The Genetic Association Between Prescription Pain Medication Use and the Risk for Fibromyalgia: A Bidirectional and...

Area of Science:

• Genetics
• Pain Medicine
• Pharmacology

Background:

• Growing evidence links prescription opioid use to poor fibromyalgia prognosis.
• The causal relationship between opioid use and fibromyalgia remains unclear.

Purpose of the Study:

• To investigate the causal association between prescription opioid use and fibromyalgia using Mendelian randomization.
• To examine potential mediating roles of major depressive disorder, anxiety disorders, and insomnia.

Main Methods:

• Bidirectional two-sample Mendelian randomization (MR) analysis.
• Multivariable Mendelian randomization (MVMR) to adjust for confounders.
• Mediation MR analysis to assess mediating effects.

Main Results:

• Prescription opioid use showed a causal effect on increasing fibromyalgia risk (IVW OR=1.42, p=3.55E-04; Weighted Median OR=1.40, p=0.01).
• This association remained significant after adjusting for major depressive disorder, anxiety disorders, and insomnia.
• No significant reverse causality from fibromyalgia to opioid use was found, nor associations with non-opioid pain medications.

Conclusions:

• Genetic evidence supports a causal link between prescription opioid use and higher fibromyalgia risk.
• The association is robust against common comorbidities like depression, anxiety, and insomnia.
• Clinicians should consider alternative pain management strategies to mitigate fibromyalgia risk associated with opioid prescriptions.