A review of the evidence for carbamazepine and oxcarbazepine in the treatment of bipolar disorder

Bipolar disorder is a recurrent lifelong condition associated with significant morbidity and mortality. The main goals of treatment are the acute management of manic/depressive episodes and the prevention of recurrence. Mood stabilizers are the basis of most treatment regimens. Although lithium is the classical mood stabilizer, dissatisfaction with its efficacy and tolerability has led to increased use of other mood- stabilizing agents, including anticonvulsants. Newer anticonvulsants such as oxcarbazepine may offer improved tolerability and fewer drug-drug interactions compared to older drugs like carbamazepine. A search of the literature shows that data from controlled clinical studies support the efficacy of carbamazepine in treating acute mania and as maintenance therapy. In addition, a growing body of data for oxcarbazepine suggests that this newer agent may have a similar efficacy profile to carbamazepine, with improved tolerability. This review presents a balanced selection of the key studies on carbamazepine and oxcarbazepine in bipolar disorder.     

Person first and patient first: Tailoring language to individual patient needs

ABSTRACT

The authors examine both the alcohol consumption pattern of freshmen students during their first semester and the degree to which social modeling of peer behavior impacts consumption. A total of 534 students, residing on campus, were prospectively examined at four 30-day intervals. Data were evaluated on the basis of age, gender, and the effects of time using generalized estimating equations (GEEs). Results reflected nonsignificant increases in the amount of alcohol consumed; however, affiliations with alcohol-consuming peer groups was significantly associated with increased alcohol consumption. The mean number of drinks consumed in the past 30 days remained the same for whites (χ² = 3.35, 3 df, P = .3411) but increased slightly for blacks (χ² = 7.99, 3 df, P = .0462). Prevention programs should include screening for growth in alcohol consumption among first-year university students, and such screenings should include the extent and nature of affiliation with peers who consume alcohol.     

奥卡西平和卡马西平治疗脑卒中后继发性癫痫疗效与安全性的Meta分析

目的 系统评价奥卡西平与卡马西平治疗脑卒中后继发性癫痫的疗效和安全性。方法 计算机检索PubMed、Cochrane Library、EMbase、万方、中国知网、维普、中国生物医学文献数据库（CBM）等收录的奥卡西平和卡马西平治疗脑卒中后继发性癫痫的相关文献,检索时限为建库以来到2017年8月,使用RevMan5.3软件进行Meta分析。结果 共纳入6项研究,包含517例患者。Meta分析结果显示：奥卡西平组控制癫痫的总体有效率高于卡马西平组,差异有统计学意义（RR=1.44,95%CI：1.29~1.60,P<0.000 01）;奥卡西平组总不良反应发生率低于卡马西平组,差异有统计学意义（RR=0.39,95%CI：0.26~0.57,P<0.000 01）;皮疹、头晕、嗜睡、恶心、呕吐发生率的比较差异均无统计学意义。结论 奥卡西平治疗脑卒中后继发性癫痫的疗效优于卡马西平,安全性较卡马西平好。由于本研究纳入的文献数量和样本量较少,因此还需更多大样本、多中心的高质量临床随机对照试验（randomized controlled trials,RCT）进一步研究验证。     

The effect of adjunctive mood stabilizers on antipsychotic utilization pattern and health resource utilization for Medicaid enrollees with schizophrenia

ABSTRACT

Background: Prescribing adjunctive mood stabilizers to manage schizophrenia is prevalent, despite the lack of substantial evidence to support the long-term use of this treatment regimen.

Objective: The objective of this study was to assess the impact of using adjunctive mood stabilizers on antipsychotic utilization, total health expenditures, inpatient hospital­izations, long-term care stays, and emergency room (ER) visits for patients with schizophrenia.

Methods: Georgia Medicaid claims from 1999 through 2001 were analyzed to identify recipients diagnosed with schizophrenia (International Classification of Diseases, Ninth Revision, Clinical Modification [ICD?9?CM]: 295.XX). The treatment groups consisted of subjects who received combination therapy of mood stabilizers and anti­psychotics (including both atypical and typical medica­tions), while the comparison group consisted of subjects who were on antipsychotic medications without exposure to the mood stabilizers under investigation. Four treatment groups (valproate, lithium, carbamazepine, and combina­tion mood stabilizer therapy) were formed based on the mood stabilizers patient received. Differences in annual health care use and expenditures were estimated between propensity score matched treatment and comparison groups controlling for comorbidity, prior utilization, demographic, and health provider specialty.

