利培酮、托吡酯对难治性抑郁症的辅助治疗

目的：比较利培酮与托吡酯分别合并帕罗西汀治疗难治性抑郁症的疗效及不良反应。方法：60例难治性抑郁症患者随机分为两组，在使用帕罗西汀的基础上分别合用利培酮或托吡酯进行为期6周的治疗。使用汉密尔顿抑郁量表(HAMD)、临床疗效总评量表(CGI)及副反应量表(TESS)评定临床疗效及不良反应。结果：两组总体疗效相当，总有效率分别为73．3％、76．7％。利培酮组起效时间迟于托吡酯组，但不良反应轻，依从性好。结论：利培酮对难治性抑郁症有辅助治疗作用。     

托吡酯治疗躁狂症的临床研究

目的为探讨托吡酯治疗躁狂症的疗效及安全性。方法对符合入组标准的100例躁狂症患者（实际完成94例）单一服用托吡酯治疗,并在入组前和入组后1,2,4周进行血、尿、肝功能检查、心电图、血压、体重的检查及BRMS、CGI、TESS量表评定,疗程最终为4周。结果有效率84.04%,BRMS、CGI-SI评分疗后4周极显著低于治疗前（P〈0.01）,在第2周时BRMS评分显著低于治疗前（P〈0.01）,第2周就有明显的疗效,托吡酯的平均治疗剂量为（268.47±50.96）mg;在副反应方面恶心、呕吐、厌食、静坐不能、口干、视力模糊、便秘、头昏、头痛发生率较高,疗后体重与疗前比较有显著性差异（P〈0.01）,疗后体重明显下降。结论托吡酯安全、有效,有降低体重的作用。     

托吡酯治疗抽动障碍的剂量探讨

以托吡酯(商品名:妥泰)治疗抽动障碍,报告如下。1对象和方法为我院小儿神经专科门诊患者。共73例,男61例,女11例;年龄5~15岁,平均9·5岁;病程1个月~5年;符合美国精神障碍诊断与统计手册第4版抽动障碍诊断标准;除外严重躯体疾病;脑电图有非特异性慢波增多21例。托吡酯开始每日剂     

托吡酯在精神疾病治疗中的应用

本文对托吡酯在双相情感性精神障碍、癫痫伴精神障碍、Tourette综合征、暴食性障碍、氯氮平所致癫痫发作治疗中的应用情况作一介绍。托吡酯具有药物相互作用及副作用相对较少 ,患者对治疗的依从性较高等优点 ,今后若能进一步验证其疗效 ,则有可能为许多精神疾病的治疗提供新的手段。     

托吡酯的药理学作用机制

托吡酯 (Topiramate,商品名为妥泰 Topamax,以下简称TPM)是一种新型广谱的抗癫痫药物 ,它在结构上与其它的抗癫痫药物 (AEDs)不同 ,是一个带有磺胺基团的单糖衍生物 [1 ] 。用最大电休克试验 (MES)筛检发现 TPM的抗癫痫作用与苯妥因和卡马西平相似 ,但疗效更高 ,毒性更小[2 ] 。目前 TPM的许多药理学作用机制是在培养的神经元中发现的 ,它可以影响电压依赖性钠离子及钙离子通路、GABAA受体及谷氨酸受体的海人藻酸受体亚型的活性 ,也可以选择性抑制碳酸酐酶同工酶 CA 、CA 的活性。本文就目前有关TPM的作用机制的最新进展做一综…     

托吡酯治疗癫痫的临床观察

目的:本文观察应用托吡酯(妥泰)治疗癫痫的效果及安全性。方法:57例癫痫病人给予口服托吡酯,观察不同发作类型、年龄、用药方法、病程长短及影像改变与疗效的关系。结果:托吡酯对部分性、全面性发作及婴儿痉挛均有效,不良反应较轻。结论:托吡酯是一广谱、安全、有效的新型抗癫痫药物。     

