What is the first line of treatment for depression?

First-Line Treatment for Depression

Second-generation antidepressants, specifically SSRIs such as sertraline (50 mg daily), escitalopram, or citalopram, are the recommended first-line pharmacologic treatment for depression, with cognitive behavioral therapy (CBT) representing an equally valid first-line nonpharmacologic alternative based on patient preference. 1, 2

Treatment Selection Framework

Pharmacotherapy as First-Line

• The American College of Physicians recommends second-generation antidepressants as first-line treatment, with selection based on adverse effect profiles, cost, and patient preferences 1
• Start with sertraline 50 mg once daily, escitalopram, or citalopram as these have the most favorable adverse effect profiles 2, 3
• All second-generation antidepressants (SSRIs, SNRIs, bupropion, mirtazapine) demonstrate similar efficacy with no clinically significant differences for acute major depressive disorder 1, 2
• Medications show modest superiority over placebo with a number needed to treat of 7-8 for SSRIs, with more pronounced benefits in patients with severe depression 1, 2

Nonpharmacologic Alternative

• Cognitive behavioral therapy (CBT) is supported by moderate-certainty evidence to achieve similar treatment effects as second-generation antidepressants and represents an equally valid first-line option 2
• Network meta-analyses demonstrate that cognitive therapy, behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy all have medium-sized effects over usual care 4

Specific Medication Considerations

• Avoid paroxetine as first-line due to higher rates of sexual dysfunction and anticholinergic effects 2
• Bupropion should be considered when sexual side effects are a concern, as it is associated with lower rates of sexual dysfunction compared to fluoxetine or sertraline 1, 2
• For elderly patients, use a "start low, go slow" approach with preferred agents including citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, or bupropion 5

Critical Early Monitoring Requirements

Timeline and Focus

• Begin monitoring within 1-2 weeks of treatment initiation, focusing on therapeutic response, adverse effects, and patient status 1, 2
• Close monitoring for increases in suicidal thoughts and behaviors is particularly important in the first 1-2 weeks after starting therapy, as SSRIs are associated with increased risk for suicide attempts compared with placebo 1, 2

Response Assessment

• Response to treatment is defined as a 50% reduction in measured severity using standardized assessment tools such as PHQ-9 6, 2
• If adequate response is not achieved within 6-8 weeks, treatment modification should be considered 1, 2

Treatment Duration

Acute and Continuation Phases

• For an initial episode of major depression, continue treatment for 4-12 months 1, 2
• After achieving remission, treatment should continue for at least 4-9 months to prevent relapse 1, 2, 5
• Patients with recurrent depression may benefit from prolonged treatment of at least one year to prevent recurrence 1, 2, 5

Common Pitfalls to Avoid

• Do not wait beyond 6-8 weeks to reassess treatment strategy if response is inadequate 2
• Antidepressants have higher risks for discontinuation due to adverse events compared to most nonpharmacologic treatments, requiring proactive adverse effect management 6, 2
• Avoid fluoxetine in elderly patients due to its long half-life that increases the risk of drug accumulation 5
• Monitor for hyponatremia, falls risk, drug interactions, and gastrointestinal symptoms, particularly in elderly patients 5

Special Population Considerations

Elderly Patients

• Use lower initial doses with gradual titration as tolerated 5
• Preferred agents include sertraline, escitalopram, citalopram, mirtazapine, venlafaxine, and bupropion 5

Breastfeeding Mothers

• Sertraline and paroxetine transfer to breast milk in lower concentrations than other antidepressants 1