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.     

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.     

65例精神病患者红细胞锂评价研究

对锂盐治疗获显效的55例和效差(无效和好转)的10例情感性和分裂情感性精神病作了红细胞锂(ELL)和血清锂(SLL)的测定和分析。服锂剂量:从0.3-0.6g/d开始,10d左右加至1.2-2.1g/d。结果。效差组ELL低于显效组并有显著差异。提示对锂盐效差与ELL浓度低有关。     

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.     

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。     

Lithium augmentation of topiramate for bipolar disorder with comorbid binge eating disorder and obesity

OBJECTIVE: To evaluate the effectiveness of lithium augmentation of topiramate on mood symptoms, binge eating behavior, and body weight in obese bipolar patients with binge eating disorder (BED) seeking weight management. METHOD: We conducted a naturalistic study of 12 consecutive outpatients with bipolar disorders, BED, and obesity who received lithium augmentation for mood instability during the course of topiramate-based pharmacotherapy for obesity and BED. Lithium was added to topiramate (mean dose 514 mg i.d.) and titrated to a mean dose of 1009 mg i.d. (mean plasma concentration 0.7 mmol/L). Treatment response was assessed by comparing changes in clinical severity scales for mood and eating disorders, weekly binge eating frequency, and weight for the 2 months before and the first 2 months during lithium treatment. RESULTS: A statistically significant improvement in global severity of mood symptoms was observed after as compared to before lithium augmentation. Statistically insignificant reductions in weight and in binge frequency and severity were also observed after lithium addition. CONCLUSION: Optimal weight loss treatment in obese patients with comorbid bipolar and BEDs may require stabilization of mood. The combination of lithium and topiramate may have a role in the management of this difficult-to-treat population.     

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.     

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.     

Clinical outcome in patients with bipolar I disorder, obsessive compulsive disorder or both

BACKGROUND: Bipolar disorder (BPD) is often comorbid with obsessive-compulsive (OCD) and other anxiety disorders, but the impact of such comorbidity on long-term outcome has not been evaluated systematically. METHODS: Extensive follow-up assessments were carried out at 4.3 years after index hospitalizations in a mixed BPD-OCD group (N=20) compared to matched groups with BPD (N=22) or OCD (N=20) alone. RESULTS: At follow-up, ratings of functional status were similar across groups. Rehospitalizations were similar among BPD-OCD and BPD subjects, but 2.9-times more frequent among comorbid than OCD patients. OCD symptoms averaged 150% more severe in OCD than comorbid subjects, and were not measured in BPD subjects. CONCLUSIONS: Despite potential sampling bias with previously hospitalized subjects, the findings suggest that comorbid BPD-OCD patients may be clinically more similar to BPD than OCD patients, and that BPD-OCD comorbidity may not negatively impact the long-term clinical outcome.     

Association studies of 5-HT2A and 5-HT2C serotonin receptor gene polymorphisms with prophylactic lithium response in bipolar patients

Lithium is one of the most commonly used drugs in the prophylaxis and treatment of bipolar disorder. The mechanisms of mood stabilization by lithium incorporate its effect on serotonergic neurotransmission. This paper investigates a relationship between response to lithium prophylaxis and polymorphisms in two genes: T102C of 5-HT2A receptor and G68C (Cys23Ser) of 5-HT2C serotonin receptor gene. Genotypes were estimated in 92 bipolar patients (39 males and 53 females) who have been taking lithium for at least 5 years. The patients were classified as excellent responders, partial responders and non-responders to lithium. The obtained results suggest that these polymorphisms may not be related to the degree of prophylactic lithium response.