拉莫三嗪与碳酸锂治疗双相抑郁的对照研究

目的:评价拉莫三嗪治疗双相抑郁的疗效和安全性.方法:采用开放,随机,活性药物平行对照设计.入选双相抑郁患者34例,随机分为拉莫三嗪组18例,碳酸锂组16例.分别口服拉莫三嗪50～200mg·d-1,碳酸锂750～1 500 mg·d-1,疗程8周,疗效观察指标包括基线以及治疗终点的17项汉密尔顿抑郁量表(HAMD17)、蒙哥马利抑郁量表(MADRS)、临床总体印象量表(CGI)评分.结果:治疗结束时,两组HAMD17总分与基线相比均明显降低,两组HAMD减分率差异有显著性,分别为24.8%和47.4%;以HAMD17减分率判断的有效率,两组间差异无显著性,分别为33.3%和50%.拉莫三嗪组治疗结束时体重无变化,有2例皮疹报告,其他不良事件两组发生频率相当.结论:拉莫三嗪治疗轻中度的双相抑郁部分有效.安全性较好.     

碳酸锂联合喹硫平治疗双相情感障碍的临床研究

目的 观察碳酸锂联合喹硫平治疗双相情感障碍的临床疗效和安全性.方法 368例双相情感障碍患者随机分为对照组180例和观察组188例.对照组给予碳酸锂和喹硫平安慰剂治疗;观察组给予碳酸锂联合喹硫平治疗,每天2次,两组患者疗程均为8周.治疗1、2、4、8周后,用17项汉密顿抑郁量表(HAMD-17)评分和阳性与阴性症状量表(PANSS)评价两组患者的恢复情况,同时在治疗前和治疗8周后检测患者血液中白细胞介素(IL)-1,IL-10和肿瘤坏死因子-α(TNF-α)浓度并比较.采用药物不良反应量表(TESS)评估药物引起的副作用.结果 两组患者治疗8周后,临床症状明显改善(P<0.05);并且观察组HAMD评分和PANSS评分明显优于对照组(P<0.05).观察组治疗后显效率为73.9%,显著高于对照组的50.5%(P<0.05).两组患者血液中IL-1,IL-10和TNF-α较治疗前均有所改善,且观察组患者改善更加明显(P<0.05).两组不良反应发生率差异无统计学意义(P>0.05).结论 碳酸锂联合喹硫平治疗双相情感障碍临床疗效显著,且不增加不良反应的发生率.     

An update on the treatment of bipolar depression

Background: Although depression accounts for a large part of the burden associated with bipolar disorder, its drug treatment has been under-studied. Objective: To provide the best available evidence supporting the pharmacotherapy of bipolar depression. Methods: A systematic review was conducted, focusing on randomized, controlled trials (RCTs) and meta-analyses. Results/conclusions: Despite FDA approval of both the olanzapine–fluoxetine combination and quetiapine for the treatment of acute bipolar depression, independent RCTs (i.e., not trials conducted ‘under the umbrella’ of a drug company) have not found any drug to have antidepressant effects similar to those seen in unipolar depression. A practice-based suggestion, valuable for both short- and long-term treatment, might be to have a background of mood stabilizers and to add drugs, following one of several treatment options, trusting to find a drug with a degree of effectiveness by trial and error. The list of drugs that could be used would include all the current antidepressants, the olanzapine–fluoxetine combination and probably quetiapine too. Special features and situations might also influence treatment options.     

No association of three GRIN2B polymorphisms with lithium response in bipolar patients

We investigated three polymorphisms in the NMDAreceptor 2B subunit gene (GRIN2B) as a candidate gene for lithium response involved in glutamatergic neurotransmission. One hundred five bipolar patients treated with lithium for at least 5 years were analyzed. The lithium response was assessed as excellent – no affective episodes during lithium treatment; partial – 50% reduction in the episode index; or no response – less than 50% reduction, no change or worsening in the episode index. Genotypes for the -200G/T, 366C/G and rs890G/T GRIN2B polymorphisms were established using the PCR-RFLP method. Genotype distributions were in Hardy-Weinberg equilibrium for all three polymorphisms. No association was found between the three polymorphisms studied and the treatment response to lithium. The authors conclude that polymorphisms of the GRIN2B gene did not show an association with the treatment response to lithium in bipolar patients.     

