Evidence for long-acting methylprednisolone acetate in dogs: A critically appraised topic on efficacy, safety, and clinical applications across administration routes.

Background and Aim: Long-acting methylprednisolone acetate (MPA) is widely used in canine medicine for its prolonged glucocorticoid activity. However, uncertainty remains regarding its disease-specific efficacy, safety profile, and overall benefit-risk balance across different routes of administration. This critically appraised topic (CAT) aimed to systematically evaluate and synthesize the available evidence on the efficacy, safety, and clinical applications of depot MPA in dogs, with emphasis on clinically meaningful outcomes and evidence-based recommendations for veterinary practice. Materials and Methods: A structured literature search was performed in PubMed, CAB Abstracts, and Scopus from database inception to May 17, 2026. Eligible studies evaluated depot MPA administered through any route in dogs and reported clinical efficacy, safety outcomes, pharmacokinetics, endocrine responses, or clinicopathological changes. Study quality was assessed using design-specific risk-of-bias tools, including Cochrane RoB 2, ROBINS-I, and SYRCLE's risk-of-bias tool. Data were synthesized narratively todue of substantial heterogeneity in study designs, routes of administration, and outcome measures. Results: Fourteen studies involving more than 200 dogs were included, comprising one blinded randomized controlled trial, two clinical cohort studies, one case series, and ten pharmacokinetic, physiological, safety, or experimental investigations. The strongest evidence supported epidural MPA administered during surgery for thoracolumbar intervertebral disc disease (IVDD), significantly reducing the median time to ambulation from 7 to 3 days. Evidence for degenerative lumbosacral stenosis demonstrated favorable short-term clinical improvement but frequent relapse during long-term follow-up. Perineural, paravertebral, intra-articular, and musculoskeletal applications were supported only by low-level evidence. Pharmacokinetic and physiological studies consistently demonstrated prolonged systemic exposure, hypothalamic-pituitary-adrenal axis suppression, and measurable clinicopathological changes after depot administration. However, controlled evidence supporting routine systemic intramuscular MPA for naturally occurring inflammatory or immune-mediated diseases was lacking. Adverse event reporting was inconsistent, with prolonged endocrine suppression, systemic glucocorticoid effects, and occasional serious complications reported. Conclusion: Current evidence indicates that the clinical utility of depot MPA in dogs is highly route dependent. Moderate-quality evidence supports epidural administration for selected cases of thoracolumbar IVDD, whereas evidence for other regional applications remains limited. Routine systemic intramuscular depot MPA cannot currently be recommended as an evidence-based first-line treatment because disease-specific comparative trials are lacking. This CAT provides the first comprehensive evidence synthesis evaluating depot MPA across multiple administration routes in dogs, identifies important knowledge gaps, and highlights priorities for future controlled clinical studies to optimize therapeutic decision-making.