Medication use and risk of amyotrophic lateral sclerosis—a systematic review

• Published in: BMC medicine 2022-08, Vol.20 (1), p.1-251, Article 251
• Main Authors: Cui, Can, Sun, Jiangwei, McKay, Kyla A, Ingre, Caroline, Fang, Fang
• Format: Article
• Language: English
• Subjects: Amyotrophic lateral sclerosis; Anti-inflammatory agents; Antibiotics; Antidepressants; Antidiabetics; Antihypertensives; Aspirin; Association; Care and treatment; Case reports; Cholesterol; Clinical trials; Contraceptives; Control charts; Diagnosis; Dietary supplements; Drug development; Drug dosages; Drug therapy, Combination; Drugs; Etiology; Hormone replacement therapy; Immunosuppressive agents; Inflammation; Medication; Medicin och hälsovetenskap; Muscle relaxants; Muscles; Neurological diseases; Oral contraceptives; Patient outcomes; Population studies; Quality assessment; Quality control; Risk; Risk analysis; Risk factors; Scandals; Signs and symptoms; Skeletal muscle; Statins; Therapeutic targets
• ISSN: 1741-7015; 1741-7015
• DOI: 10.1186/s12916-022-02442-w

Background Studying whether medications act as potential risk factors for amyotrophic lateral sclerosis (ALS) can contribute to the understanding of disease etiology as well as the identification of novel therapeutic targets. Therefore, we conducted a systematic review to summarize the existing evidence on the association between medication use and the subsequent ALS risk. Methods A systematic review was conducted in Medline, Embase, and Web of Science from the date of database establishment to December 10, 2021. References of identified articles were further searched for additional relevant articles. Studies were included if (1) published in English, (2) explored medication use as exposure and development of ALS as outcome, and (3) the design was a human observational study. Clinical trials, reviews, comments, editorials, and case reports were excluded. Quality assessment was performed using a pre-validated tool for non-randomized studies, the Newcastle-Ottawa Assessment Scale (NOS). Results Of the 4760 studies identified, 25 articles, including 13 case-control studies, five nested case-control studies, six cohort studies, and one retrospective chart review, were included in the review. Among these studies, there were 22 distinct study populations that included 171,407 patients with ALS, seven classes of medication examined, and 23 studies with a NOS [greater than or equal to] 5. There was a general lack of agreement between studies on the associations of cholesterol-lowering drugs, anti-inflammatory drugs, immunosuppressants, antibiotics, oral contraceptives (OCs) or hormone replacement therapy (HRT), antihypertensive drugs, antidiabetics, and drugs for psychiatric and neurological disorders with the subsequent risk of ALS. However, it appeared that statins, aspirin, OCs/HRT, antihypertensives, and antidiabetics were unlikely related to a higher risk of ALS. The positive associations noted for antibiotics, antidepressants, and skeletal muscle relaxants might be attributable to prodromal symptoms of ALS. Conclusions There is currently no strong evidence to link any medication use with ALS risk. Keywords: Medication, Amyotrophic lateral sclerosis, Risk, Association