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psych.depression.core.v1PRODUCTION
psych.depression.core.v1

Major Depressive Disorder (MDD) — chronic stepwise + acute crisis (APA 2023; VA/DoD 2022)

psychiatrychronicacuteadult
Hard-required inputs
0 / 10
Care setting:

Encounter flow

12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Confirm DSM-5-TR 2022 MDD criteria (≥5 symptoms ≥2 weeks including depressed mood or anhedonia, functional impairment, not better explained by SUD / medical / bereavement / bipolar)

Inputs
0
Actions
0
Advance rule
Set
Advance when

MDD criteria met and bipolarity ruled out (DSM-5-TR 2022; APA 2023)

Patient inputs (17)

Drug selection; geriatric (lower starting doses); adolescent (FDA 2004 black-box reassessment; TADS March JAMA 2004)

SSRI choice (sertraline preferred APA 2023); avoid paroxetine (FDA Category D); bupropion + mirtazapine considerations

STAR*D (Rush AJP 2006) — prior response determines next step in failure ladder

Rule out bipolar — MDD treatment differs and antidepressant alone may precipitate switch (APA 2023; CANMAT 2016)

Concurrent SUD worsens prognosis; tailor regimen + counsel (VA/DoD 2022; Anton JAMA 2006 COMBINE)

CV, renal, hepatic, seizure, eating disorder affect drug choice (e.g., bupropion contraindicated in seizure / eating disorder; APA 2023; VA/DoD 2022)

MAOI washout; serotonergic load; CYP interactions; QTc; tamoxifen + paroxetine/fluoxetine (FDA 2011); SSRI + NSAID bleeding (APA 2023)

Hypothyroidism mimics depression — baseline before initiating SSRI (APA 2023; VA/DoD 2022)

C-SSRS — passive vs active vs intent vs plan drives disposition (Posner 2011; VA/DoD 2022)

PHQ-9 stratifies severity → drug + therapy intensity; Q9 flags suicidality (Kroenke 2001; APA 2023)

Acute stressors / abuse / housing affect plan and safety (APA 2023)

Baseline before therapy; rule out anemia / occult illness (VA/DoD 2022)

Baseline electrolytes; SIADH risk on SSRI; lithium readiness (APA 2023)

Hepatic-cleared antidepressants (VA/DoD 2022)

Atypical antipsychotic augmentation requires metabolic baseline (APA/ADA 2004 consensus)

Atypical antipsychotic baseline metabolic monitoring (APA/ADA 2004 consensus)

QTc baseline before TCAs / citalopram >20 mg (FDA 2012) / atypical antipsychotic augmentation

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (11)

11 need judgement
  • informationallife_threateningactive_si_with_intent_or_plan (C-SSRS; Posner 2011)
    C-SSRS positive for active SI with intent, plan, or recent preparatory behaviour (Posner 2011)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationallife_threateningserotonin_syndrome_signs (Boyer 2005; APA 2023)
    Tremor, hyperreflexia, clonus, hyperthermia, autonomic instability, AMS in patient on serotonergic agents (Hunter criteria; Boyer NEJM 2005)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverephq9_severe_score (Kroenke 2001; APA 2023)
    PHQ-9 ≥20 (severe MDD per Kroenke 2001)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepsychotic_features_or_catatonia (DSM-5-TR 2022)
    Hallucinations, delusions, or catatonia in MDD (DSM-5-TR 2022)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepregnancy_with_severe_mdd (APA 2023)
    Severe MDD in pregnancy or postpartum, with or without psychosis (APA 2023)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverelithium_toxicity_signs (APA 2023)
    Tremor coarse, ataxia, confusion, GI symptoms with lithium augmentation (APA 2023)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereantidepressant_induced_mania (STEP-BD Sachs NEJM 2007 PMID 17392295; CANMAT 2016 Kennedy; APA 2023)
    Manic or hypomanic episode emerged on SSRI / SNRI / bupropion in patient previously screened MDQ-negative — DSM-5-TR criteria for manic / hypomanic episode now met (DSM-5-TR 2022; APA 2023; CANMAT 2016)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalsevereantidepressant_discontinuation_syndrome (Horowitz Lancet Psych 2019; APA 2023)
    Flu-like + dizziness + electric-shock / "brain-zaps" + irritability + insomnia + rebound depressive symptoms within 1–3 days of abrupt cessation OR rapid taper of SSRI / SNRI — most severe with short-half-life agents (paroxetine, venlafaxine); commonly misdiagnosed as MDD relapse (Horowitz Taylor Lancet Psych 2019)
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveretreatment_resistant_depression (STAR*D Trivedi AJP 2006 PMID 16390886; APA 2023; VA/DoD 2022)
    Treatment-resistant depression = failure of ≥2 adequate trials of antidepressants from different classes at adequate dose × adequate duration (≥4–8 wk at therapeutic dose). Pseudo-resistance (subtherapeutic dose / inadequate duration / non-adherence / unrecognised bipolar / medical mimic — TSH, B12, anemia, sleep apnea) must be ruled out FIRST (APA 2023; STAR*D Trivedi AJP 2006).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverepostpartum_mdd_or_psychosis_features (DSM-5-TR 2022 peripartum-onset specifier; APA 2023; Meltzer-Brody Lancet 2018)
    Severe depression OR psychotic features (delusions / hallucinations / disorganisation / suicidal or infanticidal ideation) with onset within 1 year of delivery (DSM-5-TR 2022 peripartum-onset specifier). Postpartum psychosis is a psychiatric emergency with infanticide / suicide risk; postpartum depression with SI also requires urgent evaluation (APA 2023).
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatemania_or_hypomania_history_uncovered (APA 2023)
    Past or current mania / hypomania revealed on screening — MDQ / CIDI (APA 2023; CANMAT 2016)
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

