Depressive disorders share sad, empty, or irritable mood with physical and cognitive changes that significantly impair functioning. Major depressive disorder (MDD) is one of the leading causes of disability worldwide and is about twice as common in women as in men after puberty.

Contributing factors

• Biological: reduced monoamine activity (serotonin, norepinephrine, dopamine), hypothalamic–pituitary–adrenal axis overactivity with high cortisol, inflammation, reduced neuroplasticity, genetic loading
• Psychological: negative cognitive triad (negative views of self, world, and future) and cognitive distortions (Beck); learned helplessness; loss and unresolved grief
• Social: stressful life events, poverty, isolation, abuse, chronic medical illness, substance use
• Medical and drug causes to rule out: hypothyroidism, anemia, vitamin B12 deficiency, Cushing's syndrome, stroke, Parkinson's disease, cancer, and drugs such as corticosteroids and interferon

DSM-5-TR depressive disorders

The nine MDD symptoms (mnemonic SIG E CAPS plus mood): depressed mood; loss of interest; sleep change (insomnia or hypersomnia); guilt or worthlessness; energy loss or fatigue; concentration difficulty or indecisiveness; appetite or weight change (significant loss or gain); psychomotor agitation or retardation; suicidal thoughts. Memory loss is not itself a criterion — prominent memory impairment should prompt evaluation for a neurocognitive disorder (older adults can have "pseudodementia").

Useful specifiers: with anxious distress, with melancholic features, with atypical features (mood reactivity, increased appetite, hypersomnia), with psychotic features, with catatonia, with peripartum onset (onset during pregnancy or within 4 weeks after delivery), and with seasonal pattern (typically fall–winter onset). Grief after a death does not exclude MDD; a separate diagnosis, prolonged grief disorder, is covered with trauma- and stressor-related disorders.

Affective: sadness, hopelessness, anhedonia, irritability (common in adolescents), guilt, worthlessness ("I'm a burden to everyone").

Cognitive: slowed thinking, poor concentration, indecisiveness, rumination, negative self-talk, suicidal ideation.

Behavioral and physical: withdrawal, neglected hygiene, psychomotor slowing or agitation, sleep and appetite change, fatigue, decreased libido, constipation, and somatic complaints (headache, dyspepsia, vague pain) — often the presenting problem in primary care and in older adults. Panic attacks can co-occur but are not a core feature of depression.

Suicide risk assessment — always ask directly

• Asking about suicide does not increase risk
• Ideation, plan, intent, access to means, preparatory behavior, timeline
• A previous suicide attempt is the strongest single predictor of a future suicide
• Other risk factors: hopelessness, male sex with lethal means, older age, substance use, chronic pain or illness, recent loss, isolation, psychosis, access to firearms
• Sudden calmness or giving away possessions after deep depression may signal a decision to die
• Risk can rise as energy returns in early treatment, before mood fully improves

Mild depression: psychotherapy or guided self-help. Moderate to severe: psychotherapy plus antidepressant is more effective than either alone. Most antidepressants need 2–4 weeks for early benefit and 6–8 weeks for full effect; after remission, continue for at least 6–12 months to prevent relapse.

Psychotherapy — cognitive behavioral therapy (identify and change negative, distorted automatic thoughts), behavioral activation, interpersonal therapy, problem-solving therapy.

Antidepressants

Class-wide antidepressant safety

• Boxed warning: increased suicidal thoughts and behaviors in children, adolescents, and young adults under 25; monitor closely in the first weeks and after dose changes
• Serotonin syndrome: agitation, confusion, tachycardia, hyperthermia, diaphoresis, tremor, hyperreflexia and clonus, diarrhea — risk with combinations (MAOIs, triptans, tramadol, linezolid, St. John's wort, dextromethorphan). Stop the drugs and notify; cyproheptadine may be ordered
• Discontinuation syndrome on abrupt stopping (dizziness, "electric shock" sensations, irritability, flu-like symptoms) — taper (least with fluoxetine; worst with paroxetine and venlafaxine, which have short half-lives)
• Can trigger mania in undiagnosed bipolar disorder

