What is the most appropriate initial medication for a patient presenting with symptoms of depression, including decreased mood, loss of interest in activities, and changes in sleep and appetite?

Initial Medication for Depression

For a patient presenting with decreased mood, loss of interest in activities, and changes in sleep and appetite, start with a selective serotonin reuptake inhibitor (SSRI) as first-line pharmacologic treatment. 1, 2

Rationale for SSRI Selection

SSRIs are the preferred initial antidepressant class based on their efficacy, tolerability, and safety profile compared to older agents 1. All second-generation antidepressants (SSRIs, SNRIs, atypical agents) demonstrate equivalent efficacy for treatment-naive patients, so medication choice should prioritize adverse effect profiles, cost, and dosing convenience 1.

Specific SSRI Recommendations

Choose among the following SSRIs based on individual patient factors:

• Sertraline, escitalopram, or citalopram are preferred first-line options due to favorable side effect profiles 1, 3
• Fluoxetine is also effective and FDA-approved for major depressive disorder 4, though it may be less preferred in older adults due to its long half-life 1
• Avoid paroxetine as initial therapy due to higher rates of sexual dysfunction and anticholinergic effects 1, 3

Critical Patient Assessment Before Prescribing

Before initiating antidepressant therapy, evaluate for:

• Suicide risk: Assess for self-harm ideation, intent, or plan—if present, this requires emergency psychiatric evaluation 1
• Bipolar disorder screening: Rule out history of manic or hypomanic episodes, as antidepressants alone can precipitate mood destabilization 3
• Psychotic symptoms: Presence of delusions or hallucinations requires antipsychotic medication, not antidepressants alone 1
• Substance use disorders: Active substance use may require concurrent addiction treatment 1
• Medical comorbidities: Consider drug interactions and contraindications based on cardiac, hepatic, or renal disease 1

Severity-Based Treatment Approach

Antidepressant efficacy varies by depression severity:

• Mild depression: Antidepressants show minimal benefit over placebo; consider psychotherapy first 1, 5
• Moderate depression: Antidepressants demonstrate small but clinically meaningful benefit 1
• Severe depression: Antidepressants show medium-sized effects and are clearly indicated 1, 5

For moderate to severe depression, combining antidepressant medication with psychotherapy (cognitive behavioral therapy, interpersonal therapy, or behavioral activation) produces superior outcomes compared to either treatment alone 5. The combination shows an additional standardized mean difference of 0.30-0.33 over monotherapy 5.

Monitoring and Follow-Up

Close monitoring significantly improves treatment success 5:

• Assess response within 1-2 weeks of initiating treatment, then regularly thereafter 6
• Monitor specifically for increased suicidality in the first weeks of treatment, particularly in adolescents and young adults 3
• Evaluate for treatment response at 6-8 weeks; 38-54% of patients may not achieve adequate response or remission 3
• Screen for emergent hypomanic or manic symptoms that could indicate unrecognized bipolar disorder 3

Dosing Strategy

Start SSRIs at standard initial doses and titrate based on response and tolerability 3. The number needed to treat for SSRIs ranges from 7-8 for achieving 50% symptom reduction or remission 1.

Treatment Duration

Continue antidepressant therapy for at least 4-6 months after achieving remission for a first depressive episode 1. For recurrent depression, consider maintenance treatment for 12-24 months or longer 3.

Common Pitfalls to Avoid

• Do not prescribe antidepressants for subsyndromal depressive symptoms (fewer than 5 DSM criteria) without a current or prior moderate-to-severe depressive episode 1
• Do not use tricyclic antidepressants as first-line therapy due to higher discontinuation rates (number needed to harm: 4-30) compared to SSRIs (20-90) 1
• Do not routinely combine antidepressants with anticholinergics—there is no evidence supporting routine prophylaxis for side effects 1