II. Management: Step 1
- Assess Major Depression Differential Diagnosis
- Maximize non-medication therapies (e.g. Exercise, psychotherapy)
- Assess Adequacy of Antidepressant trial
- Minimum Duration: 6-8 weeks
- Minimum Dose: one dose increase at 2-4 weeks
- Assess for comorbid confounding factors
- Anxiety Disorder
- Increased Psychosocial Stressors
- Alcohol or Drug Abuse
- Excessive Caffeine intake
- Chronic medical illness
- Medications Predisposing to Depression
- Assess Compliance
- Has patient abruptly discontinued Antidepressant
- Has patient missed or skipped Antidepressant doses
- Has Antidepressant been temporarily interrupted
- Missed medication refill
- Travel or lifestyle interfering with dosing
III. Management: Step 2
- Consider alternative Antidepressant
- Indications
- Little or no response to Antidepressant at 6 to 8 weeks of optimal dosing
- Adverse effects limit continued use, adequate dosing or compliance
- Single medication therapy is preferred by patient to reduce cost and risk of adverse effects
- Consider switching from one SSRI to another
- Consider switching from an SSRI to a unique Antidepressant class
- Protocol for cross-tapering to a new SSRI
- First 5-7 days
- Cut dose of agent 1 to 50%
- Start low dose of agent 2
- Delay start of new agent when switching from Fluoxetine (Prozac) due to very long half life
- Next
- Stop agent 1
- Increase dose of agent 2
- Example: Celexa to Lexapro over 5 days
- Example: Paxil to Zoloft over at least 7 days
- Decrease Paxil 20 to 10 and then stop
- Start Zoloft 25 mg, then increase to 50 mg
- Paroxetine taper often needs longer duration
- First 5-7 days
- Indications
- Consider Augmenting current Antidepressant regimen
- Indications
- Partial response to first Antidepressant (intended to be continued)
- Desire for faster response rate with augmentation (in contrast to delays with a new single agent)
- Augment Selective Serotonin Reuptake Inhibitor (SSRI)
- Add Bupropion (Wellbutrin)
- Consider in comorbid Fatigue or Antidepressant Induced Sexual Dysfunction
- Add SNRI (Venlafaxine, Duloxetine)
- Risk of Serotonin Syndrome
- Consider in comorbid anxiety
- Add Miratazapine (Remeron)
- Add Buspirone (Buspar) 15 to 30 mg orally daily
- Consider in comorbid anxiety
- Add Tricyclic Antidepressant (e.g. Desipramine, Nortriptyline) at low dose
- Add Trazodone
- Consider in comorbid Insomnia
- Add Bupropion (Wellbutrin)
- Atypical Antipsychotics at low dose (however associated with other adverse effects)
- See Atypical Antipsychotics for adverse effects
- Aripiprazole (Abilify)
- Preferred of the Atypical Antipsychotics for augmentation due to cost, tolerability
- Olanzapine (Zyprexa)
- Quetiapine (Seroquel)
- Risperidone (Risperdal)
- Agents used by Psychiatrists to augment therapy (response to these agents is often rapid within 10 days)
- Lithium 300 to 600 mg daily in divided doses (blood levels 0.4 to 0.8 mEq/L)
- Consider if associated Suicidality
- Liothyronine (Cytomel, T3) 25-50 mcg daily
- Similar efficacy to Lithium in refractory depression
- May increase nervousness and anxiety
- Methylphenidate (Ritalin) 10 to 15 mg daily
- Consider in comorbid apathy and Fatigue
- Pindolol (Visken) 2.5 to 7.5 mg daily
- Esketamine (Spravato)
- Administered intranasally twice weekly for 4 weeks, then every 1-2 weeks
- Monitor for 2 hours after each dose (for Hypertension, dissociation, sedation)
- Must be given at hospital or clinic within designated REMS program
- Lithium 300 to 600 mg daily in divided doses (blood levels 0.4 to 0.8 mEq/L)
- Indications
IV. Management: Step 3
- Consider Electroconvulsive Therapy
V. References
- (2023) Presc Lett 30(9): 51-2
- Ables (2003) Am Fam Physician 67(3):547-4 [PubMed]
- Bridges (1995) Br J Hosp Med 54:501-6 [PubMed]
- Cadieux (1998) Am Fam Physician 58(9):2059-62 [PubMed]
- Little (2009) Am Fam Physician 80(2):167-72 [PubMed]
- Preston (2013) Curr Psychiatry Rep15(7):370 [PubMed]
- Ruhe (2006) J Clin Psychiatry 67:1836-1855 [PubMed]