Newer agents with special safety rules

• Esketamine nasal spray — indications: treatment-resistant depression, alone (since January 2025) or with an oral antidepressant; and MDD with acute suicidal ideation or behavior, with an oral antidepressant only. Schedule III, available only through a REMS program in certified settings. The client self-administers under supervision and is monitored for at least 2 hours; check BP before and after dosing. Boxed warnings: sedation, dissociation, respiratory depression, abuse and misuse, and suicidality in young people. No driving until the next day after restful sleep. Contraindicated with aneurysmal vascular disease, arteriovenous malformation, or history of intracerebral hemorrhage
• Zuranolone (oral, for postpartum depression): 50 mg once daily in the evening with fat-containing food for 14 days. Schedule IV CNS depressant. Boxed warning — impaired driving: do not drive or do hazardous activities for at least 12 hours after each dose. Can cause embryo-fetal harm — use effective contraception during and for 1 week after treatment
• Dextromethorphan-bupropion (2022): seizure and serotonin syndrome precautions of both components

Somatic treatments — ECT for severe, psychotic, catatonic, or suicidal depression and when rapid response is needed; repetitive transcranial magnetic stimulation (TMS) for treatment-resistant depression (details in the brain stimulation topic). Bright light therapy for seasonal pattern: about 10,000 lux for about 30 minutes each morning; may trigger mania in bipolar disorder and requires caution with retinal disease or photosensitizing drugs.

Listed in priority order.

1. Safety — suicide prevention
   • A client with a plan and intent → immediate 1:1 continuous observation and a safe environment (remove belts, cords, sharps, medications); do not leave the client alone
   • Reassess risk at every shift, at transitions, and before passes or discharge; collaborative safety planning (warning signs, coping steps, contacts, crisis lines, means restriction)
   • Check that medications are swallowed (cheeking and stockpiling)
2. Physiological needs — nutrition (small frequent high-protein meals, preferred foods), fluids, weight, bowel pattern, sleep routine, hygiene. Early goals focus on basic self-care and daily activity
3. Therapeutic communication
   • Sit with the client; tolerate silence; use open-ended questions and simple language
   • Avoid false reassurance, arguing, or cheerful advice ("Don't think that way," "You have so much to live for")
   • Acknowledge the feeling and explore it: "You feel you are a burden. What makes you feel that way?" Help the client see negative thinking as a symptom of depression
   • Point out small strengths and accomplishments realistically
4. Activity and social contact — simple, structured, noncompetitive activities with guaranteed success; make decisions for a severely depressed client and gradually return choices
5. Short-term goals must be specific, measurable, and realistic — e.g., "Client will initiate a 10-minute conversation with the nurse once daily during week 1," not "Client will be free of negative thoughts"
6. Medication monitoring — adverse effects, adherence, suicidality with dose changes, sodium in older adults, BP with SNRIs, esketamine REMS observation

Common nursing diagnoses: risk for suicide; hopelessness; chronic low self-esteem (worthlessness and guilt); social isolation; self-care deficit; imbalanced nutrition; disturbed sleep pattern.

• Antidepressants take 2–4 weeks to begin working and longer for full benefit; keep taking them even when feeling better
• Do not stop suddenly — taper with the prescriber
• Expect early nausea, restlessness, or trouble sleeping with SSRIs; these usually ease in 1–2 weeks. Take SSRIs in the morning if they disturb sleep
• Report worsening mood, agitation, or new suicidal thoughts immediately, especially in the first weeks
• Avoid alcohol; check with the prescriber before any over-the-counter cold or pain medication, supplements (St. John's wort), or triptans
• MAOIs: follow the low-tyramine diet; carry a list of restricted foods and drugs; report severe occipital headache, stiff neck, or palpitations
• Esketamine: arrange a ride home; no driving until the next day after sleep
• Zuranolone: take in the evening with a fat-containing meal; do not drive for at least 12 hours after a dose
• Regular exercise, sleep routine, daylight exposure, and social contact support recovery
• Know crisis resources and your safety plan

• MDD = ≥ 5 symptoms for ≥ 2 weeks, one must be depressed mood or anhedonia
• Persistent depressive disorder = ≥ 2 years (1 year in youth)
• Previous suicide attempt = strongest predictor; always ask directly about suicide
• Plan and intent → 1:1 observation and safe environment first
• Suicide risk may rise as energy improves early in treatment
• SSRIs: early nausea, jitteriness, insomnia; full effect in weeks; do not stop abruptly
• Boxed warning: suicidality under age 25
• Serotonin syndrome = hyperthermia + clonus/hyperreflexia + agitation
• MAOIs + tyramine → hypertensive crisis; 2-week washout (5 weeks after fluoxetine)
• Esketamine: REMS, ≥ 2-hour monitoring, BP before and after, no driving until next day
• Zuranolone: 14 days for postpartum depression, no driving for 12 hours after each dose
• Seasonal pattern → morning bright light therapy