Introduction: Physical pain is a common issue in people with bipolar disorder (BD). It worsens mental health and quality of life, negatively impacts treatment response, and increases the risk of suicide. Lithium, which is prescribed in BD as mood stabilizer, has shown promising effects on pain.Methods: This naturalistic study included 760 subjects with BD (French FACE-BD cohort) divided in two groups: with and without self-reported pain (evaluated with the EQ-5D-5L questionnaire). In this sample, 176 subjects were treated with lithium salts. The objectives of the study were to determine whether patients receiving lithium reported less pain, and whether this effect was associated with the recommended mood stabilizing blood concentration of lithium.Results: Subjects with lithium intake were less likely to report pain (OR = 0.59, 95% CI [0.35-0.95]; p = 0.036) after controlling for sociodemographic variables, BD type, lifetime history of psychiatric disorders, suicide attempt, personality traits, current depression and anxiety levels, sleep quality, and psychomotor activity. Subjects taking lithium were even less likely to report pain when lithium concentration in blood was ≥0.5mmol/l (OR = 0.44, 95% CI [0.24-0.79]; p = 0.008).Discussion: This is the first naturalistic study to show lithium promising effect on pain in subjects suffering from BD after controlling for many confounding variables. This analgesic effect seems independent of BD severity and comorbid conditions. Randomized controlled trials are needed to confirm the analgesic effect of lithium salts and to determine whether lithium decreases pain in other vulnerable populations, such as people with chronic pain.< Leer menos