MDD (Adult)

MDD treatment guideline for Adult: first-line and later treatments by phase, with sources.

Based on: Canadian Network for Mood and Anxiety Treatments (CANMAT) 2016 Clinical Guidelines for the Management of Adults with Major Depressive Disorder: Section 3. Pharmacological Treatments and Canadian Network for Mood and Anxiety Treatments (CANMAT) 2023 Update on Clinical Guidelines for Management of Major Depressive Disorder in Adults: Réseau canadien pour les traitements de l'humeur et de l'anxiété (CANMAT) 2023 : Mise à jour des lignes directrices cliniques pour la prise en charge du trouble dépressif majeur chez les adultes

acute

  • mild — 1st line — lifestyle intervention — Monotherapy — Supervised Exercise — Low to moderate intensity for 30-40 min at a time, 3-4x a week, for a minimum of 9
  • seasonal (winter pattern) — 1st line — lifestyle intervention — Monotherapy — Light therapy — 10,000 lux white light 30 min daily, shortly after awakening
  • mild (nonseasonal) — 2nd line — lifestyle intervention — Monotherapy — Light therapy
  • moderate — 2nd line — lifestyle intervention — adjunctive — Exercise
  • moderate (nonseasonal) — 2nd line — lifestyle intervention — adjunctive — Light therapy
  • mild — 1st line — psychotherapy — Cognitive behavioural therapy (CBT)
  • moderate — 1st line — psychotherapy — Cognitive behavioural therapy (CBT)
  • severe — 1st line — psychotherapy — Cognitive behavioural therapy (CBT)
  • mild — 1st line — psychotherapy — Interpersonal therapy (IPT)
  • moderate — 1st line — psychotherapy — Interpersonal therapy (IPT)
  • severe — 1st line — psychotherapy — Interpersonal therapy (IPT)
  • mild — 1st line — psychotherapy — Behavioural acitivation (BA)
  • moderate — 1st line — psychotherapy — Behavioural acitivation (BA)
  • severe — 1st line — psychotherapy — Behavioural acitivation (BA)
  • mild — 1st line — medication — monotherapy — Citalopram
  • moderate — 1st line — medication — monotherapy — Citalopram
  • severe — 1st line — medication — monotherapy — Citalopram
  • mild — 1st line — medication — monotherapy — Escitalopram
  • moderate — 1st line — medication — monotherapy — Escitalopram
  • severe — 1st line — medication — monotherapy — Escitalopram
  • mild — 1st line — medication — monotherapy — Fluoxeitine
  • moderate — 1st line — medication — monotherapy — Fluoxeitine
  • severe — 1st line — medication — monotherapy — Fluoxeitine
  • mild — 1st line — medication — monotherapy — Fluvoxamine
  • moderate — 1st line — medication — monotherapy — Fluvoxamine
  • severe — 1st line — medication — monotherapy — Fluvoxamine
  • mild — 1st line — medication — monotherapy — Paroxetine
  • moderate — 1st line — medication — monotherapy — Paroxetine
  • severe — 1st line — medication — monotherapy — Paroxetine
  • mild — 1st line — medication — monotherapy — Sertraline
  • moderate — 1st line — medication — monotherapy — Sertraline
  • severe — 1st line — medication — monotherapy — Sertraline
  • mild — 1st line — medication — monotherapy — Desvenlafaxine
  • moderate — 1st line — medication — monotherapy — Desvenlafaxine
  • severe — 1st line — medication — monotherapy — Desvenlafaxine
  • mild — 1st line — medication — monotherapy — Duloxetine
  • moderate — 1st line — medication — monotherapy — Duloxetine
  • severe — 1st line — medication — monotherapy — Duloxetine
  • mild — 1st line — medication — monotherapy — Levomilnacipran
  • moderate — 1st line — medication — monotherapy — Levomilnacipran
  • severe — 1st line — medication — monotherapy — Levomilnacipran
  • mild — 1st line — medication — monotherapy — Venlafaxine-XR
  • moderate — 1st line — medication — monotherapy — Venlafaxine-XR
  • severe — 1st line — medication — monotherapy — Venlafaxine-XR
  • mild — 1st line — medication — monotherapy — Bupropion
  • moderate — 1st line — medication — monotherapy — Bupropion
  • severe — 1st line — medication — monotherapy — Bupropion
  • mild — 1st line — medication — monotherapy — Mirtazapine
  • moderate — 1st line — medication — monotherapy — Mirtazapine
  • severe — 1st line — medication — monotherapy — Mirtazapine
