What is the recommended initial treatment approach for depression?

Recommended Initial Treatment Approach for Depression

For treatment-naive adults with moderate to severe major depressive disorder, initiate treatment with a second-generation antidepressant (SSRI or SNRI) at standard starting doses, selecting the specific agent based on the patient's target symptom profile, adverse effect considerations, cost, and patient preference. 1

First-Line Pharmacologic Treatment

Standard Approach for General Depressive Symptoms

• All second-generation antidepressants demonstrate equivalent efficacy for treatment-naive patients with general depressive symptoms, with SSRIs achieving remission with a number needed to treat of 7-8. 1, 2
• The American College of Physicians recommends selecting among second-generation antidepressants based on adverse effect profiles, cost, and patient preferences rather than presumed efficacy differences. 2

Symptom-Targeted Selection

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

• First choice: Bupropion due to its dopaminergic and noradrenergic effects and lower rate of cognitive side effects. 1
• Second choice: SNRIs (venlafaxine or duloxetine) as their noradrenergic component may improve attention and concentration better than SSRIs. 1

For older adults (≥60 years):

• Preferred agents: Citalopram, sertraline, venlafaxine, or bupropion using a "start low, go slow" approach. 1, 2
• Avoid: Paroxetine and fluoxetine due to higher anticholinergic effects and less favorable profiles in this population. 1

Critical Severity-Based Considerations

• Do not prescribe antidepressants for mild depression or subsyndromal depressive symptoms without a current moderate-to-severe episode, as the drug-placebo difference increases with initial severity. 1
• Antidepressants are most effective in patients with severe depression. 1

Initial Dosing

Standard starting doses:

• Sertraline: 50 mg once daily (optimal therapeutic dose for most patients). 3
• For panic disorder, PTSD, or social anxiety disorder: Start at 25 mg daily for one week, then increase to 50 mg daily. 3
• Dose adjustments should not occur at intervals less than 1 week given sertraline's 24-hour elimination half-life. 3

Monitoring and Response Assessment

• Begin monitoring within 1-2 weeks of initiation for therapeutic response, adverse effects, and emergence of suicidal thoughts or behaviors. 2
• Regularly assess both mood and cognitive symptoms using standardized measures. 1
• If inadequate response after 6-8 weeks, modify treatment by switching agents, augmenting therapy, or adding psychotherapy. 2

Treatment Duration

• Continue treatment for 4-9 months after symptom resolution for a first episode of major depression. 2, 1
• For patients with 2 or more prior episodes, extend treatment duration as longer maintenance therapy may be beneficial. 2
• Maintenance treatment should continue for at least 2 years after the last episode in recurrent depression. 4

Alternative First-Line Option: Cognitive Behavioral Therapy

• CBT and antidepressants have comparable efficacy and are both viable first-line choices for initial MDD treatment. 2
• Treatment choice should follow discussion with patients about advantages, disadvantages, risks, drug interactions, and preferences. 2

Common Adverse Effects to Anticipate

• Approximately 63% of patients on second-generation antidepressants experience at least one adverse effect. 1
• Most common: Nausea, vomiting, diarrhea, dizziness, dry mouth, fatigue, headache, and sexual dysfunction. 1
• Bupropion has lower rates of sexual adverse events than fluoxetine or sertraline. 2, 1
• Paroxetine has higher rates of sexual dysfunction than other SSRIs. 2, 1

Critical Pitfalls to Avoid

• Never use tricyclic antidepressants as first-line agents due to higher adverse effect burden and overdose risk. 1
• Do not assume all SSRIs have identical profiles—paroxetine has notably higher anticholinergic effects and sexual dysfunction rates. 1
• In bipolar disorder, never use antidepressants as monotherapy as they may trigger manic episodes or rapid cycling; always combine with a mood stabilizer. 4
• Do not prescribe for subsyndromal symptoms without a current moderate-to-severe episode. 1