Run this disease's risk and dosing calculators inline.

RISK_STRATIFICATIONrequiredDrives severity classification
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Recommended regimen

MDD stepwise pharmacotherapy ladder — Step 1 SSRI → Step 4 ECT/TMS/esketamine (APA 2023; STAR*D Rush AJP 2006; VA/DoD 2022)
axis: mdd_stepwise_pharmacotherapystep 1 - Step 1 — SSRI first-line (APA 2023; Cipriani Lancet 2018; NICE 2022)
Selected step "Step 1 — SSRI first-line (APA 2023; Cipriani Lancet 2018; NICE 2022)" — PHQ-9 ≥10, no prior SSRI failure, no contraindication (APA 2023)
  • sertraline
    first line
    SSRI
    25–50 mg PO daily • PO • once daily (max: 200 mg/day)
    triggers: pregnancy, cardiac_comorbidity, lactation
    Cipriani 2018 — among most effective + tolerable; preferred in pregnancy + cardiac disease
    rxcui 36437
  • escitalopram
    first line
    SSRI
    5–10 mg PO daily • PO • once daily (max: 20 mg/day)
    Cipriani 2018 — most effective SSRI; favourable interactions; QTc concern at higher doses
    rxcui 321988
  • fluoxetine
    first line
    SSRI
    10–20 mg PO daily • PO • once daily (mornings) (max: 60 mg/day (80 mg in OCD))
    triggers: adolescent, desired_long_half_life
    Long half-life buffers missed doses; FDA-approved adolescent MDD
    rxcui 4493
  • paroxetine
    second line
    SSRI
    10–20 mg PO daily • PO • once daily (max: 50 mg/day (60 mg PD))
    Effective but anticholinergic; high discontinuation syndrome; AVOID in pregnancy — cardiac teratogen (FDA Category D); avoid in tamoxifen co-Rx — CYP2D6 (FDA 2011; APA 2023)
    rxcui 32937
  • citalopram
    second line
    SSRI
    10–20 mg PO daily • PO • once daily (max: 40 mg/day (20 mg if >60 yr or CYP2C19 poor metaboliser per FDA))
    Effective; FDA 2012 QTc warning caps dose 20 mg in elderly
    rxcui 2556

outpatient playbook — drug actions (5)

