cognitive behavioral therapy (CBT) has a strong research base to show it helps with symptoms of depression. This structured therapy helps assess and change negative thinking patterns associated with depression. The goal of CBT is to recognize negative thoughts and learn new coping strategies. CBT is often time-limited and the number of sessions may vary from person to person.
Interpersonal therapy (IPT) focuses on improving problems in personal relationships that may be contributing to depressive disorder. Therapists teach individuals to evaluate their interactions and to improve how they relate to others. IPT is often time-limited like CBT.
Psychodynamic therapy is a therapeutic approach rooted in recognizing and understanding problems rooted in past experiences and working to resolve them. Looking at a person’s unconscious processes is another component of this psychotherapy. It can occur in short-term or longer-term sessions.
Psychoeducation and Support Groups
Psychoeducation involves teaching individuals about their illness, how to treat it and how to recognize signs that their symptoms may be coming back or worsening. Family psychoeducation is also helpful for family members who want to understand what their loved one is experiencing.
Support groups, meanwhile, offer participants an opportunity to share experiences and coping strategies. Support groups may be for the person with a mental health condition, for family/friends or both. Mental health professionals lead some support groups, but groups can also be peer-led.
Explore NAMI’s nationwide offerings of free, peer-led educational programs and support groups that provide outstanding education, skills training and support.
Medications
For some people, antidepressant medications may help reduce or manage symptoms. Antidepressants often take 2-4 weeks to begin having an effect and up to 12 weeks to reach full effect. Most people will have to try different doses and/or medications to find what works for them. It’s important to be aware that if there is an underlying bipolar condition, the use of antidepressant medications can initiate a manic episode. Sharing family history with the treating professional is important in identifying this and other potential risks. Here are some antidepressants commonly used to treat depression:
Selective serotonin reuptake inhibitors (SSRIs) act on serotonin, a brain chemical. They are the most common medications prescribed for depression.
Norepinephrine-dopamine reuptake inhibitors (NDRIs) increase dopamine and norepinephrine. Bupropion (Wellbutrin) is a popular NDRI medication, which causes fewer (and different) side effects than other antidepressants. For some people, bupropion causes anxiety symptoms, but for others it is an effective treatment for anxiety.
Tetracyclic antidepressants, like Mirtazapine (Remeron), target serotonin and norepinephrine receptors in the brain, increasing the activity of several brain circuits. Mirtazapine is used less often than newer antidepressants (SSRIs, SNRIs and bupropion) because it is associated with more weight gain, sedation and sleepiness. However, it appears to be less likely to result in insomnia, sexual side effects and nausea than SSRIs and SNRIs.
Second-generation antipsychotics (SGAs), or “atypical antipsychotics,” treat schizophrenia, acute mania, bipolar disorder and bipolar mania and other mental illnesses. SGAs can be used for treatment-resistant depression.
Tricyclic antidepressants (TCAs) are older medications, rarely used today as initial treatment for depression. They work similarly to SNRIs but have more side effects. They are sometimes used when other antidepressants have not worked. TCAs may also ease chronic pain.
Amitriptyline (Elavil)
Desipramine (Norpramin)
Doxepin (Sinequan)
Imipramine (Tofranil)
Nortriptyline (Pamelor, Avantyl)
Protriptyline (Vivactil)
Monoamine oxidase inhibitors(MAOIs) are less used today because of newer medications with fewer side effects. These medications can never be used in combination with SSRIs. MAOIs can sometimes be effective for people who do not respond to other medications. There are also dietary restrictions associated with MAO inhibitors that should be discussed with your treatment professional.
Other medications have been developed in recent years and work differently than those traditionally used to treat depression. Each of the following are approved for use in MDD:
For some, brain stimulation therapies may be effective, typically after other treatments have not been effective.
Electroconvulsive Therapy (ECT) involves transmitting short electrical impulses into the brain. ECT does cause some side effects, including memory loss. Individuals should understand the risks and benefits of this intervention before beginning a treatment trial.
Repetitive Transcranial Magnetic Stimulation (rTMS) is a relatively new type of brain stimulation that uses a magnet instead of an electrical current to activate the brain. It is not effective as a maintenance treatment. rTIMS is FDA approved for treatment-resistant depression.
Vagus Nerve Stimulation (VNS) has a complex history. For a fuller understanding of this treatment, read the NIMH summary of this and other brain stimulation interventions.
Deep Brain Stimulation. This treatment has been used to treat Parkinson’s disease. See the NIMH page on brain stimulation for more information.
Light Therapy
Light therapy involves sitting close to a specialized light box that generates intense artificial light to mimic sunlight. These devices can be helpful for depression with a seasonal dimension. Usually, people use them in the morning. Some devices are covered by insurance even though they are not FDA approved.
As with antidepressants, if you experience manic or hypomanic symptoms (rare with light therapy) this should be immediately discussed with your provider as bipolar disorder requires a different approach.
Complementary and Alternative Medicine (CAM)
Relying solely on CAM methods is not enough to treat depression, but they may be useful when combined with psychotherapy and medication. Discuss your ideas of CAM interventions with your health care professional to be sure they will not cause side effects or adverse reactions.
The National Center for Complementary and Integrative Health reviews research on complementary treatments. You can search for each intervention on their website.
Exercise. Studies show that aerobic exercise can help treat mild depression because it increases endorphins and stimulates norepinephrine, which can improve a person’s mood.
Folate. Some studies have shown that when people with depression lack folate (also called folic acid or vitamin B9), they may not be receiving the full benefit from any antidepressants they may be taking. Studies suggest that in some situations taking L-methylfolate (an active form of folate) can be an additional treatment with other psychiatric medications.
