What can be added to sertraline (selective serotonin reuptake inhibitor) for generalized anxiety disorder (GAD) not well controlled despite 100mg daily?

Augmentation Options for Sertraline in Generalized Anxiety Disorder

For generalized anxiety disorder not well controlled on sertraline 100 mg daily, adding an SNRI such as duloxetine or venlafaxine is the most effective augmentation strategy to improve outcomes related to morbidity, mortality, and quality of life.

First-Line Augmentation Options

SNRIs (Serotonin-Norepinephrine Reuptake Inhibitors)

• Duloxetine: Start at 30 mg daily for 1 week, then increase to 60 mg daily 1

  • Particularly beneficial when anxiety co-occurs with chronic pain
  • Shows consistent efficacy in anxiety disorders with effectiveness sustained long-term
  • Less likely to cause cardiac conduction abnormalities compared to venlafaxine

• Venlafaxine: Start at 37.5 mg daily, gradually titrate to 150-225 mg daily over 2-4 weeks 2, 1

  • Effective for anxiety disorders but requires careful monitoring
  • Use with caution in patients with cardiac disease due to potential for blood pressure increases and cardiac conduction abnormalities

Second-Line Augmentation Options

Pregabalin

• Start at low dose (75 mg twice daily) and titrate up to 300-600 mg/day in divided doses 3
• Advantages:
  • More rapid onset of action compared to sertraline monotherapy
  • Different mechanism of action (calcium channel α2-δ ligand)
  • Well-tolerated with short-lasting adverse effects
  • May be particularly helpful for somatic symptoms of anxiety

Mirtazapine

• Start at 15 mg at bedtime, can increase to 30-45 mg 1
• Benefits:
  • Helps with insomnia and anxiety symptoms
  • Complementary mechanism to sertraline (enhances noradrenergic and specific serotonergic transmission)
  • Faster onset of action compared to SSRIs

Cognitive Behavioral Therapy (CBT)

• Should be strongly considered as an augmentation strategy 2, 1
• Combination of medication and CBT shows superior outcomes compared to either treatment alone
• Particularly beneficial for long-term maintenance of improvement

Monitoring and Assessment

1. Evaluate response after 4-6 weeks of augmentation therapy
2. Use standardized measures like GAD-7 to track progress
3. Monitor for potential adverse effects:
   • With SNRIs: blood pressure, heart rate, sexual dysfunction
   • With pregabalin: dizziness, sedation, weight gain
   • With mirtazapine: sedation, increased appetite, weight gain

Important Considerations and Cautions

• Avoid combining multiple serotonergic agents without careful monitoring due to risk of serotonin syndrome 2
• Start with low doses of augmentation agents and titrate slowly to minimize adverse effects
• Monitor for drug-drug interactions, particularly with sertraline which may interact with drugs metabolized by CYP2D6 2
• Be cautious with benzodiazepines as augmentation - while effective short-term, they carry risks of dependence and sedation 4
• Regular reassessment of symptoms, functioning, and quality of life is essential to determine if the augmentation strategy is effective

Treatment-Resistant Cases

If inadequate response after 8 weeks of augmentation:

1. Consider switching to a different augmentation agent
2. Evaluate for comorbid conditions that may be complicating treatment
3. Consider referral to a psychiatrist for more specialized care
4. Assess for potential underlying medical conditions contributing to anxiety symptoms

The goal of augmentation therapy should be complete remission of anxiety symptoms, not just partial improvement, with restoration of normal functioning and quality of life.