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Annual age\u2010standardized mortality rates (ASMRs) per million person\u2010years were estimated. Joinpoint regression assessed changes in trends using annual percentage change (APC) and average APC (AAPC). Overdose deaths were grouped by the underlying drug categories involved:\n                      <jats:italic>nonopioid analgesics, antipyretics and antirheumatics<\/jats:italic>\n                      (X40\/X60\/Y10);\n                      <jats:italic>antiepileptic, sedative\u2010hypnotic, antiparkinsonism and psychotropic drugs<\/jats:italic>\n                      (X41\/X61\/Y11);\n                      <jats:italic>narcotics and psychodysleptics<\/jats:italic>\n                      (X42\/X62\/Y12);\n                      <jats:italic>other drugs acting on the autonomic nervous system<\/jats:italic>\n                      (X43\/X63\/Y13);\n                      <jats:italic>other and unspecified drugs, medicaments and biological substances<\/jats:italic>\n                      (X44\/X64\/Y14); and\n                      <jats:italic>drugs, medicaments and biological substances in the context of assault<\/jats:italic>\n                      (X85). Intentionality (based on ICD\u201010 code characters) within the underlying drug categories was assessed. All analyses were stratified by sex.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Findings<\/jats:title>\n                    <jats:p>\n                      In Spain, 15\u2009862 overdose deaths occurred during 2001\u20132022. ASMR increased by 49.0% over the period, from 24.7 [95% confidence interval (95%\u00a0CI)\u2009=\u200923.0, 26.5] to 36.8 (95%\u00a0CI\u2009=\u200934.7, 39.0) deaths per million person\u2010years. APC showed a statistically significant change in trends in 2010, shifting from a \u22123.3% (95%\u00a0CI\u2009=\u2009\u22127.3 to \u22121.7) decline to an increase of 3.4% (95%\u00a0CI\u2009=\u2009\u22120.3 to 6.5). In 2018, a more abrupt change was observed, with the APC further increasing to 13.8% (95%\u00a0CI\u2009=\u00a09.3, 22.5). Females showed an earlier trend change (2006) with an AAPC 1.7 times higher (3.4%; 95%\u00a0CI\u2009=\u00a02.4, 4.7) than males (2.0%; 95%\u00a0CI\u2009=\u00a01.2, 2.7). Leading drug categories were\n                      <jats:italic>other and unspecified drugs, medicaments and biological substances<\/jats:italic>\n                      , followed by\n                      <jats:italic>narcotics and psychodysleptics<\/jats:italic>\n                      . In males, trends followed the overall pattern; in females, the\n                      <jats:italic>antiepileptic, sedative\u2010hypnotic, antiparkinsonism and psychotropic drugs<\/jats:italic>\n                      category predominated, mostly due to\n                      <jats:italic>intentional<\/jats:italic>\n                      overdoses.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Between 2001 and 2022, drug overdose deaths in Spain increased substantially, beginning in 2010 and further accelerated in 2018, though population rates remain low. The most prevalent underlying ICD\u201010 drug categories were\n                      <jats:italic>other and unspecified drugs, medicaments and biological substances<\/jats:italic>\n                      \u2014likely reflecting polydrug use\u2014and\n                      <jats:italic>narcotics and psychodysleptics<\/jats:italic>\n                      . The observed rise in deaths involving\n                      <jats:italic>antiepileptic, sedative\u2010hypnotic, antiparkinsonism and psychotropic drugs<\/jats:italic>\n                      , particularly\n                      <jats:italic>intentional<\/jats:italic>\n                      overdoses among females, highlights the need for sex\u2010based interventions.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/add.70121","type":"journal-article","created":{"date-parts":[[2025,7,11]],"date-time":"2025-07-11T02:19:08Z","timestamp":1752200348000},"page":"261-272","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Changing trends in drug overdose mortality in Spain, 2001\u20132022"],"prefix":"10.1111","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-2254-3622","authenticated-orcid":false,"given":"Florencia","family":"Gin\u00e9","sequence":"first","affiliation":[{"name":"Complejo Hospitalario Universitario Insular Materno Infantil  Gran Canaria Canary Islands Spain"},{"name":"National School of Public Health Carlos III Health Institute  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Donat","sequence":"additional","affiliation":[{"name":"National School of Public Health Carlos III Health Institute  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Juan Miguel","family":"Guerras","sequence":"additional","affiliation":[{"name":"Biomedical Research Center Network for Epidemiology and Public Health (CIBERESP)  Madrid Spain"},{"name":"National Center of Epidemiology  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6257-3213","authenticated-orcid":false,"given":"Gregorio","family":"Barrio","sequence":"additional","affiliation":[{"name":"National School of Public Health Carlos III Health Institute  Madrid Spain"},{"name":"Biomedical Research Center Network for Epidemiology and Public Health (CIBERESP)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Jos\u00e9","family":"Belza","sequence":"additional","affiliation":[{"name":"National School of Public Health Carlos III Health Institute  Madrid Spain"},{"name":"Biomedical Research Center Network for Epidemiology and Public Health (CIBERESP)  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julieta","family":"Politi","sequence":"additional","affiliation":[{"name":"National School of Public Health Carlos III Health Institute  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrique","family":"Regidor","sequence":"additional","affiliation":[{"name":"Biomedical Research Center Network for Epidemiology and Public Health (CIBERESP)  Madrid Spain"},{"name":"Department of Public Health and Maternal &amp; Child Health, Faculty of Medicine Complutense University of Madrid  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,7,10]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jsat.2012.11.002"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/add.16420"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(23)00057-8"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2214-109X(17)30375-3"},{"key":"e_1_2_10_6_1","volume-title":"European drug report 2022: trends and developments","author":"European monitoring Centre for Drugs and Drug Addiction (EMCDDA)","year":"2022"},{"key":"e_1_2_10_7_1","volume-title":"European drug report 2024: trends and developments","author":"European monitoring Centre for Drugs and Drug Addiction (EMCDDA)","year":"2024"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD004145.pub4"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/14651858.CD002209.pub2"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciac928"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2468-2667(18)30208-1"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drugalcdep.2017.08.040"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.5114\/ait.2020.94756"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1192\/j.eurpsy.2021.2219"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.15620\/cdc\/170565"},{"key":"e_1_2_10_16_1","volume-title":"Informe 2024. 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