St John’s Wort. This supplement has similar chemical properties to some SSRIs. Risks of combining St John’s Wort with SSRIs and other medications are well-known and substantial.
Innovative Treatments for Depression
In recent years, new types of medications have emerged that offer hope for people whose depression has not improved with traditional treatments like SSRIs or therapy. One of the most promising is ketamine, along with a growing number of similar, fast-acting medications that target the brain in different ways. These treatments can be helpful for people with treatment-resistant depression, meaning they have not responded to at least two other antidepressants as well as those experiencing severe depressive symptoms or suicidal thoughts.
Ketamine and Esketamine (Spravato)
Ketamine is an anesthetic that, at lower doses, has been found to rapidly reduce symptoms of treatment-resistant depression, sometimes within hours. Ketamine is not approved for use in MDD by the FDA.
Esketamine is a nasal spray version of ketamine approved by the FDA for use in adults with treatment-resistant depression. It’s usually given in a clinic under medical supervision, alongside a traditional antidepressant.
These medications are thought to work by targeting the brain’s glutamate system, which is different from most antidepressants that act on serotonin, dopamine, or norepinephrine. There is also some evidence that these medications may promote brain growth and neuroplasticity.
Many patients report not just symptom relief but a shift in perspective that helps them feel more emotionally “unstuck.” These effects are typically shorter term.
Drug Administration
Ketamine is typically administered by intravenous (IV) infusion, while esketamine is given as a nasal spray in a certified treatment center.
Treatment is closely monitored due to the potential for side effects, such as dissociation, dizziness, or elevated blood pressure.
Other Emerging Therapies
Researchers are exploring psychedelic-assisted therapies, such as those using psilocybin (the active compound in “magic mushrooms”), for depression and other mental health conditions.
These treatments are still in clinical trials and not yet widely available, but early results are promising, especially when combined with therapy. They are not FDA approved as of the time of this page’s most recent update.
Reviewed and updated June 2025
Living with depression isn’t just about medical treatment – how you support yourself, a family member or a friend in other ways can also make a big difference.
Helping Yourself
There’s a lot you can do to understand your own symptoms and what you need to feel supported:
Learn all you can. Learn about the many treatment options available. Connect with other people experiencing depression in support groups or meetings. Attend local conferences and conventions. Build a personal library of useful websites and helpful books.
Recognize early symptoms. Identify possible warning signs and triggers that may aggravate your depression symptoms. With this knowledge, you can recognize an emerging episode and get the help you need as soon as possible. Don’t be afraid to ask your friends and family for help — they can help you monitor your symptoms and behavior.
Partner with your health care providers. Give your health care provider all the information they need to help you recover – including any reactions to medications, your symptoms or any triggers you notice. Develop trust and communicate openly. If you don’t feel comfortable with your provider, that’s okay, too. Not all providers will be a good fit for everyone. Consider exploring other options – you might try to find providers that share your cultural background or have worked with people who have similar experiences.
Know what to do in a crisis. Be familiar with your community’s crisis hotline or emergency walk-in center. Know how to contact them and keep the information handy. Wherever you are, you can call or text or chat 988, the national Suicide & Crisis Lifeline, 24 hours a day, 7 days a week for support during a mental health crisis.
Consider sharing your story. When you are ready there can be great power in helping others and yourself when you share your experience. This can be done in a confidential support group or on larger public platform as you see fit.
Find emotional support from others who experience depression. Discuss your thoughts, fears and questions with other people who have the same condition. Connect through online message boards or peer-education programs like NAMI Peer-to-Peer or peer support groups like NAMI Connection.
Avoid drugs and alcohol. Some people use drugs and alcohol to cope with symptoms, but these substances can make symptoms worse and interact with mental health medications.
Get physically healthy. Eat well and exercise. To relieve stress, try activities like meditation, yoga or Tai Chi. Even walking can improve your health and well-being.
Helping a Family Member or Friend
When someone you love experiences symptoms of mental illness, you face unique challenges yourself, including complex family dynamics, social isolation and often unpredictable behavior. Getting support for yourself is essential for you to be helpful to the person you care about.
Learn more about your loved one’s condition. Learning about the condition your loved one experiences will help you better understand and support them. Read personal accounts of lived experience, full of tips and advice on the NAMI Blog:
Recognize early symptoms. Depression often has warning signs, such as a low mood, feeling fatigued or having trouble sleeping. Discuss your friend or family member’s past episodes with them to help them improve their ability to recognize the signs early.
Communicate. Speak honestly and kindly. Don’t scold or blame people with depression or urge them to “try harder” to “just be happy.” Instead, make specific offers to help and follow through. Tell the person you care about them. Ask them how they feel and truly listen.
React calmly and rationally. Even if your family member or friend is in a crisis, it’s important to remain calm. Listen to their concerns and make them feel understood – then take the next step toward getting help.
Find emotional support from others. Share your thoughts, fears and questions with other people who have loved ones with similar conditions. Connect with others through online message boards or NAMI peer-education programs.
Additional Resources
For advice from professionals, advocates, and other NAMI experts related to depression and other mental health topics, view past recordings of NAMI’s Ask the Expert series
For stories from real people about their experiences with mental health, including depression, check out NAMI’s book series: You Are Not Alone: The NAMI Guide to Navigating Mental Health and You Are Not Alone for Parents and Caregivers: The NAMI Guide to Navigating Your Child’s Mental Health.
