A prospective trial of sertraline for chronic subjective dizziness

OBJECTIVES/HYPOTHESIS: The authors previously reported that selective serotonin reuptake inhibitors (SSRIs) reduce chronic subjective dizziness in patients with and without psychiatric illnesses. To extend those preliminary findings and test the hypothesis that SSRIs may offer a novel treatment for chronic subjective dizziness, the authors conducted a prospective study of sertraline in patients with dizziness for more than 6 months, in the absence of active physical neurotologic illness. STUDY DESIGN: Sixteen-week, prospective, open-label, flexible-dose clinical trial. METHODS: Twenty-four patients with subjective dizziness for more than 6 months and no active physical neurotologic illness were studied. Eighteen patients had major anxiety disorders. Six had minor frustration or worry that did not warrant a psychiatric diagnosis. Sertraline was administered at a daily dose of 25 mg, which was increased to a maximum daily dose of 200 mg. Dizziness, functional impairment, and psychological distress were measured using the Dizziness Handicap Inventory (DHI) and Brief Symptom Inventory-53 (BSI-53). Treatment outcomes were analyzed using repeated-measures multivariate analyses of variance, with last observations carried forward. RESULTS: Three patients were excluded from data analysis for disqualifying medical conditions, one for protocol violations. Fifteen (75%) patients completed treatment. Five (25%) withdrew for adverse effects or lack of efficacy. The median daily dose of sertraline was 100 mg. Sertraline significantly reduced scores on all three DHI subscales and the BSI-53. Eleven of 15 (73%) patients who completed treatment had a positive response, including 8 of 11 (73%) with major anxiety disorders and 3 of 4 (75%) with no psychopathological conditions. Six patients enjoyed a full remission of symptoms. CONCLUSION: Sertraline significantly reduced chronic subjective dizziness in patients without active physical neurotologic illness, including those with and without psychiatric comorbidity.     

Induction of kf-1 after repeated electroconvulsive treatment and chronic antidepressant treatment in rat frontal cortex and hippocampus

Summary. It has been proposed that signaling pathways involved in adaptive neural plasticity are long-term targets for the action of electroconvulsive treatment (ECT), which is widely used in the treatment of drug-resistant depression. We have previously performed EST analysis to identify some molecular machinery responsible for antidepressant effect. One of the cDNA fragments identified as antidepressant related genes/ESTs was identified as kf-1 which has a RING-H2 finger motif at the carboxy-terminus. In the present study, we have demonstrated the induction of kf-1 in rat frontal cortex and hippocampus not only after chronic antidepressant treatment, but also after a single and repeated ECT. RING finger proteins are proposed to play some important roles in the ubiquitin-proteasome system. In conclusion, the current investigation has identified kf-1 as a novel molecular target for antidepressants and ECT. Received May 7, 2002; accepted July 24, 2002 Published online November 22, 2002 Acknowledgments Sertraline was kindly supplied from Pfizer Pharmaceuticals Inc., NY, USA. M. Yamada was supported by a fellowship from the Japan Foundation for Aging and Health. This work was in part supported by Research Grants from Ministry of Health, Labour and Welfare and Ministry of Education, Culture, Sport, Science, and Technology, and Japan Society for the Promotion of Science. Authors' address: M. Yamada, M.D., Ph.D., Department of Psychiatry, Showa University Karasuyama Hospital, 6-11-11 Kitakarasuyama, Setagaya, Tokyo 157-8577, Japan, e-mail: mitsu@med.showa-u.ac.jp     

安非他酮与舍曲林治疗抑郁症疗效比较

目的比较安非他酮与舍曲林对抑郁症的疗效及其安全性。方法125例抑郁症分为2组。安非他酮组63例[男性30例,女性33例,年龄(36±s 13)岁,本次抑郁病期(3±5)mo]予安非他酮300～450 mg·d~(-1),po,bid;舍曲林组62例[男性28例,女性34例,年龄(40±11)岁,本次抑郁病期(3±4)mo]予舍曲林50～100 mg,po,qd;均6 wk为一个疗程。结果对抑郁症状的治疗,安非他酮组显效率71%,舍曲林组显效率74%,2组疗效比较差异无显著意义(P>0.05);对伴随焦虑症状的治疗,安非他酮组显效率48%,舍曲林组显效率45%,2组疗效比较差异无显著意义(P>0.05)。整体药物不良反应发生率2组相当。结论安非他酮与舍曲林疗效相当,能有效治疗抑郁症及伴随焦虑症状,不良反应轻微。     

