Sex differences in autonomic adverse effects related to antipsychotic treatment and associated hormone profiles.

IF 3 Q2 PSYCHIATRY Schizophrenia (Heidelberg, Germany) Pub Date : 2024-01-06 DOI:10.1038/s41537-023-00430-4
Ingrid T Johansen, Nils Eiel Steen, Linn Rødevand, Synve H Lunding, Gabriela Hjell, Monica B E G Ormerod, Ingrid Agartz, Ingrid Melle, Trine V Lagerberg, Mari Nerhus, Ole A Andreassen
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Abstract

Autonomic adverse effects of antipsychotic drugs (APs) cause clinical challenges, but few studies have investigated sex differences and their underlying biological pathways. Sex-specific regulation of relevant hormones could be involved. We investigated sex differences in autonomic adverse effects related to olanzapine, quetiapine, risperidone, and aripiprazole, and the role of hormones related to APs. Patients with severe mental disorders (N = 1318) were included and grouped based on AP monotherapy: olanzapine (N = 364), quetiapine (N = 211), risperidone (N = 102), aripiprazole (N = 138), and no AP (N = 503). Autonomic symptoms from the Udvalg for Kliniske Undersøgelser (UKU) side effect scale was analyzed with logistic regression, adjusting for age, diagnosis, and polypharmacy. Further, we analyzed associations between autonomic symptoms and hormones related to APs. We found associations between autonomic adverse effects and APs, with sex-specific risk for palpitations/tachycardia associated with hormonal changes related to APs. Results showed increased salivation associated with aripiprazole, reduced salivation with quetiapine, and nausea/vomiting and palpitations/tachycardia with olanzapine, and higher risk of nausea/vomiting, diarrhea, constipation, polyuria/polydipsia, and palpitations/tachycardia in females. Significant sex x AP interaction was found for palpitations/tachycardia, with higher risk in risperidone-treated males, which was associated with different hormone profiles of prolactin, cortisol, and insulin. Our findings implicate a role of several hormones in the sex-specific autonomic adverse effects related to APs.

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与抗精神病治疗相关的自律神经不良反应的性别差异及相关激素谱。
抗精神病药物(APs)的自主神经不良反应给临床带来了挑战,但很少有研究对性别差异及其潜在的生物学途径进行调查。这可能与相关激素的性别特异性调节有关。我们研究了与奥氮平、喹硫平、利培酮和阿立哌唑相关的自主神经不良反应的性别差异,以及与抗精神病药物相关的激素的作用。研究纳入了严重精神障碍患者(N = 1318),并根据 AP 单一疗法进行分组:奥氮平(N = 364)、喹硫平(N = 211)、利培酮(N = 102)、阿立哌唑(N = 138)和无 AP(N = 503)。通过逻辑回归分析了Udvalg for Kliniske Undersøgelser (UKU) 副作用量表中的自主神经症状,并对年龄、诊断和多重用药进行了调整。此外,我们还分析了自律神经症状和与 APs 相关的激素之间的关联。我们发现自律神经不良反应与 APs 之间存在关联,其中心悸/心动过速的性别特异性风险与 APs 相关的激素变化有关。结果显示,阿立哌唑会导致流涎增加,喹硫平会导致流涎减少,奥氮平会导致恶心/呕吐和心悸/心动过速,而女性出现恶心/呕吐、腹泻、便秘、多尿/多尿、心悸/心动过速的风险更高。在心悸/心动过速方面发现了显著的性别 x AP交互作用,利培酮治疗的男性风险更高,这与催乳素、皮质醇和胰岛素的不同激素谱有关。我们的研究结果表明,在与 APs 相关的特定性别自律神经不良反应中,多种激素发挥了作用。
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