Symptoms and Approaches to Major Depression
- Nov 11, 2024
- 14 min read
Updated: Mar 21
Major/Clinical Depression
So, here you are. How did you get to this point?
Once in a while, sadness leads you to this place where your emotions take over reasoning. Other times, when it is not caused by a particular trigger or obvious situation, you look around and realize you have no idea feeling this way at all.
It can be a very tough journey, and time, support, and sometimes the self‑help approaches can help ease the pain. But when sadness becomes severe, incapacitating, or long‑lasting, we’re no longer talking about ordinary sadness — we’re talking about major depression.
The following discusses major depression — the signs, symptoms, and treatment options (also included on the resource page, depression overview). It also includes a brief mention of persistent depressive disorder (PDD), or dysthymia, a long‑lasting, lower‑grade form of depression that lacks some of the more severe symptoms seen in major depression.
Symptoms and Approaches to Major Depression
Symptoms of Major Depression
In most cases, major depression is not caused by a single incident. The length and disabling nature of these symptoms are key in diagnosing major depression. UpToDate cites the DSM‑5 criteria for this diagnosis: a person must have five or more of the following symptoms most of the day or nearly every day for at least two weeks. One of the symptoms MUST be either a depressed mood or a loss of interest or pleasure. The remaining symptoms may include:
Persistently low or depressed mood
Decreased interest in usually pleasurable activities (anhedonia),
Feelings of guilt or worthlessness.
Poor concentration.
Appetite and weight changes,
Psychomotor retardation (like sluggish speech, OR agitation (restlessness, agitation),
Poor concentration
Sleep disturbances (too little or too much),
Suicidal thoughts or thoughts of death (need help suicide prevention hotline (1-800-273-TALK ).
Lack of energy/fatigue almost every day
Sad, anxious, or empty mood, hopeless feelings
In addition to the five or more depressive symptoms above, according to the DSM 5, major depression must be accompanied by impaired social or work activities, not due to substance or medical problems, and cannot be accompanied by other serious mental health problems like schizophrenia, psychotic symptoms, or manic behaviors.
Major depression can also occur alongside other mental health issues. Very often, it appears with anxiety — which makes sense: debilitating depression can make a person anxious, and anxiety can intensify depression. Pain may also accompany depression, whether physical or emotional. Depression can be intensified by coexisting social, psychological, and/or medical problems, some of which are discussed in other sections.
Major depression likes to take over rational thought. It hijacks your brain by taking over normal neurotransmitter actions, subsequently causing changes in the gray matter of your brain.
Without treatment, major depression can usually last for several weeks, sometimes months (usually six months), and even years. According to the NIH, “the recurrence rate is about 50% after the first episode, 70% after the second episode, and 90% after the third”.
The PHQ-9 The PHQ‑9 is a simple depression rating scale used by many mental health professionals to assess the severity of a person’s symptoms and to track improvement during treatment. Below is a general interpretation of PHQ‑9 score ranges:
0–4: Minimal symptoms (may not require treatment; monitor how you’re feeling)
5–9: Mild depression (symptoms are manageable; consider self‑care or preventive strategies)
10–14: Moderate depression (symptoms are noticeable and may interfere with daily life; professional support is recommended)
15–19: Moderately severe depression (significant symptoms affecting daily functioning; seek professional help)
20–27: Severe depression (intense symptoms that severely impact daily functioning; immediate professional support is important)
You can use this screening tool to get a sense of what level of support you may need, but it should not be used to diagnose yourself. Many factors can influence mood, and a trained mental health professional can help determine what’s really going on and what next steps make sense.
It’s also important to trust your feelings and not wait for symptoms to worsen. If you’re experiencing distress or noticing that your symptoms are affecting your daily life, that’s a sign to reach out for support. Reaching out early—before symptoms deepen or begin to take over your daily life—can help prevent things from getting worse. The PHQ‑9 can help you get a sense of how severe your symptoms may be, but it is not meant to replace a conversation with a healthcare provider. When in doubt, it’s always best to talk with a mental health professional who can help you sort through what you’re experiencing and guide you toward the right next steps.
