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Psychiatry · NICE

Depression in adults

NICE
A
Source:NICE Guideline NG222 — Depression in Adults: Treatment and Management (2022)BAP Evidence-Based Guidelines for Treating Depressive Disorders (2022)
Verified Apr 2026
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Red Flags

  • Active suicidality, severe self-harm, or psychotic features — same-day mental health assessment under safeguarding pathway; admission if risk to life[1]
  • Severe depression with psychomotor retardation, food/fluid refusal, or catatonia — admission and consideration of ECT[1]
  • Worsening on antidepressant in first 2 weeks (activation, insomnia, agitation) or in adolescents/young adults — close monitoring; review weekly[1]
  • Bipolar features (prior mania/hypomania, family history, antidepressant-induced mood elevation) — switch to mood stabiliser; do not start antidepressant alone[1]

First-line treatment

Interventions

  • Stepped-care model with shared decision making[1]
    Step 1: assessment, education, monitoring. Step 2: low-intensity (guided self-help, CCBT, group CBT). Step 3: high-intensity psychological therapy or antidepressant. Step 4: complex / treatment-resistant — specialist team
  • Cognitive behavioural therapy (CBT) or interpersonal therapy (IPT)[1]
    First-line high-intensity psychological therapy; 12–20 sessions; equivalent to antidepressant in moderate depression at 12 months; lower relapse rate
  • Lifestyle and behavioural activation[1]
    Sleep hygiene, regular exercise, social engagement, goal setting; behavioural activation specifically; reduce alcohol
  • Combined therapy for severe or treatment-resistant[1]
    CBT/IPT + antidepressant; consider augmentation (lithium, atypical antipsychotic, second antidepressant); ECT for very severe with risk to life or refractory; transcranial magnetic stimulation in selected

First-line drug therapy

DrugClassAdultPaediatricNotes
Sertraline[1]SSRI50 mg PO daily start, titrate to 100–200 mg/day; review at 2–4 weeks—First-line SSRI in adults; activating, weight-neutral; counsel about initial activation and suicide warning <25 years; full effect 4–6 weeks
Escitalopram[1]SSRI10 mg PO daily start, titrate to 10–20 mg/day—Alternative first-line; QTc warning at higher doses; check baseline ECG in cardiac comorbidity
Mirtazapine[1]Tetracyclic antidepressant — α2 antagonist + 5-HT2 + 5-HT3 blocker15 mg PO night start, titrate to 30–45 mg night—Useful with insomnia, weight loss, comorbid anxiety; sedating at lower doses; weight gain; less sexual dysfunction than SSRIs
Venlafaxine extended-release[1]SNRI75 mg PO daily start, titrate to 150–225 mg/day—Second-line if SSRI inadequate; monitor BP at higher doses; discontinuation syndrome — taper
Lithium (augmentation)[1]Mood stabiliserStart 400 mg PO daily, titrate to plasma 0.4–0.8 mmol/L (0.6–1.0 in mania)—Augmentation in treatment-resistant depression; renal and thyroid function monitoring; narrow therapeutic index — drug interactions matter; teratogen
Esketamine (intranasal) — TRD[1]NMDA receptor antagonist56–84 mg intranasally with concurrent oral antidepressant; specialist-supervised in clinic with 2 h post-administration monitoring—Treatment-resistant depression; effects within hours; specialist setting with monitoring; dissociation, hypertension, abuse potential
Olanzapine + fluoxetine combination (TRD or psychotic depression)[1]Atypical antipsychotic + SSRIOlanzapine 5–10 mg PO + fluoxetine 20–40 mg PO daily—Treatment-resistant or psychotic depression; metabolic monitoring; sedation; FDA OFC fixed-dose combination available
Sertraline[1]
SSRI
Adult
50 mg PO daily start, titrate to 100–200 mg/day; review at 2–4 weeks
Paediatric
—
First-line SSRI in adults; activating, weight-neutral; counsel about initial activation and suicide warning <25 years; full effect 4–6 weeks
Escitalopram[1]
SSRI
Adult
10 mg PO daily start, titrate to 10–20 mg/day
Paediatric
—
Alternative first-line; QTc warning at higher doses; check baseline ECG in cardiac comorbidity
Mirtazapine[1]
Tetracyclic antidepressant — α2 antagonist + 5-HT2 + 5-HT3 blocker
Adult
15 mg PO night start, titrate to 30–45 mg night
Paediatric
—
Useful with insomnia, weight loss, comorbid anxiety; sedating at lower doses; weight gain; less sexual dysfunction than SSRIs
Venlafaxine extended-release[1]
SNRI
Adult
75 mg PO daily start, titrate to 150–225 mg/day
Paediatric
—
Second-line if SSRI inadequate; monitor BP at higher doses; discontinuation syndrome — taper
Lithium (augmentation)[1]
Mood stabiliser
Adult
Start 400 mg PO daily, titrate to plasma 0.4–0.8 mmol/L (0.6–1.0 in mania)
Paediatric
—
Augmentation in treatment-resistant depression; renal and thyroid function monitoring; narrow therapeutic index — drug interactions matter; teratogen
Esketamine (intranasal) — TRD[1]
NMDA receptor antagonist
Adult
56–84 mg intranasally with concurrent oral antidepressant; specialist-supervised in clinic with 2 h post-administration monitoring
Paediatric
—
Treatment-resistant depression; effects within hours; specialist setting with monitoring; dissociation, hypertension, abuse potential
Olanzapine + fluoxetine combination (TRD or psychotic depression)[1]
Atypical antipsychotic + SSRI
Adult
Olanzapine 5–10 mg PO + fluoxetine 20–40 mg PO daily
Paediatric
—
Treatment-resistant or psychotic depression; metabolic monitoring; sedation; FDA OFC fixed-dose combination available

Safety-net

  1. Most antidepressants take 4–6 weeks for full effect; do not stop because of initial side effects without speaking to your prescriber[1]
  2. If suicidal thoughts emerge or worsen on starting an antidepressant — same-day medical review and crisis support[1]
  3. When stopping antidepressant — taper gradually over weeks to avoid discontinuation syndrome (flu-like symptoms, dizziness, electric shocks); never stop abruptly[1]

Referral criteria

  • Treatment-resistant depression after failure of two adequate antidepressant trials at adequate dose and durationSpecialist mental health team / mood disorder clinic[1]
  • Severe depression with psychotic features, catatonia, or risk to lifeEmergency mental health and consideration of ECT[1]
  • Bipolar features detected during assessmentPsychiatry for mood stabiliser initiation[1]
  • Pregnancy or planning pregnancy on antidepressantPerinatal mental health for medication review[1]

Clinical summary

Stepped-care diagnosis and management of depression in adults — psychological therapies, pharmacotherapy, and treatment-resistant depression.

References

  1. 1.NICE Guideline NG222 — Depression in Adults: Treatment and Management (2022); BAP Evidence-Based Guidelines for Treating Depressive Disorders (2022)

On this page

  • Red flags
  • First-line treatment
  • Safety-net
  • Referral
  • References