Creatine kinase elevation and discontinuation of clozapine: fear-driven clinical practice in a forensic case with treatment-resistant schizophrenia and persistent violent behaviour

Abstract

In forensic settings, the most common indication for clozapine is treatment-resistant schizophrenia (TRS). Clozapine has also been shown to be effective in reducing hostility, aggression and violence in patients with schizophrenia and is of benefit in comorbid substance use disorders. The decision to initiate or to discontinue recently initiated clozapine can have a profound beneficial or detrimental influence on the lives and safety of patients and the staff caring for them. We present a case in which treatment with clozapine proved effective in spite of earlier repeated discontinuation of clozapine out of fear of neuroleptic malignant syndrome (NMS). Elevation of creatine kinase was deemed to be indicative of NMS in the absence of clinical signs of NMS. In somatic medicine, it is well known that creatine kinase elevation has many causes, most of them non-harmful. Collaboration with clinical chemistry was shown to be very useful, if not essential; research in the 1980s found replicated evidence for both sex and race differences in creatine kinase levels. In addition, substantial intra-individual variation has been found over time in healthy individuals. The creatine kinase levels of this patient of African descent were within normal limits for the African population. Baseline creatine kinase assessment and repetition of this assessment after 2 weeks with careful interpretation are recommended in all clozapine-treated patients. The authors advocate the introduction of evidence-based creatine kinase cut-off points that reflect the biological differences between the sexes and among races. More intensive contact between psychiatrists and clinical chemist can facilitate faster diagnosis and better treatment.