What is the recommended first-line treatment for depression?

First-Line Treatment for Depression

Second-generation antidepressants (SGAs) are the recommended first-line pharmacological treatment for depression, with selection based on adverse effect profiles, cost, and patient preferences. 1

Medication Selection

• Selective Serotonin Reuptake Inhibitors (SSRIs), Serotonin Norepinephrine Reuptake Inhibitors (SNRIs), and other second-generation antidepressants are considered first-line treatment due to their better adverse effect profiles compared to older medications 1
• Evidence does not justify choosing one second-generation antidepressant over another based on efficacy alone, as they have similar effectiveness 1
• Medication selection should be guided by:
  • Patient's previous history with antidepressants 1
  • Adverse effect profiles (particularly sexual dysfunction, GI effects) 1
  • Potential drug-drug interactions 1
  • Cost and patient preferences 1

Specific Medication Considerations

• SSRIs are generally well-tolerated and considered appropriate initial therapy for most patients 1
• SNRIs (like venlafaxine) may provide additional benefits for patients with comorbid pain disorders but have only marginally superior remission rates compared to SSRIs (49% vs. 42%) 1
• Bupropion is associated with lower rates of sexual dysfunction compared to fluoxetine or sertraline 1
• Paroxetine has higher rates of sexual dysfunction than fluoxetine, fluvoxamine, nefazodone, or sertraline 1

Dosing and Administration

• For fluoxetine, the recommended initial dose is 20 mg/day administered in the morning 2
• For patients who may be sensitive to side effects, starting at lower doses (e.g., 5-10 mg) and gradually increasing may improve tolerability 3
• Sertraline is typically started at 50 mg/day, which is the usually effective therapeutic dose for most patients 4

Monitoring and Follow-up

• Patients should be assessed for therapeutic response and adverse effects regularly, beginning within 1-2 weeks of starting therapy 1
• Close monitoring is particularly important during the first 1-2 months of treatment when the risk for suicide attempts may be greater 1
• If patients do not have an adequate response within 6-8 weeks, treatment modification is recommended 1

Treatment Duration

• For a first episode of major depression, treatment should continue for 4-9 months after a satisfactory response 1
• For patients with two or more episodes of depression, longer duration of therapy (years to lifelong) may be beneficial 1

Special Populations

Elderly Patients

• Preferred agents for older patients include citalopram, escitalopram, sertraline, mirtazapine, and venlafaxine 1
• A "start low, go slow" approach is recommended for elderly patients 1
• Paroxetine and fluoxetine should generally be avoided in older adults due to higher rates of adverse effects 1

Nursing Home Residents

• SSRIs are considered the most appropriate first-line treatment for depression in nursing home residents 1
• Tertiary tricyclics and psychostimulants are not recommended as first-line treatment 1

Common Pitfalls and Caveats

• About 63% of patients receiving second-generation antidepressants experience at least one adverse effect during treatment 1
• Common side effects include constipation, diarrhea, dizziness, headache, insomnia, nausea, sexual side effects, and somnolence 1
• Nausea and vomiting are the most common reasons for discontinuation of therapy 1
• SSRIs may be associated with an increased risk for suicide attempts compared to placebo, particularly in young adults (18-24 years) 1
• Approximately 38% of patients do not achieve a treatment response during 6-12 weeks of treatment with second-generation antidepressants, and 54% do not achieve remission 1
• Antidepressants are most effective in patients with severe depression compared to those with mild to moderate depression 1