Myotoxicity and Neurotoxicity during Clozapine Treatment

Abstract

Some recent studies have shown that clozapine (CLZ) has myopathic side effects and causes alterations in motor force control. The aim of this study was to evaluate the neurologic and electrophysiologic characteristics of patients with schizophrenia who are undergoing long-term CLZ treatment. Ninety-four patients with schizophrenia treated with CLZ for 18.2 +/- 15.5 months were studied retrospectively and prospectively (40% and 60%, respectively) for serum creatine kinase (CK) levels before and after initiation of CLZ treatment. An electrodiagnostic study was performed on patients with CK elevation above normal limits, complained of general weakness or muscle pains, and/or had abnormal clinically significant findings. In 13 patients (13.8%), abnormal CK levels were found. Six patients complained of some muscular weakness. In two patients, clinical assessment revealed mild general muscular weakness; one revealed decreased tendon reflexes and, in both, CK levels were above 1,750 IU/L. On electrophysiologic examinations performed in the six patients with abnormal neurologic findings, the motor and sensory nerve conduction velocity were within normal range in all but one patient, who exhibited some prolongation of distal latency in the lower limbs. In two patients, the electromyography demonstrated a myopathic pattern. In 2.1% of medically healthy patients with schizophrenia treated with clozapine on a long-term basis, signs of myotoxicity were found. It seems warranted to discontinue CLZ therapy in patients who exhibit abnormal CK levels and myopathic features during treatment. Further studies are needed to provide more objective data on the impact of CLZ treatment on muscle tissue.

Comparison between risperidone, olanzapine, and clozapine in the management of chronic schizophrenia: a naturalistic prospective 12‐week observational study

“…CK levels decreased over time with all the medications, with clozapine demonstrating significant lower levels compared to risperidone in particular. This finding was somewhat unexpected considering clozapine's well-known predisposition to increase CK levels in a subset of patients (Keshavan et al, 1994;Kirson et al, 1995;Scelsa et al, 1996;Reznik et al, 2000), but not all (Boot and de Haan, 2000), treated with the medication.…”

Reason for clozapine cessation

“…However, it is arguably these individuals that require the most intensive and effective management because of the enduring disability they experience (3). For this sub-section of patients, clozapine therapy is widely known and accepted to be the most efficacious treatment option (1,(5)(6)(7)(8). For this sub-section of patients, clozapine therapy is widely known and accepted to be the most efficacious treatment option (1,(5)(6)(7)(8).…”

Effectiveness of clozapine, haloperidol and chlorpromazine in schizophrenia during a five-year period

“…Neither the cases of significant blood disorders nor the cases of muscle damage were detected in our patients. Similarly, only in 2.1% of medically healthy pa-tients with schizophrenia treated with clozapine on a longterm basis, the signs of myotoxicity were found 24 . In another study, tachycardia, hypotension and sedation disappeared during the initial phase of treatment (i.e.…”