Results: During the 1?year observation period, subjects in treatment groups filled an average of 200-days supply of adjunctive mood stabilizers. These adjunctive mood stabilizer recipients had significantly longer antipsychotic treatment durations than the subjects who did not have exposure to mood stabilizers (valproate + antipsychotic vs. antipsychotic only, net difference: 56.47 days, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: 90.25 days, p < 0.0001; carbamazepine + antipsychotic vs. antipsychotic only, net difference: 41.27 days, p = 0.0439; multiple mood stabilizers + anti­psychotic vs. antipsychotic only, net difference: 83.14 days, p < 0.0001). The intensive pharmacotherapy associated with treatment groups resulted in $900–$1300 higher pharmacy costs than the comparison groups (valproate + antipsychotic vs. antipsychotic only, net difference: $1218.43, p < 0.0001; lithium + antipsychotic vs. antipsychotic only, net difference: $985.79, p = 0.0015; carbamazepine + antipsychotic vs. anti­psychotic only, net difference: $911.63, p = 0.0497; multiple mood stabilizers + antipsychotic vs. antipsychotic only, net difference: $1281.91, p < 0.0047). However, there were no statistically significant differences for total health expenditures, hospitalizations, emergency room visits, and nursing home admissions between propensity-matched treatment and control groups.

Conclusions: There were no differences in health care costs or utilization of ER, long-term care, and inpatient services between schizophrenia patients who did and did not receive adjunctive mood stabilizer; however, longer anti­psychotic treatment durations were observed in patients receiving adjunctive mood stabilizers. Interpretation of these results is limited by the unknown selection bias between the treatment and the comparison groups and the relatively small number of patients in some treatment groups. The development of a better-controlled study to further evaluate this treatment regimen is warranted.     

Adjunctive topiramate in the maintenance treatment of bipolar disorders: an open-label study

SUMMARY

Objective: A considerable number of patients with bipolar disorder fail to respond completely to mood stabilizers. The anti-epileptic topiramate shares some pharmacological actions with carbamazepine and valproate. We therefore explored the efficacy and tolerability of topiramate in the prophylaxis of bipolar disorder.

Methods: Fifty-six patients receiving outpatient treatment for bipolar affective disorder who had been on mood stabilizers, and had relapsed at least once in the past 12?months, were treated with topiramate in an add-on design and were evaluated for 1?year. Patients were assessed biweekly for the first 3?months and every month thereafter.

Results: Fifty out of 56 patients completed the 1-year study, which indicated that adjunctive topiramate was associated with a significant reduction of new manic and depressive episodes compared to the past 12?months. The most common adverse effects were reduced appetite, fatigue and somnolence.

Conclusions: This was an open-label, uncontrolled study involving retrospective evaluation of episodes prior to the initiation of treatment, and the use of more than one mood stabilizer in a few patients. However, these preliminary observations of adjunctive topiramate as a maintenance treatment encourage further investigations, especially with controlled trials, for its long-term effect.     

Family Harmony as a Protective Factor Against Adolescent Tobacco and Alcohol Use in Wuhan,China

Purpose.?To investigate the association between family harmony (FH) and tobacco and alcohol use (TAU) in Chinese adolescents. Methods.?Participants completed a survey in 1998 as part of a larger study of adolescent health in Wuhan, China. Analyses were performed on subjects for whom complete data were available (n = 183; 50.8% male; mean age = 13.17 yrs, std dev = 0.59). Structural equation modeling was utilized to quantify the relationships between the FH, TAU, depression, and academic aptitude factors. Results.?The conceptualized structural equation model was found to have a good fit to the data (CFI = 0.995; χ² = 39.57, df = 38; p = 40). FH was a significant predictor of TAU (β = ?0.42, p<0.05) and was protective. FH' was also negatively related to depression (r = ?0.24, p<0.05) and positively related to academic achievement/aptitude (r = 0.35, p<0.05). Conclusions.?These central findings highlight the value and importance placed on FH within the Chinese culture. Future prevention programs may benefit by taking into account FH as a potential mediator of TAU in adolescents in China.     

