What is the best antidepressant to try for a 27-year-old patient with Generalized Anxiety Disorder (GAD) who experienced adverse effects on citalopram and Lexapro (escitalopram)?

Antidepressant Selection After SSRI Adverse Effects

For a 27-year-old patient with GAD who experienced vomiting and hot flashes with citalopram and escitalopram, bupropion would be the best antidepressant to try next due to its different mechanism of action and lower risk of similar side effects.

Rationale for Switching to a Different Class

The patient has failed two SSRIs (citalopram and escitalopram) with immediate adverse effects including vomiting and hot flashes. These symptoms suggest serotonergic side effects that are likely to recur with other medications in the same class.

• When a patient fails two medications within the same class, switching to a different class is recommended 1
• Approximately 25% of patients become symptom-free after switching medications, even after multiple failures 1

Recommended Medication: Bupropion

Bupropion is an optimal choice for several reasons:

• Different mechanism of action: Unlike SSRIs, bupropion primarily affects dopamine and norepinephrine reuptake rather than serotonin, reducing the likelihood of similar adverse effects 1
• Dosing: Start at 100-150 mg daily, increasing by 100 mg every 5-7 days to a maximum of 400 mg daily 1
• Evidence: The STAR*D trial showed that approximately 25% of patients became symptom-free after switching medications with no difference in efficacy between bupropion, sertraline, and venlafaxine 2

Alternative Option: Venlafaxine

If bupropion is contraindicated or ineffective, venlafaxine could be considered:

• Efficacy in GAD: Venlafaxine has demonstrated effectiveness in GAD 3
• Dosing: Start at 37.5-75mg daily and gradually titrate to 150-225mg daily over 2-4 weeks 1
• Caution: While venlafaxine affects serotonin, it has a different mechanism (SNRI vs SSRI) which may be better tolerated in this patient

Monitoring and Precautions

For Bupropion:

• Contraindications: Avoid in patients with seizure disorders, eating disorders, or recent head trauma 1
• Side effects to monitor: Insomnia, dry mouth, headache, nausea, dizziness
• Advantages: Less likely to cause sexual dysfunction or weight gain compared to SSRIs 4

For Venlafaxine (if used):

• Side effects to monitor: Increased blood pressure, nausea, headache, insomnia
• Discontinuation: Requires gradual tapering to avoid withdrawal symptoms 1

Clinical Considerations

• Titration: Start with low doses and titrate slowly to minimize side effects 1
• Timing: Allow 4-6 weeks at therapeutic doses to assess full efficacy
• Follow-up: Regular monitoring for therapeutic response and adverse effects
• Augmentation: If partial response occurs, consider augmentation strategies rather than switching again 1

Common Pitfalls to Avoid

• Inadequate trial: Ensure adequate dosing and duration before determining treatment failure
• Premature discontinuation: Side effects often improve with time
• Ignoring comorbidities: Assess for comorbid conditions that may affect treatment response
• Missing drug interactions: Review all medications for potential interactions

By selecting an antidepressant with a different mechanism of action like bupropion, this patient has a good chance of achieving symptom relief without experiencing the same adverse effects that occurred with SSRIs.