Objective To observe the efficacy, safety, and compliance of lamotrigine combined with magnesium valproate in treating children with depressive episodes of bipolar disorder, and to explore the effects on thyroid hormone levels, brain-derived neurotrophic factor (BDNF), C-reactive protein (CRP), interleukin-1 (IL-1), interleukin-10 (IL-10), tumor necrosis factor-α (TNF-α) and plasma concentration of valproate.
Methods The children with bipolar disorder diagnosed from January 2023 to February 2025 were selected, and divided into the observation group and control group. The control group was treated with magnesium valproate tablets, and the observation group was added lamotrigine in addition to the treatment given to the control group. Both groups were treated continuously for 8 weeks. The clinical efficacy, the Hamilton Depression Scale-24 (HAMD-24) score, Clinical Global Impression (CGI) assessment, thyroid hormone levels, BDNF, CRP, IL-1, IL-10 and TNF-α, daily average dose of magnesium valproate (D), blood concentration of valproate (C), C/D ratio, mean dosing interval (h), incidence of adverse reactions, and medication adherence and satisfaction scores in both groups was observed.
Results A total of 100 children were included, 50 in each group. After treatment, the total effective rate of the observation group was 98.00% which was significantly higher than that of the control group (84.00%) (P<0.05). The serum free triiodothyronine (FT3), free thyroxine (FT4), BDNF and IL-10 in both groups increased compared to the previous (P<0.05), while HAMD-24 score, CGI score, thyroid-stimulating hormone (TSH), CRP, IL-1 and TNF-α decreased (P<0.05), and all indicators in the observation group were better than those in the control group (P<0.05). Both groups had no serious or new adverse drug reactions, and the incidence of total adverse reactions, the difference in the incidence of total adverse reactions was not statistically significant (P>0.05). There was no statistically significant difference in valproic acid blood concentrations between the two groups of children (P>0.05). The medication compliance score and satisfaction score of the observation group were significantly higher than those of the control group (P<0.05).
Conclusion Combination of lamotrigine with magnesium valproate in children with depressive episodes of bipolar disorder improves treatment effective and clinical symptoms, promotes a rise in thyroid hormone and BDNF as well as improves inflammatory factors and increases medication adherence and satisfaction in children with a better safety profile.
1.Samaksha PB, Kishor M, Ramesh M. PMH50 IMPACT of clinical pharmacist intervention in patients with bipolar affective disorder in South India[J]. Expert Opin Pharmacother, 2021, 20(18): 2237-2255. DOI: 10.1080/14656566.2019.1684473.
2.Diniz BS, Teixeira AL, Cao F, et al. History of bipolar disorder and the risk of dementia: a systematic review and Meta-analysis[J]. Am J Geriatr Psychiatry, 2017, 25(4): 357-362. DOI: 10.1016/j.jagp.2016.11.014.
3.Yatham LN, Kennedy SH, Parikh SV, et al. Canadian network for mood and anxiety treatments (CANMAT) and international society for bipolar disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder[J]. Bipolar Disord, 2018, 20(2): 97-170. DOI: 10.1111/bdi.12609.
4.王威, 李胜, 谢高明, 等. 拉莫三嗪对双相障碍患者血脂、甲状腺功能和性激素的影响[J]. 中国神经精神疾病杂志, 2022, 48(10): 609-613. [Wang W, Li S, Xie GM, et al. Effects of lamotrigine on blood lipids, thyroid function and sex hormones in patients with bipolar disorder[J]. Chin J Nervous Mental Dis, 2022, 48(10): 609-613.] DOI: 10.3969/j.issn.1002-0152.2022.10.006.
5.Penninx BWJH, Lange SMM. Metabolic syndrome in psychiatric patients: overview, mechanisms, and implications[J]. Dialogues Clin Neurosci, 2018, 20(1): 63-73. DOI: 10.31887/DCNS.2018.20.1/bpenninx.
6.杨海晨, 刘铁榜, 沈其杰. 拉莫三嗪在心境障碍治疗中的应用[J]. 临床精神医学杂志, 2005, 15(1): 54-55. [Yang HC, Liu TB, Shen QJ, et al. Application of lamotrigine in the treatment of mood disorders[J]. Journal of Clinical Psychiatry, 2005, 15(1): 54-55.] DOI: 10.3969/j.issn.1005-3220.2005.01.048.