  1. 1. sertraline OR escitalopram
    Sertraline 25–50 mg → 200; escitalopram 5–10 → 20 • PO • daily
    trigger: First episode MDD without compelling alternative (APA 2023)
    APA 2023 / NICE 2022 / Cipriani Lancet 2018 — first-line SSRI
  2. 2. switch within or across class
    Venlafaxine XR 37.5 → 225; duloxetine 30 → 60–120; bupropion XL 150 → 300; mirtazapine 7.5 → 45 • PO • daily
    trigger: Failure / intolerance of first SSRI at adequate dose × 4–8 weeks (STAR*D Rush AJP 2006)
    STAR*D step 2 (Rush AJP 2006)
  3. 3. augmentation
    Lithium 300 BID target 0.6–0.8; T3 25–50 mcg; aripiprazole 2–15; quetiapine XR 150–300 • PO • daily
    trigger: TRD = ≥2 failed adequate antidepressant trials (APA 2023)
    STAR*D step 3 (Rush AJP 2006) + AUGMENT (PMID 19407731)
  4. 4. esketamine intranasal (clinic-supervised)
    56–84 mg intranasal twice weekly × 4 weeks then taper • intranasal • 2×/week induction
    trigger: TRD with acute suicidality OR ≥2 failed augmentations (FDA 2019)
    FDA 2019 REMS; TRANSFORM-2 (PMID 31290965)
  5. 5. ECT / TMS referral
    TMS daily × 4–6 weeks; ECT 6–12 sessions over 2–4 weeks • procedure • per protocol
    trigger: Severe MDD, psychotic features, catatonia, pregnancy, inability to wait, treatment-resistant (APA 2023)
    APA 2023 / VA/DoD 2022 — most effective for severe MDD; Pagnin 2004 (PMID 15087991)

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Depressed mood and/or anhedonia ≥2 weeks (DSM-5 2022 core symptoms); Sleep / appetite / energy / concentration / psychomotor changes ≥2 weeks (DSM-5 2022 criterion A); Suicidal ideation, plan, intent, or recent self-harm behavior (C-SSRS; APA 2023).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Major Depressive Disorder (MDD) — chronic stepwise + acute crisis (APA 2023; VA/DoD 2022)** (psych.depression.core.v1).
Phenotype framing: Adjustment disorder vs persistent depressive disorder vs MDD with mixed features vs bipolar depression vs PMDD vs hypothyroidism vs anemia vs medication-induced (interferon, β-blocker, isotretinoin, steroids) (DSM-5-TR 2022; APA 2023)
Scope: Confirm DSM-5-TR 2022 MDD criteria (≥5 symptoms ≥2 weeks including depressed mood or anhedonia, functional impairment, not better explained by SUD / medical / bereavement / bipolar)

No severity triggers fired against current inputs.

Plan

Regimen axis: **MDD stepwise pharmacotherapy ladder — Step 1 SSRI → Step 4 ECT/TMS/esketamine (APA 2023; STAR*D Rush AJP 2006; VA/DoD 2022)** — step "Step 1 — SSRI first-line (APA 2023; Cipriani Lancet 2018; NICE 2022)".
1. sertraline 25–50 mg PO daily PO once daily (SSRI, first line) — Cipriani 2018 — among most effective + tolerable; preferred in pregnancy + cardiac disease
2. escitalopram 5–10 mg PO daily PO once daily (SSRI, first line) — Cipriani 2018 — most effective SSRI; favourable interactions; QTc concern at higher doses
3. fluoxetine 10–20 mg PO daily PO once daily (mornings) (SSRI, first line) — Long half-life buffers missed doses; FDA-approved adolescent MDD
4. paroxetine 10–20 mg PO daily PO once daily (SSRI, second line) — Effective but anticholinergic; high discontinuation syndrome; AVOID in pregnancy — cardiac teratogen (FDA Category D); avoid in tamoxifen co-Rx — CYP2D6 (FDA 2011; APA 2023)
5. citalopram 10–20 mg PO daily PO once daily (SSRI, second line) — Effective; FDA 2012 QTc warning caps dose 20 mg in elderly

