Fibromyalgia is a complex chronic pain syndrome affecting up to 5% of the population. With unclear etiology and pathogenesis, treatment relies on symptom management. Tricyclic antidepressants (TCAs) are a cornerstone, believed to act by modulating serotonin and norepinephrine. Yet evidence on their efficacy is conflicting[1]Nishishinya B, Urrutia G, Walitt B, Rodriguez A, Bonfill X, Alegre C, Darko G. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology. 2008 Dec … Continue reading.
In Rheumatology, Nishishinya and colleagues performed a systematic review in 2008 assessing randomized controlled trials of amitriptyline for fibromyalgia. Ten trials with 615 patients were included. The review found moderate evidence that amitriptyline 25mg/day provides modest relief across multiple fibromyalgia domains including pain, sleep, fatigue, and overall well-being compared to placebo over 6-8 weeks.
The Optimal Amitriptyline Dose for Fibromyalgia is Unknown
- The review found 25mg/day was more effective than 50mg/day, contradicting the dose-response in other conditions.
- Reasons for this inverted response are unclear. Defining the ideal dosage requires further research.
- Current limited evidence only supports potential short-term benefit with 25mg/day.
Amitriptyline’s Side Effect Profile Needs Better Characterization
- Reported side effects included dry mouth, drowsiness, and weight gain.
- Adverse events were inconsistently measured and did not clearly relate to dose.
- Safety over long-term use is uncertain. Large observational studies can better characterize risks.
- Effects on hormones and sexual function need evaluation given fibromyalgia’s female predominance.
Major Limitations Restrict Clinical Recommendations
- Small samples, short duration, and incomplete outcome reporting limit strength of evidence.
- Lack of functional and quality of life impact measures hamper clinical interpretation.
- Comparisons with newer antidepressants are critically lacking.
- Given modest benefits and potential side effects, firm recommendations are premature until higher quality comparative research is available.
Limitations
However, numerous limitations undermine the strength of this conclusion. Study quality was fair at best, with small sample sizes and incomplete outcome reporting. The effect size could not be calculated, making clinical relevance unclear. Adverse events were common but inconsistently reported.
More concerning, benefits were not seen with higher doses of amitriptyline or treatment beyond 8 weeks. The 50mg/day dose failed to separate from placebo on any outcome. Reasons for this inverted dose-response are unclear. Prior studies do show reduced efficacy over time, but limitations in duration prevent firm conclusions.
Research Gaps
The review highlights important evidence gaps in tricyclic antidepressants for fibromyalgia. Well-designed trials of adequate length assessing functional and quality of life impact are needed. Optimal dosing strategies have yet to be defined. Comparisons with newer agents are lacking.
For now, low-dose amitriptyline continues to have a role in fibromyalgia pharmacotherapy, but primarily for sleep. The magnitude and duration of broader symptomatic relief remains uncertain based on available evidence. Claims of superior efficacy among tricyclics appear premature.
In summary, while suggestive of benefit, this systematic review does not provide robust evidence for amitriptyline in fibromyalgia. Significant clinical questions remain unanswered. Limitations in current studies preclude strong clinical recommendations and underscore the need for further high-quality comparative effectiveness research.
MD, PhD. Physical Medicine & Rehabilitation Physician from São Paulo - Brazil. Pain Fellowship in University of São Paulo.
References
| ↑1 | Nishishinya B, Urrutia G, Walitt B, Rodriguez A, Bonfill X, Alegre C, Darko G. Amitriptyline in the treatment of fibromyalgia: a systematic review of its efficacy. Rheumatology. 2008 Dec 1;47(12):1741-6. |
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