心境稳定剂联合新型抗精神病药物在双相障碍中的应用

众多研究显示双相障碍的治疗趋向采用心境稳定剂（锂盐和丙戊酸钠）联合新型抗精神病药物（利培酮、奥氯平、喹硫平、齐拉西酮）治疗．可增加疗效且不良反应无明显增加。本文就心境稳定剂联合新型抗精神病药物治疗双相障碍的疗效及不良反应作一综述。     

2006年我国十省市双相障碍患者药物使用的横断面调查

目的 调查2006年我国10省市双相障碍患者药物治疗现况.方法 根据经济发展水平,按照方便取样原则,在我国10省市41所精神疾病专科医院或综合医院精神科,选择760例年龄16～65岁,符合国际疾病分类第10版精神和行为障碍分类双相情感障碍诊断标准,接受精神药物治疗的双相障碍门诊和住院患者,于2006年5月22-28日使用自制修订的调查问卷调查双相障碍患者药物治疗的处方方式.结果 (1)760例患者中,门诊患者为329例(43.3％);住院患者为431例(56.7％);男436例(57.4％),女318例(41.8％),缺失6例(0.8％)数据.(2) ＞2/3的患者表现为情感高涨(481例,63.3％)、活动增多(513例,67.5％)及思维奔逸(436例,57.4％),162例(21.3％)患者以抑郁表现为主,60例(7.9％)患者伴有精神病性症状,48例(6.3％)患者有自杀观念或行为.住院患者处于急性治疗期、伴精神病性症状的患者比例显著高于门诊患者,并且功能损害更严重.(3)671例(88.3％)患者接受心境稳定剂治疗,主要是碳酸锂和丙戊酸盐;593例(78.0％)患者接受了抗精神病药治疗,按照使用频率高低前5种药物分别是:氯氮平、利培酮、氯丙嗪、奎硫平和氟哌啶醇;142例(18.7％)患者接受了抗抑郁药治疗,其中78例(63.4％)选择新型抗抑郁药选择性5-羟色胺再摄取抑制剂.(4)住院患者使用抗精神病药的比例明显高于门诊患者(87.0％vs 66.3％,x2=46.835,P=0.000),门诊患者接受抗抑郁药治疗的比例显著高于住院患者(22.5％ vs 15.8％,x2=5.538,P=0.019).(5)606例(79.8％)的患者联合2种或3种药物治疗,主要治疗方案是心境稳定剂联合抗精神病药,双相抑郁发作以心境稳定剂联合抗抑郁药治疗为主.(6)患者对治疗药物(抗精神病药、心境稳定剂或抗抑郁药)的选择受不同临床症状的影响(P＜0.05).结论 临床实践中,双相障碍以联合治疗为主,心境稳定剂联合抗精神病药及联合抗抑郁药分别是双相躁狂和双相抑郁患者的主要治疗方案,治疗药物选择主要受患者临床症状的影响.     

10省市双相情感障碍患者药物治疗的现况调查

目的了解国内双相情感障碍患者精神药物的治疗现状。方法按一定的抽样比例，选择10个省市46家专科医院或综合医院精神科同时进行药物处方方式的调查。结果（1）在558例双相情感障碍患者中，躁狂相472例（84．6％），抑郁相86例（15．4％）；555（99．5％）例患者接受精神药物治疗。（2）主要治疗药物为心境稳定剂（80．7％），404例（72．8％）患者使用了抗精神病药。（3）躁狂相患者以心境稳定剂（84．7％）和抗精神病药（81．4％）单一或联合治疗为主，抑郁相患者单一或联合使用抗抑郁药的频率较高（80．2％）。（4）联合两种及其以上药物治疗者占80．2％。（5）145例（26．1％）患者合并使用了苯二氮Zhuo类药。结论国内双相情感障碍药物处方方式与国内外的指南推荐方案基本相符；双相障碍抑郁相抗抑郁药使用频率较高，有待于将来的临床实践论证。     

