What is the recommended treatment for severe depression?

Treatment of Severe Depression

For severe depression, clinicians should select between either cognitive behavioral therapy (CBT) or second-generation antidepressants (SGAs) after discussing treatment effects, adverse effect profiles, cost, accessibility, and preferences with the patient. 1

First-Line Treatment Options

Pharmacotherapy with Second-Generation Antidepressants

• SGAs are considered first-line treatment due to their better adverse effect profile compared to older antidepressants 1
• The benefit of antidepressants over placebo is more pronounced in patients with severe depression 1
• All SGAs have similar efficacy for treatment-naive patients 1

Medication Selection Algorithm:

1. Preferred SGAs for most patients:

   • Sertraline (Zoloft): 50-200 mg/day
   • Citalopram (Celexa): 20-40 mg/day
   • Escitalopram (Lexapro): 10-20 mg/day
   • Bupropion (Wellbutrin): 100-400 mg/day
   • Mirtazapine (Remeron): 15-45 mg/day
   • Venlafaxine: 37.5-225 mg/day

2. Starting doses:

   • Begin with lower doses (e.g., sertraline 50 mg daily, citalopram 20 mg daily)
   • For patients with anxiety symptoms alongside depression, consider even lower starting doses
   • Titrate up gradually if needed after 4-8 weeks of treatment

Cognitive Behavioral Therapy

• CBT has comparable efficacy to SGAs for severe depression 1
• Typically delivered in structured sessions over 12-16 weeks
• Focuses on identifying and changing negative thought patterns and behaviors

Treatment Monitoring and Adjustment

1. Regular Assessment:

   • Assess patient status, therapeutic response, and adverse effects within 1-2 weeks of starting treatment 1
   • Continue monitoring at 4 weeks and 8 weeks 1
   • Use standardized validated instruments to measure symptom improvement

2. Treatment Adjustment:

   • If little improvement after 6-8 weeks despite good adherence, modify treatment 1
   • Options for modification:
     • Switch to a different SGA
     • Add psychological intervention to pharmacotherapy
     • Switch from group therapy to individual therapy
     • Increase medication dose if tolerated

Duration of Treatment

• Continue treatment for 4-9 months after satisfactory response for first episode 1
• For patients with 2 or more episodes of depression, longer duration of therapy is beneficial 1
• Treatment phases:
  • Acute phase: 6-12 weeks
  • Continuation phase: 4-9 months
  • Maintenance phase: ≥1 year for recurrent depression 1

Common Adverse Effects and Management

• About 63% of patients on SGAs experience at least one adverse effect 1

• Common side effects:

  • Gastrointestinal: nausea, vomiting, diarrhea
  • Neurological: dizziness, headache, tremor
  • Sexual dysfunction
  • Sleep disturbances
  • Weight changes

• Important safety warning: Monitor for suicidal thoughts and behaviors, especially during the first few months of treatment and with dose changes 2

Special Populations

Older Adults

• Use "start low, go slow" approach 1
• Preferred medications: citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, bupropion
• Avoid paroxetine and fluoxetine due to higher rates of adverse effects in older adults 1

Common Pitfalls to Avoid

1. Inadequate dose or duration: Ensure adequate trial (6-8 weeks) at therapeutic doses before concluding treatment failure
2. Ignoring side effects: Address side effects promptly to improve adherence
3. Abrupt discontinuation: Taper medications gradually to avoid discontinuation symptoms
4. Overlooking comorbidities: Assess and address comorbid conditions that may affect treatment response
5. Failure to monitor: Regular assessment is crucial for optimizing treatment outcomes

By following this structured approach to treating severe depression, clinicians can significantly improve outcomes for patients while minimizing adverse effects and complications.