The influence of food on the disposition of the antiepileptic oxcarbazepine and its major metabolites in healthy volunteers

The effect of food on the pharmacokinetics of the antiepileptic oxcarbazepine (OXC) was investigated in healthy volunteers. Six healthy male volunteers were treated with single peroral doses of 600 mg of oxcarbazepine (Trileptal®) after overnight fasting or a fat- and protein-rich breakfast. Mean (± SD) areas under the plasma concentration—time curves (AUC) of the major component in plasma, the active monohydroxy metabolite (MHD), which is responsible for the therapeutic effect in man, were 672 (25) μmol L^?1 h when given to the fasted volunteers and 780 (31) μmol L^?1 h (p = 0.042) when given after a substantial breakfast. Mean (± SD) maximum concentrations (C_max) were 25.5 (4.8) μmol L^?1 when given to the fasted volunteers and 31.4 (5.3) μmol L^?1 (p = 0.025) when given after breakfast. Thus, the average AUC was increased by 16% and C_max by 23% when oxcarbazepine was given with food. The times at which C_max was reached (t_max) as well as the terminal half-lives were not influenced by concomitant intake of food. The tolerability was the same whether oxcarbazepine was given before or after food in healthy volunteers. The slight effect of food on the kinetics of oxcarbazepine should be of little therapeutic consequence.     

Evaluation of the effects of propylisopropylacetic acid (PIA) on neuronal growth cone morphology

Propylisopropylacetic acid (PIA) is a constitutional isomer of valproic acid (VPA). It has previously been found to be a weak antiepileptic, but in common with mood stabilizers, causes inositol depletion and growth cone spreading, suggesting the basis of a new series of mood stabilizers. To assess this possibility, we have compared the effects of racemic (R,S)-PIA and its individual enantiomers to those of the mood stabilizers lithium (Li⁺), VPA and carbamazepine (CBZ). Unlike Li⁺ and VPA, but in common with CBZ and (R,S)-PIA, neither (R)-PIA nor (S)-PIA enantiomer induces T-cell factor (TCF)-mediated gene expression. However, as seen for other mood stabilizers, both enantiomers are potent inducers of growth cone spreading. To investigate the mechanism for these effects, we examined changes in the actin cytoskeleton following drug treatment with Li⁺, VPA, CBZ, (R,S)-PIA or its individual enantiomers. All exhibit a re-distribution of F-actin to the growth cone periphery, a feature of spread growth cones. (R,S)-PIA has the strongest effect as it also elevates F-actin polymerization at the cell periphery. This change in the actin cytoskeleton is associated with a substantial increase in F-actin-rich protrusions on the surface of the growth cone and in its close vicinity. These results demonstrate an effect of (R,S)-PIA on the neuronal actin cytoskeleton shared in common with other mood stabilizers, and suggest a potential to induce structural changes within the CNS.     

Sildenafil adjunctive therapy to risperidone in the treatment of the negative symptoms of schizophrenia: a double-blind randomized placebo-controlled trial

Rational

It has been suggested that phosphodiesterase 5 inhibitors such as sildenafil may be effective in the treatment of negative symptoms of schizophrenia.

Objective

This study was designed to investigate the effect of sildenafil added to risperidone as augmentation therapy in patients with chronic schizophrenia and prominent negative symptoms in a double-blind and randomized clinical trial.

Methods

Eligible participants in the study were 40 patients with chronic schizophrenia with ages ranging from 18 to 45?years. All patients were inpatients and were in the active phase of the illness and met DSM-IV-TR criteria for schizophrenia. Patients were allocated in a random fashion: 20 to risperidone (6?mg/day) plus sildenafil (75?mg/day) and 20 to risperidone (6?mg/day) plus placebo. The principal measure of outcome was Positive and Negative Syndrome Scale (PANSS).

