Antipsychotics ⿿ Postmortem fatal and non-fatal reference concentrations

Söderberg, Carl; Wernvik, Emma; Tillmar, Andreas; Spigset, Olav; Kronstrand, Robert; Reis, Margareta; Jönsson, Anna K.; Druid, Henrik

doi:10.1016/j.forsciint.2016.05.002

Cited by 25 publications

(16 citation statements)

References 63 publications

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“…The median ratios of Swedish group C median to our median and Swedish group C 90th percentile to our median were 0.6 and 1.7, respectively. For example, in case of the antipsychotic drug olanzapine, our median concentration was 0.20 mg/L, while the Swedish group C median and 90th percentile were 0.10 mg/L and 0.20 mg/L, respectively . A correspondence also existed between the Swedish group A and B 90th percentiles and our 97.5th percentile (ratios 1.2 and 0.9, respectively), representing lethal concentrations for most substances.…”

Section: Resultsmentioning

confidence: 61%

“…Table shows the comparison of selected concentration percentiles in PM femoral venous blood between the present study, involving all causes of death ( N = 144 034), and the five Swedish studies ( N = 9436), employing grouping according to the cause of death . A moderate correspondence was obtained between Swedish group C and our median concentration, both representing a “normal” PM concentration.…”

Section: Resultsmentioning

confidence: 62%

“…Comparison to the PM concentrations from the Swedish investigators' studies was based on the following concentration percentile ratios obtained from the two databases (Swedish/Finnish): median/median, 90th percentile/median, 90th/90th percentile, and 90th/97.5th percentile. First, the concentration percentile ratios were calculated for individual drugs, and second, the medians of these ratios were calculated and presented in Table .…”

Section: Methodsmentioning

confidence: 99%

“…Grouping of cases in Swedish studies: A, poisonings by one specific substance only, B, multi‐substance poisonings, C, PM controls consisting of deaths not involving incapacitation by substances…”

Section: Methodsmentioning

confidence: 99%

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Summary statistics for drug concentrations in post‐mortem femoral blood representing all causes of death

Ketola

Ojanperä

2019

Drug Testing and Analysis

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Concentration distributions for 183 drugs and metabolites frequently found in post‐mortem (PM) femoral venous blood were statistically characterized based on an extensive database of 122 234 autopsy cases investigated during an 18‐year period in a centralized laboratory. The cases represented all causes of death, with fatal drug poisonings accounting for 8%. The proportion of males was 74% with a median age of 58 years compared with 26% females with a median age of 64 years. In 36% of these cases, blood alcohol concentration was higher than or equal to 0.2‰, the median being 1.6‰. The mean, median, and upper percentile (90th, 95th, 97.5th) drug concentrations were established, as the median PM concentrations give an idea of the “normal” PM concentration level, and the upper percentile concentrations indicate possible overdose levels. A correspondence was found between subsets of the present and the previously published PM drug concentrations from another laboratory that grouped cases according to the cause of death. Our results add to the knowledge for evidence‐based interpretation of drug‐related deaths.

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Section: Resultsmentioning

confidence: 61%

Section: Resultsmentioning

confidence: 62%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Summary statistics for drug concentrations in post‐mortem femoral blood representing all causes of death

Ketola

Ojanperä

2019

Drug Testing and Analysis

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“…The analytical methods have been described in more detail previously 37, 38. During the timespan of the study, some assays had been improved and adjusted, but all modifications were cross‐validated.…”

Section: Methodsmentioning

confidence: 99%

Treatment With Antipsychotics in Pregnancy: Changes in Drug Disposition

Westin

Brekke

Molden

et al. 2017

Clin Pharma and Therapeutics

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Although pregnancy is known to cause changes in drug pharmacokinetics, little is known about its impact on serum levels of antipsychotics. In this study we retrospectively assessed 201 routine serum antipsychotic therapeutic drug monitoring concentration measurements obtained from a total of 110 pregnancies in 103 women, and 512 measurements from the same women before and after pregnancy. Serum concentrations in the third trimester were significantly lower than baseline for quetiapine (−76%; confidence interval (CI), −83%, −66%; P < 0.001) and aripiprazole (−52%; CI, −62%, −39%; P < 0.001), but not for olanzapine (−9%; CI, −28%, +14%; P = 0.40). For the remaining antipsychotics (perphenazine, haloperidol, ziprasidone, risperidone, and clozapine), our dataset was limited, but it indicates that concentrations may decline at least for perphenazine and possibly also for haloperidol. Even though the clinical consequence of the serum concentrations decline remains to be elucidated, our results warrant close clinical monitoring throughout pregnancy, preferentially supported by therapeutic drug monitoring.

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