Non‐medical use of psychoactive prescription drugs is associated with fatal poisoning

Haukka, Jari; Kriikku, Pirkko; Mariottini, Claudia; Partonen, Timo; Ojanperä, Ilkka

doi:10.1111/add.14014

Cited by 45 publications

(44 citation statements)

References 25 publications

(27 reference statements)

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“…6 Studies conducted among heroin users 7 or inpatients treated with mirtazapine for methamphetamine withdrawal similarly report these properties. 8 Recently, published studies have further validated this classification: mirtazapine was the most prevalent nonprescribed psychoactive drug found in the post-mortem toxicological analysis in drug poisoning deaths in Finland 4 and was also detected in urine samples from patients with suspected illicit drug ingestion in the United Kingdom. 9 Considering the abovementioned data and the World Health Organization definition that 'a signal is essentially a hypothesis of a risk with a medicine with data and arguments that support it, derived from data from one or more of many possible sources', 10 the aim of our study was to detect a potential safety signal of mirtazapine abuse by combining two different methods of surveillance.…”

Section: Introductionmentioning

confidence: 87%

“…2 Antidepressants are considered to have a low abuse potential and their usage has been reported mostly in patients with comorbid substance use disorder seeking euphoric and/or stimulant-like effects. 3,4 Mirtazapine is a noradrenergic and specific serotonergic antidepressant (NaSSA) marketed since 1996. 5 PsychonautWiki, a community-driven encyclopaedia covering psychoactive substances, has classified mirtazapine as a recreational substance whose hallucinogenic, sedative, and delirium-like effects make the users rapidly develop a tolerance to but without showing habit-forming actions.…”

Section: Introductionmentioning

confidence: 99%

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Combining big data search analytics and the FDA Adverse Event Reporting System database to detect a potential safety signal of mirtazapine abuse

Spachos

Siafis

Bamidis

et al. 2020

Health Informatics J

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This study sought to detect a potential safety signal of mirtazapine abuse by combining two different sources of surveillance, specifically Google Analytics (Google, Inc., Mountain View, CA, USA) and the FDA Adverse Event Reporting System database. Data from the first quarter of 2004 to the second quarter of 2017 were collected and analysed. The search interest over time, the frequencies of abuse-related terms in the search analytics domain, and the odds ratio of abuse events in FDA Adverse Event Reporting System were determined. Correlations between the two aforementioned domains using quarterly data from the timeline series were also assessed. Our results suggest a positive correlation between abuse-related searches in the Google domain and abuse-related events in FDA Adverse Event Reporting System database. These results indicate that these methods can be used in combination with each other as a pharmacovigilance supplementary tool to detect drug safety signals.

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Section: Introductionmentioning

confidence: 87%

Section: Introductionmentioning

confidence: 99%

Combining big data search analytics and the FDA Adverse Event Reporting System database to detect a potential safety signal of mirtazapine abuse

Spachos

Siafis

Bamidis

et al. 2020

Health Informatics J

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“…Overall, 10% of these deaths could be associated to PGB intake, 62% of which in a context of abuse/addiction. Surprisingly, this value was lower as opioids were concerned (fentanyl: 56%, tramadol: 55%, morphine: 43% (Haukka et al, 2018). It is thus essential to widespread the knowledge on this abuse/addiction potential among health professionals but also in the general public, to raise awareness on the risks for PGB abusers as well as for patients being prescribed PGB, which are currently underestimated or even unknown.…”

