Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome?

Andersen, Freja Drost; Simonsen, Ulf; Andersen, Charlotte Uggerhøj

doi:10.1111/bcpt.13480

Cited by 13 publications

(24 citation statements)

References 85 publications

(205 reference statements)

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“…Quetiapine and opioids are both sedatives and can induce respiratory depression, creating a basis for pharmacodynamic interactions. 14 In the present study, quetiapine was found in an increasing proportion of fatal opioid poisonings over time. This is in line with other studies showing an increase in the number of calls concerning quetiapine to a poisoning centre and deaths related to quetiapine.…”

Section: Discussionsupporting

confidence: 51%

“…Data on the combined effects of opioids and quetiapine are sparse. Based on the literature, we previously suggested a possible additive effect of morphine and methadone with other antipsychotics such as acepromazine on sedation, respiratory depression and hypotension in animal studies 14 . Therefore, we hypothesized that concomitant exposure to quetiapine and methadone or morphine might have additive effects.…”

Section: Introductionmentioning

confidence: 97%

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Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats

et al. 2022

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Fatal opioid poisonings often involve methadone or morphine. This study aimed to elucidate if quetiapine, a widely used sedative antipsychotic medication, may increase the risk of fatal opioid poisoning by additive inhibitory effects on the central nervous system. We used data from 323 cases of fatal methadone or/and morphine poisonings autopsied from 2013 to 2020, a survey of 34 drug users, and performed blinded placebo-controlled studies in 75 Flinders Resistant Line rats receiving three cumulative intraperitoneal doses of vehicle, methadone (2.5, 10 and 15 mg/kg), morphine (3.75, 15 and 22.5 mg/kg), quetiapine (3, 10 and 30 mg/kg) or quetiapine combined with methadone or morphine. Quetiapine was detected in 20.4% of fatal opioid poisonings with a significantly increased frequency over time, primarily in low or therapeutic concentrations, and was not associated with methadone or morphine concentrations. Use of quetiapine, most commonly in low-to-moderate doses to obtain a sleep-inducing or tranquillizing effect, was reported by 67.6% of survey respondents. In the animal studies, a significant impairment of sedation score, performance on the rotarod and open field mobility was observed in all treatment groups compared with vehicle. However, the effect of quetiapine plus the opioid was not significantly different from that of the opioid alone. Thus, no additive sedative effects were observed in rats. Our results suggest that quetiapine is more often an innocent bystander than a contributor to fatal opioid poisoning. However, the combined effects on other parameters, including blood pressure, cardiac rhythm and respiratory rate, need investigation.

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Section: Discussionsupporting

confidence: 51%

Section: Introductionmentioning

confidence: 97%

Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats

et al. 2022

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“…This may also reflect an altered prescription pattern. Quetiapine is one of the most used antipsychotics in Denmark, 15 and may, additionally, have abuse potential 16…”

Section: Discussionmentioning

confidence: 99%

Acute drug poisonings leading to hospitalization

Andersen

Nielsen

Møller

et al. 2021

Basic Clin Pharma Tox

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Knowledge about current trends and epidemiology in poisonings is important to maintain quality in diagnostics, treatment and prevention. We performed a cross-sectional study of all cases (n = 261) admitted with drug poisoning to Aalborg University Hospital during 1 year in 2017-2018. Median age was 30 (22-49) years, and 58% were female. Fifty percent were suicide attempts. In most cases, involved drugs were identified by history taking; blood analysis barely revealed any additional paracetamol and salicylicate poisonings. Drugs prescribed to the patient or available over the counter were involved in nearly two thirds of cases. Weak analgesics dominated by paracetamol (n = 91, 35%) was the most frequently involved group of drugs followed by opioids and benzodiazepines. Gender differences were observed with respect to involvement of weak analgesics and central stimulants. A higher prevalence of unidentified involved drugs was observed in 26 cases (10%) in which the length of admission exceeded 2 days and/or intensive care was needed. No deaths, cardiac arrhythmias or physical complications occurred. Thus, current handling of the acute poisoning seems effective in most cases. However, a more tailored use of blood analyses including a toxicological screen in selected cases may represent an opportunity for improvement.

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“…Such high levels of comorbidity are potentially due to, inter alia, shared genetic and environmental factors increasing SUD vulnerability [for review see ( 4 , 5 )] or to alleviate cognitive and psychotic symptoms ( 6 ). Use of psychoactive substances can interfere with antipsychotic medication ( 7 ), are associated with reduced adherence to SCZ interventions ( 8 ), and can lead to symptom exacerbation ( 9 ). There are mixed findings with respect to antipsychotics for treating SUDs in SCZ and preliminary support for the use of naltrexone in reducing alcohol use in SCZ ( 10 ).…”

Section: Introductionmentioning

confidence: 99%

Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review

et al. 2022

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BackgroundSubstance use disorders (SUDs) are a common yet poorly studied comorbidity in individuals with psychotic disorders. The co-occurrence of the two complicates recovery and interferes with pharmacological and behavioral treatment response and adherence. Recently, researchers have been exploring both invasive and non-invasive neuromodulation techniques as potential treatment methods for SUDs. We review the evidence that neuromodulation may reduce substance craving and consumption in individuals with schizophrenia.MethodsA comprehensive literature search of PubMed, MEDLINE, and PsycINFO databases was conducted (N = 1,432). Of these, we identified seven studies examining the effects of repetitive transcranial magnetic stimulation (rTMS) and two studies using transcranial direct current stimulation (tDCS) on drug consumption and craving in schizophrenia or schizoaffective disorders.ResultsDespite the limited number of studies in this area, the evidence suggests that rTMS to the dorsolateral prefrontal cortex (DLPFC) may reduce cannabis and tobacco use in patients with schizophrenia and schizoaffective disorder. Findings with tDCS, however, were inconclusive.DiscussionOur systematic review suggests that rTMS applied to DLPFC is a safe and promising therapeutic technique for the management of comorbid schizophrenia and SUDs, with the majority of the evidence in tobacco use disorder. However, there was substantial heterogeneity in study methods, underscoring the need to optimize stimulation parameters (e.g., frequency, duration, and target regions). Larger clinical trials are needed to establish the efficacy of rTMS in reducing drug consumption and craving in psychotic patients, ideally in comparison to existing pharmacological and behavioral interventions.

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Quetiapine and other antipsychotics combined with opioids in legal autopsy cases: A random finding or cause of fatal outcome?

Cited by 13 publications

References 85 publications

Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats

Combined effects of quetiapine and opioids: A study of autopsy cases, drug users and sedation in rats

Acute drug poisonings leading to hospitalization

Neuromodulation to Treat Substance Use Disorders in People With Schizophrenia and Other Psychoses: A Systematic Review

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