Rate of switch in bipolar patients prospectively treated with second-generation antidepressants as augmentation to mood stabilizers

Introduction: Bipolar patients with breakthrough major depressive episodes despite ongoing adequately‐dosed mood stabilizer medication were randomized in a double‐blind manner to one of three antidepressants with different mechanisms of action: bupropion, sertraline, or venlafaxine. Preliminary data are presented on the switch rates into hypomania or mania for the antidepressants as a group prior to unblinding the specific individual drug efficacy and tolerability data in this ongoing clinical trial.

Methods: Subjects included 64 bipolar patients who participated at five sites in a 10‐week double‐blind trial for depression and a 1‐year blinded continuation maintenance phase for responders. Nonresponders were re‐randomized such that there were 95 acute treatment phases. In the acute phase, doses were titrated to clinical response, side effects, or maximum dose of bupropion (450 mg/day), sertraline (200 mg/day), or venlafaxine (375 mg/day). Daily ratings on the National Institute of Mental Health‐Life Chart Methodology (NIMH‐LCM) were inspected for the degree of improvement on the Clinical Global Impressions scale as revised for bipolar illness (CGI‐BP) and the occurrence of hypomania or mania.

Results: Thirty‐five (37%) of the 95 acute treatment phases were associated with a much or very much improved rating in depression on the CGI‐BP. Thirteen (14%) of these 95 acute trials of antidepressants as adjuncts to mood stabilizers were associated with switches, seven into hypomania and six into mania. Forty‐two patients elected to go into the continuation phase in 48 instances. Sixteen (33%) of the continuation phase trials were associated with mood switches, 10 into hypomania and six into mania.

Conclusions: In this randomized double‐blind prospective study of three second‐generation antidepressants (bupropion, sertraline, and venlafaxine) in bipolar patients whose depression broke through ongoing treatment with mood stabilizers, switches into hypomania or mania occurred in 14% of the acute phases and 33% of the continuation phases. Individual data on each drug will be assessed in the next phase of the study after more subjects are recruited and the blind is broken.     

盐酸舍曲林片与原研制剂溶出一致性及药典方法合理性的研究

目的 考察8厂家盐酸舍曲林片与原研制剂溶出行为的一致性,探讨中国药典方法的可行性。方法 分别以0.1 mol·L^-1盐酸（pH=1.2）、乙酸盐缓冲液（pH=4.5）、磷酸盐缓冲液（pH=6.8）和水为溶出介质,选用中国药典溶出度色谱条件考察溶出曲线,采用相似因子法评价8厂家产品在各介质中与原研制剂溶出行为的相似性。结果 8厂家的仿制药与原研制剂在不同介质中溶出曲线差异较大,说明各企业的处方工艺差异较大;在pH=4.5介质、75 r·min^-1条件下原研和各厂制剂溶出量在15 min内均>85%。结论 通过不同介质溶出曲线的比较和f₂的计算,仿制药与原研制剂存在较大差异,建议企业改进工艺。同时中国药典的溶出条件有待商榷,建议国家药典委员会参考国外药典标准,修改转速或限度。     

舍曲林治疗高血压合并焦虑抑郁的临床疗效

目的观察舍曲林治疗高血压合并焦虑抑郁患者的临床疗效。方法将80例患者随机分成治疗组40例,对照组40例。对照组给予氨氯地平控制血压;治疗组给予氨氯地平控制血压的同时给予舍曲林(50mg早晨顿服)持续治疗4周。疗程结束后观察血压的变化及焦虑自评量表(SAS)和抑郁自评量表(SDS)评分的变化。结果 4周后治疗组收缩压低于治疗前,(133.05±13.27)mmHg vs(166.80±16.82)mmHg,舒张压也低于治疗前(82.75±8.47)mmHg vs(94.25±7.82)mmHg(均P0.01)。治疗组总有效率显著高于对照组(77.5%vs 57.5%,P0.05);治疗组治疗后与治疗前比较SAS评分(32.63±4.35)分vs(21.78±4.91)分和SDS评分(37.7±9.75)分vs(34.45±6.70)分均明显下降(P0.05)。结论舍曲林治疗高血压合并焦虑抑郁的临床疗效显著。     

