丙戊酸镁与碳酸锂治疗躁狂症的对照性研究

３０例躁狂症病人随机分为丙戊酸镁与碳酸锂两个组，进行为期４周的治疗，使用Ｂｅｃｈ－Ｒａｆａｅｌｓｏｎ躁狂量表和１９８１年中华医学会神经精神科分会制定的５级疗效标准进行疗效评定，两组ＢＲＭＳ评分在治疗前后均有显著差异，丙戊酸镁的显效率为６４．２９％，碳酸锂为６８．７５％。两组间疗效无显著性差异。     

丙戊酸镁与碳酸锂及安慰剂治疗躁狂症双盲对照研究

本研究用国产丙戊酸镁与碳酸锂及安慰剂治疗躁狂症,通过随机双盲对照,结果显示,丙戊酸镁组显效率92.3%。碳酸锂组显效率80%,安慰剂组显效率16.67%。丙戊酸镁组除2例有头晕及轻度共济失调外,无其它严重副作用,可以认为丙戊酸镁是一种安全有效的抗躁狂药物。     

丙戊酸镁与碳酸锂对躁狂症预防治疗的对照研究

目的　评价丙戊酸镁预防治疗躁狂症的疗效和副反应。方法　１１５ 例躁狂症患者出院时按原服用丙戊酸镁或碳酸锂自然分为丙戊酸镁组（４６ 例） 和碳酸锂组（６９ 例） ,进行预防治疗研究。使用 Ｂ Ｒ Ｍ Ｓ、 Ｔ Ｅ Ｓ Ｓ 帮助评定疗效和副反应。结果　平均随访３６ 个月,丙戊酸镁组有效率８６９５ ％ ,副反应发生率４５６５ ％ ;碳酸锂组有效率８４０６ ％ ,副反应发生率４４９２ ％ ,经 Ｒｉｄｉｔ 分析２ 组比较无显著性差异。丙戊酸镁对碳酸锂预防治疗无效的病例依然有效。结论　丙戊酸镁可作为预防治疗躁狂症的选用药物。     

丙戊酸镁治疗躁狂症的对照研究

丙戊酸镁治疗躁狂症的对照研究余国汉，黄雄，单飞豹，蒋铁平丙戊酸镁原为一种抗癫痛药物。近年来，国内外不少报告认为它是一种新型的抗躁狂药物。为了进一步探讨其对躁狂症的疗效，本研究设计了丙戊酸镁与碳酸及治疗躁狂症的对照研究，报告如下：资料１．入组标准：（１...     

丙戊酸镁联用氯硝西泮治疗躁狂症对照研究

目的：探讨丙戊酸镁联用氯硝西泮治疗躁狂症的疗效与安全性。方法：对符合中国精神疾病分类方案与诊断标准第2版修订本62例躁狂症患者，其中40例用丙戊酸镁联用氯硝西泮，22例用碳酸锂治疗。疗程6周。以躁狂量表(BRMS)评定疗效，副反应量表(TESS)评定不良反应。结果：两组疗效差异无显著性。联用组不良反应明显低于对照组。结论：丙戊酸镁联用氯硝西泮治疗躁狂症．疗效确切，起效时间与安全性优于碳酸锂。     

丙戊酸镁与碳酸锂治疗躁狂症的对照研究

探讨丙戊酸镁治疗躁狂症的疗效及副反应。方法 用丙戊酸镁与碳酸锂对照治疗躁狂症１１８例。采用躁狂量表，临床疗效总评量表及副反应量表评定疗效及副反应。结果 两组疗效近似，治疗后ＢＲＭＳ总分减分率及各因子分明显低于疗前。丙戊酸镁的副反应以口干，恶心，心动过速为主，与碳酸锂近似，镇静作用较碳酸锂弱。结论丙戊酸镁对躁狂症有较好的疗效。     

