From the Guidelines
The recommended dosing for taking nortriptyline and pregabalin together for fibromyalgia involves starting nortriptyline at 25 mg at bedtime and pregabalin at 50 mg three times daily or 75 mg twice daily, with gradual increases as tolerated. When considering the combination of these medications, it's crucial to prioritize the management of potential side effects and monitor for increased drowsiness, dizziness, and dry mouth.
Key Considerations for Dosing:
- Nortriptyline should be started at 25 mg at bedtime and increased by 25 mg every 3-7 days as tolerated, with a maximum dose of 150 mg daily 1.
- Pregabalin can be initiated at 50 mg three times daily or 75 mg twice daily, with increases to 300 mg daily after 3-7 days, and further titration to 600 mg daily if necessary and tolerated 1.
Mechanism and Rationale:
The combination of nortriptyline and pregabalin works through complementary mechanisms, with nortriptyline affecting serotonin and norepinephrine levels and pregabalin modulating calcium channels and neurotransmitter release. This combination may provide better pain relief than either medication alone for patients with fibromyalgia.
Administration and Monitoring:
Patients should take nortriptyline at night due to its sedating effects and divide pregabalin doses throughout the day. Regular follow-up with a healthcare provider is essential to assess effectiveness, monitor for side effects, and adjust dosing as needed to optimize pain management and minimize adverse effects.
From the Research
Recommended Dosing for Nortriptyline and Pregabalin
There is limited direct evidence on the recommended dosing for taking nortriptyline and pregabalin together for fibromyalgia. However, we can look at the available evidence on the use of these medications separately and in combination with other drugs for fibromyalgia.
- The studies provided do not specifically address the combination of nortriptyline and pregabalin for fibromyalgia 2, 3, 4, 5, 6.
- However, one study compared the combination of pregabalin and duloxetine to each monotherapy for fibromyalgia, and found that the combination improved multiple clinical outcomes vs monotherapy 2.
- Another study compared the effectiveness of duloxetine, pregabalin, and milnacipran for fibromyalgia, and found that duloxetine was the most effective treatment, improving pain, quality of life, and sleep quality 3.
- A systematic review and network meta-analysis compared the effectiveness of amitriptyline, pregabalin, duloxetine, and milnacipran for fibromyalgia, and found that duloxetine 120 mg was associated with the highest improvement in pain and depression, while amitriptyline was associated with higher efficacy for improving sleep, fatigue, and overall quality of life 5.
- A pilot study found that low-dose amitriptyline (10mg) improved clinical symptom scores and anxiety scores, and increased blood flow to affected sites in patients with fibromyalgia 6.
Key Findings
- There is limited direct evidence on the recommended dosing for taking nortriptyline and pregabalin together for fibromyalgia.
- Combination therapy with pregabalin and another medication (e.g. duloxetine) may improve clinical outcomes for fibromyalgia.
- Amitriptyline, a tricyclic antidepressant similar to nortriptyline, has been found to improve sleep, fatigue, and overall quality of life in patients with fibromyalgia.
- The optimal dosing for nortriptyline and pregabalin in combination for fibromyalgia is not established, and may require individualized titration and monitoring.