Guidelines for maintenance treatment of bipolar disorder: are there discrepancies between European and North American recommendations?

Practice policies and guidelines for the long-term management of bipolar patients have appeared in many parts of Europe and North America. Although recommendations in most areas do concur remarkable differences are apparent both regarding diagnostic practice and pharmacological management. Differences among recommendations point towards professional and cultural differences between Europe and North America but also towards areas with unresolved research questions and lack of scientific evidence.     

Ultrastructure of astrocytes in the cortex of the hippocampal gyrus and in the neocortex of the temporal lobe in experimental valproate encephalopathy and after valproate withdrawal

The aim of the study was to analyse the astrocyte ultrastructure within the hippocampal gyre cortex and neocortex of the temporal lobe in valproate encephalopathy induced by chronic administration of an anti-epileptic drug - sodium valproate (VPA) to rats for 1, 3, 6, 9 and 12 months, once daily intragastrically, in a dose of 200 mg/kg b.w. and after its withdrawal for 1 and 3 months. Prolonged application of VPA caused damage to protoplasmic astrocytes of the cortex regions examined, mainly in the pyramidal layer, which intensified in the later stages of the experiment, especially after 9 and 12 months. Ultrastructural alterations in astroglia during this experiment did not differ significantly between the hippocampal cortex and neocortex. The most pronounced astroglial abnormalities, concerning about 2/3 of protoplasmic astrocytes after 9 and 12 months, were characterized by considerable swelling of cells, with the presence of empty vacuolar structures in the cytoplasm, a substantial decrease in the number of gliofilaments or even their complete loss, which indicated fibrillopoietic failure of the cell, and the appearance of astrocytes showing phagocytic activity. The astrocytic changes coexisted with distinct damage to neurones and structural elements of the blood-brain barrier. One month after termination of chronic exposure to the drug, the abnormalities did not subside, whereas after 3 months features of distinct normalization could be observed in a considerable number, more than a half, of astrocytes. In valproate encephalopathy, apart from any direct effect of VPA and/or its metabolites on astrocytes, the main cause of the protoplasmic astroglial damage in the cortex of the CNS structures examined could be associated with changes in microcirculation in the cortex (vasogenic factor), leading to its ischaemia.     

Bipolar depression: criteria for treatment selection,definition of refractoriness,and treatment options

Objective:  This paper reviews controlled studies of bipolar depression, outlines criteria for choosing treatment, defines refractoriness in bipolar depression, and provides options for treatment of refractory bipolar depression.
Methods:  Controlled studies that examined the efficacy of treatments for acute and long-term treatment of bipolar depression were located through electronic searches of several databases and by manual crosssearch of references and proceedings of international meetings.
Results:  Lithium comes close to fulfilling the proposed criteria for first-line treatment for bipolar depression, and those not responding to lithium should be considered to have refractory bipolar depression. Options for such patients include addition of lamotrigine or a second mood stabilizer, or a newer-generation antidepressant such as a serotonin re-uptake inhibitor or bupropion, or the atypical antipsychotic olanzapine.
Conclusions:  Although there is a paucity of research in the treatment of refractory bipolar depression, available data could be used for providing rational treatment options for such patients. However, further studies are urgently needed to determine which options are most appropriate for which type of patients .     

Valproate Induces in Vitro Accumulation of Long-Chain Fatty Acylcarnitines

To elucidate the interference mechanisms of valproate (VPA) with mitochondrial fatty acid β-oxidation (FAO), the profile of acylcarnitine formation was studied in vitro. Human fibroblasts were incubated with 0.2 mmol/L [U-¹³C]palmitate, 0.4 mmol/L -carnitine, ± VPA (2 mmol/L) (96 h at 37°C). Acylcarnitines (AC) were analyzed by GC-CI-MS. VPA induced an impaired production of acetylcarnitine (C2) and an increase on long-chain AC (C10 to C16) both in control and in FAO-deficient cell lines (VLCAD, LCHAD, MTP).     