丙戊酸镁缓释剂合并帕罗西汀治疗难治性抑郁症对照研究

目的：观察丙戊酸镁合并帕罗西汀治疗难治性抑郁症组的疗效及安全性。方法：将50例难治性抑郁症患者随机分为合用组（丙戊酸镁缓释剂合并帕罗西汀）25例和单用组（帕罗西汀组）25例。疗程6周。分别评定汉密尔顿抑郁量表（HAMD）和治疗中出现的症状量表（TESS）。结果：合用组HAMD量表分于治疗3周显著下降,单用组HAMD分于治疗4周显著下降,合用组有效率显著高于单用组35％（P〈0．05）。结论：丙戊酸镁缓释剂合并帕罗西汀治疗难治性抑郁疗效确切。     

丙戊酸镁与碳酸锂治疗躁狂发作对照研究的循证医学评价

目的评价丙戊酸镁与碳酸锂治疗躁狂症的疗效与安全性。方法应用循证医学方法对符合标准的17项研究进行分析,评价丙戊酸镁与碳酸锂治疗躁狂症的有效率、症状学变化以及副作用的差异。结果丙戊酸镁与碳酸锂治疗躁狂症的疗效相似（287／491VS274／465,OR=0．99,95％CI：0．76～1．29,Z=0．10,P〉0．05）,但是丙戊酸镁比碳酸锂治疗躁狂症起效快,在第一周末（WMD：-1．73,95％CI：-2．75--0．70,Z=3．30,P〈0．001）和第二周末（WMD：-0．88,95％CI：-1.46--0．30,Z=2．98,P〈0．001）,丙戊酸镁比碳酸锂改善症状学明显（WMD：11．08,95％CI：-1．59--0．58,Z=4．22,P〈0．0001）。而且无论是副作用出现的频率（118／431vs162／375,OR=0．55,95％CI：0．40-0．76,Z=3．66,P〈0．001）还是严重程度（WMD：-1．33,95％CI：-1．86--0．81,Z=4．96,P〈0．001）,丙戊酸镁均比碳酸锂轻。结论丙戊酸镁与碳酸锂治疗躁狂症的疗效相似,但丙戊酸镁起效快、副作用更少。     

丙戊酸钠与碳酸锂治疗躁狂症的对照研究

丙戊酸钠与碳酸锂治疗躁狂症的对照研究孙建中，张桂云，宁南义，王天样锂盐是标准的治疗躁狂症的药物，但约有１５～３０％的病人治疗失败，对混合型和快速循环型疗效不甚理想［１］，国外有报道丙戌酸钠可用于治疗躁狂症，对碳酸锂反应差的病人也能收效［３］，所以我们...     

丙戊酸镁富马酸奎硫平及高压氧联合治疗急性脑梗死后躁狂症临床疗效观察

目的探讨丙戊酸镁、富马酸奎硫平及高压氧联合治疗急性脑梗死后躁狂症的临床效果。方法选择52例急性脑梗死后躁狂症患者,其中26例行丙戊酸镁、富马酸奎硫平及高压氧联合治疗,设为联合治疗组,26例单用丙戊酸镁口服治疗设为对照组;2组均治疗2周。结果治疗后联合治疗组BRMS评分与对照组比较,差异有统计学意义(P0.05);2组TESS评分比较,差异有统计学意义(P0.05)。结论丙戊酸镁、富马酸奎硫平联合高压氧治疗急性脑梗死后躁狂症比单用丙戊酸镁疗效满意,值得临床推广应用。     

Linear relationship of valproate serum concentration to response and optimal serum levels for acute mania

