A case of clozapine-induced creatine kinase elevation after initiation of clozapine with successful continuation

To the Editor

Antipsychotic-induced serum creatine kinase (CK) elevations are defined as those not mediated through other side effects of antipsychotics, such as seizures, neuroleptic malignant syndrome and extrapyramidal symptoms (Laoutidis and Kioulos, 2014). We report a case of clozapine-induced CK elevation after initiation of clozapine with successful continuation.

A 25-year-old Japanese man with treatment-resistant schizophrenia was admitted to our university hospital for clozapine treatment. He received a combination of 6 mg per day of risperidone, 600 mg per day of quetiapine, 175 mg per day of levomepromazine and 800 mg per day of lithium. His serum CK level was 154 U/L. On day 5, 12.5 mg per day of clozapine was administered; this was increased to 25 mg per day on day 6. On day 12, 8 days after clozapine initiation, his CK level rose dramatically to 13,930 U/L, and he had a high serum myoglobin level (787.5 ng/mL). His white blood cell count, serum liver enzymes, renal function and serum electrolytes remained within normal ranges. His vital signs were stable, and he did not show rigidity or muscle aches. Electrocardiography showed no abnormalities. Despite the extreme elevations in CK levels, he was asymptomatic. We decided to continue clozapine treatment. He was treated with intravenous hydration from day 12 to day 16, and his serum CK and myoglobin levels gradually decreased and returned to within normal ranges on day 22 (187 U/L) and day 19 (44.7 ng/mL), respectively. On day 69, we succeeded in switching his antipsychotic polypharmacy to 600 mg per day of clozapine monotherapy and 1200 mg per day of lithium.

Risperidone, quetiapine and levomepromazine also caused antipsychotic-induced CK elevation; however, the combination of these antipsychotics did not increase his serum CK level before the initiation of clozapine. Therefore, we diagnosed him with clozapine-induced CK elevation. A previous review revealed that there have been nine reported cases of clozapine-induced CK elevation (Laoutidis and Kioulos, 2014). Among these, only two patients continued to receive clozapine treatment (Reznik et al., 2000; Tseng and Hwang, 2009). To our knowledge, this is the third case in which clozapine treatment was successfully continued after clozapine-induced CK elevation. In addition, the serum CK level in our case was much higher than that in the previous two cases. This case suggests that clinicians might not need to discontinue clozapine in patients with clozapine-induced CK elevation, although their clinical symptoms and laboratory tests must be followed up carefully.