What are alternative selective serotonin reuptake inhibitors (SSRIs) to start for generalized anxiety in a patient who has already tried Trintellix (vortioxetine), Cipralex (escitalopram), and Wellbutrin (bupropion)?

Alternative SSRIs for Generalized Anxiety After Failed Trials of Vortioxetine, Escitalopram, and Bupropion

For a patient with generalized anxiety who has already tried Trintellix (vortioxetine), Cipralex (escitalopram), and Wellbutrin (bupropion), sertraline is the recommended SSRI to try next, followed by fluoxetine if needed. 1, 2

First-Line Alternative: Sertraline

Sertraline is the optimal next choice for several reasons:

• It has strong evidence supporting its efficacy in anxiety disorders with response rates of 63% compared to 53% for placebo 1
• It has a favorable side effect profile compared to other SSRIs 3
• Recent algorithms specifically recommend sertraline as a preferred SSRI for anxiety disorders 2

Dosing recommendations:

• Starting dose: 25-50 mg daily
• Target dose: Up to 200 mg daily as needed and tolerated
• Common side effects: Nausea, diarrhea, headache, insomnia, sexual dysfunction 1

Second-Line Alternative: Fluoxetine

If sertraline is ineffective or not tolerated, fluoxetine should be considered:

• It has the strongest evidence base among SSRIs for anxiety disorders with response rates of 56-61% compared to 33-37% for placebo 1
• Dosing: Start at 10-20 mg daily and titrate as needed
• Common side effects: Nausea, asthenia/decreased energy, somnolence, fatigue, decreased libido, sweating 1

Third-Line Options: SNRIs

If both sertraline and fluoxetine are ineffective or not tolerated, consider an SNRI:

• Venlafaxine or duloxetine are suggested as alternative first-line pharmacological options for anxiety disorders 1, 2
• These may be particularly effective when SSRIs have failed

Additional Considerations

Why These Previous Treatments May Have Failed:

1. Trintellix (vortioxetine): While it has shown efficacy in GAD 4, it's not typically considered a first-line treatment for anxiety disorders.

2. Cipralex (escitalopram): Although escitalopram is effective for GAD 5, individual response varies, and some patients may require a different SSRI.

3. Wellbutrin (bupropion): Not typically recommended as a first-line agent for anxiety and may actually worsen anxiety symptoms in some patients due to its activating properties.

Important Monitoring Considerations:

• Monitor for serotonin syndrome, especially when switching between serotonergic medications 6
• Watch for behavioral activation/agitation, particularly in the first few weeks of treatment 1
• Assess response after 2-3 weeks initially and full effect at 4-6 weeks 1
• Continue effective treatment for approximately 1 year following symptom remission 1

Adjunctive Treatments to Consider:

• Cognitive-behavioral therapy (CBT) is strongly recommended alongside medication 1
• Pregabalin may be considered as an adjunctive treatment for anxiety disorders 1
• Buspirone can be used as an augmentation strategy for partial response to SSRIs 1

Medication Switching Protocol

When switching from previous medications to sertraline:

1. For escitalopram to sertraline: Cross-taper over 1-2 weeks due to similar mechanisms
2. For vortioxetine to sertraline: Allow a washout period of 1 week before starting sertraline
3. For bupropion to sertraline: Can typically start sertraline immediately after discontinuing bupropion

Remember that gradual tapering is essential when discontinuing any antidepressant, reducing by no more than 25% every 1-2 weeks to minimize withdrawal symptoms 1.