Results

Although both protocols significantly decreased the score of the positive, negative, and general psychopathological symptoms over the trial period, the combination of risperidone and sildenafil showed a significant superiority over risperidone alone in decreasing negative symptoms and PANSS total scores over the 8-week trial (between-subjects factor; F?=?4.77, df?=?1; P?=?0.03; F?=?5.91, df?=?1, P?=?0.02 respectively).

Conclusion

Therapy with 75?mg/day of sildenafil was well tolerated, and no clinically important side effects were observed. The present study indicates sildenafil as a potential adjunctive treatment strategy for treatment of negative symptoms of schizophrenia. This trial is registered with the Iranian Clinical Trials Registry (IRCT1138901151556N11).     

Oxcarbazepine induced toxic epidermal necrolysis - a rare case report

Carbamazepine, is well known to cause Stevens–Johnson syndrome and toxic epidermal necrolysis(TEN). Oxcarbazepine, a 10-keto analog of carbamazepine, is an anticholinergic, anticonvulsant and mood stabilizing drug, used primarily in the treatment of epilepsy. Its efficacy is similar to carbamazepine but allergic reactions and enzyme induction is low. We describe a case of oxcarbazepine induced TEN, who presented with erythematous ulcerative maculopapular rash.KEY WORDS: Carbamazepine, oxcarbazepine, Stevens–Johnson syndrome, toxic epidermal necrolysis     

Use of lithium, carbamazepine, and valproic acid in a state-operated psychiatric hospital.

OBJECTIVE: To examine the prescribing of mood stabilizers (lithium, carbamazepine, and valproic acid) in a 500-bed state-operated psychiatric hospital in New York. METHODS: All 129 inpatients receiving mood stabilizers were identified and their medical records reviewed using a standardized drug use evaluation form. Diagnosis, other indications, and prior experience with mood stabilizers were examined, as well as outcome and adverse effects. RESULTS: Approximately one-quarter of the inpatient population received a mood stabilizer. The frequency of carbamazepine use exceeded the use of lithium, with 72 patients receiving carbamazepine and only 62 receiving lithium. Twenty-eight patients received valproic acid. Indications found most frequently for carbamazepine use included assaultive or aggressive behavior (70% for those receiving carbamazepine as the only mood stabilizer). Of those patients with bipolar or schizoaffective disorder and receiving either lithium, carbamazepine, or valproic acid, 36% were prescribed carbamazepine (10% as a first-line agent) and 50% lithium (26% as a first-line agent). None of these indications for carbamazepine has been approved by the Food and Drug Administration. In general, positive outcomes were documented but without supporting objective measures. Significant adverse effects were documented in the medical record in one-quarter of the patients. CONCLUSIONS: There was widespread use of the three mood stabilizers examined, singly and in combination, for a variety of indications. Lithium and valproic acid remain more frequently prescribed for the treatment of bipolar and schizoaffective disorders. Monotherapy with carbamazepine or valproic acid results in statistically significantly fewer adverse effects than lithium or combination therapy (p values between p = 0.00038 and p = 0.006). Current clinical practice has endorsed the use of carbamazepine for aggressive or assaultive behavior, although there does not appear to be sufficient proof of effectiveness in the literature. Formal studies of carbamazepine's antiagressive effects should be conducted.     

Investigation of CNR1 and FAAH endocannabinoid gene polymorphisms in bipolar disorder and major depression

Experimental data suggest that the endogenous cannabinoid system is involved in mood regulation, but no study has been performed so far to investigate the role of endocannabinoid genes in the susceptibility to major depression (MD) and/or bipolar disorder (BD). We assessed the CB1 receptor gene (CNR1) single nucleotide polymorphism (SNP) rs1049353 (1359 G/A) and the fatty acid amide hydrolase (FAAH) gene rs324420 SNP (cDNA 385C to A) for their associations with MD and/or BD in 83 Caucasian patients with recurrent MD, 134 Caucasian individuals with BD, and 117 Caucasian healthy subjects. The distribution of the CNR1 1359 G/A genotypes and alleles significantly differed among the groups (χ² = 12.595; df = 4, P = 0.01 for genotypes; χ² = 13.773; df = 2, P = 0.001 for alleles) with MD patients showing a higher frequency of both AG, GG genotypes and A allele as compared to healthy controls. The distribution of the FAAH cDNA 385C to A genotypes, according to the CC dominant model (AA + AC vs. CC), significantly differed among the groups (χ² = 6.626; df = 2, P = 0.04), with both BD patients and MD patients showing a non-significant slightly higher frequency of the AC genotype. These findings, although preliminary, suggest that the CNR1 1359 G/A and the FAAH cDNA 385C to A gene variants may contribute to the susceptibility to mood disorders.     

