AIM To measure the evolution of drug overdose mortality in Spain between 2001 and 2022.

DESIGN, SETTING, PARTICIPANTS A repeated cross-sectional observational study using nationwide mortality data from Spain, 2001-2022, among individuals aged 15-64 years.

MEASUREMENTS The outcome was overdose deaths [International Classification of Diseases, 10th revision (ICD-10) codes: X40-X44, X60-X64, X85, Y10-Y14]. Annual age-standardized mortality rates (ASMRs) per million person-years 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: nonopioid analgesics, antipyretics and antirheumatics (X40/X60/Y10); antiepileptic, sedative-hypnotic, antiparkinsonism and psychotropic drugs (X41/X61/Y11); narcotics and psychodysleptics (X42/X62/Y12); other drugs acting on the autonomic nervous system (X43/X63/Y13); other and unspecified drugs, medicaments and biological substances (X44/X64/Y14); and drugs, medicaments and biological substances in the context of assault (X85). Intentionality (based on ICD-10 code characters) within the underlying drug categories was assessed. All analyses were stratified by sex.

FINDINGS In Spain, 15 862 overdose deaths occurred during 2001-2022. ASMR increased by 49.0% over the period, from 24.7 [95% confidence interval (95% CI) = 23.0, 26.5] to 36.8 (95% CI = 34.7, 39.0) deaths per million person-years. APC showed a statistically significant change in trends in 2010, shifting from a -3.3% (95% CI = -7.3 to -1.7) decline to an increase of 3.4% (95% CI = -0.3 to 6.5). In 2018, a more abrupt change was observed, with the APC further increasing to 13.8% (95% CI = 9.3, 22.5). Females showed an earlier trend change (2006) with an AAPC 1.7 times higher (3.4%; 95% CI = 2.4, 4.7) than males (2.0%; 95% CI = 1.2, 2.7). Leading drug categories were other and unspecified drugs, medicaments and biological substances, followed by narcotics and psychodysleptics. In males, trends followed the overall pattern; in females, the antiepileptic, sedative-hypnotic, antiparkinsonism and psychotropic drugs category predominated, mostly due to intentional overdoses.

CONCLUSIONS 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-10 drug categories were other and unspecified drugs, medicaments and biological substances-likely reflecting polydrug use-and narcotics and psychodysleptics. The observed rise in deaths involving antiepileptic, sedative-hypnotic, antiparkinsonism and psychotropic drugs, particularly intentional overdoses among females, highlights the need for sex-based interventions.