Clinically relevant treatment considerations regarding lithium use in bipolar disorder

Introduction: The goal of this paper is to provide a practical, clinically oriented review of lithium, a salt widely used to treat mania since the 1870s and formally approved as a mood stabilizer in 1970. Although lithium is still considered a first-line treatment for bipolar mania in most practice guidelines, its use may be overshadowed by newer psychotropic medications.

Areas covered: This paper addresses the historical use of lithium, modern indications for its use, guidelines for prescribing and monitoring continued lithium use, drug-drug interactions, and pharmacodynamics/pharmacokinetic properties. The paper also reviews the unique properties of lithium and their potential clinical importance.

Expert opinion: While the use of lithium does involve some unique risks to the patient, it may also has some unique advantages in certain patient populations. Two major findings that make lithium unique are its potential neuroprotective benefits and decreased risk of suicide in patients with mood disorders.     

Efficacy and safety of fluoxetine monotherapy in bipolar depression: a systematic review

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries with up to 30% of the population affected. Since NAFLD is associated with an increased risk of cardiovascular (CV) disease, these patients should be stratified for CV risk factors, including atherogenic dyslipidemia, and managed accordingly. Lifestyle modifications represent an effective treatment for NAFLD, since most patients are overweight or obese. Also, promising, but not conclusive, results are available for current pharmacologic treatment. Drugs potentially effective against NAFLD include insulin sensitisers as well as fibrates and omega-3 polyunsaturated fatty acids, while there is reluctance to use statins in patients with suspected or established chronic liver disease. Several other therapeutic options are potentially available, and more data are expected from new peroxisome proliferator-activated receptor agonists and incretin-based therapies.     

非典型抗精神病药物治疗双相抑郁

双相抑郁是双相障碍的一种发作形式,临床治疗困难。非典型抗精神病药物具有心境稳定作用,目前主要用于治疗双相躁狂,但对双相抑郁的治疗尚有争议。部分非典型抗精神病药物治疗双相抑郁有效。     

奥氮平和碳酸锂治疗双相障碍躁狂或混合性发作的随机双盲对照试验

目的:比较奥氮平与碳酸锂对双相障碍Ⅰ型躁狂或混合性发作患者的疗效和安全性。方法:60例患者随机给予奥氮平或碳酸锂双盲治疗,奥氮平的日剂量为5～20 mg,碳酸锂的日剂量为600～1800 mg。于基线时、治疗第1,2,3,4周末,分别采用临床总体印象疾病严重度量表一双相障碍版(CGI-s-BP)、Young躁狂量表(YMRS)、简明精神病量表(BPRS)、Montgomery-(?)sberg抑郁量表(MADRS)评定疗效1次。基线和终点时进行血生化、血常规、尿常规以及心电图检查,以评价安全性。结果:无论是试验组还是对照组,治疗4周末CGI-S-BP[(2.2±1.21),(2.3±1.10)]、YMRS[(7.6±10.09),(6.7±6.79)]和BPRS[(3.8±6.53),(3.9±4.92)]得分均较治疗前[(5.4±0.77),(5.1±0.70);(33.5±8.13),(31.6±7.69);(13.5±7.41),(14.5±9.20)]有明显下降,差异非常显著(P<0.01),而两组之间在上述指标方面的差异均无显著性(P>0.05)。试验组和对照组在有效率(85.7%,84.4%)和痊愈率(82.1%,81.3%)方面的差异也无显著性(P>0.05)。两组之间不良事件的总发生率没有显著差异(P>0.05)。奥氮平治疗对心电图无明显影响。结论:奥氮平治疗双相障碍Ⅰ型障碍的疗效同碳酸锂相当,但安全性更高。     

