What is the recommended first-line medication for a patient with no known medical history, experiencing depression for the first time?

First-Line Medication for Depression

For a treatment-naive patient with moderate to severe depression, start with a second-generation antidepressant (SSRI or SNRI), selecting the specific agent based on the patient's symptom profile, side effect tolerance, cost, and preferences. 1, 2

Medication Selection Algorithm

For General Depressive Symptoms

• All second-generation antidepressants are equally effective for treatment-naive patients with general depressive symptoms, so selection should be based on adverse effect profiles, cost, and patient preferences 1, 2
• SSRIs have a number needed to treat of 7-8 for achieving remission 2

For Specific Symptom Profiles

Cognitive symptoms (difficulty concentrating, indecisiveness, mental fog):

• First choice: Bupropion due to its dopaminergic and noradrenergic effects and lower rate of cognitive side effects 2
• Second choice: SNRIs (venlafaxine or duloxetine) as their noradrenergic component may improve attention and concentration better than SSRIs 2

Elderly patients (age 65+):

• Preferred agents: Citalopram, sertraline, escitalopram, or bupropion 2, 3
• Avoid paroxetine and fluoxetine in older adults due to higher anticholinergic effects (paroxetine) and long half-life with drug accumulation risk (fluoxetine) 2, 3

Common First-Line Options

The most commonly recommended SSRIs include:

• Sertraline 3, 4
• Citalopram 1, 2
• Escitalopram 1, 2

These agents are preferred because second-generation antidepressants have similar efficacy to first-generation agents (tricyclics, MAOIs) but with lower toxicity in overdose 1

Critical Monitoring Requirements

Begin monitoring within 1-2 weeks of initiation for: 1

• Therapeutic response
• Adverse effects (nausea, diarrhea, dizziness, sexual dysfunction, headache) 2
• Suicidal ideation, particularly in patients 18-24 years old 1

Modify treatment if inadequate response by 6-8 weeks of therapy 1

Treatment Duration

Continue treatment for 4-9 months after symptom resolution for a first episode of major depression 1, 2

For patients with 2 or more episodes, longer duration therapy is beneficial 1

Critical Pitfalls to Avoid

• Do not use tricyclic antidepressants as first-line therapy due to higher adverse effect burden and overdose risk 1, 2
• Do not prescribe antidepressants for mild depression or subsyndromal symptoms without a current moderate-to-severe episode 2
• Avoid paroxetine due to notably higher rates of sexual dysfunction and anticholinergic effects compared to other SSRIs 1, 2
• Do not combine with other serotonergic drugs without careful monitoring for serotonin syndrome 4

Severity-Based Approach

Antidepressants are most effective in patients with severe depression, with the drug-placebo difference increasing with initial severity 1, 2

For patients with less severe depression, the benefit over placebo is minimal, and alternative approaches should be considered first 2