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. Indications
      1. Little or no response to Antidepressant at 6 to 8 weeks of optimal dosing
      2. Adverse effects limit continued use, adequate dosing or compliance
      3. Single medication therapy is preferred by patient to reduce cost and risk of adverse effects
    2. Consider switching from one SSRI to another
    3. Consider switching from an SSRI to a unique Antidepressant class
      1. Mirtazapine (Remeron)
      2. SNRI: Venlafaxine (Effexor), Duloxetine
    4. 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. Indications
      1. Partial response to first Antidepressant (intended to be continued)
      2. Desire for faster response rate with augmentation (in contrast to delays with a new single agent)
    2. 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
    3. Atypical Antipsychotics at low dose (however associated with other adverse effects)
      1. See Atypical Antipsychotics for adverse effects
      2. Aripiprazole (Abilify)
        1. Preferred of the Atypical Antipsychotics for augmentation due to cost, tolerability
      3. Olanzapine (Zyprexa)
      4. Quetiapine (Seroquel)
      5. Risperidone (Risperdal)
    4. 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)
        3. Must be given at hospital or clinic within designated REMS program

IV. Management: Step 3

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