细胞色素P450酶1A2、2D6与多巴胺D2受体基因多态性对奥氮平治疗精神分裂症PANSS减分率的影响

目的 研究细胞色素P450酶(cytochromeSP450, CYP)1A2、2D6以及多巴胺D2(dopamine receptorSD2, DRD2)受体的基因多态性对奥氮平治疗精神分裂症阳性和阴性症状量表(positive and negative syndrome scale, PANSS)减分率的影响及其程度。方法 入组只用奥氮平治疗的精神分裂症住院患者178例,评定治疗前以及治疗4周后的PANSS量表得分,计算减分率。同时,收集血液,测定CYP1A2*1F、CYP2D6*10、DRD2 -141C Ins/Del、DRD2 -241 A>G、DRD2 Taq1A位点的基因多态性。通过方差分析,比较各基因型PANSS减分率的差异;通过多元线性回归分析,得出减分率的回归方程,并计算决定系数。结果 PANSS减分率在CYP1A2*1F(CC：65.68±11.22,CA：55.59±15.40,AA：43.75±15.20)、CYP2D6*10(CC：44.36±16.67,CT：51.78±17.81,TT：56.14±17.13)、DRD2 -141C Ins/Del(Ins/Ins：55.11±17.39,Ins/Del：39.16±14.28)和DRD2 -241 A>G(AA：45.47±17.52,GA：61.82±10.55,GG：75.43±17.71)不同基因型之间均有统计学显著差异(均P<0.01),而DRD2 Taq1A位点的基因型间PANSS减分率差异无统计学意义(P>0.05)。 PANSS减分率＝58.041-10.703╳CYP1A2*1F+4.272╳CYP2D6*10-11.921╳DRD2 -141C Ins/Del +13.443╳DRD2 -241 A>G(决定系数R_²＝0.517,P<0.05)。结论 CYP1A2*1F、CYP2D6*10、DRD2-141 C Ins/Del、DRD2-241A>G位点基因多态性影响奥氮平治疗精神分裂症疗效,但只解释了减分率的51.7%,有待纳入更多的影响因素进行分析。     

Effects of selective serotonin reuptake inhibitors on motility of isolated fallopian tube

Selective serotonin reuptake inhibitors (SSRIs) affect the smooth muscle cells acting on voltage‐dependent channels for Na⁺, K⁺ and Ca²⁺, but their action is tissue and species specific. The aim of our study was to investigate effects of selective serotonin reuptake inhibitors on motility of the isolated fallopian tubes. Isolated preparations of isthmus and ampoule were taken from fallopian tubes of 20 women during hysterectomy due to uterine fibroids and then tested for reactivity on increasing concentrations of selective serotonin reuptake inhibitors. Escitalopram (from 0.9 × 10^?9 M/L to 1.4 × 10^?6 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated ampulla (EC50 = 1.20 ± 1.06 × 10^?8 M/L, r = 0.580, P < 0.05) (F = 2.980, df₁ = 6, df₂ = 28, P < 0.05). Paroxetine (from 1.2 × 10^?9 M/L to 5.1 × 10^?5 M/L) produced concentration‐dependent increase of spontaneous contractions of the isolated isthmus (EC50 = 7.01 ± 3.50 × 10^?8 M/L, r = 0.500, P < 0.05) (F = 2.350, df₁ = 9, df₂ = 40, P < 0.05). The SSRIs differ among themselves in regard to their potential to affect motility of the fallopian tubes. Escitalopram and paroxetine have clear stimulating effect which may interfere with functioning of the fallopian tubes, and potentially impair fertility if taken by women in reproductive period of life. The other SSRIs tested in the study did not produce significant effect throughout the concentration range used in the experiments.     

