Compare conditions

Put any two — or three — conditions side by side, adult or pediatric, to spot the look-alike differences fast, row by row.

Major Depressive Disorder (MDD)

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In one line

·MDD is a discrete episode of system-wide shutdown — at least five symptoms, at least two weeks, always including depressed mood or loss of pleasure — that changes how a person eats, sleeps, moves, thinks, and values their own life.

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Normal physiology

·Mood, pleasure, sleep, appetite, and thinking are run by interlocking systems: serotonin, norepinephrine, and dopamine (brain messengers that steady mood, attention, and drive) talk between the limbic system (the brain's feeling center) and the prefrontal cortex (the front of the brain that plans and pumps the brakes). The HPA axis (a stress control loop linking the hypothalamus, pituitary, and adrenal glands) releases cortisol (the body's main stress hormone) when challenges come and then turns it back off. The reward pathway (a circuit running through the ventral tegmental area and nucleus accumbens, using dopamine) makes effort feel worth it. Healthy sadness after loss uses these systems and then releases them.

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What goes wrong

·In a major depressive episode the whole mood-reward-vegetative system fails together. For at least two weeks, nearly every day, at least five of nine defined symptoms are present — and at least one of them must be depressed mood or anhedonia (losing interest or pleasure in things that used to matter). The reward pathway stops paying out, so nothing feels worth doing. The HPA stress axis runs stuck-on-high, flooding the body with cortisol. Sleep architecture breaks — waking at 3 a.m. unable to fall back, or sleeping half the day. Appetite and weight shift. Thinking slows, guilt inflates beyond reason, and in the darkest version, the brain begins to argue that death is a solution. This is a system state, not just a feeling.

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Hallmark signs

·Sad, empty, or hopeless mood almost all day, nearly every day (or grouchy, angry mood in kids and teens)
·Loss of interest or pleasure in almost everything you used to enjoy (anhedonia)
·Big change in weight or appetite (gain or loss of more than 5% of your body weight in a month, or not gaining weight as expected in a growing child)
·Trouble sleeping or sleeping way too much, almost every night
·Moving or talking much slower than usual, or being so restless and fidgety that other people can see it
·Feeling exhausted or drained of energy nearly every day, even after rest
·Feeling worthless, or guilty in a way that's way out of proportion to anything you actually did
·Hard time concentrating, remembering things, or making even small decisions

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Red flags · escalate now

·Suicidal thoughts with a specific plan, intent to act, or access to a gun, pills, or other lethal means — needs emergency evaluation the same day, usually in an ER or crisis center
·Psychotic features — delusions (false beliefs, like 'I'm rotting inside' or 'I've lost all my money when I haven't') or hallucinations (hearing voices, often cruel ones) — requires combined medication and therapy or electroconvulsive therapy (ECT), and urgent psychiatry referral
·Refusing to eat or drink, or catatonia (frozen, unresponsive, or bizarre posturing) — medical emergency that can be life-threatening; ECT is often the fastest, most effective treatment
·Any history of a manic or hypomanic episode (days of sky-high mood, racing thoughts, risky behavior, little need for sleep) — STOP: this is bipolar disorder, not simple depression. Giving an antidepressant alone can flip the person into mania. Must treat with a mood stabilizer first.
·New or worse suicidal thoughts in the first few weeks after starting an antidepressant, especially in anyone under 25 — FDA black-box warning: the medicine can briefly increase suicide risk before it helps. Needs close follow-up.
·Started right after having a baby, with scary intrusive thoughts about harming the infant — same-day assessment to rule out postpartum psychosis, which is a psychiatric emergency

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Workup

·DSM-5 criteria checklist: count 5 out of 9 symptoms, present nearly every day during the same 2-week period, and a change from how the person was before
·PHQ-9 (Patient Health Questionnaire-9, a validated 9-question tool that maps directly to DSM criteria)
·Lifetime mania and hypomania screen: Mood Disorder Questionnaire (MDQ) plus asking family or close friends if they ever saw the person 'revved up' — abnormally high energy, needing much less sleep, talking nonstop, taking big risks, or feeling on top of the world for days
·Thyroid-stimulating hormone (TSH), complete blood count (CBC), vitamin B12 and vitamin D levels, comprehensive metabolic panel (CMP, checks kidney, liver, electrolytes, and blood sugar); urine drug screen if substance use is suspected
·Subtype specifiers: psychotic features present? Episode started during pregnancy or within 4 weeks of delivery? Pattern of fall/winter episodes and spring/summer recovery? Melancholic features (severe anhedonia, early-morning waking, worse mood in morning, marked psychomotor changes, guilt) or atypical features (mood brightens with good news, increased appetite/sleep, leaden paralysis, rejection sensitivity)?

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Treatment

·Suicide risk assessment and safety planning before starting any other treatment
·SSRI antidepressant (sertraline, escitalopram, or fluoxetine are first choices) PLUS psychotherapy (Cognitive Behavioral Therapy or Interpersonal Therapy)
·Optimize the dose to the maximum tolerated level, then switch medication class or add augmentation if response is inadequate after 4–8 weeks
·Continue antidepressant treatment for 6–12 months after full remission (all symptoms gone, back to normal functioning); if 3 or more past episodes, consider indefinite maintenance
·Electroconvulsive therapy (ECT) for psychotic depression, catatonia (immobility, mutism, rigid posture), severe depression with refusal to eat or drink, or imminently life-threatening suicidal intent
·Bright light therapy (10,000 lux light box for 30 minutes each morning) for seasonal pattern depression (fall/winter onset, spring/summer remission)

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NCLEX trap

·Loss of interest or pleasure (anhedonia) can be the main symptom instead of low mood — and children or teens may show crankiness (irritability) rather than sadness. 'Not sad' does not rule out MDD.
·Mood improvement takes 4–6 weeks; side effects (nausea, jitters, headache) often show up first. Teach the timeline up front and schedule early follow-up — especially for anyone under 25, when the black-box suicide-risk window demands close watching.
·Direct, calm questions do not increase risk — they are the single most important part of depression assessment and open the door to building a safety plan.
·Continue 6–12 months after symptoms clear (indefinitely after three or more episodes); stopping at first improvement is the classic path to relapse, and sudden stops trigger discontinuation syndrome (zaps, dizziness, rebound symptoms).
·First screen for any lifetime history of mania or hypomania (high mood, racing thoughts, less sleep but still energized) — bipolar depression treated with an antidepressant alone can flip the person into mania. The depression looks identical; the history changes the diagnosis.
·TCAs are deadly in overdose (they block the heart's sodium channels, causing arrhythmias and cardiac arrest) — a critical danger in the exact population at suicide risk. SSRIs are first-line partly because they are far safer if someone takes too many pills.

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