Refractory Depression Management

Aka: Refractory Depression Management, Depression Unresponsive to Medication

1. Step 1
   1. Assess Major Depression Differential Diagnosis
   2. Assess Adequacy of Antidepressant trial
      1. Minimum Duration: 6-8 weeks
      2. Minimum Dose: one dose increase at 2-4 weeks
   3. 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
   4. 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
2. 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
         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)
         2. Add SNRI (Venlafaxine, Duloxetine)
            1. Risk of Serotonin Syndrome
         3. Add Miratazapine (Remeron)
         4. Add Buspirone (Buspar) 15 to 30 mg PO qd
         5. Add Tricyclic Antidepressant (e.g. Desipramine)
      2. Atypical Antipsychotics
         1. Olanzapine
         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)
         2. Cytomel (T3) 25-50 mcg daily
         3. Methylphenidate (Ritalin) 10 to 15 mg qd
         4. Pindolol (Visken) 2.5 to 7.5 mg qd
3. Step 3
   1. Consider Electroconvulsive Therapy
4. References
   1. Ables (2003) Am Fam Physician 67(3):547-4
   2. Bridges (1995) Br J Hosp Med 54:501-6
   3. Cadieux (1998) Am Fam Physician 58(9):2059-62
   4. Little (2009) Am Fam Physician 80(2):167-72