  • mild — 1st line — medication — monotherapy — Vilazodone
  • moderate — 1st line — medication — monotherapy — Vilazodone
  • severe — 1st line — medication — monotherapy — Vilazodone
  • mild — 1st line — medication — monotherapy — Vortioxetine
  • moderate — 1st line — medication — monotherapy — Vortioxetine
  • severe — 1st line — medication — monotherapy — Vortioxetine
  • mild — 1st line — medication — monotherapy — Agomelatine
  • moderate — 1st line — medication — monotherapy — Agomelatine
  • severe — 1st line — medication — monotherapy — Agomelatine
  • mild — 1st line — medication — monotherapy — Mianserin
  • moderate — 1st line — medication — monotherapy — Mianserin
  • severe — 1st line — medication — monotherapy — Mianserin
  • mild — 1st line — medication — monotherapy — Milnacipran
  • moderate — 1st line — medication — monotherapy — Milnacipran
  • severe — 1st line — medication — monotherapy — Milnacipran
  • mild — 2nd line — medication — monotherapy — Amitriptyline
  • moderate — 2nd line — medication — monotherapy — Amitriptyline
  • severe — 2nd line — medication — monotherapy — Amitriptyline
  • mild — 2nd line — medication — monotherapy — Clomipramine
  • moderate — 2nd line — medication — monotherapy — Clomipramine
  • severe — 2nd line — medication — monotherapy — Clomipramine
  • mild — 2nd line — medication — monotherapy — Desipramine
  • moderate — 2nd line — medication — monotherapy — Desipramine
  • severe — 2nd line — medication — monotherapy — Desipramine
  • mild — 2nd line — medication — monotherapy — Doxepin
  • moderate — 2nd line — medication — monotherapy — Doxepin
  • severe — 2nd line — medication — monotherapy — Doxepin
  • mild — 2nd line — medication — monotherapy — Imipramine
  • moderate — 2nd line — medication — monotherapy — Imipramine
  • severe — 2nd line — medication — monotherapy — Imipramine
  • mild — 2nd line — medication — monotherapy — Nortriptyline
  • moderate — 2nd line — medication — monotherapy — Nortriptyline
  • severe — 2nd line — medication — monotherapy — Nortriptyline
  • mild — 2nd line — medication — monotherapy — Protriptyline
  • moderate — 2nd line — medication — monotherapy — Protriptyline
  • severe — 2nd line — medication — monotherapy — Protriptyline
  • mild — 2nd line — medication — monotherapy — Trimipramine
  • moderate — 2nd line — medication — monotherapy — Trimipramine
  • severe — 2nd line — medication — monotherapy — Trimipramine
  • mild — 2nd line — medication — monotherapy — Moclobemide
  • moderate — 2nd line — medication — monotherapy — Moclobemide
  • severe — 2nd line — medication — monotherapy — Moclobemide
  • mild — 2nd line — medication — monotherapy — Trazodone
  • moderate — 2nd line — medication — monotherapy — Trazodone
  • severe — 2nd line — medication — monotherapy — Trazodone
  • mild — 2nd line — medication — monotherapy — Quetiapine
  • moderate — 2nd line — medication — monotherapy — Quetiapine
  • severe — 2nd line — medication — monotherapy — Quetiapine
  • mild — 2nd line — medication — monotherapy — Dextromethorphan-bupropion
  • moderate — 2nd line — medication — monotherapy — Dextromethorphan-bupropion
  • severe — 2nd line — medication — monotherapy — Dextromethorphan-bupropion
  • mild — 2nd line — medication — monotherapy — Nefazodone
  • moderate — 2nd line — medication — monotherapy — Nefazodone
  • severe — 2nd line — medication — monotherapy — Nefazodone
  • mild — 2nd line — medication — monotherapy — Selegiline transdermal
  • moderate — 2nd line — medication — monotherapy — Selegiline transdermal
  • severe — 2nd line — medication — monotherapy — Selegiline transdermal
  • mild — 3rd line — medication — monotherapy — Phenelzine
  • moderate — 3rd line — medication — monotherapy — Phenelzine
  • severe — 3rd line — medication — monotherapy — Phenelzine
  • mild — 3rd line — medication — monotherapy — Tranycypromine
  • moderate — 3rd line — medication — monotherapy — Tranycypromine
  • severe — 3rd line — medication — monotherapy — Tranycypromine
  • mild — 3rd line — medication — monotherapy — Reboxetine
  • moderate — 3rd line — medication — monotherapy — Reboxetine
