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 major depressive disorder in adults. 1, 2
Pharmacotherapy as First-Line Treatment
The American College of Physicians establishes second-generation antidepressants as the standard first-line approach for depression, with selection guided by adverse effect profiles, cost, and patient preferences. 3, 1 These medications demonstrate modest superiority over placebo with a number needed to treat of 7-8 for SSRIs, with more pronounced benefits observed in patients with severe depression. 1, 2
No clinically significant differences in efficacy exist among SSRIs, SNRIs, or other second-generation antidepressants for treating acute major depressive disorder. 1, 2 This equivalence in effectiveness means the choice between agents should focus on tolerability and safety considerations rather than efficacy differences.
Specific Medication Selection Algorithm
Start with sertraline 50 mg once daily, escitalopram, or citalopram as these agents have the most favorable adverse effect profiles. 2, 4
Alternative First-Line Options:
- Bupropion should be selected when sexual dysfunction is a primary concern, as it demonstrates significantly lower rates of sexual side effects compared to fluoxetine or sertraline. 1, 2
- Venlafaxine (SNRI) or mirtazapine represent additional first-line options with similar efficacy. 1
Medications to Avoid as First-Line:
- Paroxetine should be avoided due to higher rates of sexual dysfunction and anticholinergic effects compared to other SSRIs. 1, 2
- Tricyclic antidepressants are NOT first-line treatment due to inferior safety profiles despite similar efficacy. 3, 2
Cognitive Behavioral Therapy as Alternative First-Line
Cognitive behavioral therapy (CBT) represents an equally valid first-line option to pharmacotherapy, supported by moderate-certainty evidence showing similar treatment effects as second-generation antidepressants. 2 Additional effective psychotherapies include behavioral activation, problem-solving therapy, interpersonal therapy, brief psychodynamic therapy, and mindfulness-based psychotherapy, all demonstrating medium-sized effects over usual care. 5
Combined psychotherapy plus antidepressant medication may be preferred for more severe or chronic depression, as network meta-analyses demonstrate greater symptom improvement with combination treatment compared to either modality alone. 5
Critical Early Monitoring Protocol
Begin monitoring within 1-2 weeks of treatment initiation, focusing specifically on suicidal thoughts and behaviors, therapeutic response, and adverse effects. 1, 2 This early monitoring window is critical because SSRIs are associated with increased risk for suicide attempts compared with placebo. 1, 2
Monitoring Parameters:
- Suicidal ideation and behaviors (highest priority in weeks 1-2) 1, 2
- Therapeutic response using standardized tools (PHQ-9 or HAM-D) 3
- Adverse effects including sexual dysfunction, gastrointestinal symptoms, and akathisia 3, 1
Response Assessment Timeline
Response to treatment (defined as ≥50% reduction in measured severity) should be assessed at 6-8 weeks. 1, 2 If adequate response is not achieved within this timeframe, treatment modification must be considered—do not wait longer than 8 weeks to reassess strategy. 2
Treatment Duration Requirements
For an initial episode of major depression, continue treatment for 4-12 months after achieving remission. 1, 2 More specifically:
- Continuation phase: minimum 4-9 months after remission 1, 2, 6
- Maintenance phase for recurrent depression: at least one year to prevent recurrence 1, 2, 6
The phases of depression treatment include acute treatment (6-12 weeks), continuation (4-9 months), and maintenance (≥1 year), with relapse occurring during acute/continuation phases and recurrence representing a new episode during maintenance. 3
Special Population: Elderly Patients
For older adults, use a "start low, go slow" approach with preferred agents including citalopram, escitalopram, sertraline, mirtazapine, or venlafaxine. 1, 6 Specifically avoid paroxetine and fluoxetine in elderly patients—paroxetine due to high anticholinergic effects and sexual dysfunction, and fluoxetine due to its long half-life increasing risk of drug accumulation. 6
Additional Monitoring in Elderly:
Common Pitfalls to Avoid
- Do not prescribe tricyclic antidepressants as first-line despite similar efficacy, due to higher toxicity in overdose and worse adverse effect profiles. 3, 2
- Do not delay treatment modification beyond 6-8 weeks if adequate response is not achieved. 2
- Antidepressants have higher discontinuation rates due to adverse events compared to nonpharmacologic treatments, requiring proactive adverse effect management. 2
- Given sertraline's 24-hour elimination half-life, dose changes should not occur at intervals less than 1 week. 4