不同起病年龄双相障碍患者的特征和用药比较

目的:研究不同起病年龄段双相障碍患者的特征和用药情况。方法:利用电子病历系统，收集住院双相障碍患者的人口学资料、临床资料和用药情况，将患者按起病年龄分为早发型、中间型和晚发型，比较3组的人口学特征、临床特征和用药差异。结果:共纳入双相障碍患者8 184例，其中早发型1 575例(19.24%),中间型5 383例(65.77%),晚发型1 226例(14.98%)。早发型年龄更小，男性和未婚比例更高，病程和住院时间更长，混合状态的比例更高(P<0.05)。早发型使用两种心境稳定剂联合抗精神病药的比例较高，药物组合以锂盐+丙戊酸盐+喹硫平/奥氮平为主(P<0.05)。晚发型使用1种心境稳定剂联合抗精神病药的比例较高，药物组合以丙戊酸盐+喹硫平/奥氮平为主(P<0.05)。晚发型联用抗抑郁药的比例较高(P<0.05)。结论:不同年龄起病的双相障碍患者在人口学特征、临床特征和用药上均存在显著差异，双相障碍的起病年龄应引起重视。     

双相障碍患者代谢综合征风险研究

目的 调查双相障碍患者长期治疗中代谢综合征的风险发生率及分析可能的相关因素.方法 采用横断面研究.以单用心境稳定剂或联用抗精神病药连续6月以上的门诊双相障碍患者为调查对象.采用统一问卷及实验室检测.代谢综合征诊断标准采用2004年中华医学会糖尿病分会代谢综合征标准.结果 共入组128例,双相障碍患者中代谢综合征的发生率为36.7%(47例).药物类别及用药时间与代谢综合征的发病风险有关(回归系数B值分别为-0.614,-0.797;P值分别为0.028,0.001).结论 与普通人群相比,双相障碍患者有较高的代谢综合征发病风险.用药时间越长代谢综合征的发生风险越高.联用抗精神病药能增加代谢综合征的发生率.临床上应注意监测代谢指标及对代谢异常进行干预.     

碳酸锂合并典型和非典型抗精神病药治疗双相障碍躁狂发作的1年随访

目的探讨碳酸锂合并典型和非典型抗精神病药物治疗双相障碍躁狂发作患者1年的疗效及安全性。方法将94例双相障碍躁狂发作患者分为两组,分别给予碳酸锂合并典型抗精神病药物(典型组,43例)和非典型抗精神病药物(非典型组,51例)治疗,随访1年。采用Bech-Rafaelsen躁狂量表(BRMS)、临床大体印象量表(CGI)、副反应量表(TESS)以及药物依从性量表分别于入组前和入组第1、2、4、8、12个月末进行评定,比较两组的疗效及安全性。结果治疗结束时,两组BRMS评分较入组时均显著减低(P<0.01);典型组和非典型组的临床总有效率分别为95.3%和96.1%,差异无统计学意义(P>0.05)。两组的不良反应发生率差异无统计学意义(P>0.05)。非典型组在12个月末依从性优于典型组(P<0.05)。结论碳酸锂合并典型和非典型抗精神病药物治疗双相障碍躁狂发作的疗效相当,但后者依从性更好     

抗精神病药物诱导代谢紊乱机制的研究进展☆

抗精神病药物是治疗精神分裂症的主要临床用药,也用于双相障碍、焦虑障碍等其它精神疾病的治疗。但因其明显的代谢紊乱不良反应而严重影响其依从性及疗效。早在1956年BettieHiles首次报告了第一代抗精神病药氯丙嗪可引起高血糖,但因     