  • severe — 3rd line — medication — monotherapy — Reboxetine
  • mild — 1st line — CAM treatments — monotherapy — St. John's wort
  • mild — 2nd line — CAM treatments — monotherapy — Acupuncture
  • moderate — 2nd line — CAM treatments — monotherapy — St. John's wort
  • moderate — 2nd line — CAM treatments — adjunctive — Acupuncture
  • mild — 2nd line — CAM treatments — adjunctive — L-methy folate
  • moderate — 2nd line — CAM treatments — adjunctive — L-methy folate
  • mild — 3rd line — CAM treatments — adjunctive — SAM-e
  • moderate — 3rd line — CAM treatments — adjunctive — SAM-e
  • mild — 3rd line — CAM treatments — monotherapy — DHEA
  • mild — 3rd line — CAM treatments — monotherapy — Omega-3 fatty acids
  • mild — 3rd line — CAM treatments — monotherapy — Saffron, lavender, or roseroot
  • mild — 1st line — Digital Health Interventions (DHI) — adjunctive — Guided iCBT DHIs — Examples: Good days ahead, BounceBack, Deprexis, MoodBeacon, Pacifica/Sanvello
  • moderate — 1st line — Digital Health Interventions (DHI) — adjunctive — Guided iCBT DHIs — Examples: Good days ahead, BounceBack, Deprexis, MoodBeacon, Pacifica/Sanvello
  • mild — 1st line — Digital Health Interventions (DHI) — monotherapy — Guided iCBT DHIs — Examples: Good days ahead, BounceBack, Deprexis, MoodBeacon, Pacifica/Sanvello
  • mild — 2nd line — Digital Health Interventions (DHI) — adjunctive — Self directed DHIs, with guidence from clinicians — Examples: Catch It, Headspace, MoodGYM, MoodKit, Spark Direct
  • moderate — 2nd line — Digital Health Interventions (DHI) — adjunctive — Self directed DHIs, with guidence from clinicians — Examples: Catch It, Headspace, MoodGYM, MoodKit, Spark Direct
  • mild — 2nd line — Digital Health Interventions (DHI) — adjunctive — Guided iBA DHIs — Examples: Good days ahead, BounceBack, Deprexis, MoodBeacon, Pacifica/Sanvello
  • moderate — 2nd line — Digital Health Interventions (DHI) — adjunctive — Guided iBA DHIs — Examples: Good days ahead, BounceBack, Deprexis, MoodBeacon, Pacifica/Sanvello
  • mild — 3rd line — Digital Health Interventions (DHI) — adjunctive — Self directed DHIs, when no other clinical interventions are available — Examples: Catch It, Headspace, MoodGYM, MoodKit, Spark Direct
  • mild — Insufficient evidence — Digital Health Interventions (DHI) — adjunctive — Chatbot and conversational agents — Insufficient evidence
  • moderate — Insufficient evidence — Digital Health Interventions (DHI) — adjunctive — Chatbot and conversational agents — Insufficient evidence
  • Difficult to treat (DTD) — 1st line — medication — adjunctive — Aripiprazole
  • Difficult to treat (DTD) — 1st line — medication — adjunctive — Brexpiprazole
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Bupropion
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Intranasal esketamine
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — IV racemic ketamine
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Olanzapine
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Quetiapine-XR
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Risperidone
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Lithium
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Cariprazine
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Mirtazapine/mianserin
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Modafinil
  • Difficult to treat (DTD) — 2nd line — medication — adjunctive — Triiodothyronine
  • Difficult to treat (DTD) — 3rd line — medication — adjunctive — Other antidepressants, including TCAs
  • Difficult to treat (DTD) — 3rd line — medication — adjunctive — Stimulants
  • Difficult to treat (DTD) — 3rd line — medication — adjunctive — Lamotrigine
  • Difficult to treat (DTD) — 3rd line — medication — adjunctive — Non-IV racemic ketamine
  • Difficult to treat (DTD) — 3rd line — medication — adjunctive — Pramilexole
  • Difficult to treat (DTD) — 3rd line — medication — adjunctive — Ziprasidone
  • Difficult to treat (DTD) — Invx — medication — adjunctive — Psychedelic-assisted psychotherapy — Investigational
