Neurodevelopmental disorders following thimerosal-containing childhood immunizations: a follow-up analysis

The authors previously published the first epidemiological study from the United States associating thimerosal from childhood vaccines with neurodevelopmental disorders (NDs) based upon assessment of the Vaccine Adverse Event Reporting System (VAERS). A number of years have gone by since their previous analysis of the VAERS. The present study was undertaken to determine whether the previously observed effect between thimerosal-containing childhood vaccines and NDs are still apparent in the VAERS as children have had a chance to further mature and potentially be diagnosed with additional NDs. In the present study, a cohort of children receiving thimerosal-containing diphtheria-tetanus-acellular pertussis (DTaP) vaccines in comparison to a cohort of children receiving thimerosal-free DTaP vaccines administered from 1997 through 2000 based upon an assessment of adverse events reported to the VAERS were evaluated. It was determined that there were significantly increased odds ratios (ORs) for autism (OR = 1.8, p < .05), mental retardation (OR = 2.6, p < .002), speech disorder (OR = 2.1, p < .02), personality disorders (OR = 2.6, p < .01), and thinking abnormality (OR = 8.2, p < .01) adverse events reported to the VAERS following thimerosal-containing DTaP vaccines in comparison to thimerosal-free DTaP vaccines. Potential confounders and reporting biases were found to be minimal in this assessment of the VAERS. It was observed, even though the media has reported a potential association between autism and thimerosal exposure, that the other NDs analyzed in this assessment of the VAERS had significantly higher ORs than autism following thimerosal-containing DTaP vaccines in comparison to thimerosal-free DTaP vaccines. The present study provides additional epidemiological evidence supporting previous epidemiological, clinical and experimental evidence that administration of thimerosal-containing vaccines in the United States resulted in a significant number of children developing NDs.     

Genetic markers in depressive disorders.

1. Association or linkage between a known genetic marker and an illness with a presumed genetic etiology supports two conclusions: a) The genetic etiology would be considered definite, and b) the illness should be considered a homogeneous disease. 2. After separating depressions on the basis of gross familial differences, a finding of linkage or association in any subgroup would indicate that the particular illness is autonomous. Data on association between bipolar and unipolar depression and subtypes of the ABO system are given. 3. Methodological problems in association studies are discussed. 4. Preliminary data suggest the possibility of linkage between the alpha-haptoglobin locus and third component of complement locus and depression spectrum disease, a depression which is familially defined by the presence of alcoholism in the first-degree family member.     

米安色林治疗脑卒中后抑郁症

目的：观察米安色林治疗由脑卒中所致抑郁症的疗效。方法：用米安色林６０ｍｇ／ｄ晚上１次顿服，疗程４ｗｋ，治疗３２例脑卒中后抑郁症。用全国统一的４级标准及ＨＡＭＤ，ＨＡＭＡ，ＣＧＩ，ＡＳＢＳ量表进行疗效和副作用评定。结果：在治疗ｗｋ２时已有明显疗效，ＨＡＭＤ，ＨＡＭＡ评分明显下降，疗效指数（ＥＩ）上升；ｗｋ４时已取得稳定疗效，总显效率为８４％；副作用有轻微头昏、嗜睡、口干、便秘、排尿困难及视物模糊；３例病人有一过性ＡＬＴ升高。结论：米安色林治疗脑卒中所致的抑郁症有良好效果，值得推广。     

香港抑郁症治疗概况(英文)

在香港抑郁症是较为普遍,病人可以适当地被曾受训处理抑郁症的家庭医生所医治,而严重者则需要接受精神专科治疗。但是共病性疾病及躁狂抑郁症仍然被忽略。虽然现今有很多种类的抗抑郁药,但因价格昂贵而未能普遍使用,在公营医疗服务中,情况更甚。     

Toward a biochemical classification of depressive disorders

Pretreatment urinary MHPG levels were examined in 28 depressed patients as a possible predictor of response to treatment with maprotiline, a tetracyclic antidepressant that exerts potent effects on norepinephrine uptake, but has little effect on serotonin uptake. Maprotiline was administered in doses up to 150 mg/day during the first 2 weeks after which time the dose could be increased incrementally up to 300 mg/day if indicated clinically. At 2 weeks, patients with low pretreatment urinary MHPG levels responded more favorably to treatment than did patients with high MHPG levels. At 4 weeks, patients with low MHPG levels continued to show more favorable responses; however, differences between the two groups were less clear-cut than at 2 weeks. The findings suggest that patients with low pretreatment urinary MHPG levels are more sensitive to, and respond more rapidly to, treatment with maprotiline than patients with high pretreatment urinary MHPG levels.This paper was presented in part at the 132nd Annual Meeting of the American Psychiatric Association in Chicago, Illinois, May 12–18, 1979     

