RECENT FINDINGS: The number of NPS has increased from 166 in 2009 to 892 in 2018, with about 36% having stimulant effects. Such trend revels some unprecedented patterns. The decline in the emergence of new synthetic cannabinoids has coincided with rising deaths due to overdose of fentanyl and non-fentanyl compounds in North America and Europe. The detection of new stimulant NPS has stabilized since 2015. Although the level of seizures of mephedrone have risen since then, they are still below the levels reported before international control. The legal status of kratom still remains unclear, whereas calls for research on its benefits continue. The nonmedical use of tramadol in Africa and Middle East is a cause of growing concern.
SUMMARY: Although the rise of NPS is a cause for concern, evidence suggests that the strategy to face the challenge should include updating international data collection systems, integrating scientific-based interventions for drug use, strengthening national monitoring, and increasing collaborative research and forensic capabilities. The legal, regulatory framework and clinical guidelines should remain dynamic, whereas enforcement agencies should measure success by destroying drug networks as seizures rarely dismantle drug markets.
Methods: Four electronic databases including Embase, Medline (via Ovid), Scopus and Google Scholar were searched from inception until October 2019 to identify the studies reporting fentanyl related deaths. Two independent reviewers screened and selected the titles and then evaluated the full texts. Only case studies and case series were included. A structured data extraction tool was used to extract data on the number of deaths, routes of administration, concomitant drug use and toxicological data. The Joanna Briggs Institute quality assessment tool was used to evaluate the quality of included studies. Data were synthesized narratively.
Results: Of 1251 articles identified during initial search, 8 case reports and 9 case series met the inclusion criteria. A total of 1969 deaths were reported in the included studies. Deaths were concentrated in the north American region (n = 1946) and the Nordic region (n = 22). Reported causes of death included fentanyl overdose (n = 321, 56.4%), mixed drug toxicity (n = 196, 34.5%), natural (n = 28, 4.9%), other drug toxicity (n = 10, 1.8%), fentanyl and ethanol intoxication (n = 8, 1.4%), incidental (n = 5, <1%) and aspiration (n = 1). Most common routes of use were intravenous (70.5%) and transdermal routes (23.0%). Deaths came swiftly via the intravenous route. Mean level of blood fentanyl amongst all reported deaths was 0.024 µg/mL.
Conclusion: Literature related to fentanyl-associated deaths predominantly come from North America. Deaths are comparatively lower or not reported in peer-reviewed publications from the rest of the world. Abuse through intravenous administration, mixed drug toxicities and self-treatment of breakthrough pain are mainly responsible for majority of the reported deaths.