Antipsychotic-induced elevation of creatine kinase: a systematic review of the literature and recommendations for the clinical practice

The primary antipsychotic-induced creatine kinase elevation (i.e., not due to neuroleptic malignant syndrome, extrapyramidal symptoms, etc.) is a poorly studied condition. The aims of the present study were to provide an overview of published cases with antipsychotic-induced creatine kinase elevation and give recommendations for the clinical practice. PubMed and EMBASE were searched for eligible trials, case series, and case reports. We set a threshold at ten times the upper normal limit of the creatine kinase value in order to define an elevation as significant. The prevalence of significant creatine kinase elevation ranged between 2 and 7 %. We found a total of 42 eligible cases. Men were overrepresented in our sample (81 %). Patients with myoglobinuria were more likely to be symptomatic (Fisher's exact test, p = 0.006), whereas neither myoglobinuria (Mann-Whitney test, p > 0.10) nor symptoms (Mann-Whitney test, p = 0.64) were related to the magnitude of the creatine kinase (CK) elevation. In the majority of the cases, the antipsychotic medication was discontinued (86 %). Forced diuresis was given in 36 % of the patients. Eighty-three percent of the patients had no further complications. Only one case was found with a de novo acute renal failure. The discontinuation of the antipsychotic medication was a sufficient measure for the CK elevation to subside in the majority of the cases. Cases with myoglobinuria should eventually be treated more aggressively. Further recommendations for the clinical practice are presented.