丁螺环酮联合高压静电治疗广泛性焦虑症对照研究

目的：探讨丁螺环酮联合高压静电治疗广泛性焦虑症的临床疗效和安全性。方法将60例广泛性焦虑症患者随机分为两组,每组30例,两组均口服丁螺环酮治疗,研究组联合高压静电治疗,观察6周。治疗前后采用汉密顿焦虑量表评定临床疗效,并随时记录治疗过程中出现的不良反应。结果治疗6周末研究组显效率为70．0％、有效率为100％,对照组分别为43．3％、86．7％,研究组显效率、有效率均显著高于对照组（χ2＝4．34、4．28,P＜0．05）;治疗过程中两组均未出现严重不良反应。结论丁螺环酮联合高压静电治疗广泛性焦虑症起效快,疗效显著,安全性高,显著优于单用药物治疗。     

Efficacy of the 5-HT1A agonist, buspirone hydrochloride, in migraineurs with anxiety: a randomized, prospective, parallel group, double-blind, placebo-controlled study

OBJECTIVE: To examine the efficacy of buspirone, a 5-HT1A agonist, for migraine combined with anxiety disorder. BACKGROUND: Modulation of the 5-hydroxytryptamine (5-HT) system is used for the neuropharmacology of migraine treatment; however, the involvement of the 5-HT1A system in migraine is not fully understood. METHODS: Seventy-four outpatients aged 20 to 70 years (mean, 46.4; SD, 12.8) were analyzed. All subjects were diagnosed to have migraine according to the International Headache Society criteria and anxiety disorder according to DSM-IV. Subjects were randomly assigned to treatment with either buspirone (10 mg/day) or placebo for 6 weeks. Efficacy variables included changes in headache frequency, headache intensity, Hamilton Anxiety Rating Scale (HAM-A), Headache Self-Efficacy Scale (HMSE), and Headache Disability Inventory (HDI). The correlation between the headache improvement and the anxiolytic effect was analyzed. RESULTS: Headache frequency showed a 43.3% reduction in the buspirone-treated group, but by only 10.3% in the placebo group. HAM-A and HDI were also significantly more lowered in buspirone-treated patients than in placebo-treated patients. However, headache intensity and HMSE score were unchanged. Correlation analysis of the relation between headache frequency reduction and HAM-A improvement, revealed no significant association. CONCLUSIONS: In this study, buspirone showed a prophylactic effect in migraine with anxiety disorder, which was not secondary to its anxiolytic effect. This suggests that the agonistic action for 5-HT1A can be directly effective in migraine prophylaxis. However, more long-term study is warranted before concluding the efficacy.     

Interaction of buspirone and its major metabolites with human organic cation transporters

Buspirone, a cationic drug, is an anxiolytic and antidepressant drug. However, whether buspirone and its metabolites are interacted with organic cationic transporter remains uncertain. In this study, we examined the interaction of buspirone and its major metabolites 1-(2-pyrimidinyl)piperazine (1-PP) and 6-hydroxybuspirone (6′-OH-Bu) with hOCTs using human hepatocellular carcinoma (HepG2), human colorectal adenocarcinoma (Caco-2) cells, and S2 cells expressing OCT1 (S2hOCT1), 2 (S2hOCT2), or 3 (S2hOCT3). Coadministration of buspirone and fluorescent 4-(4-(dimethylamino)styryl)-N-methylpyridinium (ASP⁺) was examined using HepG2 cells, and [³H]-1-methyl-4-phenylpyridinium (MPP⁺) transport was assessed in S2 cell overexpressing hOCTs. The results showed that ASP⁺ transport was suppressed by buspirone with an IC₅₀ of 26.3 ± 2.9 μM without any cytotoxic effects in HepG2 expressing hOCTs cells. Consistently, buspirone strongly inhibited [³H]-MPP⁺ uptake by S2hOCT1, S2hOCT2, and S2hOCT3 cells with an IC_50s of 89.0 ± 1.3 μM, 43.7 ± 7.5 μM, and 20.4 ± 1.0 μM, respectively. Nonetheless, 6′-OH-Bu and 1-PP caused weak or no inhibition on ASP⁺ and [³H]-MPP⁺ transport. These findings suggest the potential interaction of buspirone with organic cation drugs that are handled by hOCT3. However, further clinical relevance is needed to support these findings for preventing drug–drug interaction in patients who take prescribed drugs together with buspirone.