Background: Fibromyalgia is a chronic condition characterized by widespread pain, fatigue, nonrestorative sleep, cognitive complaints, and functional impairment. Although lithium is primarily used as a mood stabilizer, historical clinical observations and contemporary findings have raised questions about its potential analgesic properties.
Objective: To critically evaluate the evidence concerning lithium and fibromyalgia, distinguishing direct clinical observations from indirect findings involving bipolar disorder, experimental models, and sleep-related outcomes.
Methods: A critical narrative review was conducted using historical full-text publications, identifiable contemporary observational studies, and experimental evidence. The literature was examined according to study design, diagnostic characterization, psychiatric comorbidity, concomitant treatment, reported outcomes, and methodological limitations. Particular attention was given to avoiding duplication of patients across related publications.
Results: Tyber described three women with fibromyalgia who experienced marked reductions in spontaneous pain and stiffness following lithium augmentation of ongoing antidepressant treatment. One patient also reported improvement in fatigability, whereas tender-point sensitivity persisted despite symptomatic relief. Subsequent publications by Lewis and Fontrier proposed mechanisms involving calcium–parathyroid hormone regulation without introducing additional treated patients. In 2004, Fontrier reported an individual experience of approximately 70–80% pain reduction, with rapid onset and limited duration. In the FACE-BD observational cohort, lithium exposure was associated with lower odds of reporting physical pain among patients with bipolar disorder (adjusted odds ratio 0.59; 95% confidence interval 0.35–0.95). Preliminary experimental findings and observational studies of sleep in bipolar disorder provide additional indirect evidence. However, controlled clinical evidence establishing lithium efficacy in fibromyalgia remains unavailable among the reviewed publications.
Conclusions: Historical clinical observations suggest a possible analgesic signal associated with lithium, but the available evidence is insufficient to establish causality, clinical efficacy, or independence from mood stabilization. The relationship between lithium and other fibromyalgia-related manifestations, including sleep disturbances, fatigue, cognition, and quality of life, remains inadequately investigated. Given the limited evidence and established safety concerns, lithium should remain an investigational intervention for fibromyalgia.