  • Difficult to treat (DTD) — Not recommended — medication — adjunctive — Cannabis — Not Recommended: Insufficient evidence for efficacy; risk of harms
  • severe — 1st line — Neuromodulation treatment — Electroconvulsive therapy (ECT)
  • Treatment resistant (TRD) — 1st line — Neuromodulation treatment — repetitive Transcranial Magnetic Stimulation (rTMS)
  • Difficult to treat (DTD) — 2nd line — Neuromodulation treatment — Electroconvulsive therapy (ECT)
  • mild — 3rd line — Neuromodulation treatment — transcranial Direct Current Stimulation (tDCS)
  • moderate — 3rd line — Neuromodulation treatment — transcranial Direct Current Stimulation (tDCS)
  • Difficult to treat (DTD) — 3rd line — Neuromodulation treatment — Vagus Nerve Stimulation (VNS)
  • Difficult to treat (DTD) — Invx — Neuromodulation treatment — Deep Brain Stimulation (DBS) — Investigational
  • Difficult to treat (DTD) — Invx — Neuromodulation treatment — Magnetic Seizure Therapy (MST) — Investigational

maintenance

  • 2nd line — lifestyle intervention — adjunctive — Sleep hygiene and CBT-I
  • 3rd line — lifestyle intervention — adjunctive — Healthy diet — Varied diet with high content of fruits, vegetables, and fibre, and low content of saturated fat and carbohydrates
  • 3rd line — lifestyle intervention — adjunctive — Mediterranean diet
  • 3rd line — lifestyle intervention — adjunctive — Sleep deprivation (wake therapy)
  • Insufficient evidence — lifestyle intervention — Probiotics — Insufficient evidence
  • 1st line — psychotherapy — Cognitive behavioural therapy (CBT)
  • 1st line — psychotherapy — Interpersonal therapy (IPT)
  • 1st line — psychotherapy — Behavioural acitivation (BA)
  • 2nd line — psychotherapy — Cognitive behavioural analysis system of psychotherapy (CBASP)
  • 2nd line — psychotherapy — Mindfulness-based cognitive therapy (MCBT)
  • 2nd line — psychotherapy — Problem-solving therapy (PST)
  • 2nd line — psychotherapy — Short-term psychodynamic psychotherapy (STPP)
  • 2nd line — psychotherapy — Transdiagnostic psychocological treatment of emotional disorders
  • 3rd line — psychotherapy — Acceptance and commitment therapy (ACT)
  • 3rd line — psychotherapy — Long-term psychodynamic psychotherapy (PDT)
  • 3rd line — psychotherapy — Metacognitive therapy (MCT)
  • 3rd line — psychotherapy — Motivational Interviewing (MI)
  • 1st line — medication — monotherapy — Citalopram
  • 1st line — medication — monotherapy — Escitalopram
  • 1st line — medication — monotherapy — Fluoxeitine
  • 1st line — medication — monotherapy — Fluvoxamine
  • 1st line — medication — monotherapy — Paroxetine
  • 1st line — medication — monotherapy — Sertraline
  • 1st line — medication — monotherapy — Desvenlafaxine
  • 1st line — medication — monotherapy — Duloxetine
  • 1st line — medication — monotherapy — Levomilnacipran
  • 1st line — medication — monotherapy — Venlafaxine-XR
  • 1st line — medication — monotherapy — Bupropion
  • 1st line — medication — monotherapy — Mirtazapine
  • 1st line — medication — monotherapy — Vilazodone
  • 1st line — medication — monotherapy — Vortioxetine
  • 1st line — medication — monotherapy — Agomelatine
  • 1st line — medication — monotherapy — Mianserin
  • 1st line — medication — monotherapy — Milnacipran
  • 2nd line — medication — monotherapy — Amitriptyline
  • 2nd line — medication — monotherapy — Clomipramine
  • 2nd line — medication — monotherapy — Desipramine
  • 2nd line — medication — monotherapy — Doxepin
  • 2nd line — medication — monotherapy — Imipramine
  • 2nd line — medication — monotherapy — Nortriptyline
  • 2nd line — medication — monotherapy — Protriptyline
  • 2nd line — medication — monotherapy — Trimipramine
  • 2nd line — medication — monotherapy — Moclobemide
  • 2nd line — medication — monotherapy — Trazodone
  • 2nd line — medication — monotherapy — Quetiapine
  • 2nd line — medication — monotherapy — Dextromethorphan-bupropion
  • 2nd line — medication — monotherapy — Nefazodone
  • 2nd line — medication — monotherapy — Selegiline transdermal
  • 3rd line — medication — monotherapy — Phenelzine
  • 3rd line — medication — monotherapy — Tranycypromine
  • 3rd line — medication — monotherapy — Reboxetine