托吡酯对癫癎大鼠海马神经元凋亡的保护作用

目的探讨托吡酯(TPM)对癫疒间发作大鼠海马神经元凋亡的保护作用。方法给予戊四氮(PTZ)致疒间大鼠TPM 80 mg/(kg.d)(大剂量TPM组)、40 mg/(kg.d)(中剂量TPM组)和生理盐水(对照组)灌胃,共14 d。用原位末端标记(TUNEL)方法标记DNA片段,原位检测大鼠海马CA1和CA3区的凋亡神经元。结果各组大鼠海马CA1、CA3区均出现TUNEL阳性细胞。对照组海马CA1、CA3区TUNEL阳性细胞数分别为(35.83±4.58)个和(36.83±3.87)个;中剂量TPM组分别为(31.52±3.43)个和(32.35±4.69)个;大剂量TPM组分别为(23.50±2.81)个和(25.50±3.72)个。大剂量TPM组与对照组比较差异有非常显著性(均P<0.001),与中剂量TPM组比较差异有显著性(均P<0.05);中剂量TPM组与对照组相比差异无显著性(均P>0.05)。结论大剂量TPM对癫疒间发作后的神经元损伤具有一定的保护作用。     

托吡酯治疗偏头痛临床对照分析

目的探讨托吡酯治疗偏头痛的临床疗效及副反应。方法将符合偏头疼诊断标准的患者分为两组,分别应用托吡酯和氟西汀治疗。用疼痛量表及副反应量表观察疗效及副反应。结果两组患者疼痛量表（Mospm）的评分及副反应量表（Tess）的相对应同一时间的评分无显著性差异（P〈0．05）。结论托吡酯治疗偏头痛与氟西汀治疗偏头痛疗效相当,是治疗偏头痛的有效药物之一。     

托吡酯添加治疗对难治性癫痫的临床观察

目的 观察添加托吡酯（TPM）对难治性癫痫（IE）的临床效果与安全性。方法 观察IE15例,以加用TPM前1个月的发作频率为基准,按规定添加TPM,并与加TPM后稳定期3个月中最后1个月的发作频率进行比较,比观察疗效,同时观察副作用。以测原用抗癫痫药（AED）治疗前后的血浓度,协助观察患者用药的依从性。结果 患者用药依从性好,有效率为42.1％－46.7％。对多型癫痫发作有效。副反应轻至中度,且多为一过性。结论 加用TMP治疗IE是安全有效的选择方法之一。     

Use of low-dose topiramate in substance use disorder and bodyweight control

In recent years topiramate has been used for psychiatric patients, mainly for controlling substance use and food intake. A total of 46 patients who received topiramate treatment during the study period were identified from a computer database. Nineteen had received topiramate for at least 1 month. Twelve patients received topiramate for anticraving effects (alcohol, n = 9; heroin/amphetamine, n = 1; meperidine, n = 1; and nicotine, n = 1). On an average dosage of 112.5 mg/day, nine of the 12 patients (excluding three alcoholic patients) achieved complete or partial remission from the substance use disorders. The present results show that six of the nine patients achieved full or partial remission from alcohol use disorder on a dosage of 100 mg/day. Topiramate was also used to control seven patients' bodyweight (mean bodyweight change, 1.53 kg). Four of them achieved bodyweight loss in the 1-month follow up, with an average change of 2.65 kg. Based on the present findings topiramate <100 mg/day may be effective in treating patient with alcohol use disorder, and that topiramate has not shown remarkable benefit of bodyweight loss.     

