What is the recommended treatment for a patient with depression?

Treatment of Depression

For patients with depression, initiate treatment with either cognitive behavioral therapy (CBT) or a second-generation antidepressant (specifically an SSRI such as sertraline or escitalopram), as both have equivalent effectiveness as first-line options. 1

First-Line Treatment Selection

The choice between psychotherapy and pharmacotherapy depends on several factors:

• For mild depression: Start with CBT alone, as it demonstrates equivalent effectiveness to antidepressants with moderate-quality evidence 1
• For moderate to severe depression: Either CBT or an SSRI/SNRI is appropriate as initial monotherapy 2, 1
• For severe depression with high-risk features: Initiate antidepressants immediately with close monitoring 1

Pharmacotherapy Options

When selecting an antidepressant:

• SSRIs are the preferred first-line agents, with sertraline, escitalopram, and citalopram being optimal choices due to favorable side effect profiles 2, 1, 3
• All second-generation antidepressants demonstrate similar efficacy for treatment-naive patients 2
• Sertraline is FDA-approved for major depressive disorder and has established efficacy in 6-8 week controlled trials 4
• For women of reproductive age, sertraline and escitalopram are preferred due to lower concentrations in breast milk 3
• SNRIs (such as venlafaxine) are slightly more effective than SSRIs for symptom improvement but carry higher rates of nausea and vomiting 2

Psychotherapy Options

• CBT has moderate-quality evidence supporting effectiveness equivalent to second-generation antidepressants 1
• Interpersonal psychotherapy (IPT) demonstrates efficacy comparable to medications and provides delayed effects improving social relationships 5

Treatment Monitoring and Assessment

Initial Assessment Timeline

• Week 1-2: Assess for suicidality and adverse effects 1, 3
• Week 4: Evaluate symptom improvement using standardized tools (PHQ-9, HAM-D, or MADRS) 2, 1, 3
• Week 6-8: Modify treatment if inadequate response 2, 1, 3

Response Criteria

• Response is defined as ≥50% reduction in depression severity on validated assessment tools 1
• Approximately 38% of patients do not achieve treatment response during 6-12 weeks, and 54% do not achieve remission 2

Management of Inadequate Response

If there is insufficient improvement after 6-8 weeks of adequate-dose treatment:

• Switch to a different SSRI or SNRI 1, 3
• Add CBT to existing pharmacotherapy 1, 3
• Augment with a second pharmacologic agent 1
• Consider switching to CBT monotherapy if initially on medication alone 3

Treatment-Resistant Depression

• Treatment-resistant depression (TRD) is defined as failure to respond to two or more adequate antidepressant trials (minimum 4 weeks at therapeutic dose) 1
• For TRD, add CBT to pharmacotherapy, which produces statistically superior outcomes compared to antidepressant monotherapy, with remission rates nearly doubling (57.5% vs 31.0%, P < 0.001) 1

Combination Therapy

For severe major depressive disorder, combination therapy (psychotherapy + antidepressant) produces statistically superior outcomes compared to monotherapy:

• Remission rates: 57.5% (combination) vs 31.0% (monotherapy), P < 0.001 1
• Response rates: 78.7% (combination) vs 45.2% (monotherapy), P < 0.001 1
• Initiate CBT concurrently with pharmacotherapy, not sequentially 1

Treatment Duration

• First episode: Continue treatment for at least 4-9 months after satisfactory response to prevent relapse 2, 1, 3
• Recurrent depression: Maintain treatment for ≥1 year or longer 2, 1, 3
• Continuation of antidepressant therapy reduces risk for relapse based on meta-analysis of 31 randomized trials 2

Special Considerations for Comorbid Symptoms

Depression with Anxiety

• When both depression and anxiety are present, prioritize treatment of depressive symptoms 2
• Alternatively, use a unified protocol combining CBT treatments for both conditions 2
• Venlafaxine may be superior to fluoxetine for treating comorbid anxiety 2

Depression with Insomnia or Pain

• Fluoxetine, nefazodone, paroxetine, and sertraline show similar efficacy for depression with insomnia 2
• Duloxetine and paroxetine demonstrate effectiveness for depression with pain 2

Common Adverse Effects and Safety

• Approximately 63% of patients on SSRIs experience at least one adverse effect, most commonly nausea, sexual dysfunction, diarrhea, dizziness, dry mouth, fatigue, headache, or insomnia 2, 3
• Number needed to harm for discontinuation: 20-90 for SSRIs vs 4-30 for tricyclic antidepressants 2
• SSRIs are safer in overdose compared to older antidepressants 2

Critical Monitoring Parameters

• Monitor for suicidality, especially during initial treatment period and dose changes 1, 6
• Screen for bipolar disorder before initiating antidepressant treatment, as treating a depressive episode with an antidepressant alone may precipitate a manic episode in at-risk patients 6
• Assess for adherence, as up to 50% of patients with major depressive disorder demonstrate non-adherence 1

Pitfalls to Avoid

• Inadequate dosing or premature discontinuation before therapeutic effects are achieved (typically 4-6 weeks) 1
• Not continuing treatment long enough to prevent relapse (minimum 4-9 months after response) 1
• Failing to reassess and modify treatment strategy by week 8 if inadequate response 2, 1