双相障碍的药物治疗

本文以美国2000年版双相障碍药物治疗准则为基础，重点介绍锂盐与抗癫痫药物、非典型抗精神病药物、以及新的心境稳定剂等在双相障碍中的应用。     

典型和非典型抗精神病药合并碳酸锂治疗双相情感障碍躁狂发作的对照研究

目的探讨典型和非典型抗精神病药物合并碳酸锂治疗双相情感障碍躁狂发作患者的疗效。方法将94例双相情感障碍躁狂发作患者分为典型抗精神病药物组（43例）和非典型抗精神病药物组（51例），进行为期8周的疗效比较。采用Bech-Rafaelsen躁狂量表（BRMS）、临床大体印象量表（CGI）、副反应量表（TESS）以及药物依从性量表分别于入组前和入组第1、2、4、6和8周末时进行评定。结果治疗结束时，两组BRMS评分较入组时均显著减低（P〈0．01）；临床总有效率：典型抗精神病药物组83．7％，非典型抗精神病药物组82．3％；两组疗效差异无显著性。非典型药物组的不良反应较典型组少，药物依从性较典型组高。结论非典型抗精神病药物治疗双相情感障碍躁狂发作的疗效肯定，不良反应较少，安全性高，依从性好，适合临床应用。     

2006年我国十省市抗精神病药处方方式的现况调查

目的 调查2006年我国10省市抗精神病药处方方式;分析4年间我国抗精神病药处方方式的变化趋势.方法 按照作者2002年的调查方法,选择10省市41所精神疾病专科医院或综合医院精神科的5898例精神分裂症门诊和住院患者,于2006年5月22-28日使用自制修订的调查问卷进行精神分裂症处方方式的现况调查.结果 (1)5898例患者中,门诊患者为2716例(46.0%);住院患者为3182例(54.0%);男3041例(51.6%),女2803例(47.5%),缺失54例数据.(2)99.1%的患者接受了抗精神病药治疗,使用频率在前7位的药物依次为:氯氮平(31.7%),利培酮(30.5%),舒必利(14.5%),氯丙嗪(10.8%),奋乃静(9.2%)、喹硫平(7.2%),氟哌啶醇(5.8%).换算为氯丙嗪等效剂量后,住院患者平均药物剂量显著高于门诊患者.(3)72.7%的患者使用第2代抗精神病药治疗;第1代抗精神病药的使用频率为38.3%;6.19%的患者接受了长效药物治疗.(4)75.6%的患者接受了单一非长效抗精神病药治疗;24.4%的患者联合使用2种或2种以上抗精神病药.(5)54.1%的患者联合了抗胆碱能药、苯二氮革类、β-受体阻断剂、抗抑郁药和心境稳定剂,主要用于控制不良反应或增效治疗.结论 第2代抗精神病药已经成为我国治疗精神分裂症的主流药物,反映出精神分裂症治疗理念和治疗技术的进展.     

Patterns of psychotropic drug prescription for U.S. patients with diagnoses of bipolar disorders

OBJECTIVE: Bipolar disorders are prevalent major illnesses with high rates of morbidity, comorbidity, disability, and mortality. A growing number of psychotropic drugs are used to treat bipolar disorder, often off-label and in untested, complex combinations. METHODS: To quantify utilization rates for psychotropic drug classes, this study used the 2002-2003 U.S. national MarketScan research databases to identify 7,760 persons with ICD-9 bipolar disorder subtypes. Survival analysis was used to estimate times until initial monotherapies were augmented, changed, or discontinued. RESULTS: The most commonly prescribed first drug class was antidepressants (50% of patients), followed by mood stabilizers (25%: anticonvulsants, 17%, and lithium, 8%), sedatives (15%), and antipsychotics (11%). At study midpoint only 44% of patients were receiving monotherapy. Those receiving monotherapy were ranked by initial drug prescribed and percentage of patients (bipolar I and bipolar II): antidepressants (55% and 65%), lithium (51% and 41%), antipsychotics (32% and 31%), anticonvulsants (28% and 29%), and sedatives (28%, 25%). Median time to adding another psychotropic was 2.5-times less than median time to changing the initial treatment (16.4 compared with 40.9 weeks), and stopping was rare. Median weeks until therapy was changed in any way for 25% of patients was as follows: lithium, 29 weeks; antidepressants, 13; anticonvulsants, 13; antipsychotics, 13; and sedatives, 9. CONCLUSIONS: Antidepressants were the first-choice agent twice as often as mood stabilizers. Lithium was sustained longer than monotherapy with other mood stabilizers. Time to augmentation was much shorter than time to change or discontinuation.     