If you’re ever unsure about your safety or your symptoms feel overwhelming, contact a trusted friend or relative, local emergency services or call 9-8-8 - a national mental health and suicide hotline. Getting help early can make a real difference.
General Approaches to Major Depression
General Approaches to Major Depression
Reduce stress - Very often, there is a strong association between stress and depression.
Exercise, walking - Studies show that exercise can help relieve depression.
Meditation and relaxation exercises:
-Deep breathing exercises - This helps release endorphins in your brain, which are "feel-good" hormones. It also helps reduce cortisol levels, which, when high, can decrease coping. Deep breathing techniques are practiced by taking a deep breath through your mouth using your diaphragm muscle located just beneath your lower ribs (instead of using neck, shoulder, and upper chest muscles), pausing, and then releasing the breath through the mouth. Repeat this several times.
-Guided Imagery - Think of a relaxing situation or a place you have been and focus on only that - focusing on texture, smells, and visuals.
-Use Mindfulness - This is when a person focuses on the present moment, feeling and experiencing the moment with awareness and acceptance, not judgment. This reportedly helps the fronto-limbic area of the brain, which is responsible, in great part, for emotional regulation and processing.
-Progressive Muscle Relaxation Exercises: This is done by tightening muscle groups for eight seconds, then relaxing them for several seconds: Begin with facial muscles, with the face, moving to the scalp - tighten muscles for eight seconds, then relax; then the neck, doing with each muscle group of the chest, back, pelvis, extremities, and so on. This releases some tension and stress. If you do not have time to move through all of your muscle groups, do this with those muscles you believe have the most tension.
-Analytical Meditation - This meditation involves focusing on an object or a concept and focusing on only that.
-Body Scanning - Focus on a part of your body and feel relaxation, warmth, and release of tension.
-Reiki is a practice whereby a person connects with a universal positive energy. There are quite a few online sources with free instructions; additionally, many instructors also teach these methods in person.
Journaling: Write your thoughts in a journal
Talk to someone about your problem - friends, family: Don't worry, people who care about you are commonly concerned and want to help.
Practice affirmations - saying good things about yourself
Set realistic goals and work toward them: Start with small, achievable goals.
Listen to good music.
According to studies, Aromatherapy (especially with massage) can be an adjunct in the treatment of depression.
Recognize and celebrate even small successes.
Humor therapy - laugh or make yourself smile (usually used as an adjunct to other therapies).
Light therapy - May help seasonal and non-seasonal depression in conjunction with serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs).
For some people, spirituality can contribute to a deeper sense of control, purpose, hope, optimism, peace, and connection; potentially improving overall health and well-being.
Massage - Studies show that massage has been shown to help with anxiety and depression.
Counseling and Other Therapies for Depression
Counseling often helps: Sometimes just being able to talk to someone can help more than you know. The best therapies all have one common bond: establishing a trusting relationship. If a counselor is good, they can work with you on different ways to cope and provide therapy that will suit your needs. Some of the more popular of these are mentioned below.
Cognitive Behavioral Therapy (CBT) - This is currently considered one of the best — if not the best — forms of therapy. There are several subtypes of CBT, but they all share the same core goal: helping people recognize and challenge the dysfunctional thought patterns that contribute to depression.
CBT is one way people can intentionally promote neuroplasticity, the brain’s ability to change and adapt. Through this kind of therapy, neurons can be encouraged to send impulses down new, healthier pathways instead of relying on old, negative ones. The brain forms new neural connections (or strengthens existing positive ones) through purposeful learning, repetition, and practicing more constructive thought patterns and positive experiences. Essentially, it’s a form of “rewiring.”
This means you can train your brain to think differently and more positively — and that makes sense when you understand how adaptable the brain truly is.
Types of Cognitive Behavior Therapy
-Cognitive Restructuring - Cognitive restructuring helps a person change the way they think about a situation. Through this therapy, a person learns to identify and challenge their negative or irrational thought patterns and develop more constructive ways of thinking.