Differential effects of topiramate on prefrontal glutamatergic transmission when combined with raclopride or clozapine

Treatment with topiramate may improve negative symptoms in schizophrenia when added to typical antipsychotic drugs (APDs) but not to clozapine. Both dopaminergic and glutamatergic transmissions in the medial prefrontal cortex (mPFC) are facilitated by atypical, but not typical, APDs, which is thought to improve negative symptoms and cognitive dysfunction in schizophrenia. Our previous results show that topiramate increases prefrontal dopamine (DA) outflow when added to the D_2/3 receptorantagonist raclopride. Here, using intracellular recording in vitro, we investigated the effects of topiramate on glutamatergic neurotransmission in the rat mPFC, both when given alone and in combination with raclopride or clozapine. Neither topiramate nor raclopride alone had any effect on N‐methyl‐D ‐aspartate (NMDA)‐induced currents in pyramidal cells of the mPFC. However, the combination of topiramate and raclopride facilitated the NMDA‐induced currents, and this effect was blocked by the D₁ receptor antagonist SCH23390. Topiramate also facilitated the effect of a submaximal, but inhibited the effect of a maximal, concentration of clozapine on these currents. The effect of combined topiramate and a submaximal concentration of clozapine could be blocked by SCH23390. In addition, combined topiramate and raclopride facilitated excitatory postsynaptic potentials. In contrast, topiramate inhibited clozapine's facilitating effect on these potentials. These data may help explain the improvement of negative symptoms when topiramate is used as adjunctive therapy in schizophrenic patients receiving typical APDs, but they may also shed light on the observed deterioration of symptoms when topiramate is added to full dose clozapine. Synapse 63:913–920, 2009. © 2009 Wiley‐Liss, Inc.     

Profiles associated with treatment retention in Japanese patients with methamphetamine use disorder: preliminary survey

Aims: To identify profiles associated with treatment retention in Japanese patients with methamphetamine use disorder. Methods: The study used a retrospective design based on clinical records. The subjects were 101 patients at the Kanagawa Psychiatric Center, Serigaya Hospital, who were diagnosed as having methamphetamine use disorder. They were divided in two groups, namely those who remained in treatment 3 months after the initial assessment, and those who did not. The primary analysis compared patient profiles between the two groups to detect discriminating variables, which were then submitted for secondary analysis using logistic regression to determine the most relevant predictor of retention. Results: Primary analysis indicated that older age, having psychotic symptoms, receiving public assistance, and history of incarceration were associated with treatment retention after 3 months. Secondary analysis showed that positive history of incarceration was the most significant predictor of the outcome. Conclusions: History of incarceration had the most significant treatment‐retention effect on Japanese patients with methamphetamine use disorder. The development and introduction of integrated programs that link methamphetamine‐dependent offenders to drug treatment is recommended in outpatient treatment for Japanese patients with methamphetamine user disorder.     

The effect of methamphetamine on the release of glutamate from striatal slices

Summary One postulated role of dopamine in the striatum is to reduce neuronal activity in cortico-striatal glutamergic terminals. We investigated the effects of methamphetamine, which displaces dopamine, on glutamate release from rat striatal slices. Methamphetamine significantly reduced K⁺-stimulated (45 mM) glutamate release. In slices prepared from rats treated 8 days previously with methamphetamine there was enhanced (approximately 200%) release of glutamate. This study demonstrates that dopamine has a modulatory effect on glutamate release in the striatum.     

Effect of low doses of methamphetamine on rat limbic‐related neurotensin systems

Administration of methamphetamine (METH) alters limbic‐related (LR) neurotensin (NT) systems. Thus, through a D1‐receptor mechanism, noncontingent high doses (5–15 mg kg^?1), and likely self‐administration, of METH appears to reduce NT release causing its accumulation and an elevation of NT‐like immunoreactivity (NTLI) in limbic‐related NT pathways. For comparison, we tested the effect of low doses of METH, that are more like those used in therapy, on NTLI in the core and shell of the nucleus accumbens (NAc and NAs), prefrontal cortex (PFC), ventral tegmental area (VTA), the lateral habenula (Hb) and basolateral amygdala (Amyg). METH at the dose of 0.25 mg kg^?1 in particular, but not 1.00 mg kg^?1, decreased NTLI concentration in all of the LR structures studied, except for the prefrontal cortex; however, these effects were rapid and brief being observed at 5 h but not at 24 h after treatment. In all of the LR areas where NTLI levels were reduced after the low dose of METH, the effect was blocked by pretreatment with either a D1 or a D2 antagonist. Thus, opposite to high doses like those associated with abuse, the therapeutic‐like low‐dose METH treatment induced reduction in NT tissue levels likely reflected an increase in NT release and a short‐term depletion of the levels of this neuropeptide in LR structures, manifesting features comparable to the response of basal ganglia NT systems to similar low doses of METH. Synapse 69:396–404, 2015 . © 2015 Wiley Periodicals, Inc.     