Effect of Sahaj Yoga on depressive disorders

Sahaj Yoga is a meditative technique that has been found to have beneficial effects in some psycho-somatic illnesses. The study was carried out on 30 cases (19 Males, 11 females, age 18-45 years) of major depression diagnosed on the basis of DSM IV criteria. The patients were then randomly divided into two groups: Group 1: (10 Males & 5 Females) Patients who were practising Sahaj Yoga and also received conventional anti-depressants. Group 2: (9 Males & 6 Females) Patients who were only receiving conventional anti-depressants. Training in Sahaj yoga was conducted under the supervision of a trained Sahaj Yogi for 8 weeks. At start of the study, all the patients were subjected to Hamilton Rating Scale for Depression (HAM-D) and Hamilton Rating Scale for Anxiety (HAM-A). Above scales were again assessed after two months of treatment. There was significant improvement in HAM-D as well as HAM-A scores in both Group 1 and Group 2 patients (P<0.001). However, percentage improvement in HAM-D scores and HAM-A scores in patients receiving Sahaj Yoga was significantly higher than in Group 2 patients. The number of patients who went into remission after two months of intervention were also significantly higher in Group 1 patients (P=0.02). The present study demonstrates that Sahaj Yoga has got a potential role as a component in the management of depressive disorders.     

Managing depressive and anxiety disorders with escitalopram

This article reviews escitalopram, the S-stereoisomer of the racemic compound citalopram, and a highly selective and potent member of the selective serotonin re-uptake inhibitor class of antidepressants. Escitalopram has a straightforward pharmacokinetic profile, little effect on hepatic metabolism, and is relatively safe in overdose. Similar to other members of the selective serotonin re-uptake inhibitor class, escitalopram (10-20 mg/day) is a well-tolerated and effective treatment of major depressive disorder. Although relatively few head-to-head comparative studies with other antidepressants have been published, pooled analyses of studies using citalopram as the active comparator suggest a modest advantage for the stereoisomer. This advantage, which is more apparent among patients with greater symptom levels, may be attributable to a greater than predicted potency compared with citalopram, presumably as a result of the greater effect of escitalopram at the allosteric binding site of the serotonin transporter. Results of two published studies versus venlafaxine also suggest better tolerability in the context of comparable efficacy. Escitalopram is also approved for the treatment of generalised anxiety disorder (in the US) and social anxiety disorder and panic disorder (in the EU). Pharmacoeconomic models suggest that the greater drug acquisition cost of this patent-protected compound may be offset by greater efficacy (relative to generic citalopram) and tolerability (compared with extended release venlafaxine).     

Therapeutic potential of serotonin antagonists in depressive disorders

Although the precise neurochemical imbalances in depression are still unknown, a role for the neurotransmitter 5-hydroxytryptamine (serotonin) has been implicated since the identification of the first effective antidepressants, imipramine and iproniazid. This led to the development of the selective serotonin re-uptake inhibitors which are widely used in the treatment of depression and depressive disorders, including generalised anxiety disorder, social phobia, obsessive compulsive disorder etc. Studies involving chronic administration in rats led to the hypothesis that the different classes of antidepressant treatment produce a common neuroadaptive change, namely an enhancement of serotonin neurotransmission, albeit via different pre and postsynaptic mechanisms. From this, it was suggested that serotonin antagonists should induce similar neuroadaptive changes, either directly or through a potentiation of other antidepressant agents. Here, the profiles of novel serotonin antagonists currently in preclinical development are reviewed and their therapeutic potential is assessed.     

DSM-5: proposed changes to depressive disorders

The Diagnostic and Statistical Manual of Mental Disorders (DSM) is currently undergoing a revision that will lead to a fifth edition in 2013. Proposed changes for DSM-5 include the creation of several new categories of depressive disorder. Some nosologists have expressed concern that the proposed changes could yield many 'false-positive diagnoses' in which normal distress is mislabeled as a mental disorder. Such confusion of normal distress and mental disorder undermines the interpretability of clinical trials and etiological research, causes inefficient allocation of resources, and incurs risks of unnecessary treatment. To evaluate these concerns, I critically examine five proposed DSM-5 expansions in the scope of depressive and grief disorders: (1) a new mixed anxiety/depression category; (2) a new premenstrual dysphoric disorder category; (3) elimination of the major depression bereavement exclusion; (4) elimination of the adjustment disorder bereavement exclusion, thus allowing the diagnosis of subsyndromal depressive symptoms during bereavement as adjustment disorders; and (5) a new category of adjustment disorder related to bereavement for diagnosing pathological non-depressive grief. I examine each proposal's face validity and conceptual coherence as well as empirical support where relevant, with special attention to potential implications for false-positive diagnoses. I conclude that mixed anxiety/depression and premenstrual dysphoric disorder are needed categories, but are too broadly drawn and will yield substantial false positives; that the elimination of the bereavement exclusion is not supported by the evidence; and that the proposed elimination of the adjustment-disorder bereavement exclusion, as well as the new category of grief-related adjustment disorder, are inconsistent with recent grief research, which suggests that these proposals would massively pathologize normal grief responses.     

