Distinct Prescription Patterns Emerge Years Before ALS Diagnosis: A Nationwide Registry-Based Study

Area of Science:

• Neurology
• Pharmacology
• Epidemiology

Background:

• The prodromal phase of amyotrophic lateral sclerosis (ALS) remains poorly defined.
• Identifying early markers is crucial for understanding disease progression and potential interventions.

Purpose of the Study:

• To characterize prescription drug use patterns in the pre-diagnostic period of ALS.
• To identify the earliest divergence in medication use between individuals who developed ALS and healthy controls.
• To estimate the onset and duration of the ALS prodrome using prescription data.

Main Methods:

• A nested case-control study utilizing nationwide Norwegian registries (2005-2019).
• Individual matching of 2,084 ALS cases to 208,400 controls based on sex, age, and education.
• Analysis of drug prescription data up to 10 years pre-diagnosis, including lag-time analyses and machine learning prediction.

Main Results:

• Overall prescription pattern changes were evident 2-3 years before ALS diagnosis.
• Significant differences in 25 of 42 drug classes were observed between ALS patients and controls.
• Muscle relaxants and bone disease treatments showed significantly higher prescription rates 6 and 5 years prior to diagnosis, respectively.

Conclusions:

• Prescription pattern shifts, particularly for muscle relaxants and bone disease treatments, can occur as early as 6 years before an ALS diagnosis.
• These findings support the existence of a multi-year prodromal phase preceding the clinical manifestation of ALS.
• Increased medication use in the final year before diagnosis likely reflects heightened healthcare seeking for emerging symptoms.