氟西汀联用碳酸锂治疗抑郁症

目的:评价氟西汀联用碳酸锂治疗抑郁症的疗效及安全性。方法:100例符合中国精神疾病诊断分类第3版(CCMD-3)抑郁发作标准的抑郁症病人分为2组,每组各50例,分别给予氟西汀联用碳酸锂治疗(研究组)和单用氟西汀治疗(对照组),疗程均为8 wk。根据汉密尔顿抑郁量表(HAMD)减分率评定疗效,用副反应量表(TESS)评定用药的安全性,在治疗前和治疗后的wk 1,2,4,6,8末分别对2组进行检查评定。对病人随访1 a转躁狂情况。结果:研究组总有效率为94％,对照组总有效率为77％2组间,疗效比较差异有非常显著意义(P＜0．01),不良反应的发生率差异无显著意义(P＞0．05),研究组的转躁率2％低于对照组15％。结论:氟西汀联用碳酸锂治疗抑郁症可增强疗效,起效快,安全性好,转躁率低。     

Aripiprazole for the treatment of bipolar disorder: a review of current evidence

Introduction: Several medications are available for the treatment of different phases of bipolar disorder, yet many of the drugs that are currently approved carry a substantial burden of side effects or do not lead all treated patients to remission.

Areas covered: This paper comprises a review and commentary regarding the use of oral and intramuscular aripiprazole in the acute and maintenance phases of bipolar disorder. Basic principles in dosing, switching, management of side effects and co-administration of aripiprazole with other medications are provided. This paper presents practical strategies to translate the data from clinical research into clinical practice.

Expert opinion: Aripiprazole has proven to be an effective medication for the acute treatment of manic and mixed episodes, as well as for the prophylactic–maintenance phase of bipolar disorder in patients recovering from a manic/mixed episode. Choosing the appropriate dosing and tapering strategy, addressing the side effects, controlling withdrawal symptoms from previous medications and using adjunctive medications when necessary are key to successful treatment with aripiprazole.     

The association study of three FYN polymorphisms with prophylactic lithium response in bipolar patients

FYN belongs to the protein kinase family that phosphorylates NMDA receptor subunits, participating in the regulation of ion transmission and BDNF/TrkB signal transduction pathway. Lithium inhibits glutamatergic transmission via NMDA receptors, exerting neuroprotective effect against excitotoxicity. The aim of this study was to find possible association of three polymorphisms of FYN gene with prophylactic lithium response in the group of bipolar patients. We analyzed 101 bipolar patients treated with lithium carbonate for 5–27 years (mean 15 years). Twenty‐four patients were identified as excellent lithium responders (ER), 51 patients as partial responders (PRs), and 26 patients were non‐responders. Genotypes of the three analyzed polymorphisms were established by PCR‐RFLP. Statistical analysis was done with Statistica. No significant differences in genotype distribution and allele frequencies were observed between T/G and A/G FYN polymorphisms and lithium response. We observed a trend toward association of TT genotype and T allele of T/C polymorphism with worse lithium response. The results of the study demonstrated only marginal association between FYN polymorphisms and prophylactic lithium response in bipolar patients. The results are discussed in light of our previous studies on FYN gene in bipolar illness and BDNF gene in lithium response. Copyright © 2009 John Wiley & Sons, Ltd.     

抗抑郁药物在双相情感障碍治疗中的应用

抗抑郁药物在双相情感障碍中的应用备受关注。抗抑郁药物治疗双相抑郁急性期疗效较为肯定,但有转躁等问题;长期治疗的预防效果尚有待进一步研究。本文从循证医学角度,综述抗抑郁药物在双相情感障碍(主要是双相抑郁)急性期和维持期治疗中的疗效以及转躁情况,阐述双相情感障碍治疗中抗抑郁药物合理使用的重要性和必要性。     

The argument of antidepressant drugs in the treatment of bipolar depression: mixed evidence or mixed states?

Introduction: The role of antidepressant drugs in acute and maintenance treatment of bipolar depression is a matter of debate that cannot be decided from the evidence available in the current literature.

Areas covered: This review includes two sections: in the first, important contributions from the current literature, emphasizing randomized controlled trials (RCTs) and meta-analysis, highlight current controversies and methodological issues; in the second, the impact of mixed depressive features in bipolar depression is evaluated from a psychopathological perspective.

