First-Line Treatment Approach for Depression

Pharmacotherapy Options

The American College of Physicians recommends second-generation antidepressants as the first-line treatment approach for patients presenting with depression, with selection based on adverse effect profiles, cost, and patient preferences 1, 2
Second-generation antidepressants are generally considered first-line treatment due to their better adverse effect profile compared to older antidepressants such as tricyclic antidepressants (TCAs) 2
The available evidence does not support clinically significant differences in efficacy among selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), or other second-generation antidepressants for the treatment of acute major depressive disorder 1
Medications are modestly superior to placebo in achieving remission, with a number needed to treat of 7-8 for SSRIs and 7-16 for TCAs 3
The benefit of antidepressants over placebo is more pronounced in patients with severe depression 2

Choice between different second-generation antidepressants should be guided by adverse effect profiles, cost considerations, and patient preferences 1
Bupropion is associated with lower rates of sexual dysfunction compared to fluoxetine or sertraline 1
Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1
SSRIs are associated with increased risk for suicide attempts compared with placebo 1

Patient status, therapeutic response, and adverse effects should be assessed regularly, beginning within 1-2 weeks of treatment initiation 1
Close monitoring for increases in suicidal thoughts and behaviors is particularly important in the first 1-2 weeks after starting therapy 1
Response to treatment is typically defined as a 50% reduction in measured severity using standardized assessment tools 4
If adequate response is not achieved within 6-8 weeks, treatment modification should be considered 4

For an initial episode of major depression, clinical guidelines suggest treatment for 4-12 months 3, 4
After achieving remission, treatment should continue for at least 4-9 months 4
Patients with recurrent depression may benefit from prolonged treatment of at least one year to prevent recurrence 3, 4

For older persons, a "start low, go slow" approach is recommended with preferred medications including citalopram, escitalopram, sertraline, mirtazapine, and venlafaxine 3
For breastfeeding mothers, sertraline and paroxetine transfer to breast milk in lower concentrations than other antidepressants 2