Evaluation of cytochrome P450 inductions by anti-epileptic drug oxcarbazepine, 10-hydroxyoxcarbazepine,and carbamazepine using human hepatocytes and HepaRG cells

1. Anti-epileptic drug oxcarbazepine is structurally related to carbamazepine, but has reportedly different metabolic pathway. Auto-induction potentials of oxcarbazepine, its pharmacologically active metabolite 10-hydroxyoxcarbazepine and carbamazepine were evaluated by cytochrome P450 (CYP) 1A2, CYP2B6 and CYP3A4 mRNA levels and primary metabolic rates using human hepatocytes and HepaRG cells.

2. For the CYP1A2 the induction potential determined as the fold change in mRNA levels was 7.2 (range: 2.3–11.5) and 10.0 (6.2–13.7) for oxcarbazepine and carbamazepine, respectively, while 10-hydroxyoxcarbazepine did not induce. The fold change in mRNA levels for CYP2B6 was 11.5 (3.2–19.3), 7.0 (2.5–10.8) and 14.8 (3.1–29.1) for oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine, respectively. The fold change for CYP3A4 induction level by oxcarbazepine, 10-hydroxyoxcarbazepine and carbamazepine was 3.5 (1.2–7.4), 2.7 (0.8–5.7) and 8.3 (3.5–14.5), respectively. The data suggest lower induction potential of oxcarbazepine and 10-hydroxyoxcarbazepine relative to carbamazepine. The results in HepaRG cells showed similar trend as the human hepatocytes.

3. After incubation for 72?h in hepatocytes and HepaRG cells, auto-induction was evident for only carbamazepine metabolism. The 10-keto group instead of double bond at C10 position is evidently a determinant factor for limited auto-induction of P450 enzymes by oxcarbazepine.

     

Oxcarbazepine. A review of its pharmacology and therapeutic potential in epilepsy, trigeminal neuralgia and affective disorders.

Oxcarbazepine is the 10-keto analogue of carbamazepine but has a distinct pharmacokinetic profile. In contrast to the oxidative metabolism of carbamazepine, oxcarbazepine is rapidly reduced to its active metabolite, 10,11-dihydro-10-hydroxy-carbamazepine. With the possible exception of the P450IIIA isozyme of the cytochrome P450 family, neither oxcarbazepine nor its monohydroxy derivative induce hepatic oxidative metabolism. Direct comparison of oxcarbazepine and carbamazepine has shown no difference in efficacy between these 2 agents in terms of reducing seizure frequency in patients with partial epilepsy with or without secondary generalisation, or with tonic-clonic seizures. Substitution of oxcarbazepine for carbamazepine in multiple antiepileptic drug regimens improved seizure control in some patients with refractory epilepsy; however, the rise in serum concentrations of concurrent antiepileptic agents secondary to elimination of carbamazepine-associated hepatic enzyme induction may have also played a role. Substitution of oxcarbazepine for carbamazepine was associated with improved cognition and alertness in some patients with epilepsy. Limited data indicate that oxcarbazepine may be a useful alternative to carbamazepine in the management of trigeminal neuralgia. Experience in patients with acute mania is promising, but the value of oxcarbazepine in managing affective disorders, particularly as a prophylactic agent, is not established. Oxcarbazepine may be better tolerated than carbamazepine; however, the current published database is small and the potential for oxcarbazepine to induce the type of serious idiosyncratic reactions occasionally associated with carbamazepine is unknown. Hyponatraemia has been reported in patients treated with oxcarbazepine. Although apparently asymptomatic, fluid restriction may be deemed necessary in some patients to reduce the risk of precipitating seizures secondary to low serum sodium. Thus, oxcarbazepine appears to be an effective substitute for carbamazepine in those patients intolerant of this agent, or experiencing significant drug interactions. Wider clinical experience should help clarify the long term efficacy and tolerability of oxcarbazepine. Pharmacokinetic advantages over current antiepileptic drugs, carbamazepine in particular, may then favour oxcarbazepine for consideration as a first-line agent in the management of partial and tonic-clonic epilepsy.     

