What are the best medications for treating depression?

Best Medications for Depression

Second-generation antidepressants, specifically SSRIs (selective serotonin reuptake inhibitors), are the best first-line medications for depression, with sertraline, escitalopram, and citalopram being the preferred agents due to their favorable adverse effect profiles and proven efficacy. 1, 2

First-Line Medication Selection

For treatment-naive patients, choose from these preferred SSRIs:

• Sertraline - Excellent first choice with favorable side effect profile 1, 2
• Escitalopram - Equally effective with good tolerability 1, 2
• Citalopram - Strong option, though requires dose adjustment in elderly (max 40mg/day) 1, 2

Alternative first-line options include:

• Bupropion - Best choice when sexual dysfunction is a concern, as it has significantly lower rates compared to SSRIs 2
• Mirtazapine - Useful when sedation or appetite stimulation is desired 1, 2
• Venlafaxine (SNRI) - Consider for patients with comorbid pain disorders, though remission rates are only marginally better than SSRIs (49% vs 42%) and adverse effects like nausea are more common 1

Medications to Avoid

Do NOT use these as first-line agents:

• Paroxetine - Higher anticholinergic effects and sexual dysfunction rates; particularly avoid in elderly 1
• Fluoxetine - Greater risk of agitation, overstimulation, and long half-life increases drug accumulation risk; avoid in elderly 1, 3
• Tricyclic antidepressants (TCAs) - Reserve for treatment-resistant cases due to worse side effect profile, though number needed to treat is similar (7-16 vs 7-8 for SSRIs) 1

Evidence for Efficacy

Antidepressants work, but with important caveats:

• SSRIs are modestly superior to placebo with a number needed to treat of 7-8 1, 2
• The benefit is most pronounced in severe depression - patients with severe depression show robust responses while those with mild-to-moderate depression show minimal difference from placebo 1, 2
• All second-generation antidepressants are equally effective for treatment-naive patients, so selection should be based on adverse effect profile and cost 1

Dosing Strategy

Start at standard adult doses for most patients:

• Sertraline: 50mg daily, can increase to 200mg 1
• Escitalopram: 10mg daily, can increase to 20mg 1
• Citalopram: 20mg daily, can increase to 40mg 1

For elderly patients, use "start low, go slow" approach:

• Begin at approximately 50% of standard adult starting dose 1, 3
• Preferred agents remain sertraline, escitalopram, citalopram, mirtazapine, venlafaxine, and bupropion 3, 2

Critical Monitoring Requirements

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

• Suicidal thoughts and behaviors - highest risk in first 1-2 weeks, particularly in younger patients 2
• Therapeutic response - expect 50% reduction in symptom severity by 6-8 weeks; if not achieved, modify treatment 2
• Common adverse effects: nausea (most common reason for discontinuation), insomnia, sexual dysfunction 1, 2
• In elderly: falls risk, hyponatremia, drug interactions 3

Treatment Duration

Do not stop prematurely:

• First episode: Continue for 4-12 months after achieving remission 1, 2
• Recurrent depression: Treat for at least one year to prevent recurrence 2
• Approximately two-thirds of patients experience at least one adverse effect, but most are manageable 1

Common Pitfalls to Avoid

• Don't switch medications before 6-8 weeks unless intolerable side effects occur - adequate trial duration is essential 2
• Don't use paroxetine or fluoxetine in elderly despite their popularity - adverse effect rates are significantly higher 1, 3
• Don't assume all antidepressants work equally for all severities - reserve pharmacotherapy primarily for moderate-to-severe depression where benefit over placebo is clear 1, 2
• Don't forget that remission rates are modest - only 35% for SSRIs and 45% for SNRIs, so set realistic expectations 4

Special Populations

Breastfeeding mothers: Sertraline and paroxetine transfer to breast milk in lowest concentrations 1, 2

Patients with comorbid pain: SNRIs (venlafaxine, duloxetine) provide additional benefit 1