-Dialectic Behavioral Therapy (DBT) - Similar to CBT, but with DBT, a person works on validating or accepting uncomfortable thoughts, feelings, and behaviors instead of fighting them. It emphasizes acceptance and change.
-Mindfulness-Based Stress Reduction Therapy (MBSR) - MBSR helps people change their responses to depressing or intrusive thoughts by using mindfulness practices to reduce reactivity.
-Motivational Interviewing (MI) - MI helps people identify positive goals and the strengths or internal motivations that can help them work toward those goals.
-Acceptance and Commitment Therapy (ACT) - ACT helps people accept difficult feelings and develop tolerance for them while learning new coping mechanisms and committing to actions aligned with their values.
Note: CBT is also effective for those with other mental health problems like anxiety disorders, PTSD, OCD, insomnia, chronic pain, and others.
Non-CBT Therapy
Psychoanalysis - Psychoanalysis is an interpersonal therapy that explores a person’s past, looking for possible roots of depression and working through the associated thoughts and feelings. It aims to help a person develop alternative, more effective coping mechanisms.
Eye Movement Desensitization and Reprocessing (EMDR) - EMDR is a therapeutic technique used to treat traumatic memories and, in this context, depression related to trauma. The therapist guides the client to focus their eyes on an object as it moves back and forth. At the same time, the client processes negative traumatic memories and gradually shifts toward more adaptive, positive associations. This approach is effective for many people and involves changes in how the brain processes and stores traumatic information — essentially a form of “rewiring.”
Other Approaches to Depression
Transcranial Magnetic Stimulation (TMS) -
This treatment is sometimes used when other conventional treatments have not worked. A magnetic coil is placed on the scalp, and it delivers magnetic pulses, not electrical current, to stimulate specific areas of the brain involved in mood regulation. This stimulation can lead to changes in neural activity — essentially a form of “rewiring.” (See photo above.)
TMS is typically well tolerated, usually with little or no discomfort. It is often used as an adjunct to medication. Some consumer devices are available online, but they deliver much lower-intensity stimulation, are not FDA‑approved, and their safety and effectiveness cannot be assured. I’m not sure I would go this route.
TMS is a time‑consuming therapy. Treatments are, on average, about 30 minutes long, five times a week for approximately six weeks (this can vary). According to PubMed, about 36% of people experience improvement (other sources report higher numbers). Relapse can occur, but a person can undergo more than one course if needed.
This is often portrayed as an intrusive maniacal treatment straight out of One Flew Over the Cuckoo's Nest. But the fact is that it can work as a last resort when therapy and medication are not working. It is another type of electrical stimulation to the brain, more powerful than TMS, that elicits a small seizure under general anesthesia. The remission rate is higher than 50% and is best used in conjunction with and followed by antidepressant medications to avoid relapse, which can occur.
Over-the-Counter Medications
There are no reliable over‑the‑counter medications that treat major depression. You can try to support your health through lifestyle changes — getting enough sleep, reducing stress, eating a truly nutritious diet, and taking multivitamins (especially B12). While these habits may support overall well‑being and can improve mood to some degree, they cannot reliably treat moderate or severe depression.
Considered Natural and Herbal Remedies
It’s important to learn about herbs and supplements before trying them. Because most have not been extensively studied, their effectiveness for significant depression can be uncertain. Some may also interact with medications or cause unwanted side effects, so it’s wise to approach them with care and good information.
DHEA (dehydroepiandrosterone) is a substance produced by the adrenal gland. It is a prohormone or precursor to certain hormones, including estrogen and progesterone (among others). It also has neuroprotective effects and increases serotonin and dopamine levels in the brain. It has some medication interactions and quite a few potentially unwanted side effects; however, it may help with depression. As a mood enhancer in depression, DHEA usually takes up to six months for optimal effects. Because it does increase estrogen, there is a potential risk for those who have hormone-receptive cancer.