Setting playbook (outpatient) — Stepwise pharmacotherapy + psychotherapy with serial PHQ-9, suicidality screening, and side-effect surveillance to remission and maintenance (APA 2023; VA/DoD 2022)
6. sertraline OR escitalopram Sertraline 25–50 mg → 200; escitalopram 5–10 → 20 PO daily — First episode MDD without compelling alternative (APA 2023) (APA 2023 / NICE 2022 / Cipriani Lancet 2018 — first-line SSRI)
7. switch within or across class Venlafaxine XR 37.5 → 225; duloxetine 30 → 60–120; bupropion XL 150 → 300; mirtazapine 7.5 → 45 PO daily — Failure / intolerance of first SSRI at adequate dose × 4–8 weeks (STAR*D Rush AJP 2006) (STAR*D step 2 (Rush AJP 2006))
8. augmentation Lithium 300 BID target 0.6–0.8; T3 25–50 mcg; aripiprazole 2–15; quetiapine XR 150–300 PO daily — TRD = ≥2 failed adequate antidepressant trials (APA 2023) (STAR*D step 3 (Rush AJP 2006) + AUGMENT (PMID 19407731))
9. esketamine intranasal (clinic-supervised) 56–84 mg intranasal twice weekly × 4 weeks then taper intranasal 2×/week induction — TRD with acute suicidality OR ≥2 failed augmentations (FDA 2019) (FDA 2019 REMS; TRANSFORM-2 (PMID 31290965))
10. ECT / TMS referral TMS daily × 4–6 weeks; ECT 6–12 sessions over 2–4 weeks procedure per protocol — Severe MDD, psychotic features, catatonia, pregnancy, inability to wait, treatment-resistant (APA 2023) (APA 2023 / VA/DoD 2022 — most effective for severe MDD; Pagnin 2004 (PMID 15087991))

Non-pharmacologic actions:
- Cognitive-behavioural therapy (CBT) or interpersonal therapy (IPT) — combination with medication superior to either alone in moderate-severe (Cuijpers World Psych 2020; APA 2023; NICE 2022)
- Behavioural activation, sleep hygiene, exercise prescription 3×/week ≥30 min (CANMAT 2016 Kennedy; NICE 2022)
- Reduce alcohol; address substance use disorders concurrently (Anton JAMA 2006 COMBINE; VA/DoD 2022)
- Psychoeducation on medication course — 4–6 weeks to onset, 6–9 months after remission (APA 2023)
- Family / caregiver involvement with consent (APA 2023; NICE 2022)
- Horowitz hyperbolic taper plan documented at the moment any SSRI / SNRI discontinuation is considered — receptor-occupancy-anchored 50% step-downs to minimise discontinuation syndrome (Horowitz Lancet Psych 2019); short-half-life agents (paroxetine, venlafaxine) carry highest withdrawal burden — taper over ≥4 weeks minimum
- Lethal-means counseling for any patient with current or historical SI — firearm-restriction (lock-box, off-site storage, family transfer), large-quantity-medication-restriction (small-quantity prescriptions, locked storage, single-dispenser supervisor), vehicle / sharp-object review where applicable (Mann JAMA 2005; Stanley-Brown 2012; VA/DoD 2022)
- MDQ (Mood Disorder Questionnaire; Hirschfeld 2000) administered before every SSRI initiation in patient with no prior antidepressant trial history AND at every visit during induction in patients with any risk indicator (family history bipolar, early-onset MDE <25 yr, atypical features, antidepressant-induced switch history) — avoids antidepressant-induced manic switch (CANMAT 2016 Kennedy; APA 2023)
- Stanley-Brown 2012 safety-plan documented and reviewed at every visit for any patient with current or historical SI — 6 steps: warning signs / internal coping / people-for-distraction / people-for-support / professionals-and-agencies / means-restriction
- Social-determinants-of-health screen + referral — housing, food security, transportation, employment, social isolation, IPV / abuse, financial stress; all are MDD prognostic factors and modifiable via care-navigator / social-work referral (APA 2023; VA/DoD 2022)
- Relapse-prevention plan documented at remission — continuation phase ≥6–9 months after remission for first episode, ≥1–2 years for recurrent, lifelong if ≥3 episodes; CBT / MBCT relapse-prevention reduces relapse 30–50% (Cuijpers World Psych 2020; NICE NG222 2022)
- Exercise prescription specifically dosed 30 min × 5 days/week — moderate-intensity aerobic activity demonstrably antidepressant in mild-moderate MDD and as adjunct in moderate-severe (Schuch Br J Sports Med 2018 meta-analysis NEEDS_SOURCE_REVIEW; CANMAT 2016 Kennedy)

AVOID / contraindication checks:
- MAOI_washout_14_days_before_after (APA 2023; FDA)
- Bupropion_avoid_seizure_disorder_eating_disorder (FDA; APA 2023)
- Paroxetine_avoid_pregnancy_first_trimester (FDA Category D; APA 2023)
- Citalopram_QTc_dose_cap_20mg_elderly (FDA 2012)
- Lithium_baseline_renal_thyroid_pregnancy_avoid (APA 2023)
- Atypical_antipsychotic_metabolic_monitoring (APA/ADA 2004)
- Serotonin_syndrome_avoid_combo_serotonergic (Boyer NEJM 2005; APA 2023)
- SSRI_NSAID_anticoag_bleeding_caution (APA 2023)
- SSRI_hyponatremia_elderly_SIADH (APA 2023)
- Fluoxetine_paroxetine_tamoxifen_CYP2D6_avoid (FDA 2011; APA 2023)

