Abstract
To the Editor
We present a case of isolated creatine kinase (CK) rise secondary to multiple antipsychotics. Mr K is a 48 year old male with a diagnosis of schizophrenia, treated effectively with quetiapine. He was hospitalized with insomnia, urinary incontinence, social withdrawal, fixed staring, mutism, and pacing. These symptoms were unlike his usual acute presentation with persecutory delusions. His CK on admission was 1344 U/l, with electrolytes, white cell count, creatinine, and troponin within normal limits. He remained haemodynamically stable with a temperature of 35.4°C. There was no rigidity, diaphoresis, or tremor. Mr K also had a negative urine drug screen, rheumatology, and myositis immunoglobulin screen. Due to his high CK, atypical neuroleptic malignant syndrome (NMS) was considered and quetiapine was ceased.
A review of Mr K’s treatments since 2003 showed multiple trials of antipsychotics including aripiprazole, amisulpride, and olanzapine. These were ceased after similar presentations of altered mental state and isolated CK rise. Peak CK levels and time to develop this adverse effect were as follows: aripiprazole after 10 days with a CK of 1263 U/l, amisulpride after 5 years to 25810 U/l, and olanzapine after 5 years to 9728 U/l.
During this admission the patient’s CK values normalized after ceasing antipsychotics but his delusions intensified. Given CK rise to multiple antipsychotics, clozapine was considered. Patient’s CK levels were normal on clozapine and he attained remission.
In our patient the initial diagnosis for the elevated CK was a subsyndromal NMS implying central mechanisms like sympathetic dysregulation or hypothalamic dopamine antagonism (Gurrera, 1999). However a recent review of antipsychotic medication and rhabdomyolysis by Packard (2014), discusses local mechanisms, wherein antipsychotics with high 5-HT2a antagonism elevate CK by increasing sarcolemmal permeability (Packard et al., 2014). This implies that antipsychotics with greater 5HT2a binding (paliperidone, ziprasidone, asenapine, etc) would have a higher incidence of rhabdomyolysis. Whilst antipsychotic medication may elevate CK there is evidence that this can also occur intrinsically within the acute and maintenance phases of schizophrenia after controlling for nonspecific factors such as stress, trauma, or hyperactivity (Meltzer, 1976). In our patient, after ruling out other medical causes of rhabdomyolysis (cocaine use, heat stroke, Legionella infection, etc.) the recurrent CK rise most likely appears to be a local effect of antipsychotics rather than centrally mediated. Clinicians should consider CK elevation within a broader context when the classical syndrome of NMS is absent.