Pharmacopsychiatry 2016; 26 - P16
DOI: 10.1055/s-0036-1582055

Therapeutic Drug Monitoring of Psychopharmaceuticals in Intensive Care Medicine: Two case reports of severe clozapine intoxications due to different etiologies

C Müller 1, M Kochanek 3, C Tielsch 4, C Blaich 1, T Streichert 2, MHJ Wiesen 1
  • 1Department of Pharmacology, Therapeutic Drug Monitoring, University Hospital of Cologne, Cologne, Germany
  • 2Department of Clinical Chemistry, University Hospital of Cologne, Cologne, Germany
  • 3Department I of Internal Medicine, University Hospital of Cologne, Cologne, Germany
  • 4Department of Psychiatry, University Hospital of Cologne, Cologne, Germany

Therapeutic Drug Monitoring (TDM) is well established in the area of psychopharmacotherapy in the out-patient and in-patient care for decades. In particular, TDM is mandatory if drug-related toxicity is suspected, and life-threatening toxicity usually requires medical treatment at the intensive care unit (ICU). Here, we present two case reports of severe clozapine intoxications due to different causes (i.e. inflammation, drug-drug-interactions).

The first case describes a patient with paranoid hallucinatory schizophrenia and clozapine intoxication as an expression of enzyme inhibition caused by inflammation.

Symptoms associated with intoxication were sedation, considerable restrictions in particular in the area of concentration and intellectual capacity (psychomotor retardation), hyperglycemia and transient signs of inflammation. Despite the initially high clozapine serum concentration (cmax= 1367 µg/l), the patient recovered completely without residual symptoms.

In the second case we report on a 35-year-old male patient (80 kg bodyweight) with acute respiratory deterioration possibly associated with clozapine intoxication (cmax= 1175 µg/l) requiring intubation and mechanical ventilation. Disease related symptoms were as follows: development of bilateral pulmonary embolism, tachycardia, hyperglycemia, transient hypothyreoidism and thrombozytopenia. Although intensive medical measures were escalated using extracorporeal membrane oxygenation (ECMO) the patient died due to multiple organ failure.

TDM has an advisory function on ICU and therefore is used to help guide decisions regarding drug dosing/intoxications in order to optimize therapeutic efficacy/outcome and minimize adverse events.