What are the recommended treatments for depression?

Treatment of Depression

For moderate major depressive disorder (MDD), the recommended first-line treatments are second-generation antidepressants (SGAs) such as SSRIs or cognitive behavioral therapy (CBT), with combination therapy providing additional benefits for moderate to severe cases. 1

Pharmacologic Treatment Options

First-Line Pharmacotherapy

• SSRIs are recommended as first-line treatment due to their favorable side effect profile and low risk of drug interactions 1
• Preferred SSRI options include:
  • Sertraline (Zoloft): Start at 25-50 mg daily, maximum 200 mg daily 1, 2
  • Citalopram (Celexa): Start at 10 mg daily, maximum 20 mg daily in elderly (due to QT prolongation risk) 1
  • Escitalopram (Lexapro): Start at 10 mg daily, maximum 20 mg daily 1

Medication Initiation and Titration

• Begin with a low to moderate dose of an SGA and assess patient status within 1-2 weeks 1
• For sertraline, the starting dose of 50 mg/day is usually the effective therapeutic dose for most patients 2, 3
• Dose can be increased in 50 mg/day increments at no less than weekly intervals to a maximum of 200 mg/day if needed 2, 3
• Some patients, particularly those with comorbid panic disorder, may benefit from starting at lower doses (e.g., 5 mg for fluoxetine) 4

Psychotherapy Options

• CBT is a first-line treatment for moderate MDD with similar efficacy to antidepressants in the short term and potentially better long-term outcomes 1
• CBT plus an SGA provides additional benefits for moderate to severe MDD, particularly for:
  • Patients with more severe symptoms
  • Previous inadequate response to monotherapy
  • Comorbid anxiety or insomnia 1
• Other effective psychotherapy options include:
  • Interpersonal Therapy (IPT), particularly for addressing relationship problems
  • Acceptance and commitment therapy
  • Psychodynamic supportive psychotherapy 1

Monitoring and Duration of Treatment

Monitoring Protocol

• Regular assessment using standardized measures (e.g., PHQ-9) is essential 1
• Evaluate treatment efficacy at approximately 6 weeks and 12 weeks 1
• Monitor for suicidal ideation, especially in the first weeks of treatment (particularly important with SSRIs) 1, 2
• Response to treatment should be evaluated after 4 weeks; if no response, treatment is unlikely to be effective 1

Duration of Treatment

• For a first episode, continue treatment for 4-9 months after satisfactory response 1
• Patients with a first or second episode who respond well should continue on full-dose treatment for at least 6 months after significant improvement 1
• For patients with two or more episodes, longer treatment duration may be beneficial 1

Management of Inadequate Response

• If inadequate response after 6-8 weeks at therapeutic doses, consider:
  1. Switching to a different SGA
  2. Adding CBT (augmentation)
  3. Augmenting with a second pharmacologic agent 1
• Avoid premature switching - allow adequate time (6-8 weeks) at therapeutic doses before concluding treatment failure 1
• The decision to modify treatment should be made after about 4-8 weeks 5

Special Populations

Elderly Patients

• SSRIs such as sertraline, citalopram, and escitalopram are preferred due to favorable side effect profiles 1
• Avoid tertiary tricyclic antidepressants and psychostimulants due to anticholinergic effects and cardiovascular risks 1
• Ensure elderly patients are titrated to the same doses as younger adults once appropriately initiated 1

Children and Adolescents

• For children and adolescents, fluoxetine (for patients >8 years) and escitalopram (for patients ≥12 years) are FDA-approved 5
• Combined psychotherapy and medication shows greater response than either treatment alone for more severe depression 5

Common Pitfalls to Avoid

1. Inadequate duration of treatment - continuing for at least 6 months after improvement is essential to prevent relapse 1
2. Overlooking drug interactions - particularly important with medications metabolized by CYP2D6 1, 6
3. Neglecting psychosocial interventions - CBT and other therapies are critical components of treatment 1
4. Failing to monitor for suicidality - especially important in the first weeks of treatment 1, 5
5. Avoiding paroxetine and fluoxetine in patients taking tamoxifen due to CYP2D6 inhibition 1, 6

By following these evidence-based recommendations, clinicians can optimize the treatment of depression while minimizing risks and improving outcomes for patients.