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The PRISMA 2020 guideline was used for assessing and reporting data quality. Reviews were included if they reported clinical outcomes such as OUD, opioid overdose (OD), all-cause mortality, or emergency department (ED) visits. Data extraction and risk of bias assessment were performed independently by 2 reviewers. Heterogeneity of interacting drug exposure and outcomes studied precluded meta-analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Seven studies were included. All studies were observational in design, focused on patients with OUD, and evaluated only pharmacodynamic, not pharmacokinetic, interactions involving buprenorphine with central nervous system depressants. The reviewed studies showed an increased risk of OD in patients who co-used buprenorphine with benzodiazepine, Z-drugs, pregabalin, gabapentin, clonidine, or oxycodone (vs. buprenorphine only), with mixed results for non-fatal OD being noted in concomitant buprenorphine-benzodiazepine use. An increased risk of drug-related poisoning (including opioid overdose) was observed in patients with co-use of buprenorphine and benzodiazepine, with null results being noted in patients with co-use of buprenorphine with gabapentin or prescription amphetamines (vs. buprenorphine only). An increased risk of all-cause mortality was observed in patients with co-use of buprenorphine with Z-drugs or pregabalin, with mixed results being noted in concomitant buprenorphine-benzodiazepine use (vs. buprenorphine only). Only one study showed an increased risk of all-cause ED visits in patients with buprenorphine-benzodiazepine use vs. with buprenorphine alone.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>This review suggests inconclusive evidence on potential adverse outcomes associated with concomitant buprenorphine\u2013drug use compared with buprenorphine use only. Further population-based studies with rigorous study designs are needed to elucidate associations between buprenorphine\u2013drug interactions and clinical outcomes.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Registration<\/jats:title>\n                    <jats:p>PROSPERO CRD420251052355.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s13722-026-00698-8","type":"journal-article","created":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T08:13:09Z","timestamp":1783584789000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical outcomes associated with drug\u2013drug interactions involving buprenorphine: a systematic review"],"prefix":"10.1186","volume":"21","author":[{"given":"Jude Uche","family":"Eze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Easter Protiva","family":"Gain","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nistha","family":"Shrestha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu-Jung Jenny","family":"Wei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,7,9]]},"reference":[{"key":"698_CR1","doi-asserted-by":"publisher","first-page":"100133","DOI":"10.1016\/j.dadr.2023.100133","volume":"6","author":"C Heidbreder","year":"2023","unstructured":"Heidbreder C, Fudala PJ, Greenwald MK. 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