Influence of medication choice and comorbid diabetes: the cost of bipolar disorder in a privately insured US population

Background Bipolar disorder is the most expensive mental disorder for US employer health plans. No published studies have examined the impact of comorbid diabetes on the cost of treating bipolar disorder. The objectives of this work were to determine the direct costs incurred by patients with bipolar disorder in a US managed care plan, and to examine the influence (1) of drug therapy regimen on bipolar-related costs, and (2) of diabetes on bipolar-related and all-cause costs. Methods A retrospective analysis of claims in a US private insurance database from January 1, 1999 through December 31, 2002 was performed. The database included at least 4.7 million enrollees each year. Diagnosis codes were used to identify patients with bipolar disorder; patients with diabetes were identified using diagnosis codes and medication use. Results From 1999–2002, treated bipolar disorder was identified in 262 (33.9) [mean (standard deviation)] cases per 100,000 enrollees. Among patients with bipolar disorder in this cohort, between 6.3 and 7.4% were treated for diabetes each year. Among patients with newly treated bipolar disorder, 61.8% received initial therapy with only mood stabilizers, 24.3% received only atypical antipsychotics, and 13.9% received both. Mean all-cause cost for patients with bipolar disorder was US$2,690 in the 6 months before the first bipolar-related claim, and US$6,826 in the following year. Of the latter cost, bipolar-related cost was US$1,272. Patients with comorbid diabetes had much higher all-cause cost (US$11,317) than those without diabetes in the year following the first bipolar-related claim, but only slightly higher bipolar-related cost (US$1,349). Among newly treated bipolar disorder patients, all-cause and bipolar-related cost in the year after diagnosis was lowest in patients receiving only mood stabilizers. Ordinary least squares regression analysis found that treatment with mood stabilizers only was associated with 41% lower bipolar-related cost than treatment with atypical antipsychotics only (P < .001). Significant individual associations were also found between bipolar-related cost and bipolar disorder I diagnosis, severe bipolar disorder and comorbid personality disorders (P < .001 for each) but not comorbid diabetes (P = .27). Conclusions These results suggest that patients with bipolar disorder who receive only mood stabilizer therapy incur lower bipolar-related and all-cause cost than those receiving only atypical antipsychotics. In contrast to that for all-cause cost, comorbid diabetes had little impact on direct costs related to treating bipolar disorder itself.     

Atypical antipsychotics: efficacy across bipolar disorder subpopulations

Atypical antipsychotic medications, used as monotherapy or as adjunctive therapy with mood stabilizers, have shown efficacy and tolerability for 4 subpopulations of patients with bipolar disorder: patients with mixed mania, patients with psychotic episodes, children and adolescents, and the elderly. Patients experiencing mixed mania generally respond poorly to lithium therapy and are more difficult to treat than patients with pure mania. Atypical antipsychotics are increasingly being considered for this bipolar subpopulation because of their efficacy as antimanic agents, and because they are less likely to cause as many or as severe adverse events as conventional antipsychotics. Atypical antipsychotics have also demonstrated beneficial effects as monotherapy and adjunctive therapy for bipolar I disorder patients experiencing psychotic states. In addition, they have shown effectiveness and tolerability in small-scale and open-label trials and case studies with pediatric and geriatric bipolar patients.     

Adjunctive olanzapine treatment in bipolar adolescents responding insufficiently to mood stabilizers

This report was aimed to evaluate the efficacy of olanzapine treatment as an adjunct therapy to mood stabilizers in the treatment of four adolescents responding insufficiently to mood stabilizers. All patients were diagnosed with bipolar I disorder according to DSM IV criteria. YMRS (Young mania rating scale) and CGI (Clinical global impression, improvement and therapeutic effectiveness scales) were used to evaluate overall response of the episode to the drugs. All patients with no adequate response to mood stabilizers did respond to adjunctive olanzapine treatment (10-30 mg/per day). It has been suggested that antipsychotics may be useful as an adjunct to mood stabilisers in bipolar disorder. However, further research is warranted regarding the use of atypical antipsychotics in children and adolescents.     

