Ranel Troy Santos, Sandra Mullen, Ericka L Crouse, Katie S Adams
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The primary outcome was the difference in clozapine doses in patients on clozapine as monotherapy versus dual therapy with VPA. Secondary outcomes include the difference in incidence of adverse effects in monotherapy versus dual therapy, as well as clozapine and norclozapine concentrations in both treatment groups.</p><p><strong>Results: </strong>During the study period, 73 patients were included in the monotherapy group and 35 patients were included in the dual therapy group. The average clozapine dose in the dual therapy group was 250 mg (95% CI = 194.7, 305.4) which was significantly higher than the average monotherapy dose of 175.9 mg (95% CI = 134.0, 208.7; <i>P</i> = .016). However, there was no significant difference in the average clozapine concentration between the dual therapy group (392.5 ng/mL; 95% CI = 252.8, 532.2) and monotherapy group (365.9 ng/mL; 95% CI = 260.5, 471.3; <i>P</i> = .756). There were higher rates of tachycardia (45.7% vs 17.8%; <i>P</i> = .002), sedation (51.4% vs 8.2%; <i>P</i> < .001), and constipation (42.8% vs 9.5%; <i>P</i> < .001) in the dual therapy group compared to the monotherapy group, respectively.</p><p><strong>Discussion: </strong>Patients on concurrent clozapine and VPA received higher doses of clozapine and experienced a higher incidence of tachycardia, sedation, and constipation.</p>","PeriodicalId":22710,"journal":{"name":"The Mental Health Clinician","volume":"12 6","pages":"336-341"},"PeriodicalIF":0.0000,"publicationDate":"2022-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://ftp.ncbi.nlm.nih.gov/pub/pmc/oa_pdf/cd/c8/i2168-9709-12-6-336.PMC9819135.pdf","citationCount":"1","resultStr":"{\"title\":\"Comparison of clozapine doses and tolerability in patients with and without concurrent valproic acid.\",\"authors\":\"Ranel Troy Santos, Sandra Mullen, Ericka L Crouse, Katie S Adams\",\"doi\":\"10.9740/mhc.2022.12.336\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Introduction: </strong>Valproic acid (VPA) and its various formulations can be given in conjunction with clozapine for seizure prophylaxis or for augmentation in schizophrenia. There is conflicting literature on how VPA affects clozapine metabolism and the incidence of clozapine-related side effects. The purpose of this study is to compare the effects of VPA when given concurrently with clozapine to patients on clozapine monotherapy.</p><p><strong>Methods: </strong>A retrospective medical record review was completed to identify patients admitted to the inpatient psychiatry unit at an academic medical center with an order for clozapine with and without concurrent VPA from August 7, 2010 to August 7, 2020. The primary outcome was the difference in clozapine doses in patients on clozapine as monotherapy versus dual therapy with VPA. Secondary outcomes include the difference in incidence of adverse effects in monotherapy versus dual therapy, as well as clozapine and norclozapine concentrations in both treatment groups.</p><p><strong>Results: </strong>During the study period, 73 patients were included in the monotherapy group and 35 patients were included in the dual therapy group. The average clozapine dose in the dual therapy group was 250 mg (95% CI = 194.7, 305.4) which was significantly higher than the average monotherapy dose of 175.9 mg (95% CI = 134.0, 208.7; <i>P</i> = .016). However, there was no significant difference in the average clozapine concentration between the dual therapy group (392.5 ng/mL; 95% CI = 252.8, 532.2) and monotherapy group (365.9 ng/mL; 95% CI = 260.5, 471.3; <i>P</i> = .756). 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引用次数: 1
摘要
简介:丙戊酸(VPA)及其各种制剂可与氯氮平联合给予癫痫发作预防或增强精神分裂症。关于VPA如何影响氯氮平代谢和氯氮平相关副作用的发生率,文献存在矛盾。本研究的目的是比较VPA与氯氮平同时应用于氯氮平单药治疗的患者的效果。方法:对2010年8月7日至2020年8月7日期间在某学术医疗中心精神科住院的氯氮平合并或不合并VPA的患者进行回顾性病历回顾。主要结果是氯氮平单药治疗与VPA双药治疗患者氯氮平剂量的差异。次要结局包括单药治疗与双药治疗不良反应发生率的差异,以及两治疗组氯氮平和去氯氮平浓度的差异。结果:研究期间,单药治疗组73例,双药治疗组35例。双药组氯氮平平均剂量为250 mg (95% CI = 194.7, 305.4),显著高于单药组的平均剂量175.9 mg (95% CI = 134.0, 208.7;p = .016)。然而,双重治疗组之间氯氮平平均浓度无显著差异(392.5 ng/mL;95% CI = 252.8, 532.2)和单药治疗组(365.9 ng/mL;95% ci = 260.5, 471.3;p = .756)。心动过速发生率较高(45.7% vs 17.8%;P = .002),镇静(51.4% vs 8.2%;讨论:同时使用氯氮平和VPA的患者接受了更高剂量的氯氮平,并经历了更高的心动过速、镇静和便秘发生率。
Comparison of clozapine doses and tolerability in patients with and without concurrent valproic acid.
Introduction: Valproic acid (VPA) and its various formulations can be given in conjunction with clozapine for seizure prophylaxis or for augmentation in schizophrenia. There is conflicting literature on how VPA affects clozapine metabolism and the incidence of clozapine-related side effects. The purpose of this study is to compare the effects of VPA when given concurrently with clozapine to patients on clozapine monotherapy.
Methods: A retrospective medical record review was completed to identify patients admitted to the inpatient psychiatry unit at an academic medical center with an order for clozapine with and without concurrent VPA from August 7, 2010 to August 7, 2020. The primary outcome was the difference in clozapine doses in patients on clozapine as monotherapy versus dual therapy with VPA. Secondary outcomes include the difference in incidence of adverse effects in monotherapy versus dual therapy, as well as clozapine and norclozapine concentrations in both treatment groups.
Results: During the study period, 73 patients were included in the monotherapy group and 35 patients were included in the dual therapy group. The average clozapine dose in the dual therapy group was 250 mg (95% CI = 194.7, 305.4) which was significantly higher than the average monotherapy dose of 175.9 mg (95% CI = 134.0, 208.7; P = .016). However, there was no significant difference in the average clozapine concentration between the dual therapy group (392.5 ng/mL; 95% CI = 252.8, 532.2) and monotherapy group (365.9 ng/mL; 95% CI = 260.5, 471.3; P = .756). There were higher rates of tachycardia (45.7% vs 17.8%; P = .002), sedation (51.4% vs 8.2%; P < .001), and constipation (42.8% vs 9.5%; P < .001) in the dual therapy group compared to the monotherapy group, respectively.
Discussion: Patients on concurrent clozapine and VPA received higher doses of clozapine and experienced a higher incidence of tachycardia, sedation, and constipation.