Meltzer H Y, Cola P A, Parsa M
Department of Psychiatry, Case Western Reserve University School of Medicine, Cleveland, OH, USA.
Neuropsychopharmacology. 1996 Oct;15(4):395-405. doi: 10.1016/0893-133X(95)00276-J.
Serum creatine kinase (SCK) activity of the skeletal muscle (MM) form is sometimes moderately increased in acutely psychotic patients and may be massively increased as a result of muscle damage. The objective of this study was to characterize the SCK increases in patients treated with novel antipsychotic drugs. SCK activity and myoglobinuria, an index of gross muscle damage, were monitored at varying intervals in schizophrenic or schizoaffective patients treated with antipsychotic drugs. Possible causes of increases in SCK activity, such as trauma, excessive physical activity, exacerbation of psychosis, were assessed. Fifteen instances of massive increases in SCK activity were observed in 11 out of 121 patients (10%) treated with the following antipsychotic drugs: clozapine, loxapine, haloperidol, melperone, risperidone, or olanzapine. These increases in SCK activity were of the MM type and ranged from 1,206 to 177,363 IU/L (median, 9,600 IU/L). Thus, they were much larger than the increases usually found in acutely psychotic patients or patients with neuroleptic malignant syndrome (range, 500-3,000 IU/L). Only the patient with SCK activity of 177,363 IU/L had rhabdomyolysis as evidenced by myoglobinuria. The onset of the increases was from 5 days to 2 years after initiating treatment, and the increases lasted 4 to 28 days (median, 8 days). Flulike symptoms were present in two of the patients, but the others were asymptomatic. The increases were self-limiting in three cases, despite continuing treatment. Two of three cases rechallenged with the same drug again developed large increases in SCK activity within a week. It is unlikely these increases in SCK activity are related to acute psychosis, trauma, or the neuroleptic malignant syndrome. The increase in SCK activity may reflect the ability of the drugs to increase intermittently cell membrane permeability, especially in skeletal muscle, in some vulnerable subjects. A possible role of serotonin in this process is suggested by the pharmacology of most of the offending drugs. However, in some instances, the increases may have been unrelated to drug treatment. There was no evidence that these increases in SCK activity, despite their magnitude, compromised renal function. Routine monitoring of SCK activity of myoglobinuria during treatment with the antipsychotic drugs studied here is probably not necessary.
急性精神病患者的骨骼肌（MM）型血清肌酸激酶（SCK）活性有时会中度升高，并且可能由于肌肉损伤而大幅升高。本研究的目的是描述使用新型抗精神病药物治疗的患者中SCK升高的特征。在使用抗精神病药物治疗的精神分裂症或分裂情感性障碍患者中，以不同的时间间隔监测SCK活性和肌红蛋白尿（严重肌肉损伤的一个指标）。评估了SCK活性升高的可能原因，如创伤、过度体力活动、精神病加重等。在121例接受以下抗精神病药物治疗的患者中的11例（10%）观察到15例SCK活性大幅升高：氯氮平、洛沙平、氟哌啶醇、美哌隆、利培酮或奥氮平。这些SCK活性升高为MM型，范围为1206至177363 IU/L（中位数为9600 IU/L）。因此，它们比急性精神病患者或患有抗精神病药物恶性综合征的患者中通常发现的升高幅度大得多（范围为500 - 3000 IU/L）。只有SCK活性为177363 IU/L的患者出现了肌红蛋白尿所证实的横纹肌溶解。升高的起始时间为开始治疗后5天至2年，升高持续4至28天（中位数为8天）。两名患者出现了流感样症状，但其他患者无症状。三例患者尽管继续治疗，但升高是自限性的。三例中有两例再次使用相同药物进行激发试验，在一周内SCK活性再次大幅升高。这些SCK活性升高不太可能与急性精神病、创伤或抗精神病药物恶性综合征有关。SCK活性升高可能反映了这些药物在一些易感个体中使细胞膜通透性间歇性增加的能力，尤其是在骨骼肌中。大多数致病药物的药理学提示5-羟色胺在这一过程中可能起作用。然而，在某些情况下，升高可能与药物治疗无关。没有证据表明这些SCK活性升高，尽管幅度很大，但会损害肾功能。在此研究中用抗精神病药物治疗期间常规监测肌红蛋白尿的SCK活性可能没有必要。