重复性经颅磁刺激与舍曲林改善CUMS大鼠焦虑抑郁样行为的比较及其机制研究

目的:比较重复性经颅磁刺激(repetitive transcranial magnetic stimulation,rTMS)和舍曲林处理对慢性不可预见温和应激(chronic unpredictable mild stress,CUMS)大鼠焦虑抑郁样行为的改善作用及其可能的作用机制。方法:32只SD大鼠随机分为对照组、CUMS组、CUMS+rTMS组以及CUMS+舍曲林组,每组8只。采用糖水偏好实验、强迫游泳实验及旷场实验观察各组大鼠行为,并以蛋白质印迹法(Western blot)检测各组大鼠海马内源性大麻素I型受体(cannabinoid type 1 receptor,CB1R)的表达。结果:CUMS组糖水偏好值、水平活动度、中央活动次数以及CB1R的表达水平均显著低于对照组、CUMS+rTMS组和CUMS+舍曲林组,而CUMS+rTMS组和CUMS+舍曲林组两者之间没有统计学差异;CUMS组的强迫游泳不动时间大于其它三组,而CUMS+rTMS组和CUMS+舍曲林组两者之间没有统计学差异。结论:rTMS与舍曲林均能改善CUMS大鼠的焦虑抑郁样行为,二者的改善作用没有统计学差异,其作用可能是通过上调海马CB1R的表达实现的。     

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.     

Pharmacokinetic interactions between clozapine and sertraline in smokers and non‐smokers

Clozapine is an effective antipsychotic drug for treatment‐resistant schizophrenia. Sertraline is a widely prescribed antidepressant and often concomitantly applied to address negative symptoms or depression. However, data on interactions between clozapine and sertraline are inconsistent. The aim of our study was to evaluate pharmacokinetic interactions between clozapine and sertraline analysing a therapeutic drug monitoring database of 1644 clozapine‐medicated patients. We compared four groups: non‐smokers (n = 250) and smokers (n = 326) with co‐medication without known effects on cytochrome P450 and without sertraline, and non‐smokers (n = 18) and smokers (n = 17) with sertraline co‐medication. Measured and dose‐corrected concentrations (C/D) of clozapine were compared between the groups using non‐parametrical tests with a significance level of 0.05. Post hoc analyses included pairwise comparisons to account for smoking status. Although we detected significant differences for clozapine levels and C/D values between study groups (P < .001 for Kruskal‐Wallis test in both cases), post hoc analyses revealed no differences for concentrations and C/D values of clozapine (P > .05 for Mann‐Whitney U test in both cases). A negative correlation between the sertraline dose and the clozapine concentration was found in non‐smokers (Spearman's rank correlation, rs = ?0.535, P = .048). A potential pharmacokinetic interaction between clozapine and a standard therapeutic sertraline dose seems to be of minor clinical importance.     

舍曲林联合多奈哌齐治疗对脑卒中后功能恢复的影响

目的：探讨舍曲林联合多奈哌齐治疗对脑卒中功能恢复影响。方法：81例脑卒中患者被分成舍曲林＋多奈哌齐治疗组（25例）、舍曲林治疗组（27例）和对照组（29例）3组,分别于治疗前、治疗后4周及8周进行汉密尔顿抑郁量表（HAMD）、简易精神状况表（MMSE）、美国国立卫生研究院卒中量表（NIHSS）、Barthe指数评定,并对3组结果进行比较。结果：3组患者治疗前HAMD、MMSE、NIHSS、Barthel指数评分差异无统计学意义（P〉0.05）。治疗4周舍曲林＋多奈哌齐组及舍曲林组HAMD评分低于对照组（P〈0.05）;治疗8周3组HAMD评分差异无统计学意义（P〉0.05）。治疗8周舍曲林＋多奈哌齐组及舍曲林组MMSE评分高于对照组（P〈0.001,P〈0.05）。治疗8周舍曲林＋多奈哌齐组及舍曲林组NIHSS评分低于对照组（P〈0.01,P〈0.05）。治疗8周舍曲林＋多奈哌齐组Barthel评分高于舍曲林组及对照组（P〈0.05,P〈0.001）,舍曲林组Barthel指数评分高于对照组（P〈0.05）。结论：联合使用舍曲林与多奈哌齐可明显促进脑卒中患者病后功能恢复。