7.黄善情, 倪晓佳, 肖桃, 等. 拉莫三嗪在双相情感障碍治疗中剂量校正浓度影响因素分析[J]. 中国医院药学杂志, 2021, 41(20): 2091-2094. [Huang SQ, Ni XJ, Xiao T, et al. Influencing factors for dose-adjusted serum concentration of lamotrigine in the treatment of bipolar disorder[J]. Chinese Journal of Hospital Pharmacy, 2021, 41(20): 2091-2094.] DOI: 10.13286/j.1001-5213.2021.20.09.
8.方贻儒, 洪武, 刘铁榜, 等. 《中国双相障碍防治指南》(2025年版)计划书[J]. 中华精神科杂志, 2023, 56(6): 413-417. [Fang YR, Hong W, Liu TB, et al. Protocol for the Chinese guideline for the prevention and treatment of bipolar disorder (2025 edition) [J]. Chinese Journal of Psychiatry, 2023, 56(6): 413-417.] DOI: 10.3760/cma.j.cn113661-20230919-00077.
9.晋文学, 史坤林, 彭津津. 丙戊酸钠联合拉莫三嗪治疗癫痫的疗效及安全性分析[J]. 癫痫与神经电生理学杂志, 2020, 29(1): 21-24. [Jin WX, Shi KL, Peng JJ, et al. Efficacy and safety of sodium valproate combined with lamotrigine in the treatment of epilepsy[J]. Journal of Epileptology and Electroneurophysiology, 2020, 29(1): 21-24.] DOI: 10.19984/j.cnki.1674-8972.2020.01.006.
10.刘蕊, 张叶. 丙戊酸镁联合拉莫三嗪在双相情感障碍患者中的应用效果及对WAIS-RC和WMS评分的影响研究[J]. 中国现代药物应用, 2024, 18(6): 39-43. [Liu R, Zhang Y. Study on effects of magnesium valproate combined with lamotrigine in patients with bipolar disorder and its influence on WAIS-RC and WMS score[J]. Chinese Journal of Modern Drug Application, 2024, 18(6): 39-43. ] DOI: 10.14164/j.cnki.cn11-5581/r.2024.06.009.
11.Amerio A, Russo D, Miletto N, et al. Polypharmacy as maintenance treatment in bipolar illness: a systematic review[J]. Acta Psychiatr Scand, 2021, 144(3): 259-276. DOI: 10.1111/acps.13312.
12.马晓, 张丽霞, 李猛, 等. 青少年双相情感障碍抑郁发作患者甲状腺激素水平与外显攻击行为的关系[J]. 临床心身疾病杂志, 2024, 30(1): 25-28. [Ma X, Zhang LX, Li M, et al. The relationship between thyroid hormone levels and overt aggressive behavior in adolescents with depressive episode of bipolar disorders[J]. Journal of Clinical Psychosomatic Diseases, 2024, 30(1): 25-28.] https://www.cnki.com.cn/Article/CJFDTotal-LCSX202401004.htm.
13.戴边, 杨致蓉, 刘冰. 拉莫三嗪联合丙戊酸钠对双相障碍抑郁发作患者甲状腺功能、脑源性神经营养因子和C反应蛋白的影响[J]. 中国临床药学杂志, 2024, 33(7): 525-528. [Dai B, Yang ZR, Liu B. Effect of lamotrigine and sodium valproate on thyroid hormone and BDNF and CRP in patients with depressive episodes of bipolar disorder[J]. Chinese Journal of Clinical Pharmacy, 2024, 33(7): 525-528.] DOI: 10.19577/j.1007-4406.2024.07.008.
14.沈其杰, 刘铁榜. 双相情感障碍药物治疗规范化程序草案 [J]. 临床精神医学杂志, 2002, 12(1): 51-53. [Shen QJ, Liu TB. Draft standardized procedures for the pharmacological treatment of bipolar disorder[J]. Journal of Clinical Psychiatry, 2002, 12(1): 51-53.] DOI: 10.3969/j.issn.1005-3220.2002.01.039.
15.Yamamoto Y, Usui N, Kagawa Y, et al. Time-course changes in lamotrigine concentration after addition of valproate and the safety and long-term tolerability of lamotrigine-valproate combination therapy[J]. Biol Pharm Bull, 2024, 47(1): 43-48. DOI: 10.1248/bpb.b23-00608.