OBJECTIVE: Several studies have shown that achieving adequate serum valproate levels is critical to rapid stabilization of acute mania, but estimates of the target therapeutic level have been imprecise. A post hoc analysis of pooled intent-to-treat data from three randomized, placebo-controlled studies of divalproex treatment for acute mania was performed to test a hypothesized linear relationship between serum concentration and response and to determine optimal blood levels for treatment of acute mania. METHOD: Subjects (N=374) were stratified into seven groups (six valproate serum level ranges and placebo), and effect size was determined for each. Linearity of dose response was tested with both parametric and nonparametric techniques. ANOVA was used to compare the response at each serum level range with that of placebo as well as the lowest valproate level (< =55.0 microg/ml). The mean serum valproate level was then determined for all subjects with an effect size greater than or equal to the maximal effect derived from linear modeling. RESULTS: The fit of blood level and response to a linear model was good. Efficacy was significantly greater than placebo beginning at the 71.4-85.0 microg/ml range and for all higher valproate levels; the 94.1-107.0 and >107.0 microg/ml groups were superior to the lowest valproate serum level group. The effect size associated with highest serum levels (>94 microg/ml) was 1.06 (0.59 after placebo correction). Subjects obtaining this effect or greater (N=84) had a mean serum level of 87.5 microg/ml. Blood levels in the lowest effective range were 60% more effective than placebo and in the higher ranges were 120% more effective. Tolerability appeared similar for all groups. CONCLUSIONS: The results of this study suggest that there is a linear relationship between valproate serum concentration and response and that the target blood level of valproate for best response in acute mania is above 94 microg/ml.     

Spectrum of effectiveness of valproate in neuropsychiatry

Valproate is principally effective in manic aspects of bipolar disorder. Tolerability has been somewhat more favorable for valproate than comparators, with the frequent adverse effects being gastrointestinal disturbances and weight gain. Total cholesterol and low-density lipoproteins are reduced by valproate. Valproate is effective and well tolerated when combined with lithium or antipsychotic drugs. Valproate is efficacious in mixed and euphoric mania. In studies of maintenance versus placebo and active comparators, patients initially treated with divalproex for mania had more robust long-term benefits than in the full sample analyses. In maintenance treatment, patients whose valproate serum levels were between 75 and 99 microg/ml had longer time to discontinuation for any reason or a new mood episode than did patients receiving placebo. The profile of utility in bipolar disorders is principally for core features of manic symptomatology (e.g., impulsivity, hyperactivity and irritability), with little evidence of benefit for anxiety or psychosis. Valproate appears useful in other disorders that have behavioral dimensions inclusive of the domains that valproate benefits in bipolar disorders, such as schizophrenia.     

Folic acid efficacy as an alternative drug added to sodium valproate in the treatment of acute phase of mania in bipolar disorder: a double‐blind randomized controlled trial

Objective: The purpose of this study was to evaluate the efficacy of adding folic acid to sodium valproate in the acute phase of mania. Method: Following a double‐blind randomized controlled trial, 88 clinically manic patients with diagnosis of type I bipolar disorder (BID) were divided randomly into two groups (case and control). The case group was treated with folic acid and sodium valproate and the control group with sodium valproate and placebo. The severity of mania was assessed using the Young Mania Rating Scale (YMRS) at the beginning and end of the first, second and third weeks of the study. Results: The case group’s mean manic YMRS measurements (SD) before the initiation of therapy and in the first, second and third weeks of treatment were 34.0 ± 7.7, 26.7 ± 2.1, 18.1 ± 2.1 and 7.1 ± 0.9 respectively. The control group’s measurements were 34.7 ± 3.8, 27.3 ± 2.3, 20.7 ± 2.5 and 10.1 ± 1.1. There was a statistically significant difference in YMRS scaling results between the case and control groups after 3 weeks of treatment (7.1 ± 0.9 vs. 10.1 ± 1.1, P = 0.005). Conclusion: Based on our findings, folic acid seems to be an effective adjuvant to sodium valproate in the treatment of the acute phase of mania in patients with bipolar disorder.     

