II. Management: Step 1

  1. Assess Major Depression Differential Diagnosis
  2. Maximize non-medication therapies (e.g. Exercise, psychotherapy)
    1. See Depression Management
  3. Assess Adequacy of Antidepressant trial
    1. Minimum Duration: 6-8 weeks
    2. Minimum Dose: one dose increase at 2-4 weeks
  4. Assess for comorbid confounding factors
    1. Anxiety Disorder
    2. Increased Psychosocial Stressors
    3. Alcohol or Drug Abuse
    4. Excessive Caffeine intake
    5. Chronic medical illness
    6. Medications Predisposing to Depression
  5. Assess Compliance
    1. Has patient abruptly discontinued Antidepressant
    2. Has patient missed or skipped Antidepressant doses
    3. Has Antidepressant been temporarily interrupted
      1. Missed medication refill
      2. Travel or lifestyle interfering with dosing

III. Management: Step 2

  1. Consider alternative Antidepressant
    1. Consider switching from one SSRI to another
    2. Consider switching from an SSRI to a unique Antidepressant class
      1. Mirtazapine (Remeron)
      2. SNRI: Venlafaxine (Effexor), Duloxetine
    3. Protocol for cross-tapering to a new SSRI
      1. First 5-7 days
        1. Cut dose of agent 1 to 50%
        2. Start low dose of agent 2
          1. Delay start of new agent when switching from Fluoxetine (Prozac) due to very long half life
      2. Next
        1. Stop agent 1
        2. Increase dose of agent 2
      3. Example: Celexa to Lexapro over 5 days
        1. Decrease Celexa 40 to 20 and then stop
        2. Start Lexapro 5 mg, then increase to 10 mg
      4. Example: Paxil to Zoloft over at least 7 days
        1. Decrease Paxil 20 to 10 and then stop
        2. Start Zoloft 25 mg, then increase to 50 mg
        3. Paroxetine taper often needs longer duration
  2. Consider Augmenting current Antidepressant regimen
    1. Augment Selective Serotonin Reuptake Inhibitor (SSRI)
      1. Add Bupropion (Wellbutrin)
        1. Consider in comorbid Fatigue or Antidepressant Induced Sexual Dysfunction
      2. Add SNRI (Venlafaxine, Duloxetine)
        1. Risk of Serotonin Syndrome
        2. Consider in comorbid anxiety
      3. Add Miratazapine (Remeron)
        1. Consider in comorbid Insomnia or Nausea
      4. Add Buspirone (Buspar) 15 to 30 mg orally daily
        1. Consider in comorbid anxiety
      5. Add Tricyclic Antidepressant (e.g. Desipramine, Nortriptyline) at low dose
        1. Consider in comorbid Insomnia, Headaches or neuropathic pain
      6. Add Trazodone
        1. Consider in comorbid Insomnia
    2. Atypical Antipsychotics at low dose (however associated with other adverse effects)
      1. Olanzapine (Zyprexa)
      2. Aripiprazole (Abilify)
      3. Quetiapine (Seroquel)
      4. Risperidone (Risperdal)
    3. Agents used by Psychiatrists to augment therapy (response to these agents is often rapid within 10 days)
      1. Lithium 300 to 600 mg daily in divided doses (blood levels 0.4 to 0.8 mEq/L)
        1. Consider if associated Suicidality
      2. Liothyronine (Cytomel, T3) 25-50 mcg daily
        1. Similar efficacy to Lithium in refractory depression
        2. May increase nervousness and anxiety
      3. Methylphenidate (Ritalin) 10 to 15 mg daily
        1. Consider in comorbid apathy and Fatigue
      4. Pindolol (Visken) 2.5 to 7.5 mg daily
      5. Esketamine (Spravato)
        1. Administered intranasally twice weekly for 4 weeks, then every 1-2 weeks
        2. Monitor for 2 hours after each dose (for Hypertension, dissociation, sedation)

IV. Management: Step 3

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Ontology: Major Depressive Disorder (C1269683)

