What are the recommended second-generation antidepressants (SGAs) for treating depression?

Second-Generation Antidepressants for Treating Depression

Second-generation antidepressants (SGAs), including selective serotonin reuptake inhibitors (SSRIs), serotonin-norepinephrine reuptake inhibitors (SNRIs), and selective serotonin-norepinephrine reuptake inhibitors (SSNRIs), are the recommended first-line pharmacological treatments for depression due to their similar efficacy to first-generation antidepressants but with lower toxicity in overdose and better side effect profiles. 1

Types of Second-Generation Antidepressants

The main classes of SGAs include:

1. Selective Serotonin Reuptake Inhibitors (SSRIs):

   • Fluoxetine
   • Sertraline
   • Paroxetine
   • Citalopram
   • Escitalopram
   • Fluvoxamine

2. Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs):

   • Venlafaxine
   • Duloxetine

3. Other SGAs:

   • Bupropion
   • Mirtazapine
   • Nefazodone
   • Trazodone

Efficacy Considerations

When selecting among SGAs, consider the following evidence-based findings:

• Venlafaxine has demonstrated superior efficacy compared to SSRIs for treatment-resistant depression, with dose-dependent effects 1
• Sertraline has shown better efficacy than fluoxetine in some comparative studies 2
• Mirtazapine has demonstrated better efficacy than fluoxetine in clinical trials 2

Selection Algorithm Based on Symptom Profile

1. For patients with predominant fatigue or sexual dysfunction:

   • Bupropion (150-300mg daily) is recommended due to its lower incidence of sexual side effects 1

2. For severe depression:

   • SNRIs like venlafaxine may be more effective than SSRIs 1
   • Starting dose should be low with gradual titration

3. For depression with anxiety symptoms:

   • SSRIs (particularly sertraline or escitalopram) are often preferred 3

4. For elderly patients:

   • Sertraline is well-tolerated with low potential for drug interactions 4
   • No dosage adjustments are needed based solely on age

Side Effect Considerations

SGAs have varying side effect profiles that should guide selection:

• Common side effects include diarrhea, dizziness, dry mouth, fatigue, headache, sexual dysfunction, sweating, tremor, and weight gain 1
• Approximately 63% of patients experience at least one adverse effect 1
• SSRIs are associated with an increased risk for suicidal ideation, particularly in adults 18-24 years old 1
• Venlafaxine requires monitoring for blood pressure increases at higher doses 1

Treatment Duration

• For first episode depression: continue treatment for 4-9 months after achieving remission 1
• For recurrent depression: consider maintenance treatment for 1+ years 1

Monitoring and Follow-up

• Begin assessment of treatment response within 1-2 weeks of starting treatment 1
• Monitor closely for suicidality in the first 1-2 weeks, especially in young adults 1
• If inadequate response after 6-8 weeks, consider dose adjustment, switching to a different antidepressant, adding psychotherapy, or augmentation strategies 1

Important Caveats

• Abrupt discontinuation can lead to withdrawal symptoms, particularly with shorter-acting agents; taper slowly when discontinuing 1
• Be vigilant for potential drug interactions, especially with medications metabolized by cytochrome P450 enzymes 5
• Serotonin syndrome can occur when combining with other serotonergic medications 5

While novel antidepressants have shown promising results in recent research 6, the established SGAs remain the standard first-line treatments based on their well-documented efficacy and safety profiles.