托吡酯与丙戊酸钠对婴幼儿癫痫体重及相关代谢指标的影响

[目的]观察托吡酯(topiramate,TPM)与丙戊酸钠(sodium valproate,VPA)对婴幼儿癫痫患者体重及相关代谢指标的影响.[方法]选择首次单独服用TPM、VPA的婴幼儿癫痫患者各30例为治疗组,同期健康体检婴幼儿20例为对照组.治疗组在治疗前及治疗后3个月、对照组在首次体检时及3个月后分别测定体重、甘油三酯(triglycer-ide,TG)、总胆固醇(total cholesterol,TC)、早晨空腹血糖、胰岛素、瘦素水平.[结果]TPM组治疗3个月后患儿体重增长较缓慢,血清TG、TC、胰岛素、瘦素均较对照组明显下降(P＜0.05),早晨空腹血糖值两组间差异无显著性(P＞0.05).VPA组治疗3个月后患儿体重增长加速,血清TG、TC、胰岛素、瘦素均较对照组明显增加(P＜0.05),早晨空腹血糖值两组间差异无显著性(P＞0.05).[结论] TPM可使婴幼儿体重增长缓慢,并降低TG、TC、胰岛素、瘦素水平;VPA可使婴幼儿体重增长加速,并升高TG、TC、胰岛素、瘦素水平;TPM、VPA对血糖无明显影响.TPM、VPA对婴幼儿癫痫患者生长发育有一定影响.     

The Prognosis of Photosensitivity

Since 1968, annual EEG recordings during photic stimulation using a standardised technique have been made on photosensitive patients and siblings. In 1983, 72 were aged greater than or equal to 20 years and 14 were aged 16-19 years. Mean duration of follow-up was 9.8 +/- 4.8 years. Seventy-five patients were treated with sodium valproate (VPA), which was withdrawn in 15 but restarted in eight because of return of photosensitivity. Eighty-two patients had seizures at some time; at follow-up 58 were receiving monotherapy with VPA, seven were receiving comedication, and three were taking other drugs. Fifty-four of them were seizure free, as were 10 of the 15 who were not being treated with drugs. Photosensitivity disappeared in 44 of 65 patients at a mean dosage of VPA at 21.5 +/- 6 mg/kg day. In 55 of 86 patients photosensitivity was no longer present at follow-up; in 18, slight abnormality was evoked by intermittent photic stimulation, and in 13, photoconvulsive responses were still present. Eighteen patients were not receiving drugs, 10 of them being no longer photosensitive at the mean age of 24.5 +/- 4.9 years. Thirty-one treated and untreated patients were still photosensitive at age 21.5 +/- 3.4 years. Photosensitivity disappeared earlier in those treated with VPA than in the untreated. Spontaneous remission in the treated cases may have occurred at 22.9 +/- 2.5 years of age. Photosensitivity appears around puberty and may disappear around 24 years of age. Photosensitive epilepsy is easily and rapidly controlled by VPA.     

托吡酯和丙戊酸钠预防小儿偏头痛的对比研究

目的探索托吡酯预防小儿偏头痛发作的有效性、安全性和耐受性。方法采用前瞻性的方法,给予小儿偏头痛患者口服托吡酯25~50mg/d,分早晚两次口服,从第1周12.5 mg/d开始,每周递增12.5mg,最大量至50 mg/d;丙戊酸钠则从200mg/d,分早晚两次口服,必要时增至400 mg/d。观察患者治疗前后头痛发作频率、天数和疼痛程度,同时将托吡酯和丙戊酸钠的上述指标进行对比。结果平均每月发作频率均较前减少,托吡酯组和丙戊酸钠组分别从12.38次减至3.52次和14.33次减至6.48次,2组差别无显著性;平均每月头痛天数均较前减少,分别从12.43d减至3.38d和14.58d减至7.19d,2组差别无显著性。头痛程度均较前减轻,分别从7.52分减轻至2.00分和7.24分减轻至3.19分,2组无显著差别。托吡酯的不良反应为记忆力下降、食欲减退、发热、上呼吸道感染、头痛加重。结论托吡酯和丙戊酸钠均能有效预防偏头痛发作,且二者疗效无显著性差异。     

丙戊酸钠辅助治疗难治性精神分裂症的作用

目的：评价氯氮平合并丙戊酸钠治疗难治性精神分裂症的疗效和安全性。方法：62例难治性精神分裂症患者随机分为合用组和单用组，分别给予氯氮平合并丙戊酸钠和氯氮平治疗，疗程12周。采用阳性与阴性症状量表（PANSS）及治疗中出现的症状量表（TESS）评定疗效和不良反应结果：单用组显效率为16．7％，有效率为50．0％；合用组显效率43．3％，有效率73．3％，以合用组疗效显著较好（P〈0．05），两组不良反应差异无显著性（P〉0．05）。结论：氯氮平合用丙戊酸钠治疗难治性精神分裂症疗效优于单用氯氮平，不良反应少。