16.Zimmerman M, Martinez JH, Young D, et al. Severity classification on the Hamilton Depression Rating Scale[J]. J Affect Disord, 2013, 150(2): 384-388. DOI: 10.1016/j.jad.2013.04.028.
17.吴宛焰, 冯杰, 张惠兰, 等. 新疆地区双相情感障碍患者丙戊酸钠血药浓度的影响因素及效果分析[J].中国医院用药评价与分析, 2025, 25(3): 294-296. [Wu WY, Feng J, Zhang HL, et al. Influencing factors of blood concentration and efficacy of sodium valproate in patients with bipolar affective disorder in Xinjiang[J]. Evaluation and Analysis of Drug-use in Hospitals of China, 2025, 25(3): 294-296.] DOI: 10.14009/j.issn.1672-2124.2025.03.008.
18.吴园园, 黄凌斐, 罗优优, 等. 中文版Morisky服药依从性评估量表在炎症性肠病患儿中应用的信效度评价[J]. 中国现代应用药学, 2023, 40(22): 3117-3123. [Wu YY, Huang LF, Luo YY, et al. Reliability and validity of Morisky Medication Adherence Scale for assessing medication adherence in children with inflammatory bowel disease[J]. Chinese Journal of Modern Applied Pharmacy, 2023, 40(22): 3117-3123. ] DOI: 10.13748/j.cnki.issn1007-7693.20232567.
19.蒋欢欢, 王紫监, 王志秀, 等. 稳定性冠心病患者实施药物治疗管理服务的经济学评价[J]. 中国药房, 2022, 33(8): 981-986. [Jiang HH, Wang ZJ, Wang ZX, et al. Economic evaluation of medication therapeutical management services for patients with stable coronary heart disease[J]. China Pharmacy, 2022, 33(8): 981-986.] DOI: 10.6039/j.issn.1001-0408.2022.08.13.
20.胡传存, 赵婷婷, 张爱国, 等. 综合心理干预对双相情感障碍抑郁相患者康复的影响[J]. 神经损伤与功能重建, 2021, 16(12): 779-781. [Hu CC, Zhao TT, Zhang AG, et al. The effect of comprehensive psychological intervention on the recovery of patients with depressive phase of bipolar disorder[J]. Neural Injury and Functional Reconstruction, 2021, 16(12): 779-781.] DOI: 10.16780/j.cnki.sjssgncj.20200140.
21.Parker G, Ricciardi T, Tavella G, et al. The utility of daily mood ratings in clinical trials of patients with bipolar II disorder[J]. Australas Psychiatry, 2021, 29(6): 648-651. DOI: 10.1177/10398562211014226.
22.何慧萍, 白卫华, 何轶欧. 奥氮平联合丙戊酸镁治疗女性双相情感障碍躁狂发作的疗效及对神经递质的影响[J]. 临床合理用药, 2023, 16(33): 55-57. [He HP, Bai WH, He YO. The efficacy and effects on neurotransmitters of olanzapine combined with magnesium valproate in the treatment of manic episodes of bipolar disorder in women[J]. Chinese Journal of Clinical Rational Drug Use, 2023, 16(33): 55-57.] DOI: 10.15887/j.cnki.13-1389/r.2023.33.015.
23.祁晓媛, 范桂梅, 贾鸿宁, 等. 拉莫三嗪辅助治疗前庭性偏头痛的临床效果及对血清神经递质水平的影响[J]. 卒中与神经疾病, 2020, 27(2): 205-208. [Qi XY, Fan GM, Jia HN, et al. Clinical effect of lamotrigine in the adjuvant treatment of vestibular migraine and its effect on serum neurotransmitter levels[J]. Stroke and Nervous Diseases, 2020, 27(2): 205-208.] DOI: 10.3969/j.issn.1007-0478.2020.02.014.
24.郝楷荣, 纪家武, 黄少雅, 等. 双相情感障碍与甲状腺激素水平变化之间的关系[J]. 中国卫生标准管理, 2023, 14(2): 112-116. [Hao KR, Ji JW, Huang SY, et al. Relationship between bipolar affective disorder and thyroid hormone levels[J]. China Health Standard Management, 2023, 14(2): 112-116.] DOI: 10.3969/j.issn.1674-9316.2023.02.024.