Section: Resultsmentioning

confidence: 99%

Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse

et al. 2019

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Pregabalin is a psychoactive drug indicated in the treatment of epilepsy, neuropathic pain and generalized anxiety disorders. Pregabalin acts on different neurotransmission systems by inactivating the alpha2-delta subunit of voltage-gated calcium channels. In light of this pharmacological property, the hypothesis has been raised that pregabalin may regulate the mesolimbic dopamine pathway and thereby display a potential for misuse or abuse as recently observed in humans. Although some preclinical data support this possibility, the rewarding properties of gabapentinoid is still a matter for debate. The aim of this work was to evaluate the rewarding properties of pregabalin and to determine its putative mechanism of action in healthy mice. Pregabalin alone (60 mg/kg; s.c.) produced a rewarding effect in the conditioned place preference (CPP) test albeit to a lower extent than cocaine (30 mg/kg; s.c.). Interestingly, when assessing locomotor activity in the CPP, the PGB60 group, similarly to the cocaine group, showed an increased locomotor activity. In vivo single unit extracellular recording showed that pregabalin had mixed effects on dopamine (DA) neuronal activity in the ventral tegmental area since it decreased the activity of 50% of neurons and increased 28.5% of them. In contrast, cocaine decreased 75% of VTA DA neuronal activity whereas none of the neurons were activated. Intracerebal microdialysis was then conducted in awake freely mice to determine to what extent such electrophysiological parameters influence the extracellular DA concentrations ([DA]ext) in the Nucleus Accumbens. Although pregabalin failed to modify this parameter, cocaine produced a robust increase (800%) in [DA]ext. Collectively these electrophysiological and neurochemical experiments suggest that the rewarding properties of pregabalin result from a different mode of action than that observed with cocaine. Further experiments are warranted to determine whether such undesirable effects can be potentiated under pathological conditions such as neuropathic pain, mood disorders or addiction and to identify the key neurotransmitter system involved.

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“…Regarding the co-administration of ethanol and opioids, it can be dangerous because it enhances the positive subjective effects that contribute to the abuse and affects physical and cognitive functions. It is no coincidence that alcohol and opioid abuses often coexist [ 116 ]. Fatal intoxications involving opioids are frequently associated with alcohol use and are likely due to combined CNS- and respiratory-depressant effects [ 117 , 118 ].…”

Section: Discussionmentioning

confidence: 99%

Novel Synthetic Opioids: The Pathologist’s Point of View

et al. 2018

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Background: New Psychoactive Substances (NPS) constitute a broad range of hundreds of natural and synthetic drugs, including synthetic opioids, synthetic cannabinoids, synthetic cathinones, and other NPS classes, which were not controlled from 1961 to 1971 by the United Nations drug control conventions. Among these, synthetic opioids represent a major threat to public health. Methods: A literature search was carried out using public databases (such as PubMed, Google Scholar, and Scopus) to survey fentanyl-, fentanyl analogs-, and other synthetic opioid-related deaths. Keywords including “fentanyl”, “fentanyl analogs”, “death”, “overdose”, “intoxication”, “synthetic opioids”, “Novel Psychoactive Substances”, “MT-45”, “AH-7921”, and “U-47700” were used for the inquiry. Results: From our literature examination, we inferred the frequent implication of fentanyls and synthetic opioids in side effects, which primarily affected the central nervous system and the cardiovascular and pulmonary systems. The data showed a great variety of substances and lethal concentrations. Multidrug-related deaths appeared very common, in most reported cases. Conclusions: The investigation of the contribution of novel synthetic opioid intoxication to death should be based on a multidisciplinary approach aimed at framing each case and directing the investigation towards targeted toxicological analyses.

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Non‐medical use of psychoactive prescription drugs is associated with fatal poisoning

Abstract: Non-prescribed psychoactive drugs are found commonly at postmortem in drug poisoning deaths in Finland, with history of drug abuse being a major contributing factor.

Cited by 45 publications

References 25 publications

Combining big data search analytics and the FDA Adverse Event Reporting System database to detect a potential safety signal of mirtazapine abuse

Combining big data search analytics and the FDA Adverse Event Reporting System database to detect a potential safety signal of mirtazapine abuse

Lack of correlation between the activity of the mesolimbic dopaminergic system and the rewarding properties of pregabalin in mouse

Novel Synthetic Opioids: The Pathologist’s Point of View

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