DSM-5: proposed changes to depressive disorders

Abstract

The Diagnostic and Statistical Manual of Mental Disorders (DSM) is currently undergoing a revision that will lead to a fifth edition in 2013. Proposed changes for DSM-5 include the creation of several new categories of depressive disorder. Some nosologists have expressed concern that the proposed changes could yield many ‘false-positive diagnoses’ in which normal distress is mislabeled as a mental disorder. Such confusion of normal distress and mental disorder undermines the interpretability of clinical trials and etiological research, causes inefficient allocation of resources, and incurs risks of unnecessary treatment. To evaluate these concerns, I critically examine five proposed DSM-5 expansions in the scope of depressive and grief disorders: (1) a new mixed anxiety/depression category; (2) a new premenstrual dysphoric disorder category; (3) elimination of the major depression bereavement exclusion; (4) elimination of the adjustment disorder bereavement exclusion, thus allowing the diagnosis of subsyndromal depressive symptoms during bereavement as adjustment disorders; and (5) a new category of adjustment disorder related to bereavement for diagnosing pathological non-depressive grief. I examine each proposal’s face validity and conceptual coherence as well as empirical support where relevant, with special attention to potential implications for false-positive diagnoses. I conclude that mixed anxiety/depression and premenstrual dysphoric disorder are needed categories, but are too broadly drawn and will yield substantial false positives; that the elimination of the bereavement exclusion is not supported by the evidence; and that the proposed elimination of the adjustment-disorder bereavement exclusion, as well as the new category of grief-related adjustment disorder, are inconsistent with recent grief research, which suggests that these proposals would massively pathologize normal grief responses.     

Pharmacokinetics of reboxetine in elderly patients with depressive disorders

OBJECTIVES: To examine the pharmacokinetic characteristics of the selective norepinephrine reuptake inhibitor, reboxetine, in elderly patients with depression. PATIENTS: Twelve female inpatients (mean age 80 +/- 4 years) with major depressive or dysthymic disorder were enrolled in a 4-week uncontrolled study of oral reboxetine 2-8 mg/day. METHODS: After a one-week washout period, patients were randomized into two groups (groups A and B, n = 6/group). Reboxetine was given twice daily, starting with 2 mg/day during week 1 and increasing by 2 mg/day each week to 8 mg/day in week 4. Pharmacokinetic evaluations were carried out at two dosage levels in each group: at the end of weeks 1 and 3 in group A (2 and 6 mg/day), and at the end of weeks 2 and 4 in group B (4 and 8 mg/day). Blood and urine samples were taken for determination of reboxetine pharmacokinetics. RESULTS: Reboxetine displayed linear pharmacokinetics, with dose-proportional changes, in elderly depressed patients. Mean total urinary recovery ranged from 4.06 to 6.17%. The mean area under the plasma concentration-time curve (AUCtau) and the maximum plasma drug concentration (Cmax) showed considerable variation between patients; at a dosage of 4 mg/day, AUCtau was 1,466-6,866 ngxh/ml and Cmax ranged from 169 to 663 ng/ml. CONCLUSIONS: The pharmacokinetics of reboxetine are linear across the dosage range of 2-8 mg/day in elderly depressed patients, although Cmax and AUCtau values are higher (and more variable) than in young adults. These results support the use of a lower starting dose (4 mg/day) of reboxetine in the elderly.     

Fluoxetine treatment of depressive disorders in methadone-maintained opioid addicts

This study tested the effectiveness of fluoxetine as a treatment for depression in a population of methadone-maintained opioid addicts. Methadone-maintained opioid addicts (44) with depression received fluoxetine or placebo in addition to their methadone, in a double-blind randomized trial, for 12 weeks. Depressive symptoms decreased significantly overall with no significant differences between the groups treated with fluoxetine versus placebo. In addition, drug use outcomes, including cocaine and heroin self-reported use and urine toxicology were measured. There was a significant decrease in heroin use in treatment, but no medication effect. Cocaine use, was unchanged from pre-treatment to endpoint. In separately analyzing data for the subsample of subjects with the most severe depression, there was a significant decrease in depression during treatment and a significant decrease in self-reported cocaine use, but no medication effect on either depressive symptoms or on cocaine use. This study suggests that fluoxetine is not an effective agent in treating depression or cocaine use in this population.     

Size and burden of depressive disorders in Europe.

We review epidemiological studies of depression in Europe. Community surveys are essential. Methodological differences in survey methods, instruments, nuances in language and translation limit comparability, but consistent findings are emerging. Western European countries show 1 year prevalence of major depression of around 5%, with two-fold variation, probably methodological, and higher prevalences in women, the middle-aged, less privileged groups, and those experiencing social adversity. There is high comorbidity with other psychiatric and physical disorders. Depression is a major cause of disability. Incidence has been less studied and lifetime incidence is not clear, with longitudinal studies required. There is pressing need for prevalence studies from Eastern Europe. The considerable differences in health care systems among European countries may impact on proportions of depressives receiving treatment and its adequacy, particularly in the key area of primary care, and require further study. There is a need for public health programmes aimed at improving treatment, reducing rates and consequences of depressive disorders.     

抗抑郁药临床治疗的选择

新型抗抑郁药在国内过去10余年得到了广泛应用,本文简述近年来的文献,重点介绍美国抑郁障碍最新治疗指南的要点、最新循证医学证据对相关抗抑郁药的疗效评估,以及针对不同临床亚型的抑郁患者如何选择抗抑郁药,旨在规范、合理地使用抗抑郁药。