25.郭伟坚, 李荷花, 李含秋, 等. 双相情感障碍临床特征与甲状腺功能变化的性别差异及其相关性[J]. 国际精神病学杂志, 2023, 50(1): 45-4756. [Guo WJ, Li HH, Li HQ, et al. Gender difference and their correlations in clinical features and changes of thyroid function in bipolar disorder[J]. Journal Of International Psychiatry, 2023, 50(1): 45-4756.] DOI: 10.13479/j.cnki.jip.2023.01.014.
26.Seshadri A, Sundaresh V, Prokop LJ, et al. Thyroid hormone augmentation for bipolar disorder: a systematic review[J]. Brain Sci, 2022, 12(11): 1540. DOI: 10.3390/brainsci12111540.
27.Roosen L, Sienaert P. Evidence-based treatment strategies for rapid cycling bipolar disorder, a systematic review[J]. J Affect Disord, 2022, 311: 69-77. DOI: 10.1016/j.jad.2022.05.017.
28.张振学, 王佳慧. 认知矫正联合常规药物治疗双相情感障碍患者疗效及对TBIL、UA和BDNF的影响[J]. 中南医学科学杂志, 2023, 51(2): 246-249. [Zhang ZX, Wang JH. Effect of cognitive correction combined with conventional drugs on patients with bi-polar disorder and its effect on TBIL, UA and BDNF[J]. Medical Science Journal of Central South China, 2023, 51(2): 246-249.] DOI: 10.15972/j.cnki.43-1509/r.2023.02.022.
29.斯亮, 王燕燕, 卢远波. 喹硫平联合丙戊酸镁缓释片对双相情感障碍躁狂发作患者血清BDNF、GDNF及炎性因子水平的影响[J]. 川北医学院学报, 2021, 36(10): 1383-1386. [Si L, Wang YY, Lu YB. Effects of quetiapine combined with magnesium valproate sustained release tablets on serum BDNF, GDNF and inflammatory factors in patients with manic episode of bipolar disorder[J]. Journal of North Sichuan Medical College, 2021, 36(10): 1383-1386.] DOI: 10.3969/j.issn.1005-3697.2021.10.028.
30.Demir M, Akarsu EO, Dede HO, et al. Investigation of the Roles of New Antiepileptic drugs and serum BDNF levels in efficacy and safety monitoring and quality of life: a clinical research[J]. Curr Clin Pharmacol, 2020, 15(1): 49-63. DOI: 10.2174/1574884714666190312145409.
31.王永良, 王敬巍, 李士龙. 双相障碍抑郁发作患者治疗前后E2、PRL、CRP水平变化及其与疗效的关系[J]. 国际精神病学杂志, 2022, 49(3): 458-461. [Wang YL, Wang JW, Li SL. Changes of E2, PRL, CRP levels in bipolar patients in depressive episode before and after treatment and their related with the treatment efficacy[J]. Journal Of International Psychiatry, 2022, 49(3): 458-461.] DOI: 10.13479/j.cnki.jip.2022.03.039.
32.刘华, 刘可智, 梁雪梅. 双相情感障碍患者血浆脑源性神经营养因子水平变化观察[J]. 山东医药, 2023, 63(27): 66-68.[Liu H, Liu KZ, Liang XM. Changes in plasma BDNF levels in patients with bipolar disorder[J]. Shandong Medical Journal, 2023, 63(27): 66-68.] DOI: 10.3969/j.issn.1002-266X.2023.27.013.
33.赖子梅, 钟涛. 拉莫三嗪联合丙戊酸钠治疗儿童难治性癫痫的疗效及对电生理指标的影响[J]. 现代电生理学杂志, 2024, 31(4): 217-220. [Lai ZM, Zhong T. Efficacy of lamotrigine combined with sodium valproate in the treatment of refractory epilepsy in children and its influence on electrophysiological indexes[J]. Journal of Modern Electrophysiology, 2024, 31(4): 217-220.] DOI: 10.3969/j.issn.1672-0458.2024.04.006.
34.蒙雪芳, 梁倩, 韦英秀. 拉莫三嗪联合丙戊酸钠治疗小儿癫痫疗效与安全性的Meta分析[J]. 儿科药学杂志, 2024, 30(4): 44-50. [Meng XF, Liang Q, Wei YX. Meta-analysis on efficacy and safety of lamotrigine combined with sodium valproate in the treatment of epilepsy in children[J]. Journal of Pediatric Pharmacy, 2024, 30(4): 44-50.] DOI: 10.13407/j.cnki.jpp.1672-108X.2024.04.012.