Expert opinion: Methodological issues may complicate evaluation of the evidence from RCTs regarding antidepressants and mixed states. Moreover, nosological constructs may also contribute to the inconclusive findings, by introducing heterogeneity in patient selection and diagnosis. Acknowledging the impact of mixed features in the course of bipolar depression, essentially by the careful reading of classical Kraepelinian contributions, could enhance clinical management. This would in turn allow a more judicious use of antidepressants, ideally helping to shed some light on the much controversial ‘antidepressant-related suicidality', and help to further clarify the reasons for the current literature discordance on this topic.     

Olanzapine monotherapy for acute depression in patients with bipolar I or II disorder: results of an 8‐week open label trial

We evaluated the efficacy, tolerability, and safety of olanzapine monotherapy in 20 adult patients with bipolar I or II disorder, depressed phase. Patients received open‐label olanzapine monotherapy (mean modal dose, 15 mg/day) for 8 weeks. Assessments of psychopathology (Montgomery–Asberg Depression Rating Scale [MADRS], Quick Inventory of Depressive Symptomatology [QIDS‐SR‐16], Young Mania Rating Scale [YMRS]), clinical global state (Clinical Global Impressions [CGI] scale), and safety/tolerability were performed at baseline, and at 1, 2, 4, 6, and 8 weeks. Seventeen patients (85.0%) completed the study. Improvement in MADRS total scores was observed after the first week of treatment, and at all remaining follow‐up time points (p ≤ 0.005). Parallel improvement in QIDS‐SR‐16 (p < 0.001) and CGI‐Severity (p < 0.001) was observed between baseline and study endpoint. Nine (45%) subjects achieved positive treatment response, eight of whom (40%) also achieved symptom remission. There were significant increases in weight (+3.2 kg, p = 0.001) and body mass index (+1.1 kg/m², p = 0.001), but not fasting glucose or lipids, with the exception of reduced triglyceride levels in the overall sample, and reduced HDL cholesterol in females. Olanzapine may be an effective, well‐tolerated option for treating acute non‐psychotic depression across a variety of bipolar disorder subtypes. Copyright © 2009 John Wiley & Sons, Ltd.     

Lamotrigine in the treatment of bipolar disorder

Lamotrigine is a novel anticonvulsant agent that has recently been introduced as a long-term treatment in bipolar disorder. Its role in the treatment of epilepsy is based on its actions to decrease ion channel conductance and antagonise glutamatergic function. Therefore, it has a mode of action unlike other agents used on a long-term basis in mood disorders. The evidence for efficacy is stronger for the prevention of depressive, rather than manic, episodes. The pivotal trials are in bipolar I disorder, but there is interest in its actions in patients with bipolar II and spectrum conditions. Its efficacy in other psychiatric conditions remains to be properly established. It is well tolerated and, with careful prescribing, the incidence of rash occurs no more than with placebo; however this is still a concern. Although usually well tolerated, headache, insomnia and drowsiness are probably the most common side effects.     

The effect of concurrent administration of psychotropic drugs and lithium on lithium ratio in bipolar patients

There are conflicting results regarding the effect of neuroleptic drugs on lithium ratio (LR) and methodological problems may be a reason for this. The effect of concurrent use of some psychotropic agents with lithium on the LR was studied in 113 patients with bipolar mood disorder (BMD) during a prospective inpatient study by using the new direct method of measuring the erythrocyte lithium concentration (ELC). Results revealed that patients taking a combination of lithium and neuroleptics had significantly lower LR and ELC values than those on lithium alone. Such differences were not found in patients who received carbamazepine, benzodiazepines or ECT concurrently with lithium. No relationship was found between the LR and lithium dosage or duration of treatment. The plasma lithium concentration may not significantly correlate with lithium dosage or duration. The effect of neuroleptics on the LR may be mediated through a stabilizing effect on the cell membrane with a consequent reduction on lithium transport into the erythrocyte. © 1998 John Wiley & Sons, Ltd.