Muscle relaxants (Skeletal muscle relaxants or SMRs) are a group of medications, which are used to treat different conditions such as low back pain, muscular or spastic pain from multiple sclerosis, spinal cord injuries, and cerebral palsy amongst others. It is estimated that nearly 2 million people use these drugs every year and amongst these 300,000 are elderly individuals.
Antihistamines are a class of drugs, which are commonly used for
treatment of rhinitis
, conjunctivitis, pruritus, eczema, urticaria and for prophylaxis of anaphylactic reactions. Age-related physiological changes could possibly enhance or complicate the actions of H1-receptor antagonists.
Research has shown that high-risk medication exposure in the elderly population is quite common. According to Healthcare Effectiveness Data and Information Set (HEDIS), the most common High Risk Medications in the Elderly (HRME) drugs were muscle relaxants and first-generation antihistamines.
These drugs are particularly dangerous in the elderly population due to the potential risk of side effects such as sedation, confusion, and extremity weakness, which are all associated with falls,
however the clinical evidence has been lacking if these side effects can be harmful in the elderly population.
Hence a retrospective cohort study was conducted to establish whether these medications are associated with increased death, emergency department visits, and hospitalizations in elderly patients after adjusting for potential confounders and selection bias using propensity-score matching.
The study was a new-user, retrospective cohort design, using data from national Veteran Affairs (VA) from 128 hospitals. The study participants were veterans ≥65 years of age on October 1, 2005 who received VA inpatient/outpatient care at least once in each of fiscal year (FY) 2005 and FY 2006.
The primary outcomes were visits to emergency departments (ED), hospitalization or death within one year of the index date. ED visits or hospitalizations due to falls and fracture within one year of index date were also assessed using International Classification of Diseases, Ninth Revision (ICD-9-CM).
Patients exposed to both these group of medications were identified using the VA Pharmacy Benefits Management (PBM) dataset. Antihistamines
such as diphenhydramine, hydroxyzine, promethazine, cyproheptadine, chlorpheniramine and tripelennamine were included. Skeletal muscle relaxants included in the study were methocarbamol, cyclobenzaprine, carisoprodol, chlorzoxazone, metaxalone and orphenadrine.
Propensity score matching (1 to 1 match) was used to balance measured covariates between patients exposed to antihistamines or skeletal muscle relaxants and unexposed patients.
Out of the 1,807,404 elderly veteran patients in this cohort 55,566 patients were included in the propensity-matched cohort for skeletal muscle relaxants and 60,058 patients were included in the propensity-matched cohort for antihistamines.
In the antihistamine-exposed group, it was observed that mortality (AOR 1.93, 95% CI 1.82-2.04), ED visits (AOR 2.35, 95% CI 2.27-2.43), and hospitalizations (AOR 2.21, 95% CI 2.11-2.32) were higher at one year, with similar findings for falls and fractures outcomes.
In the skeletal muscle relaxants-exposed patients (adjusted odds ratio [AOR] 0.87, 95% CI 0.81-0.94) at one year the mortality was significantly lower, however risk of emergency care (AOR 2.25, 95% CI 2.16-2.33) and hospitalization (AOR 1.56, 95% CI 1.48-1.65) was significantly higher for patients exposed to skeletal muscle relaxants as compared to patients who were not exposed. Emergency department visits and hospitalizations for falls or fractures were also greater in patients prescribed SMR.
The study demonstrated that both skeletal muscle relaxants and antihistamines in the elderly population were associated with adverse events. Both groups of medications were associated with an increased risk of Emergency department visits and hospitalizations. The results revealed that antihistamines caused nearly 93% increase in mortality rate. Both groups of drugs were also associated with an increased fall and /or fracture related ED visits.
The study thus provides evidence to support the harmful effects of antihistamine and skeletal muscle relaxants in the elderly patients. Based on the substantial evidence, these drug classes were classified as "high risk" for the elderly patients.