From the Guidelines
Amitriptyline is a recommended medication for the management of fibromyalgia, particularly for its ability to modulate pain signals and improve sleep quality, with a weak recommendation for its use at a low dose, as stated in the 2017 EULAR revised recommendations for the management of fibromyalgia 1. The medication is typically started at a low dose of 10-25 mg taken at bedtime and gradually increased if needed to 25-50 mg daily.
- The goal of using amitriptyline in fibromyalgia management is to improve health-related quality of life by balancing the benefits and risks of treatment, which often requires a multidisciplinary approach with a combination of non-pharmacological and pharmacological treatment modalities tailored according to pain intensity, function, associated features, and patient preferences and comorbidities 1.
- Patients should take amitriptyline 1-2 hours before bedtime to minimize morning grogginess, and improvement may take 2-4 weeks to become noticeable, with the medication continued for at least 3-6 months before evaluating its full effectiveness.
- Common side effects of amitriptyline include dry mouth, constipation, drowsiness, and weight gain, which often improve with time as the body adjusts to the medication.
- It is essential to inform the doctor about all other medications being taken, as amitriptyline can interact with many drugs, and it should not be stopped abruptly but rather tapered slowly under medical supervision 1.
- While not FDA-approved specifically for fibromyalgia, amitriptyline is widely used as a first-line treatment due to its effectiveness in managing chronic pain conditions and its ability to address multiple fibromyalgia symptoms simultaneously, as supported by the 2017 EULAR revised recommendations 1 and other studies 1.
From the Research
Role of Amitriptyline in Fibromyalgia Management
- Amitriptyline, a tricyclic antidepressant, has been extensively studied for the treatment of fibromyalgia, with evidence suggesting its efficacy in reducing symptoms such as pain, sleep disturbances, and fatigue 2, 3, 4.
- Clinical practice guidelines recommend multidisciplinary treatment using a combination of pharmacological and non-pharmacological therapies, with amitriptyline considered a first-line drug for the treatment of fibromyalgia 2.
- Low doses of amitriptyline (10-75 mg/day) have been found to be effective in treating fibromyalgia, with minimal tolerability or safety issues 2, 5.
Efficacy of Amitriptyline
- Studies have shown that amitriptyline is associated with significant improvement in patient and physician global assessments, patient pain, sleep difficulties, fatigue on awakening, and tender point score 4.
- A systematic review and network meta-analysis found that amitriptyline was associated with reduced sleep disturbances, fatigue, and improved quality of life, with a relatively high efficacy for improving sleep, fatigue, and overall quality of life 3.
- However, another review found that there is no first or second tier evidence for amitriptyline in the treatment of fibromyalgia, with very low quality evidence suggesting a risk ratio of 3.0 for at least 50% pain relief, or equivalent, with amitriptyline compared with placebo 5.
Mechanism of Action
- The mechanism of action of amitriptyline in fibromyalgia is not fully understood, but it is thought to involve modulation of neurotransmitters such as serotonin and noradrenaline, as well as potassium channel modulation and NMDA receptor antagonism 6.
- Investigation of the importance of each of the pharmacological properties of amitriptyline and related molecules in the management of fibromyalgia could provide clues for the rational design of new drugs 6.
Comparison with Other Treatments
- A comparison of amitriptyline with US Food and Drug Administration-approved treatments for fibromyalgia 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 3.
- The study suggests that clinicians should consider how treatments could be tailored to individual symptoms, weighing the benefits and acceptability, when prescribing medications to patients with fibromyalgia 3.