Atypical antipsychotic augmentation of mood stabilizer therapy in bipolar disorder

Although monotherapy with lithium or divalproex is the recommended initial therapy for bipolar disorder, these agents are associated with prolonged favorable outcomes in only 30% of patients. Increasingly, the medical literature is demonstrating that augmentation of mood stabilizers with atypical antipsychotics is a more effective therapy. This form of combination therapy is recommended as first-line treatment for severe bipolar mania. Recent clinical studies have shown that augmentation therapy with the atypical antipsychotics risperidone, olanzapine, quetiapine, and ziprasidone is effective in long-term maintenance treatment, and preliminary evidence is emerging that use of atypicals with mood stabilizers can help control the depressive phase of bipolar disorder. The atypical antipsychotics also have relatively mild side effect profiles, although augmentation therapy with some antipsychotics and mood stabilizers has been associated with excessive weight gain.     

Comparative efficacy of typical and atypical antipsychotics as add-on therapy to mood stabilizers in the treatment of acute mania.

BACKGROUND: Typical antipsychotics are commonly used in combination with mood stabilizers for acute mania. Although typical antipsychotics are effective, they have undesirable side effects such as induction of depressive symptoms and tardive dyskinesia. Atypical antipsychotics have more favorable side effect profiles, and recent evidence shows their efficacy in treating mania. Apart from a previous small study that compared risperidone with typical neuroleptics as add-on therapy to mood stabilizers, no studies to date have directly compared atypical antipsychotics with typical antipsychotics as add-on therapy to mood stabilizers in a clinically relevant, naturalistic setting. METHOD: This study is a chart review of all patients with DSM-IV-defined bipolar disorder, current episode mania (N = 204), admitted to the University of British Columbia Hospital during a 30-month period. Patients were separated into 3 groups according to the medications used: (1) mood stabilizer and typical antipsychotic, (2) mood stabilizer and atypical antipsychotic, and (3) combination: mood stabilizer plus a typical antipsychotic, then switched to mood stabilizer plus risperidone or olanzapine within I week. The atypical group was further subdivided into risperidone and olanzapine subgroups. Outcome was measured using Clinical Global Impressions-Severity of Illness (CGI-S) and -Improvement (CGI-I) ratings generated by review of clinical information in the chart. RESULTS: Patients treated with typical antipsychotics were more severely ill at admission and at discharge than those treated with atypical antipsychotics. Patients in the atypical (p < .005) and combination (p < .05) groups showed significantly greater clinical improvement at discharge than patients treated with typical antipsychotics. This difference was also significant in the subset of patients with psychotic features (p < .03). Risperidone and olanzapine were associated with fewer extrapyramidal side effects than were typical antipsychotics (risperidone vs. typical antipsychotics, chi2 = 8.72, p < .01; olanzapine vs. typical antipsychotics, chi2 = 16.9, p < .001). CONCLUSION: Due to their superior effectiveness and side effect profile when compared with typical antipsychotics. atypical antipsychotics are an excellent choice as add-on therapy to mood stabilizers for the treatment of patients with mania.     

Toward convergence in the medication treatment of bipolar disorder and schizophrenia

Reaching a correct differential diagnosis among patients with psychotic symptoms was especially important during the era of first-generation antipsychotics, when treatments for the different disorders varied in terms of adverse events and likelihood of response. The historical "overdiagnosis" of schizophrenia and "underdiagnosis" of bipolar disorder in the United States was blamed for an increased exposure to neuroleptics among patients who might have benefited from lithium. With the recognition that second-generation antipsychotics are useful in the treatment of both schizophrenia and bipolar mania, and that combining them with classic mood stabilizers such as valproate may results in increased efficacy, the field is witnessing a convergence of pharmacological approaches to the treatment of schizophrenia and bipolar disorder. Substantially more data is available regarding combination treatments for bipolar disorder than for schizophrenia, and appropriate diagnosis remains important in predicting prognosis, but until the precise pathophysiology of psychotic disorders can be elucidated, and specific targeted treatments crafted, we will continue to see similar blended treatments for these two disease states.     