Monitoring

Regimen monitoring:
- PHQ-9 at 2 4 6 8 12 weeks (APA 2023)
- Suicide risk q visit first 4 weeks (FDA 2004 black-box; VA/DoD 2022)
- Side effect screen q visit (APA 2023)
- Sodium at 2 4 weeks in elderly on SSRI (APA 2023)
- Lithium level q 5 7 days during titration then q 3 6 months (APA 2023)
- Atypical antipsychotic A1c lipids weight baseline 3mo 6mo annual (APA/ADA 2004)
- BP on SNRI or bupropion (APA 2023)
- TSH annually on lithium (APA 2023)
- Continue >=6 9mo after remission first episode (APA 2023; CANMAT 2016)
- Continue >=1 2yr recurrent (APA 2023; NICE 2022)
- Lifelong if >=3 episodes (APA 2023; CANMAT 2016 Kennedy)

Setting (outpatient) monitoring:
- PHQ-9 q 2 weeks until remission then q 1–3 months (APA 2023; VA/DoD 2022)
- C-SSRS at every visit for first 4 weeks of any new antidepressant (FDA 2004 black-box; VA/DoD 2022)
- Side-effect screen q visit (APA 2023)
- Sodium at 2–4 weeks if elderly on SSRI (APA 2023)
- Lithium level q5–7 days during titration; renal + TSH q6 months (APA 2023)
- Atypical antipsychotic A1c + lipids + weight baseline / 3 mo / 6 mo / annual (APA/ADA 2004)

Follow-up plan: Continue treatment ≥6–9 months after remission for first episode; ≥1–2 years for recurrent; lifelong if ≥3 episodes (APA 2023; CANMAT 2016 Kennedy); relapse-prevention therapy (CBT / MBCT) reduces relapse 30–50% (Cuijpers World Psych 2020); lifestyle (exercise, sleep hygiene, alcohol reduction, social engagement)
- Close-out criterion: Maintenance plan in place

Monitoring phase: PHQ-9 at 2, 4, 6, 8, 12 weeks (APA 2023); first 4 weeks of any antidepressant high suicide watch (FDA 2004 black-box); side-effect screen (sexual, GI, sleep, weight, hyponatremia in elderly); response = 50% PHQ-9 reduction; remission = PHQ-9 <5 (STAR*D Rush AJP 2006)

Disposition

Current setting: outpatient — Stepwise pharmacotherapy + psychotherapy with serial PHQ-9, suicidality screening, and side-effect surveillance to remission and maintenance (APA 2023; VA/DoD 2022)

Disposition criteria:
- Continue current step if responding — 50% PHQ-9 reduction (STAR*D Rush AJP 2006; APA 2023)
- Step up if inadequate response at adequate dose / duration (STAR*D Rush AJP 2006)
- Refer to psychiatry if at Step 3 augmentation or beyond, complex comorbidity, or pregnancy (APA 2023; VA/DoD 2022)

Escalation triggers (move to higher acuity):
- Active SI with intent / plan / means → ED (APA 2023; VA/DoD 2022)
- Psychotic features / catatonia → urgent psychiatric admission (APA 2023)
- Severe agitation or self-neglect → urgent psychiatric admission (APA 2023)
- Pregnancy / postpartum with severe MDD or psychosis → urgent psychiatric + OB consult (APA 2023)

Patient Action Plan

**Depression action plan + Stanley-Brown 2012 safety plan (APA 2023; VA/DoD 2022)**
Personalised values: baseline_PHQ9, current_medication_list, identified_supports, crisis_line_numbers, reasons_for_living, means_restriction_steps.

