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
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Sertraline[1] | SSRI | 50 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] | SSRI | 10 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 blocker | 15 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] | SNRI | 75 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 stabiliser | Start 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 antagonist | 56–84 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 + SSRI | Olanzapine 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
- Most antidepressants take 4–6 weeks for full effect; do not stop because of initial side effects without speaking to your prescriber[1]
- If suicidal thoughts emerge or worsen on starting an antidepressant — same-day medical review and crisis support[1]
- 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.