What is the recommended initial treatment for a patient newly diagnosed with depression, specifically regarding the choice of medication?

Initial Pharmacologic Treatment for Newly Diagnosed Depression

For treatment-naive patients with moderate to severe depression, initiate a second-generation antidepressant (SSRI or SNRI) at standard starting doses, with medication selection based on adverse effect profile, cost, and patient preference rather than efficacy differences. 1, 2

Medication Selection Strategy

All second-generation antidepressants demonstrate equivalent efficacy in treatment-naive patients, with SSRIs achieving remission in 1 out of 7-8 patients treated (NNT = 7-8). 1, 2 The American College of Physicians emphasizes that no single second-generation antidepressant demonstrates superior efficacy over another, making selection dependent on factors other than effectiveness. 1

Target Symptom-Based Selection

For cognitive symptoms (difficulty concentrating, indecisiveness, mental fog):

• First choice: Bupropion - most effective due to dopaminergic and noradrenergic effects with lower cognitive side effects 2
• Second choice: SNRIs (venlafaxine or duloxetine) - noradrenergic component may improve attention better than SSRIs 2

For general depressive symptoms without specific cognitive complaints:

• Any SSRI is appropriate as first-line therapy 1
• Fluoxetine 20 mg daily is sufficient for most patients and can be started at therapeutic dose 3

Age-Specific Considerations

For older adults, preferred agents include: 1, 2

• Citalopram
• Sertraline
• Venlafaxine
• Bupropion

Avoid in older adults: 1, 2

• Paroxetine (higher anticholinergic effects and sexual dysfunction rates)
• Fluoxetine (less favorable profile in elderly)

Practical Dosing

Fluoxetine (representative SSRI): 3

• Start 20 mg every morning
• This dose is sufficient for most patients
• May increase after several weeks if insufficient response
• Maximum 80 mg/day

Key advantage: Fluoxetine can be started at full therapeutic dose, potentially providing more rapid onset compared to other SSRIs that require titration. 4

Severity-Based Treatment Decisions

Antidepressants are most effective in severe depression. 1, 2 The drug-placebo difference increases with baseline severity. 1

Critical caveat: Do not prescribe antidepressants for mild depression or subsyndromal symptoms without a current moderate-to-severe episode. 2 In mild depression, the benefit over placebo is minimal. 1

Tolerability Profile

Approximately 63% of patients experience at least one adverse effect. 1 Common adverse effects include: 1, 2

• Nausea and vomiting (most common reason for discontinuation)
• Diarrhea
• Dizziness
• Sexual dysfunction
• Headache
• Fatigue

Sexual dysfunction considerations: 1, 2

• Bupropion has the lowest rates
• Paroxetine has the highest rates among SSRIs

Tolerability advantage: SSRIs have better tolerability than TCAs (NNT to cause dropout = 20 for SSRIs vs. 4-30 for TCAs). 1

Monitoring Requirements

Begin monitoring within 1-2 weeks of initiation. 1 This early assessment is critical for:

• Suicidal ideation (highest risk in first 1-2 months, particularly in adults 18-24 years) 1
• Emergence of agitation or unusual behavioral changes 1
• Adverse effects 1

Assess treatment response at 6-8 weeks. 1 If inadequate response, modify treatment. 1 Full therapeutic effect may require 4 weeks or longer. 3

Treatment Duration

For first episode: Continue for 4-9 months after satisfactory response. 1, 2

For recurrent depression (≥2 episodes): Consider longer duration or indefinite maintenance therapy. 1

Critical Pitfalls to Avoid

• Do not use TCAs as first-line agents - higher adverse effect burden, greater overdose risk, and similar efficacy to SSRIs 1, 2
• Do not assume all SSRIs are identical - paroxetine has notably worse anticholinergic and sexual dysfunction profiles 1, 2
• Do not prescribe for mild/subsyndromal depression - minimal benefit over placebo 1, 2
• Do not delay monitoring - suicidality risk peaks early in treatment 1