**Doing well — PHQ-9 <5, no SI, functioning at baseline (APA 2023)** (green):
Triggers:
- Mood + sleep + energy + interest at baseline (APA 2023)
- No suicidal thoughts (C-SSRS; Posner 2011)
- Engaging with usual activities and relationships (APA 2023)
Actions:
- Take antidepressant as prescribed every day — do not stop suddenly (APA 2023; CANMAT 2016)
- Continue therapy / coping practices — exercise, sleep schedule, social engagement (NICE 2022; Cuijpers World Psych 2020)
- Keep follow-up appointments (APA 2023)
- Keep crisis line numbers available even when feeling well (VA/DoD 2022)

**Caution — PHQ-9 rising or 5–14, return of symptoms, passive SI without plan (APA 2023)** (yellow):
Triggers:
- Sleep / appetite / energy declining (DSM-5-TR 2022 criterion A)
- Loss of interest, hopelessness, increased irritability (DSM-5-TR 2022)
- Passing thoughts that life is not worth living without intent or plan (C-SSRS; Posner 2011)
- Increased alcohol or substance use (VA/DoD 2022)
- Withdrawal from supports (APA 2023)
Actions:
- Use coping strategies from your safety plan — call a support person, use distraction or grounding, reduce alcohol, increase activity (Stanley-Brown 2012)
- Contact your provider for an early appointment — within 1 week (APA 2023)
- Review medication adherence with provider — consider dose increase or augmentation if at adequate dose ≥4 weeks (STAR*D Rush AJP 2006; APA 2023)
- Avoid means of self-harm — lock or remove firearms; secure or limit medications to short supply (VA/DoD 2022)
Contact provider when:
- Symptoms not improving after 2 weeks of self-care (APA 2023)
- PHQ-9 rises by ≥5 points (APA 2023)
- Any thoughts of suicide become more frequent (VA/DoD 2022)
- Functioning at work / home declines (APA 2023)

**Medical alert — active SI with intent or plan, plan to use means, recent self-harm, psychosis (APA 2023; VA/DoD 2022)** (red):
Triggers:
- Specific thoughts of how to end your life (C-SSRS; Posner 2011)
- Access to means — firearms, large-quantity meds (VA/DoD 2022)
- Recent self-harm or attempt (APA 2023)
- Hearing voices or feeling unsafe with reality (APA 2023)
- Inability to keep yourself safe (APA 2023)
Actions:
- Call 988 (US) / your local crisis line / emergency services NOW (VA/DoD 2022)
- Go to the nearest emergency department; do not be alone (APA 2023)
- Hand any means (firearms, pills) to a trusted person before going (VA/DoD 2022)
- Tell someone you trust what is happening (Stanley-Brown 2012)
- Do not use alcohol or non-prescribed substances (APA 2023)
Contact provider when:
- Any red zone trigger — emergency department immediately, do not wait (APA 2023; VA/DoD 2022)

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] C-SSRS positive for active SI with intent, plan, or recent preparatory behaviour (Posner 2011)
- [LIFE_THREATENING] Tremor, hyperreflexia, clonus, hyperthermia, autonomic instability, AMS in patient on serotonergic agents (Hunter criteria; Boyer NEJM 2005)
- [SEVERE] PHQ-9 ≥20 (severe MDD per Kroenke 2001)

Citations

- APA Practice Guideline 3rd ed. (Gelenberg 2010) + APA 2023 update + VA/DoD MDD CPG 2022 + NICE NG222 2022 (CG222 superseded) + CANMAT 2016 Kennedy + CANMAT 2024 (verify) [PMID:17074942](https://pubmed.ncbi.nlm.nih.gov/17074942/)
- Cited evidence (PMID 19880458) [PMID:19880458](https://pubmed.ncbi.nlm.nih.gov/19880458/)
- Cited evidence (PMID 29477251) [PMID:29477251](https://pubmed.ncbi.nlm.nih.gov/29477251/)
- Cited evidence (PMID 15704999) [PMID:15704999](https://pubmed.ncbi.nlm.nih.gov/15704999/)
- Cited evidence (PMID 19407731) [PMID:19407731](https://pubmed.ncbi.nlm.nih.gov/19407731/)

Last reconciled with current guidelines: 2026-05-14.
References
  • APA Practice Guideline 3rd ed. (Gelenberg 2010) + APA 2023 update + VA/DoD MDD CPG 2022 + NICE NG222 2022 (CG222 superseded) + CANMAT 2016 Kennedy + CANMAT 2024 (verify) — PMID:17074942
  • Cited evidence (PMID 19880458) — PMID:19880458
  • Cited evidence (PMID 29477251) — PMID:29477251
  • Cited evidence (PMID 15704999) — PMID:15704999
  • Cited evidence (PMID 19407731) — PMID:19407731