Omega-3 - Fish oil/krill oil - has a lot of beneficial properties for the brain (and possibly for depression): Decreases inflammation of the brain tissue, thereby protecting neurons from damaging effects. It reportedly has neuroplasticity benefits, and because it enhances communication between neurons, it promotes neuroplasticity. In general, Omega-3 protects the gray matter and white matter of the brain from some degeneration.
Omega-3s can take up to six months to work, so you may want to use them to supplement a prescription antidepressant medication.
Turmeric/Curcumin
Prescriptive Medications for the Treatment of Depression
In general, medication works better when used in conjunction with counseling. However, if a person truly does not want to engage in counseling, taking medication alone is usually still better than doing nothing at all.
Some people worry that they won’t be able to “feel” their emotions while taking an antidepressant. This effect, sometimes called emotional blunting, is one reason people stop their medications. If you notice this happening, it’s important to talk with the person prescribing your medication. There are many different antidepressants available, and finding the right one can be like finding a shoe that fits — sometimes you have to try several before you find the best match. In some cases, none of them fit well, and you may want or need to explore other approaches discussed here.
SSRIs (selective serotonin reuptake inhibitors) and SNRIs (serotonin and norepinephrine reuptake inhibitors) are widely used antidepressants. These medications increase the availability of neurotransmitters involved in mood regulation — primarily serotonin and norepinephrine, and indirectly dopamine in some cases.
Common medications in this group include escitalopram (Lexapro), citalopram (Celexa), fluoxetine (Prozac), paroxetine (Paxil, Pexeva), sertraline (Zoloft), and vilazodone (Viibryd).
Tricyclic antidepressants also increase the availability of serotonin and norepinephrine. The best‑known of these is amitriptyline (Elavil). Because TCAs tend to have more side effects, they are prescribed less often than SSRIs and SNRIs. They are sometimes used off‑label to help reduce neuropathic pain.
MAO inhibitors are the oldest class of antidepressants, developed in the 1950s. They have many interactions with foods, drinks, medications, and herbs, so they are not used as frequently today.
Lithium is occasionally used off‑label (not FDA approved for a certain use) for treatment‑resistant depression when other treatments have not been effective. People taking lithium need close monitoring for side effects, and blood levels must be checked regularly.
Some newer potential treatments are in the early stages of testing and development. While early research shows promising results for depression, these approaches remain controversial because they involve substances that are currently classified as illicit drugs. These include:
Ketamine was originally used as an anesthetic during the Vietnam War and has been used for that purpose ever since. It is now a relatively new off‑label approach to treatment‑resistant depression. The benefit of ketamine is that, if it is going to work for depression (in roughly half of patients), it tends to work quickly—often within a few hours—and the effects can last for several days. For a person with severe, acute depression and suicidality, this may offer short‑term relief. The downside is that it can cause psychiatric or dissociative effects (such as feeling disconnected or experiencing perceptual changes or hallucinations). It has some potential for misuse, so it is generally not recommended for people with active substance use disorders.
Exactly how ketamine works in the brain is not yet fully understood. Several theories exist, but the primary premise is that ketamine blocks NMDA (N‑methyl‑D‑aspartate) receptors, which leads to changes in glutamate signaling and increased activity at AMPA receptors. This appears to enhance neuroplasticity and strengthen connections in brain regions such as the prefrontal cortex, which is involved in mood regulation. Because ketamine works on different brain receptors than SSRIs and SNRIs, it may be a useful option when a person does not respond to conventional antidepressants. Ketamine is also thought to promote greater neuroplasticity, helping the brain form new pathways that may support shifts in depressive thinking patterns.
Other theories are far beyond the scope of this site. For more detailed information, see the NIH‑linked review article Ketamine Treatment for Depression: A Review. There is a good deal of ongoing research and emerging information on ketamine.
Esketamine (Spravato) is an FDA‑approved relative of ketamine with similar antidepressant effects. It is a controlled substance used for treatment‑resistant depression and for depression with acute suicidal ideation or behavior. Treatment is administered under close monitoring in a clinic, and while some follow‑up steps may occur at home, the medication itself is not self‑administered outside a supervised setting.
