Treatment of Depression

First-Line Treatment

The American College of Physicians recommends initiating treatment with either a second-generation antidepressant, specifically an SSRI, or cognitive behavioral therapy (CBT) as monotherapy, as both demonstrate equivalent efficacy for adult patients with no significant medical history presenting with depression 1, 2.
The American Academy of Family Physicians suggests that second-generation antidepressants are preferred over tricyclic antidepressants due to better tolerability and lower toxicity in overdose 6.
All SSRIs, SNRIs, and other second-generation antidepressants show no clinically significant differences in efficacy for acute major depressive disorder 3, 4.
The number needed to treat for SSRIs is 7-8, with more pronounced benefits in severe depression 3, 4.

The American Family Physician recommends choosing bupropion if sexual dysfunction is a primary concern, as it has significantly lower rates of sexual side effects compared to fluoxetine or sertraline 7, 3, 4.
The American College of Physicians advises avoiding paroxetine as first-line due to higher rates of sexual dysfunction and anticholinergic effects 3, 4.
SNRIs provide marginal superiority over SSRIs (49% vs 42% remission rate) and should be considered for patients with comorbid pain disorders 7.

CBT monotherapy achieves similar response and remission rates as second-generation antidepressants based on moderate-quality evidence 1, 2, 3.
Interpersonal therapy and psychodynamic therapy also show no difference in efficacy compared to SGAs, though evidence quality is lower 1, 2.

Suicidality assessment is mandatory, as SSRIs carry increased risk for suicide attempts compared to placebo, particularly in adults 18-24 years old 7, 3, 4, 5.
Adverse effects monitoring is necessary, as approximately 63% of patients on SSRIs experience at least one adverse effect, most commonly nausea, sexual dysfunction, or insomnia 5.
Early therapeutic response and patient adherence should be monitored 3, 4.
If adequate response is NOT achieved, modify treatment strategy immediately, do not wait beyond 8 weeks 3, 5.

Continue treatment for 4-9 months minimum for a first episode to prevent relapse 3, 4, 5.
For recurrent depression, extend treatment to at least 12 months to prevent recurrence 3, 4.

For women of reproductive age, prefer sertraline and escitalopram due to favorable side effect profiles 5.
For breastfeeding mothers, sertraline and paroxetine transfer in lower concentrations to breast milk 7, 4.
For older adults, preferred medications include citalopram, escitalopram, sertraline, mirtazapine, and venlafaxine, and use lower starting doses with gradual titration 4, 3, 4.
For patients with severe depression, antidepressant benefit over placebo is more pronounced, and consider combination therapy with CBT and SSRI for severe or chronic depression 7, 3, 4, 5.