Can amitriptyline (tricyclic antidepressant) and trazodone (serotonin antagonist and reuptake inhibitor) be used together?

Amitriptyline and Trazodone Combination Therapy

Amitriptyline and trazodone can be used together with caution, but require careful monitoring for serotonin syndrome and additive sedation. 1

Safety Considerations

Potential Risks

• Serotonin Syndrome: Both medications affect serotonergic pathways, which can increase the risk of serotonin syndrome when used together 2
• Cardiac Effects: Both medications can affect cardiac conduction; trazodone may be arrhythmogenic in patients with preexisting cardiac disease 2
• Excessive Sedation: Both medications have sedative properties that can be additive 1

Documented Case Reports

• There is at least one documented case of serotonin syndrome occurring with the combination of low-dose trazodone, amitriptyline, and lithium 3

Dosing Recommendations

When using these medications in combination:

1. Start with lower doses than typically used for monotherapy:

   • Amitriptyline: Start at 10-25 mg at bedtime, increasing gradually to 25-75 mg as tolerated 4, 1
   • Trazodone: Start at 25-50 mg at bedtime, generally not exceeding 100 mg when used in combination 1

2. Titration:

   • Increase doses gradually every 3-7 days 1
   • Monitor closely for side effects during dose adjustments
   • Aim for the lowest effective dose for symptom control

Clinical Applications

This combination may be particularly useful in specific clinical scenarios:

Neuropathic Pain with Insomnia

• Amitriptyline is a first-line agent for neuropathic pain 4
• Trazodone can help address comorbid insomnia 4, 1

Cancer Pain Management

• Tricyclic antidepressants like amitriptyline are recognized as coanalgesics for cancer-related neuropathic pain 4
• Low-dose trazodone may be added for sleep disturbances 1

Refractory Gastroparesis with Pain

• Amitriptyline is listed as a medication for visceral pain in gastroparesis 4
• The combination may help with both pain control and sleep

Monitoring Recommendations

1. Initial Period (First 2 Weeks):

   • Monitor for signs of serotonin syndrome: mental status changes, autonomic instability, neuromuscular symptoms, seizures, and gastrointestinal symptoms 2
   • Assess for excessive sedation and cognitive impairment
   • Watch for cardiovascular effects, particularly in patients with cardiac history

2. Ongoing Monitoring:

   • Regular follow-up every few weeks during initial treatment period
   • ECG monitoring may be warranted, especially in patients with cardiac risk factors
   • Assess for therapeutic benefit and continued need for both medications

Contraindications

This combination should be avoided in:

• Patients taking MAO inhibitors 2
• Patients with severe hepatic impairment 1
• Patients with a history of cardiac arrhythmias 2
• Patients with angle-closure glaucoma 1

Practical Considerations

• Administration timing: Both medications are typically given at bedtime to minimize daytime sedation
• Patient education: Warn about potential sedation and advise against driving or operating machinery until effects are known
• Elderly patients: Use lower starting doses and more gradual titration 1

By following these guidelines and monitoring closely, the combination of amitriptyline and trazodone can be used safely and effectively in appropriate clinical scenarios, though caution is warranted due to the potential for additive side effects and drug interactions.