心境稳定剂在治疗儿童精神障碍中的应用

心境稳定剂在儿童和青少年心理和行为障碍治疗中的应用广泛,适用于治疗双相情感障碍、破坏性行为障碍和注意力缺陷-多动障碍等行为障碍患者出现的冲动和攻击行为以及情绪不稳定和易激惹等表现,同时对发育迟缓儿童如精神发育迟滞和孤独症等患者出现的伤害他人或自伤行为治疗也有效果。在经典的心境稳定剂中,锂盐是唯一获准可一线用于儿童和青少年双相情感障碍患者躁狂发作和维持治疗的药物,而丙戊酸盐、卡马西平、奥卡西平和拉莫三嗪在治疗儿童攻击性或破坏性行为中也有一定的临床应用。选用心境稳定剂治疗儿童精神障碍时应考虑药物的疗效证据、安全性和不良反应以及患者的靶症状、疾病史、用药史和家族史等,以确保儿童用药安全、有效。     

Association study of a novel functional polymorphism of the serotonin transporter gene in bipolar disorder and suicidal behaviour

A serotonin transporter gene linked polymorphic region (5-HTTLPR) has been investigated in several genetic association studies, including studies of bipolar disorder (BD) and suicidality. The current study was designed to examine whether the new long (A/G) variant polymorphism of the 5-HTT gene may be associated with the suicide attempts in 305 families with at least one member having BD. No association with history of suicide attempt was found either in the multiallelic HTTLPR (LRS=0.15, df=2, P=0.92), or with the intron 2 variable number tandem repeat (VNTR) polymorphism (LRS=0.87 df=2 P=0.64). When we performed a haplotype analysis, we found no association between suicide attempt and haplotype distribution (LRS=1.84 df=4 P=0.76). These findings suggest that this new polymorphism in the 5-HTT gene may not influence suicidal behaviour in patients with bipolar disorder.     

加巴喷丁治疗糖尿病周围神经痛的Meta分析

目的 评价加巴喷丁治疗糖尿病性周围神经痛的有效性和安全性.方法 采用循证医学的文献分析评价方法,计算机检索Cochrane图书馆系统评价数据库、Pubmed、中国学术期刊全文数据库、万方数据库、维普数据库等,采用RevMan5.2软件进行Meta分析.结果 纳入研究12项,共931例患者,Meta分析显示加巴喷丁反应有效率[OR=2.99,95%CI(1.72,5.20),P <0.000 1]及不良反应发生率[OR=4.05,95%CI(1.10,14.95),P=0.04]均高于安慰剂,加巴喷丁治疗效果高于卡马西平/奥卡西平[OR=3.60,95%CI(1.14,11.31),P=0.03]和维生素B₁₂,而不良反应则较卡马西平轻;加巴喷丁与度洛西汀、普瑞巴林比较,治疗效果相当,但度洛西汀[OR=2.06,95%CI(1.22,3.48),P=0.007]和普瑞巴林的不良反应较少.结论 加巴喷丁治疗糖尿病性周围神经痛效果显著,安全性较好.     

Adjunctive topiramate in the maintenance treatment of bipolar disorders: an open-label study

OBJECTIVE: A considerable number of patients with bipolar disorder fail to respond completely to mood stabilizers. The anti-epileptic topiramate shares some pharmacological actions with carbamazepine and valproate. We therefore explored the efficacy and tolerability of topiramate in the prophylaxis of bipolar disorder. METHODS: Fifty-six patients receiving outpatient treatment for bipolar affective disorder who had been on mood stabilizers, and had relapsed at least once in the past 12 months, were treated with topiramate in an add-on design and were evaluated for 1 year. Patients were assessed biweekly for the first 3 months and every month thereafter. RESULTS: Fifty out of 56 patients completed the 1-year study, which indicated that adjunctive topiramate was associated with a significant reduction of new manic and depressive episodes compared to the past 12 months. The most common adverse effects were reduced appetite, fatigue and somnolence. CONCLUSIONS: This was an open-label, uncontrolled study involving retrospective evaluation of episodes prior to the initiation of treatment, and the use of more than one mood stabilizer in a few patients. However, these preliminary observations of adjunctive topiramate as a maintenance treatment encourage further investigations, especially with controlled trials, for its long-term effect.