What is the recommended approach for starting antidepressant medication in a patient with depression?

Starting Antidepressant Medication for Depression

Initial Medication Selection

Select a second-generation antidepressant (SSRI, SNRI, or atypical agent) based on adverse effect profile, cost, and patient preference, as all second-generation antidepressants demonstrate equivalent efficacy for treatment-naive patients. 1

Preferred First-Line Agents

• SSRIs are the recommended first-line option when initiating pharmacotherapy for major depressive disorder, with sertraline, citalopram, escitalopram, and fluoxetine being appropriate choices 1
• Medication selection should prioritize the adverse effect profile over efficacy differences, as no second-generation antidepressant demonstrates superior effectiveness in head-to-head comparisons 1
• Bupropion should be considered when sexual dysfunction is a primary concern, as it causes significantly lower rates of sexual adverse effects compared to SSRIs 1

Special Population Considerations

• For older adults, preferred agents include citalopram, escitalopram, sertraline, mirtazapine, venlafaxine, and bupropion using a "start low, go slow" approach 1
• Avoid paroxetine and fluoxetine in older patients due to higher rates of adverse effects 1
• For adolescents aged 12-18 years, fluoxetine is FDA-approved and escitalopram is approved for those 12 years and older, with lower effective doses than adults 1

Dosing Strategy

Starting Doses

• Begin with lower starting doses and titrate gradually to minimize seizure risk and improve tolerability 1, 2
• For sertraline: start 25-50 mg daily, increase to effective dose of 50-100 mg 1
• For citalopram/escitalopram: start 10 mg daily 1
• For fluoxetine: start 10-20 mg daily 1
• For bupropion XL: start 150 mg daily for 4 days, then increase to target dose of 300 mg daily 2

Dose Titration

• Increase to the maximum tolerated dose within the therapeutic range before declaring treatment failure 1
• Allow 6-8 weeks at therapeutic doses before modifying treatment for inadequate response 1

Monitoring Schedule

Initial Phase (First 1-2 Weeks)

Assess patient status within 1-2 weeks of initiation, either in-person or by telephone, to monitor for suicidal ideation, behavioral activation, and adverse effects. 1, 3

• Evaluate for emergence of suicidal thoughts or behaviors, particularly in the first 1-2 months when risk is highest 1
• Screen for agitation, irritability, or unusual behavioral changes indicating worsening depression 1
• Assess common adverse effects: nausea, diarrhea, dizziness, headache, insomnia, sexual dysfunction, and somnolence 1
• For adolescents, FDA black-box warning requires close monitoring for clinical worsening and suicidality, especially during initial months and dose changes 1

Ongoing Monitoring

• Continue regular assessments every 1-2 weeks initially, then extend intervals as patient stabilizes 1, 3
• At each visit, inquire about: (1) ongoing depressive symptoms, (2) suicide risk, (3) adverse effects, (4) medication adherence, and (5) environmental stressors 1, 3

Treatment Duration

Acute and Continuation Phases

Continue treatment for a minimum of 4-9 months after achieving remission for a first episode of major depression. 1, 3

• Patients with two or more depressive episodes require longer-term maintenance treatment, potentially indefinitely 1, 3
• The optimal duration beyond initial response remains unclear, requiring periodic reassessment of need for continued therapy 2

Discontinuation Strategy

• When discontinuing, taper the dose gradually to minimize withdrawal symptoms 1, 3
• For patients on 300 mg daily, decrease to 150 mg daily before complete discontinuation 2
• For SSRIs, slow tapering is essential due to risk of withdrawal effects 1

Common Pitfalls to Avoid

• Do not use multiple serotonergic agents concurrently, as this significantly increases serotonin syndrome risk 3
• Avoid starting SSRIs at higher-than-recommended doses, which increases risk of deliberate self-harm and suicide-related events 1
• Do not add a second antidepressant for inadequate response before optimizing the dose of the first agent to maximum therapeutic levels 3
• Approximately 63% of patients experience at least one adverse effect, with nausea and vomiting being the most common reasons for discontinuation—anticipate and address these proactively 1

Efficacy Expectations

• Antidepressants demonstrate modest superiority over placebo in primary care populations, with number needed to treat of 7-8 for SSRIs 1
• Benefit over placebo is most pronounced in patients with severe depression 1
• Published trials overestimate effectiveness due to publication bias; FDA analysis shows only 51% of all studies had positive results versus 94% of published trials 1