Massive Asymptomatic Creatine Kinase Elevation in Youth During Antipsychotic Drug Treatment: Case Reports and Critical Review of the Literature

Abstract

A massive asymptomatic creatine kinase elevation (MACKE) has been described during antipsychotic exposure in adult psychotic patients without signs of neuroleptic malignant syndrome (NMS), or other most frequent reasons for high creatine kinase (CK) serum level (intramuscular injections, restraints, intense physical activity, dystonic reactions). In this article, we review this clinical condition, and report three cases of MACKE in nonpsychotic, drug-naïve youth during treatment with second generation antipsychotics. The diagnosis of MACKE should be considered after ruling out other possible common reasons of CK increase. The finding of MACKE should indicate a need for weekly monitoring of the CK level only when there are reasons to believe elevated CK is toxic or harmful. Further investigations are recommended when signs and symptoms raise a suspicion of NMS or rhabdomyolysis, including flu-like syndrome, fever, weakness, alteration of consciousness, muscle rigidity, tachycardia, hyper-/hypotension, and dark urine. A drug discontinuation should be considered when possible signs of NMS or rhabdomyolysis are suspected, or in cases of very high and persisting CK levels. Empirical evidence indicates that there is not a "safe" antipsychotic medication; therefore, a switch to another antipsychotic with a different profile is not necessarily a safe option. The spontaneously remitting or intermittent course suggests that the "true" MACKE should be kept distinct from both rhabdomyolysis and NMS. Raising awareness with MACKE may reduce the need for unnecessary diagnosis of NMS or rhabdomyolysis, which may otherwise lead to an unnecessary discontinuation of an effective therapeutic agent.

Update on the safety of second generation antipsychotics in youths: a call for collaboration among paediatricians and child psychiatrists

“…They suggest that the “real” MACKE undergoes spontaneous remission, and does not represent a prodrome of NMS or rhabdomyolysis. However, in case of a random finding of CK elevation, close monitoring of the patient is warranted [ 81 ].…”

Neuroleptic Malignant Syndrome in Children with Autism Spectrum Disorder (ASD): A Case Report and Brief Review of Recent Literature

“…CK monitoring not only serves diagnostic purposes, but also for monitoring the condition, since levels of CK must decrease over time as the condition improves [ 2 ]. However, misleading high levels of CK may occur after intramuscular injections, restraints, intense physical activity, or dystonic reactions [ 11 ]. Furthermore, a massive asymptomatic CK elevation has been described during antipsychotic exposure in nonpsychotic, drug-naïve youth during treatment with second-generation antipsychotics.…”

Massive Assymptomatic Creatine Kinase Elevation with Quetiapine – A Case Report

“…Masi and colleagues have outlined that the described syndrome -Massive Asymptomatic Creatine Kinase Elevation (MACKE) -is an autonomous clinical entity (or a possible side effect) that can occur during antipsychotic drug treatment, in the absence of any additional sign of NMS or rhabdomyolysis, without any progression toward these severe clinical conditions, being self-limiting or reversible after drug discontinuation. In that extensive review, the authors also stated that MACKE can occur during antipsychotic exposure, even in patients without a psychotic disorder and that it is independent of drug type and dosage [5].…”