Wirshing D A, Spellberg B J, Erhart S M, Marder S R, Wirshing W C
Department of Psychiatry, West Los Angeles Veterans Affairs Medical Center, CA 90073, USA.
Biol Psychiatry. 1998 Oct 15;44(8):778-83. doi: 10.1016/s0006-3223(98)00100-0.
The new antipsychotics induce minimal extrapyramidal side effects, probably due to their relatively greater affinity for certain nondopaminergic receptors than their older, conventional counterparts; however, this polyreceptor affinity may be responsible for the development of other adverse effects. One serious adverse effect that may be linked to these effects is non-insulin-dependent diabetes mellitus.
We summarize 6 new cases of clozapine- and olanzapine-associated diabetes that we have documented in our clinic. We compare our cases to previous reports and tabulate the pertinent similarities among cases.
Two of the cases were olanzapine-associated and 4 were clozapine-associated diabetes. Five of our 6 patients had risk factors for diabetes, as have 7 of the 9 previously reported in the literature. Four of our 6 patients, and 2 of the 4 prior cases in which such data were reported, experienced substantial weight gain after starting their antipsychotics.
Novel antipsychotics should be administered with great care to patients with risk factors for diabetes. Although the precise mechanism of the novel antipsychotic-associated diabetes is unclear, we hypothesize that histaminic and possibly serotonergic antagonism induces weight gain, which in turn leads to changes in glucose homeostasis. Additionally, serotonin1A antagonism might decrease pancreatic beta-cell responsiveness, resulting in inappropriately low insulin and hyperglycemia.
新型抗精神病药物引起的锥体外系副作用极小，这可能是因为它们相对于传统的老一代药物对某些非多巴胺能受体具有更高的亲和力；然而，这种多受体亲和力可能会导致其他不良反应的发生。与这些效应可能相关的一种严重不良反应是非胰岛素依赖型糖尿病。
我们总结了在我们诊所记录的6例与氯氮平和奥氮平相关的糖尿病新病例。我们将我们的病例与之前的报告进行比较，并将病例之间的相关相似之处制成表格。
其中2例与奥氮平相关，4例与氯氮平相关。我们的6例患者中有5例有糖尿病危险因素，文献中之前报道的9例中有7例也有。我们的6例患者中有4例，以及之前报告的4例中有2例在开始使用抗精神病药物后体重显著增加。
对于有糖尿病危险因素的患者，应极其谨慎地使用新型抗精神病药物。虽然新型抗精神病药物相关糖尿病的确切机制尚不清楚，但我们推测组胺能以及可能的5-羟色胺能拮抗作用会导致体重增加，进而导致葡萄糖稳态的改变。此外，5-羟色胺1A拮抗作用可能会降低胰腺β细胞的反应性，导致胰岛素分泌不足和血糖升高。