Esketamine is given intranasally (Spravato). Ketamine itself may be given intravenously in off‑label settings, but esketamine — the FDA‑approved version — is not administered by IV. Treatment schedules vary, but esketamine is typically given twice weekly for the first few weeks, then gradually reduced as symptoms improve.
Psilocybin mushrooms are another emerging approach to treatment‑resistant depression. Like ketamine, psilocybin appears to enhance neurotransmitter activity and promote neuroplasticity. Research shows that psilocybin‑assisted therapy can produce rapid reductions in depressive symptoms, often within hours to days, and the antidepressant effects may last for several weeks or longer. More research is underway, and although psilocybin has shown significant promise for many people, it has not been approved by the FDA for the treatment of depression.
Because psilocybin can cause side effects such as anxiety, confusion, or paranoia, it is not appropriate for everyone. And because it can produce hallucinations and a psychedelic “high,” it is still classified as an illicit drug under federal law. When used for depression in research or clinical settings, psilocybin is always paired with counseling as part of a structured therapeutic process. It is administered under controlled conditions, and as of January 2026, the only state with licensed psilocybin service centers is Oregon. Colorado is in the planning phases.
MDMA - MDMA (3,4‑methylenedioxymethamphetamine) is another emerging approach being studied for mental‑health treatment. Although often associated with recreational use, clinical MDMA is a purified, precisely dosed medication used in combination with psychotherapy. It is not the same as street “ecstasy,” which is frequently contaminated or mixed with other substances.
In research settings, MDMA‑assisted therapy has shown promise for conditions such as PTSD, and early studies suggest it may also help people with severe or treatment‑resistant depression. MDMA increases the release of serotonin, dopamine, and norepinephrine, and it also reduces fear
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Hopefully, the above symptoms and approaches to major depression will help you understand depression and the many strategies that can be used to help deal with it successfully. If one does not work, try another. If you believe you are depressed, you need to do something about it ; otherwise you just remain your old "dumpy" self. The answer rarely just comes to you; you need to seek it out.
If you are suffering from depression, contact someone - a counselor, a friend, or a family member. You don't have to face this alone. If you are going through a difficult time and/or are considering suicide, call 9-8-8 - All three options connect you with real people who are trained to offer emotional support, help you stay safe, and guide you toward next steps. They are available 24/7, and you can talk, text, or chat via phone or PC.
Even when life feels unbearable, it can change. Painful moments don’t last forever, and support can help you get through to the other side. Relationship problems, heartbreak, or conflict — none of these are worth your life. You deserve care, safety, and a chance to feel better.
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Persistent Depressive Disorder (PDD)
A Note About Persistent Depressive Disorder (PDD) (Dysthymia)
Knowing how PDD differs from major depression can help you make sense of your symptoms and your experience. From here, it’s helpful to explore the strategies and supports that can make a real difference over time.
Persistent Depressive Disorder (PDD) is, as the name suggests, persistent. Unlike major depression, which often lasts six to twelve months, PDD is a long‑lasting, lower‑grade depression that is present most days and continues for more than two years. The symptoms are similar to those of major depression but typically do not include anhedonia (loss of pleasure) or psychomotor symptoms such as agitation or slowed movement. Although the symptoms are usually less intense, they can still interfere with daily functioning — including social interactions, work and family responsibilities, and even basic self‑care tasks like bathing or changing clothes.
The underlying physiologic patterns in PDD suggest imbalances in neurotransmitters such as serotonin, epinephrine, norepinephrine, and glutamate, along with changes in certain brain structures, including the orbitofrontal cortex and hippocampus. These changes may arise from many of the same factors that contribute to major depression, including genetics, environment, trauma, and other influences. (see Depression Overview for more information)
Treatment Approaches
While treatment for PDD is similar to treatment for major depression, the focus is often on long‑term support, steady symptom improvement, and building coping skills and daily routines that help lift mood over time. Psychotherapy, medication, and lifestyle strategies can all play a role, and progress tends to be gradual but meaningful.