丙戊酸镁缓释片合并喹硫平治疗反复躁狂发作的长期疗效及安全性

目的探讨丙戊酸镁合并喹硫平治疗反复躁狂发作的长期疗效及安全性．方法将66例各类情感障碍躁狂发作患者分为丙戊酸镁组和丙戊酸镁合并喹硫平组（下称合并治疗组）,每组各33例。急性期治疗6周后随访5年。基线及疗效采用倍克-拉范森躁狂量表（BRMS）评定。随访内容包括复发次数,药物剂量,长期疗效及安全性。结果急性期治疗后BRMS减分率丙戊酸镁组为（42±27）％,合并治疗组为（57±24）％,两组间的差异有统计学意义（P〈0．05）。5年内躁狂复发次数丙戊酸镁组为（3．3±2．0）次,合并治疗组为（1．9±1．6）次,两组间的差异有统计学意义（P〈0．01）;抑郁复发次数丙戊酸镁组为（1．8±2．0）次,合并治疗组为（1．9±1．8）次,两组间的差异无统计学意义（P〉0．05）。合并治疗组的丙戊酸镁剂量明显低于单用丙戊酸镁组（P〈0．01）。两组总体不良反应的差异无统计学意义。结论丙戊酸镁合并喹硫平维持治疗情感障碍可减少躁狂复发率,且安全性较高。     

碳酸锂联合丙戊酸钠和利培酮治疗急性躁狂发作的对照研究

目的探讨碳酸锂分别联合丙戊酸钠和利培酮治疗急性躁狂发作的疗效和安全性。方法将94例急性躁狂发作患者随机分为两组,碳酸锂联合丙戊酸钠47例,碳酸锂联合利培酮47例,疗程均为8周。分别于治疗前及治疗后的第2、4、8周,采用躁狂量表（BRMS）评定临床疗效,治疗时出现的症状量表（TESS）评定安全性。结果碳酸锂分别联合戊酸钠和利培酮治疗急性躁狂发作的疗效相当（P〉0.05）,但前者起效快、不良反应少（P〈0.05）。结论碳酸锂联合丙戊酸钠治疗急性躁狂发作起效快、疗效显著、不良反应少,安全性高。     

Efficacy of lithium vs. valproate in the treatment of mania in the elderly: a retrospective study

BACKGROUND: This retrospective study was conducted to assess the efficacy of lithium and valproate and associated serum levels in the treatment of mania in elderly patients. METHOD: Records of 59 patients aged 55 years and older with minimal or no neurologic impairment, hospitalized for mania, and discharged on lithium (N = 30) or valproate (N = 29) therapy were reviewed. Data on mood stabilizer choice, serum levels, and type of mania were recorded. A clinician blinded to medications rated improvement in each case with Clinical Global Impressions (CGI) scores based on abstracted notes. RESULTS: Overall, the percentage of patients improved was significantly greater in the lithium group than in the valproate group (67% vs. 38%, chi2 = 4.88, p = .027). Patients taking lithium with serum levels > or =0.8 mmol/L were more improved at discharge than those outside this range (> or =0.8, CGI 2.0+/-0.6 vs. <0.8, CGI 2.6+/-0.8, t = 2.15, p = .043). Patients taking valproate with serum levels between 65-90 microg/mL were more improved at discharge than those outside this range (65-90, CGI 2.1+/-0.6 vs. <65, >90, CGI 3.3+/-0.8, t = 3.73, p = .002). When response rates among only patients with these "therapeutic" levels were assessed, they were similar for lithium (82%) and valproate (75%). The difference in efficacy between drugs was maintained in classic mania, but the 2 drug groups were similar when only mixed mania was analyzed (lithium 63% vs. valproate 67% improved). CONCLUSION: Results suggest that lithium may be more efficacious than valproate overall, but response rates for the 2 drugs were similar when "therapeutic" serum levels were achieved. For lithium, levels similar to those reported for younger adults were associated with response. For valproate, a "therapeutic window" different from that in younger adults was found. While the retrospective and naturalistic design of this study has limitations, these data may help direct further studies and treatment of mania in the elderly.     