Definition (MSH) Marked depression appearing in the involution period and characterized by hallucinations, delusions, paranoia, and agitation.
Definition (PSY) Affective disorder marked by dysphoric mood, inactivity, lack of interest, insomnia, feelings of worthlessness, diminished ability to think, and thoughts of suicide. Use DEPRESSION (EMOTION) for nonclinical depression.
Definition (CSP) one or more periods of depression in the absence of history of manic or hypomanic episodes; chronic type lasts 2 or more years; melancholic type is more severe, has vegetative signs, and responds well to somatic therapy.
Concepts Mental or Behavioral Dysfunction (T048)
MSH D003865
ICD10 F32.9
SnomedCT 370143000, 35489007
English Disorder, Major Depressive, Disorders, Major Depressive, Major Depressive Disorders, MDD, MAJOR DEPRESSIVE DISORDER, DEPRESSIVE DIS MAJOR, MAJOR DEPRESSIVE DIS, Major depressive disorder NOS, Major depressive illness, Major depression NOS, Depressive Disorder, Major [Disease/Finding], major depressive illness, major depressive disorder, major depression, Major depressive disorder (diagnosis), Major depression, Major depressive disorder (disorder), Major depressive disorder, Major depression, NOS, Major depressive disorder, NOS, Depressive Disorder, Major, Depressive Disorders, Major, Major Depressive Disorder, Major Depression
Dutch depressieve ziekte, depressieve stoornis NAO, major depression, Depressieve stoornis, ernstige, Ernstige depressieve stoornis, Involutiepsychose, Melancholie, involutionele, Parafrenie, involutionele, Psychose, involutionele, Involutiedepressie, Involutionele depressie
French Syndrome dépressif majeur SAI, Épisode dépressif majeur, Dépression grave, Grave dépression, Dépression majeure, Trouble dépressif majeur
German Major Depression NNB, schwere depressive Krankheit, Endogene Depression, Involutionsdepression, Melancholie, Involutions-, Paraphrenie, Involutions-, Psychose, Involutions-, Depressive Störung, majore, Majore depressive Störung
Italian Depressione maggiore NAS, Malattia depressiva maggiore, Depressione maggiore, Disturbo depressivo maggiore
Portuguese Doença depressiva major, Perturbação depressiva major NE, Depressão grave, Transtorno Depressivo Maior
Spanish Trastorno depresivo mayor NEOM, Enfermedad depresiva mayor, depresión mayor, trastorno depresivo mayor (trastorno), trastorno depresivo mayor, Depresión mayor, Trastorno Depresivo Mayor
Japanese 大うつ病NOS, オオウツビョウ, ダイウツビョウ, ダイウツビョウNOS, うつ病-退行期, 大うつ病性障害, 大鬱病, うつ病-更年期, 大うつ病, 初老期うつ病, 更年期うつ病, 更年期鬱病, 精神病-更年期, 退行期うつ病, 退行期パラフレニー, 退行期メランコリア, 退行期精神病, 鬱病-更年期, パラフレニー-退行期, 更年期うつ状態, 更年期メランコリー, 更年期精神病, 更年期鬱状態, 精神病-退行期, 退行期鬱病
Swedish Involutionsdepression
Czech psychóza involuční, deprese involuční, depresivní porucha unipolární, melancholie involuční, parafrenie involuční, Velké depresivní onemocnění, Velká deprese, Velká depresivní porucha NOS
Finnish Laaja-alainen masentuneisuushäiriö
Polish Wielkie zaburzenie depresyjne, Zaburzenie depresyjne wielkie, Ciężkie zaburzenie depresyjne, Depresja wielka, Parafrenia inwolucyjna, Depresja głęboka, Epizod depresji dużej, Depresja inwolucyjna
Hungarian Major depressiós betegség, Major depressio, Major depressiós zavar k.m.n.
Norwegian Depresjon, alvorlig, Markert depresjon, Depresjon, markert, Alvorlig depresjon, Markant depressiv forstyrrelse