What is the best first-line medication for mild depression?

Best First-Line Medication for Mild Depression

For mild depression, antidepressant medication should generally NOT be prescribed as first-line therapy, as the evidence shows minimal benefit over placebo in this population. 1, 2

Evidence Against Medication for Mild Depression

• Antidepressants demonstrate significantly greater efficacy in severe depression compared to mild depression, with the drug-placebo difference increasing proportionally with baseline severity 1
• Meta-analyses of FDA-submitted studies concluded that there is little difference between antidepressant therapy and placebo in patients with less severe depression 1
• Do not use antidepressants for initial treatment of adults with depressive symptoms in the absence of a current or prior moderate-to-severe depressive episode 2

When Medication IS Appropriate (Moderate-to-Severe Depression)

If the patient actually has moderate-to-severe depression rather than mild depression, then medication becomes appropriate:

First-Line Medication Selection

Select any second-generation antidepressant (SSRI or SNRI) based on adverse effect profile, cost, and patient preference, as all are equally effective 1, 2

• SSRIs have a number needed to treat of 7-8 for achieving remission 1, 2
• No second-generation antidepressant demonstrates superior efficacy over another for general depressive symptoms 1, 2

Specific Medication Recommendations by Clinical Profile

For cognitive symptoms (difficulty concentrating, indecisiveness, mental fog):

• Bupropion is the most effective first choice due to dopaminergic/noradrenergic effects and lower cognitive side effects 2
• SNRIs (venlafaxine or duloxetine) are second-line for cognitive symptoms 2

For patients concerned about sexual dysfunction:

• Bupropion has lower rates of sexual adverse events than fluoxetine or sertraline 1, 2
• Avoid paroxetine, which has higher rates of sexual dysfunction than other SSRIs 1, 2

For older adults:

• Preferred agents: citalopram, sertraline, venlafaxine, or bupropion 1, 2
• Avoid paroxetine and fluoxetine in older adults due to higher anticholinergic effects and less favorable profiles 1, 2

Critical Monitoring Requirements

• Begin monitoring within 1-2 weeks of initiation for suicidal thoughts, agitation, irritability, or unusual behavioral changes 1
• Assess therapeutic response at 6-8 weeks; if inadequate response, modify treatment 1
• SSRIs carry an increased risk for nonfatal suicide attempts compared to placebo 1

Common Adverse Effects

• Approximately 63% of patients experience at least one adverse effect 2
• Most common: nausea/vomiting (most common reason for discontinuation), diarrhea, dizziness, headache, insomnia, sexual dysfunction, somnolence 1, 2

Treatment Duration

• Continue for at least 4-9 months after symptom resolution for a first episode of major depression 2
• Patients with recurrent depression may benefit from prolonged treatment 1

Key Pitfall to Avoid

The most critical error is prescribing antidepressants for mild depression or subsyndromal symptoms when evidence shows minimal benefit over placebo in this population 1, 2. Consider psychotherapy (cognitive behavioral therapy) as first-line treatment for mild depression instead.