Valproate

Objectives: This article summarizes the role of valproate as a treatment for bipolar disorder and related conditions. Methods: Published studies and reviews were systematically reviewed. Results from randomized, parallel group, double‐blind, placebo‐controlled studies that included an active comparator are emphasized. Results: Valproate is an effective treatment for manic patients. Valproate was superior to placebo in one 1‐year randomized, parallel group study in rate of recurrence requiring discontinuation, rate of depression requiring discontinuation, total early termination and time to 25% of patients relapsing with mania, and in controlling mild depressive symptoms. On some measures, including time to development of a manic episode, valproate did not differ from placebo. Assessments of maintenance efficacy of valproate and other putative prophylactic treatments for bipolar disorder are problematic, because of the need to analyze multiple indices of efficacy, and practical and ethical issues that limit generalizability of results of placebo‐controlled studies. Valproate has some advantages over lithium in treatment of mania for persons with more severe illnesses. Valproate benefits a broader spectrum of bipolar conditions than lithium. Valproate appears at best modestly effective for bipolar depression. Used in combination with several other treatments, additive benefits result, that are greater than with any of the treatments as monotherapy. Side effects are generally mild and manageable, particularly with divalproex. Weight gain and pharmacokinetic interaction with lamotrigine are perhaps the most consistent problems in use. Valproate contributes to neural tube defects if taken during the first trimester of pregnancy, and this risk must be conveyed to women. Conclusions: Valproate is an effective and useful treatment for bipolar disorder. Studies clarifying its spectrum of efficacy, its safety and efficacy in combination regimens, and its mechanisms of action are warranted.     

Review of olanzapine in the management of bipolar disorders

Olanzapine is an atypical antipsychotic currently with indications for the treatment of schizophrenia, acute mania and the prevention of relapse in bipolar disorder. A growing body of clinical evidence supports these indications. Acute mania trials have demonstrated superior efficacy of olanzapine to placebo, equal or superior efficacy to valproate and superior efficacy in combination therapy with lithium or valproate compared to mood stabilizer monotherapy. Olanzapine demonstrated a modest effect in the treatment of bipolar depression with a substantially enhanced effect in combination with fluoxetine. Maintenance trials showed olanzapine to be more efficacious than placebo in the prevention of manic and depressive relapses and non-inferior to lithium or valproate. Combination of olanzapine with lithium or valproate was also found to be more efficacious than lithium or valproate monotherapy in the prevention of manic relapse in patients with a partial response to monotherapy with lithium or valproate. These trials suggest that olanzapine is a viable option and an invaluable addition to the pharmacological armamentarium in the treatment of bipolar I disorder. However, this can often be mitigated by safety and tolerability concerns with this agent including weight gain and metabolic syndrome that warrants clinician vigilance and discernment that is imperative in today’s clinical practice.     

The manic syndrome: factors which may predict a patient''s response to lithium, carbamazepine and valproate.

Studies suggest that 80% to 90% of all patients in the manic state respond to lithium provided that they are relatively free of dysphoria ("pure mania"). In contrast, less than 40% of individuals in the manic state who cycle rapidly or are substantially dysphoric ("dysphoric mania") respond to lithium. These patients appear to be more responsive to carbamazepine and valproate. The authors conclude that carbamazepine and valproate are the drugs of choice if one desires to treat a rapidly cycling individual or patient with dysphoric mania with just one agent. However, they emphasize that a prospective study designed to identify the predictors of response of primary mania to lithium, carbamazepine and valproate is required. Studies assessing the relative value of lithium, carbamazepine or valproate as prophylactic agents in the care of patients with specific subtypes of mania are also needed. These studies would address the most important issues confronting researchers interested in the drug treatment of mania.     

丙戊酸镁与碳酸锂治疗躁狂发作对照研究国内文献Meta分析

目的探讨丙戊酸镁治疗躁狂发作的疗效和不良反应。方法用Meta分析方法对14项丙戊酸镁与碳酸锂治疗躁狂发作对照研究文献再分析。结果丙戊酸镁治疗躁狂发作其治疗前后组内比较,加权平均效应d=17.50,95%CI为14.54～20.46,效应极强（Z=11.59,P〈0.01）。丙戊酸镁与碳酸锂治疗躁狂发作比较,加权平均效应d=0.50,95%CI为-0.57～1.58,差异无统计学意义（Z=0.92,P〉0.05）。结论丙戊酸镁与碳酸锂治疗躁狂发作的疗效及不良反应相当。