Depression (Major Depressive Disorder)

What happens in depression

Depression involves changes in brain networks that regulate mood, reward, stress and sleep. Brain imaging shows altered activity in areas such as the prefrontal cortex, amygdala and hippocampus. The stress hormone system is often overactive, and inflammation may play a role in some people. The old idea of a simple "chemical imbalance" of serotonin is now seen as too simple; antidepressants seem to work partly by helping the brain form new connections over weeks.

Symptoms

For a diagnosis of major depressive disorder, at least five of these nine symptoms must be present for at least 2 weeks, including at least one of the first two:

1. depressed mood most of the day, nearly every day
2. markedly reduced interest or pleasure in almost all activities
3. significant weight loss or gain, or appetite change
4. insomnia or sleeping too much
5. slowed movement or restlessness noticeable to others
6. fatigue or loss of energy
7. feelings of worthlessness or excessive guilt
8. reduced ability to think, concentrate or decide
9. recurrent thoughts of death or suicide

The symptoms must cause real distress or impairment and not be better explained by a substance, a medical condition, or bipolar disorder. For a plain-language list of warning signs and a self-check, see signs of depression.

Types of depression

Bipolar depression matters because antidepressants alone can trigger mania. Doctors ask about past periods of unusually high energy before treating.

Causes and risk factors

• Genetics: having a parent or sibling with depression raises risk about two to three times.
• Stressful life events: loss, divorce, unemployment, caring for someone, financial strain.
• Childhood adversity and trauma.
• Chronic medical conditions: heart disease, stroke, diabetes, chronic pain, cancer, Parkinson's disease, multiple sclerosis, thyroid disease.
• Hormonal changes: pregnancy, postpartum, perimenopause.
• Substance use: alcohol and drugs both cause and worsen depression. See substance use disorder.
• Other mental health conditions: anxiety disorders, PTSD, eating disorders.
• Social factors: loneliness, discrimination, poverty.

Women are diagnosed about twice as often as men.

Diagnosis

There is no blood test or scan for depression. A doctor or mental health professional will:

• ask about symptoms, how long they have lasted and their effect on daily life
• use questionnaires such as the PHQ-9 to measure severity and track progress
• ask directly about suicidal thoughts. Asking does not increase risk
• ask about past high-energy episodes, alcohol and drug use, and family history
• check for physical causes, often with blood tests for thyroid function, blood count, vitamin B12 and folate, and blood sugar

Treatment

Mild depression

Guided self-help, cognitive behavioral therapy (CBT) delivered individually or in groups, structured exercise programs and active monitoring. Antidepressants are not usually first choice for mild depression unless it persists or there is a past history of more severe episodes.

Moderate to severe depression

• Psychotherapy: CBT, behavioral activation, interpersonal therapy and problem-solving therapy all have strong evidence.
• Antidepressants: SSRIs (such as sertraline, escitalopram, fluoxetine) are usually first choice. SNRIs, bupropion and mirtazapine are alternatives.
• Combination: therapy plus medicine is more effective than either alone for moderate to severe depression.

What to expect from antidepressants

• Some benefit often appears in 2 to 4 weeks; full effect takes 6 to 8 weeks.
• Common early side effects include nausea, headache, sleep changes and anxiety, which often settle.
• Sexual side effects are common with SSRIs and SNRIs; tell your doctor, as options exist.
• After recovery, treatment usually continues for at least 6 to 12 months to prevent relapse, and longer after repeated episodes.
• Do not stop suddenly: discontinuation symptoms such as dizziness, irritability and "brain zaps" are common. Taper with your doctor.
• Antidepressants carry a warning about increased suicidal thinking in people under 25 in the early weeks. Close follow-up is important.

Treatment-resistant depression

If two adequate trials of treatment do not work, options include switching or combining medicines, adding lithium or an antipsychotic, esketamine nasal spray under supervision, repetitive transcranial magnetic stimulation (rTMS), and electroconvulsive therapy (ECT), which is the most effective treatment for severe, psychotic or life-threatening depression.

Lifestyle measures that help

Regular exercise, a consistent sleep schedule, daylight exposure, limiting alcohol, staying connected with people and doing small rewarding activities each day. These support treatment but do not replace it for moderate or severe depression.

Complications

Untreated depression can lead to suicide, self-harm, substance misuse, relationship and job loss, and worse outcomes from heart disease, diabetes and other illnesses. People with depression are more likely to develop physical illness, partly through effects on sleep, activity, diet and inflammation.

Outlook

Most people with depression improve with treatment. About half of people who have one episode will have another, and the risk rises with each episode, which is why maintenance treatment and relapse-prevention skills matter. Early warning signs, such as poor sleep or withdrawing from people, are worth knowing and acting on.

Frequently asked questions

What causes depression?

Depression results from a combination of factors: genetic risk, changes in brain circuits and stress hormones, life events such as loss or trauma, medical illness, hormonal changes and substance use. Often there is no single cause, and depression can occur even when life seems to be going well.

What is the best treatment for depression?

For mild depression, talking therapy, guided self-help and exercise are often enough. For moderate to severe depression, a combination of psychotherapy such as CBT and an antidepressant works best. The right choice depends on severity, past response and personal preference.

How long does it take for antidepressants to work?

Some improvement in sleep, energy or appetite may appear in 1 to 2 weeks, with mood improving over 2 to 4 weeks. The full effect usually takes 6 to 8 weeks. If there is little benefit by then, your doctor may adjust the dose or try another medicine.

Is depression a lifelong condition?

Not necessarily. Many people have one episode and recover fully. Others have recurrent episodes, and some have long-lasting milder symptoms. Continuing treatment after recovery, learning relapse-prevention skills and acting early on warning signs greatly reduce the chance of it coming back.

Can depression be cured without medication?

Yes, for many people. Psychotherapy such as CBT is as effective as medication for mild to moderate depression and has lower relapse rates after it ends. Exercise also helps. Severe depression usually responds best to a combination of therapy and medicine.