Abstract
OBJECTIVES: This study aims to quantitatively analyse nortriptyline's analgesic potency, safety and tolerability. DESIGN: Systematic review and meta-analysis. DATA SOURCES: The systematic search was conducted in Scopus, Web of Science and PubMed in February 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Clinical trials evaluating the efficacy of nortriptyline in reducing pain scores (open-label studies and comparisons of nortriptyline with placebo or other analgesics) in different pain types were included. DATA EXTRACTION AND SYNTHESIS: The data extraction procedure and the screening phases were carried out based on predetermined eligibility criteria. To pool the data, the standardised mean difference (SMD) and standardised mean change (SMC) methods, along with random-effect and fixed-effect meta-analysis, were used. The risk of bias was assessed using the Cochrane Collaboration method, and the Grading of Recommendations Assessment, Development and Evaluation criteria were used to measure the certainty of the results. RESULTS: 14 of the initial 648 studies were eventually imported. Nortriptyline was reported to significantly reduce pain severity in chronic low back pain, painful symptoms in major depressive disorder, neuropathy, chronic pelvic pain and neuropathic corneal pain. However, it was not superior to placebo in fibromyalgia and knee osteoarthritis. In comparison to placebo and various alternative analgesics, the pooled SMD for lowering pain scores was 0.43 (0.23-0.64) and -0.18 (-0.39 to 0.03), respectively. In the pretreatment and post-treatment analyses, the pooled SMC was -1.20 (-1.48 to -0.93). Although constipation and xerostomia were the most commonly reported side effects, all references indicated that the adverse events were well tolerated at the administered dosages. CONCLUSION: While nortriptyline is effective in some chronic pains, such as neuropathies, it lacks efficacy in some other chronic pains, such as fibromyalgia and osteoarthritis. Nortriptyline is well tolerated when administered in doses intended for its analgesic effects. Moreover, several studies suggested that the analgesic effects of nortriptyline are comparable to those of amitriptyline and gabapentin.