Introduction

Pipamperone is an antipsychotic drug, which is prescribed in all age groups. It is applied for chronic psychosis and has calmative, antidopaminergic and sedative effects and is also suitable for the treatment of insomnia, especially for geriatric patients. The neuroleptic effect is attributed to a blockade of dopamine receptors, whereby pipamperone has a 15-fold higher affinity to D4-receptors in comparison to D2-receptors. Moreover, it has a high affinity to serotonergic 5-HT2 receptors, where it acts as an antagonist [1].

Doses for pipamperone treatment are based on indication and vary between 20 mg (initial dose for insomnia in geriatric patients) to maximum 360 mg per day (for psychosis, separated to three single doses of 120 mg) for adults. After single oral administration of 40 mg average peak plasma concentrations of 0.044 ± 0.017 mg/L were observed [2]. A single oral dose of 120 mg led to plasma concentrations in a range of 0.12–0.50 mg/L [3], whereby steady-state concentrations in patients receiving daily oral doses of 360 mg resulted in plasma concentrations in a range of 0.29–0.39 mg/L [4]. Nevertheless, availability of pharmacokinetic data is still limited, especially for bioavailability and the volume of distribution.

Cases of intoxications with pipamperone have been described in literature, but mostly after concomitant application of other antipsychotics or antidepressants [5, 6]. Bont et al. reported a case of a 16-year-old girl, who survived the ingestion of an unknown quantity of pipamperone, which led to a concentration of 3.2 mg/L in plasma. The patient developed a torsade-de-pointes tachycardia [7]. In general, cardiac complications are mainly described in case of an overdose with pipamperone and are also listed as side effects and symptoms of intoxications in the expert information leaflet. After overdose, cardiac arrest and torsade-de-pointes can occur [8]. Besides cardiac effects, somnolence, convulsive attacks, respiratory arrest, acidosis, cerebral oedema, anoxia, cerebral ischemia and coma have been described in patients with pipamperone overdoses.

Fatal mono-intoxications with pipamperone are rarely found in literature. Henning et al. [9] published three cases and measured femoral blood concentrations of 15, 18 and 39 mg/L, and heart blood concentrations of 15, 20 and 51 mg/L. Concomitant medications were found in each case, however in therapeutic concentrations. These authors also investigated the organ distribution of pipamperone in those cases [8]. Ormandy et al. [10] described a case of a pipamperone intoxication with fatal outcome, with 0.99 mg/L in heart and 1.1 mg/L in femoral blood. It was assumed, that pipamperone either might have caused a convulsive attack or lead to cardiac arrhythmia and thus, contributed to the death.

Overall, data on pipamperone intoxications with and without fatal outcome are limited. Since data on pharmacokinetics also remain incomplete, the interpretation of forensic cases is challenging. Regarding the analysis of postmortem samples, possible postmortem redistribution (PMR) – as supposed by Henning et al. [9] - increases the complexity of interpretation. Accordingly, the present study aims to further contribute to the scientific data regarding pipamperone and thereby support forensic-toxicological case work.