齐拉西酮联合奥氮平治疗双相情感障碍患者的临床疗效及对血清TBARS、NGF水平的影响

Clinical efficacy of ziprasidone combined with olanzapine in patients with bipolar disorder and its effects on serum levels of TBARS and NGF

摘要:

目的 探讨齐拉西酮联合奥氮平治疗双相情感障碍患者的临床疗效，分析其对患者血清硫代巴比妥酸反应物（TBARS）和神经生长因子（NGF）水平的影响。方法 前瞻性选取2022年1月—2025年1月在南京脑科医院进行治疗的112例双相情感障碍患者，采用随机数字表法分为对照组与观察组，每组56例。两组患者均接受丙戊酸钠治疗，对照组在丙戊酸钠治疗基础上接受奥氮平口服治疗，观察组在对照组治疗基础上联合齐拉西酮治疗。两组患者均治疗7个周期。比较两组患者治疗前后精神行为症状改善评分、倍克-拉范森躁狂量表（BRMS）评分、简易智力状态检查量表（MMSE）评分、炎症因子水平、细胞因子水平，统计并比较两组治疗疗效。结果 观察组治疗总有效率高于对照组（P <0.05）。治疗后两组敌对猜疑、激越性、思维障碍和缺乏活力评分均低于治疗前（P <0.05）；观察组治疗后敌对猜疑、激越性、思维障碍、缺乏活力4个方面评分均低于对照组（P <0.05）。治疗后两组BRMS评分均低于治疗前、MMSE评分均高于治疗前（P <0.05）；观察组治疗后BRMS评分低于对照组，MMSE评分高于对照组（P <0.05）。两组治疗后血清肿瘤坏死因子-α（TNF-α）、C反应蛋白（CRP）、白细胞介素-1（IL-1）、白细胞介素-6（IL-6）、TBARS水平均低于治疗前（P <0.05），观察组治疗后血清TNF-α、CRP、IL-1、IL-6水平均低于对照组（P <0.05）。两组治疗后血清TBARS水平低于治疗前，NGF、脑源性神经营养因子（BDNF）均高于治疗前（P <0.05），观察组治疗后血清TBARS水平低于对照组，NGF、BDNF水平均高于对照组（P <0.05）。结论 在丙戊酸钠背景治疗基础上，齐拉西酮联合奥氮平相较于单用奥氮平能显著提高双相情感障碍患者的临床疗效，更有效改善精神行为症状和抑郁躁狂症状，其作用机制可能与减轻系统炎症、降低氧化应激损伤及提升神经营养因子水平有关。

Abstract:

Objective To explore the clinical efficacy of ziprasidone combined with olanzapine versus olanzapine monotherapy in the treatment of patients with bipolar disorder, and to analyze their effects on serum levels of thiobarbituric acid reactive substances (TBARS) and nerve growth factor (NGF).Methods A total of 112 patients with bipolar disorder treated at Nanjing Brain Hospital from January 2022 to January 2025 were prospectively enrolled and randomly divided into the control group and the observation group, with 56 cases in each group. All patients received background treatment with valproate. The control group was given oral olanzapine on the basis of valproate, and the observation group was treated with ziprasidone combined with the regimen of the control group. Both groups received treatment for 7 cycles. Before and after treatment, the two groups were compared in terms of improvement in psychiatric and behavioral symptoms assessed by the Positive and Negative Syndrome Scale, Bech-Rafaelsen Mania Rating Scale (BRMS) scores, Mini-Mental State Examination (MMSE) scores, inflammatory factor levels and cytokine levels. The clinical efficacy of the two groups was statistically compared.Results The overall effective rate in the observation group was higher than that in the control group (P < 0.05). After treatment, scores for hostility-suspicion, excitement, thought disturbance, and anergia were significantly lower in both groups than before treatment (P < 0.05). Moreover, the observation group showed significantly lower scores in these four domains of psychiatric and behavioral symptoms than the control group after treatment (P < 0.05). After treatment, scores on the BRMS and the MMSE were significantly lower than those before treatment in both groups. In addition, the observation group had significantly lower BRMS and MMSE scores than the control group after treatment (P < 0.05). Following treatment, serum levels of tumor necrosis factor-α (TNF-α), C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-6 (IL-6), and TBARS were significantly lower than baseline levels in both groups. Furthermore, serum TNF-α, CRP, IL-1, and IL-6 levels were significantly lower in the observation group than in the control group after treatment (P < 0.05). After treatment, serum TBARS levels decreased, whereas NGF and brain-derived neurotrophic factor (BDNF) levels increased in both groups compared with baseline. Compared with the control group, the observation group exhibited significantly lower serum TBARS levels and significantly higher NGF and BDNF levels after treatment (P < 0.05).Conclusion On the basis of valproate background therapy, ziprasidone combined with olanzapine can significantly improve clinical efficacy and more effectively relieve psychiatric behavioral symptoms as well as manic and depressive symptoms in bipolar disorder patients compared with olanzapine monotherapy. The mechanism may be related to the reduction of systemic inflammation and oxidative stress injury, and the upregulation of neurotrophic factor levels.