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]
- Bipolar features (prior mania/hypomania, family history, antidepressant-induced mood elevation) — switch to mood stabiliser; do not start antidepressant alone[1]
- Pregnancy or planning pregnancy on antidepressant — perinatal mental health and obstetric review[1]
First-line treatment
Interventions
- Severity-guided treatment selection[1]Mild: CBT, behavioural activation, structured self-help. Moderate–severe: combined antidepressant + psychological therapy. Severe with psychosis or risk: psychiatry / ECT consideration
- Cognitive behavioural therapy or interpersonal therapy[1]12–20 sessions; equivalent to antidepressant in moderate depression at 12 months; lower relapse rate; combine with medication for severe
- Continuation and maintenance phase[1]Continue antidepressant ≥6 months after first episode achieves remission; ≥1–2 years for second episode; lifelong for ≥3 episodes or severe relapse history
- Treatment-resistant pathway[1]Failure of 2 adequate trials → augmentation (lithium, atypical antipsychotic, T3, second antidepressant) or switch class; consider ECT, esketamine, rTMS for refractory illness
First-line drug therapy
| Drug | Class | Adult | Paediatric | Notes |
|---|---|---|---|---|
| Escitalopram[1] | SSRI | 10 mg PO daily start, titrate to 10–20 mg/day | — | First-line; QTc warning at higher doses; relatively few drug interactions; review at 2–4 weeks, full effect 4–6 weeks |
| Sertraline[1] | SSRI | 50 mg PO daily start, titrate to 100–200 mg/day | — | First-line; activating, weight-neutral; counsel about initial activation and suicide warning <25 years |
| Mirtazapine[1] | Tetracyclic antidepressant | 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 |
| Amitriptyline (TCA)[1] | Tricyclic antidepressant | Start 25 mg PO night, titrate to 75–150 mg | — | Effective but anticholinergic, cardiotoxic in overdose; reserve for refractory or comorbid neuropathic pain/insomnia; ECG before higher dose |
| Lithium (augmentation)[1] | Mood stabiliser | Start 400 mg PO daily, titrate to plasma 0.4–0.8 mmol/L | — | Augmentation in treatment-resistant depression; renal and thyroid function monitoring; teratogen |
| 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 |
Escitalopram[1]
SSRI
- Adult
- 10 mg PO daily start, titrate to 10–20 mg/day
- Paediatric
- —
First-line; QTc warning at higher doses; relatively few drug interactions; review at 2–4 weeks, full effect 4–6 weeks
Sertraline[1]
SSRI
- Adult
- 50 mg PO daily start, titrate to 100–200 mg/day
- Paediatric
- —
First-line; activating, weight-neutral; counsel about initial activation and suicide warning <25 years
Mirtazapine[1]
Tetracyclic antidepressant
- 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
Amitriptyline (TCA)[1]
Tricyclic antidepressant
- Adult
- Start 25 mg PO night, titrate to 75–150 mg
- Paediatric
- —
Effective but anticholinergic, cardiotoxic in overdose; reserve for refractory or comorbid neuropathic pain/insomnia; ECG before higher dose
Lithium (augmentation)[1]
Mood stabiliser
- Adult
- Start 400 mg PO daily, titrate to plasma 0.4–0.8 mmol/L
- Paediatric
- —
Augmentation in treatment-resistant depression; renal and thyroid function monitoring; teratogen
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
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); never stop abruptly[1]
Referral criteria
- Treatment-resistant depression after failure of two adequate antidepressant trialsSpecialist 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
Diagnosis and stepwise pharmacological + psychological management of depressive disorder in adults.