The effect of methamphetamine on histamine release in the rat hypothalamus

Abstract In the present study, the effect of methamphetamine (MAP) on histamine (HA) release measured by in vivo brain microdialysis in the rat hypothalamus was investigated. Administration of MAP (3 mg/kg) significantly increase HA release from 40 to 160 min after the injection. This finding suggests that a moderate dose of MAP activates the hypothalamic HA neuron system, which may be related to effects of MAP on intrinsic biological rhythms.     

Studies on the mechanism of tolerance to methamphetamine

We have reported that the ability of high doses of methamphetamine to impair dopamine and serotonin synthesis in the rat brain is attenuated when animals are pretreated with gradually increasing doses of methamphetamine. To examine the mechanism of this tolerance phenomenon, the effect of methamphetamine on several neurochemical parameters was determined in naive and methamphetamine-pretreated rats. The elevation of nigral substance P concentrations by methamphetamine was attenuated in pretreated compared to naive rats. The methamphetamine-induced reduction in [3H]sulpiride binding in the rat neostriatum and nucleus accumbens was similarly attenuated in animals pretreated with methamphetamine. Determination of brain concentrations of methamphetamine and amphetamine revealed significantly lower concentrations of both compounds in the brains of pretreated compared to naive animals. The results indicate a reduction in the ability of methamphetamine to increase dopamine transmission in the brains of methamphetamine-pretreated rats. Furthermore, this effect appears to be due, at least in part, to a change in the disposition of methamphetamine in pretreated animals.     

妥泰与癫痫儿童轻度代谢性酸中毒

目的:观察妥泰治疗儿童癫痫时其体内酸碱平衡的变化。方法:56例分成三组:(1)A组10例(未服药);(2)B组32例(单独服用妥泰);(3)C组14例(妥泰与其他抗癫痫药CBZ、VPA、NZP等联合应用)。观察指标:血气电解质分析(pH,Pco2HCO3-,BE,K+,Ca2+,Cl-,AG)。结果:与A组比较,B组和C组的癫痫患儿血浆HCO3-(mmol/L)分别降低22%(P<0.01)和16%(P<0.01)。BE值(mmol/L)分别降低225%(P<0.01)和154%(P<0.01)。但B组和C组之间上述指标比较,无显著性差异。各组的pH、Pco2和AG相比较,均无显著性差异。B、C两组血CI(mmol/L)均高于A组,差异有显著意义(P<0.01)。结论:妥泰可导致癫痫患儿代偿性AG正常型高氯性代谢性酸中毒(98%为轻度酸中毒)。     

Management of atypical antipsychotic-induced weight gain in schizophrenic patients with topiramate

Patients treated with atypical antipsychotic drugs commonly gain excess weight. Because obesity is associated with considerable morbidity and decreased life expectancy, treatment of weight gain in these patients is critical. Topiramate, a fairly new anticonvulsant, promotes bodyweight loss in healthy obese subjects, patients with bipolar disorder, and patients with eating disorder. However, there are very few reports about the efficacy of topiramate for weight management in schizophrenic patients. We present the cases of three Taiwanese patients with schizophrenia whose bodyweight increased as a result of atypical antipsychotics treatment, then was controlled by topiramate without aggravation of their psychotic symptoms.