What are the recommended antidepressants for treating depression?

Recommended Antidepressants for Depression Treatment

Selective serotonin reuptake inhibitors (SSRIs) are the first-line treatment for depression, with sertraline, escitalopram, and fluoxetine being the preferred options due to their favorable efficacy and safety profiles. 1

First-Line Antidepressant Options

SSRIs (First Choice)

• Sertraline (Zoloft)

  • Initial dose: 25-50 mg daily
  • Maximum dose: 200 mg daily
  • Advantages: Better efficacy profile compared to fluoxetine 2, favorable side effect profile 1
  • Monitoring: Regular assessment using standardized measures (e.g., PHQ-9)

• Escitalopram (Lexapro)

  • Initial dose: 10 mg daily
  • Maximum dose: 20 mg daily
  • Advantages: May have lower risk of suicide-related outcomes compared to some other antidepressants 3

• Fluoxetine

  • Currently the only antidepressant specifically recommended for first-line prescribing in adolescents 3
  • Note: May have slightly lower efficacy than sertraline and venlafaxine 2

• Citalopram (Celexa)

  • Initial dose: 10 mg daily
  • Maximum dose: 20 mg daily (maximum in elderly due to QT prolongation risk) 1
  • Caution: QT interval prolongation risk limits maximum dose

Second-Line Options

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Venlafaxine

  • Potentially greater efficacy than SSRIs at higher doses 4
  • Caution: Dose-dependent blood pressure elevation (uncommon below 225 mg/day) 4
  • More effective than fluoxetine in multiple studies 2

• Duloxetine

  • More balanced serotonin and norepinephrine reuptake inhibition (10:1 ratio) 4
  • Additional indications: Diabetic peripheral neuropathic pain, fibromyalgia, and musculoskeletal pain 4
  • Moderate inhibitor of CYP2D6 (potential drug interactions) 4

• Desvenlafaxine

  • Primary metabolite of venlafaxine
  • Favorable drug-drug interaction profile 4
  • Approved in narrow dose range of 50-100 mg daily 4

Other Antidepressants

• Mirtazapine
  • More effective than fluoxetine in some studies 2
  • Different mechanism of action (tetracyclic antidepressant)

Treatment Algorithm

1. Initial Treatment Selection:

   • Start with an SSRI (sertraline, escitalopram, or fluoxetine)
   • Consider patient factors:
     • For elderly: Start with lower doses of sertraline (25mg), citalopram (10mg), or escitalopram (10mg) 1, 5
     • For adolescents: Fluoxetine is the preferred first option 3

2. Dosing and Titration:

   • Start with a low to moderate dose 1
   • Assess patient status within 1-2 weeks of starting therapy 1
   • Evaluate treatment efficacy at approximately 6 weeks and 12 weeks 1

3. Inadequate Response (after 6-8 weeks):

   • Options include:
     • Switch to a different SSRI
     • Switch to an SNRI (venlafaxine or duloxetine)
     • Add cognitive behavioral therapy (CBT)
     • Consider augmentation with a second agent 1

4. Treatment-Resistant Depression:

   • Consider atypical antipsychotic augmentation (aripiprazole, brexpiprazole, cariprazine, quetiapine extended-release, or olanzapine-fluoxetine combination) 6
   • Electroconvulsive therapy (ECT) may be considered for severely impaired patients when medications are ineffective or cannot be tolerated 1

Important Monitoring Considerations

• Suicide Risk: Regular monitoring is essential, especially in the first weeks of treatment and in adolescents and young adults 1

  • SSRIs are associated with increased risk for nonfatal suicide attempts 1
  • Venlafaxine may have higher risk of suicide-related outcomes compared to some other antidepressants 3

• Drug Interactions:

  • SSRIs and SNRIs inhibit CYP2D6 to varying degrees, potentially increasing plasma concentrations of co-administered drugs 7, 4
  • Sertraline at lower doses has less prominent inhibitory effect on CYP2D6 than some others in the class 7
  • Monitor plasma levels of drugs with narrow therapeutic indices (e.g., TCAs) when co-administered with SSRIs 7

• Response Assessment:

  • Use standardized measures (e.g., PHQ-9) for regular assessment 1
  • Up to 70% of patients do not achieve remission during initial treatment attempt 1

Special Populations

• Elderly Patients:

  • Lower starting doses for citalopram, paroxetine, and sertraline 5
  • Maximum citalopram dose: 20 mg daily (due to QT prolongation risk) 1
  • Monitor for cognitive changes, falls risk, and orthostatic hypotension 1

• Children and Adolescents:

  • Fluoxetine is currently the only treatment recommended for first-line prescribing 3
  • Close monitoring of treatment effects and suicide-related outcomes is critical 3
  • Consider psychotherapy, particularly cognitive behavioral therapy 3

Remember that while the average effects of antidepressants may show small differences in efficacy, individual responses can vary significantly, and some patients may experience greater benefits from specific medications.