Obsessive-compulsive-bipolar comorbidity: a systematic exploration of clinical features and treatment outcome

BACKGROUND: Notwithstanding the emerging literature on comorbidity between obsessive-compulsive disorder (OCD) and bipolar disorder, relatively few systematic data exist on the clinical characteristics of this interface and its treatment. The aim of the present study is to address this challenge as it appears in a setting of routine clinical practice. METHOD: The sample comprised 68 patients with comorbid DSM-IV diagnoses of OCD and major depressive episode admitted and treated at the day-hospital in the Department of Psychiatry at the University of Pisa (Pisa, Italy) during a 3-year period (January 1995-December 1998). Thirty-eight patients (55.8%) showed lifetime comorbid bipolar disorder (12 [31.6%] bipolar I and 26 [68.4%] bipolar II). Diagnoses and clinical features were collected by means of structured (Structured Clinical Interview for DSM-IV) and semistructured interviews (OCD-Interview). Assessments of drug treatments, clinical outcome, and adverse effects were made prospectively as part of routine clinical care throughout the course of their day-hospitalization. RESULTS: In contrast with non-bipolar OCD patients, OCD-bipolar patients showed a more episodic course with a greater number of concurrent major depressive episodes. They reported a significantly higher rate of sexual obsessions and significantly lower rate of ordering rituals. Furthermore, they reported more frequent current comorbidity with panic disorder-agoraphobia and abuse of different substances (alcohol, sedatives, nicotine, and coffee). Drug treatment with clomipramine and, to a lesser extent, with selective serotonin reuptake inhibitors was associated with hypomanic switches in OCD-bipolar patients, especially in those not concomitantly treated with mood stabilizers. A combination of multiple mood stabilizers was necessary in 16 OCD-bipolar patients (42.1%) and a combination of mood stabilizers with atypical antipsychotics was required in 4 cases (10.5%). OCD-bipolar patients tended to show a less positive outcome for mood symptomatology and general functioning. Three patients required hospitalization for severe mixed episode. CONCLUSION: In a tertiary care center, comorbidity between OCD and bipolar disorder is a significant clinical problem affecting a large number of patients and has a substantial impact on the clinical characteristics and treatment outcome of both disorders.     

Clinical research on antipsychotics in bipolar disorder

Antipsychotics are commonly used in bipolar disorder, both for acute mania and in maintenance treatment. The authors review available clinical research concerning the use of both conventional and atypical antipsychotics in bipolar disorder and present recommendations for a number of key clinical situations based on this review. They also consider a number of important related questions, including whether there is evidence for an increased risk of tardive dyskinesia (TD) in patients with bipolar disorder, the potential role for antipsychotics in the treatment of bipolar depression, the role of antipsychotics in maintenance treatment of bipolar disorder, the potential for antipsychotics to induce depression in bipolar illness, and whether antipsychotics can be considered mood stabilizers with a place as monotherapy for bipolar mania. They conclude that standard treatment for acute mania should begin with a mood stabilizer, with benzodiazepines used as an adjunct for mild agitation or insomnia and antipsychotics used as an adjunct for highly agitated, psychotic, or severely manic patients. They also conclude that atypical antipsychotics are preferable to conventional antispychotics because of their more favorable side effect profile and reduced risk of tardive dyskinesia. They review the evidence for using atypical antipsychotics as first-line monotherapy for mania and conclude that more evidence concerning the risk of TD and their efficacy as maintenance treatment in bipolar disorder is needed before a conclusion can be made. Should the eventual risk of TD associated with atypical antipsychotics be found to be minimal and their efficacy in maintenance treatment found to be high, they could eventually be considered first line monotherapy for bipolar disorder. They conclude that treatment with an antipsychotic during bipolar depression should be limited to those patients who have psychosis and that atypical antipsychotics are preferred over conventional antipsychotics in this situation, not only because of their reduced risk of side effects but also because theoretically they may have antidepressant efficacy due to their effects on the serotonin system. The clinical research findings summarized in the article are, for the most part, supported by a recently published guideline based on a consensus of clinical experts.