Can you take amitriptyline, Lyrica (pregabalin), and trazodone together?

Taking Amitriptyline, Lyrica (Pregabalin), and Trazodone Together

Yes, amitriptyline, Lyrica (pregabalin), and trazodone can be taken together, but this combination requires careful monitoring for additive sedative effects and potential drug interactions.

Safety and Efficacy of This Combination

• The combination of medications from different classes targeting multiple mechanisms can be used together safely and effectively when properly monitored 1
• Amitriptyline (tricyclic antidepressant) and trazodone (sedating antidepressant) are both used at lower than antidepressant doses for insomnia and pain management 1
• Pregabalin (Lyrica) is an anti-epileptic medication that is also used for neuropathic pain, often in combination with other agents 2

Potential Benefits of Combination Therapy

• Each medication works through different mechanisms, potentially providing complementary effects for patients with both pain and sleep issues 3
• Low-dose combinations may allow for lower doses of each individual medication while maintaining efficacy, potentially reducing side effects 2
• A study comparing pregabalin and amitriptyline monotherapy with their low-dose combination showed that the combination was equally effective but more tolerable than higher-dose monotherapy 2

Important Precautions

• All three medications have CNS depressant effects, so the combined sedative effect will be additive and may cause excessive sedation 1
• There is a documented case of serotonin syndrome occurring with the combination of trazodone and amitriptyline (even at low doses), particularly when combined with lithium 4
• Symptoms of serotonin syndrome include anxiety, restlessness, tremor, myoclonus, hyperreflexia, diaphoresis, rigidity, and hyperthermia 4

Dosing Considerations

• Start with lower doses of each medication when using them in combination to minimize adverse effects 3
• For insomnia, typical doses are lower than those used for depression or pain:
  • Trazodone: 25-100 mg at bedtime 1
  • Amitriptyline: 10-25 mg at bedtime 5
  • Pregabalin: Starting at 75 mg daily, potentially in divided doses 2
• Elderly patients or those with hepatic impairment may require even lower doses due to increased sensitivity to sedative effects 3

Monitoring and Management

• Monitor for excessive daytime sedation, especially during the initial period of combined use 3
• Avoid combining with other CNS depressants including alcohol, which could dangerously increase sedation 1, 3
• Take medications as prescribed, typically with trazodone and amitriptyline at bedtime to minimize daytime sedation 3
• Amitriptyline should be taken after meals to reduce side effects 6

Potential Side Effects to Watch For

• Common side effects include dry mouth, sedation, dizziness, and orthostatic hypotension 1, 5
• The combination may cause additive anticholinergic effects (dry mouth, constipation, blurred vision) 5
• Watch for signs of serotonin syndrome, especially when starting the combination or increasing doses 4
• Patients should be cautioned about activities requiring alertness until the effects of the medication combination are known 3

Follow-up Recommendations

• Regular follow-up every few weeks during the initial treatment period is recommended to assess efficacy and monitor for side effects 1
• Efforts should be made to use the lowest effective maintenance dosage of each medication 1