Critical appraisal of effects of estrogen replacement therapy on symptoms of depressed mood

That estrogen plays a role in the regulation of mood has been postulated since extracts of animal ovarian tissue were administered to oophorectomized women at the end of the last century to alleviate psychological symptoms thought to be related to the removal of the ovaries. The occurrence of depressive symptoms in the perimenopause is associated with a variety of factors. A previous history of either depression and/or premenstrual syndrome as well as cognitive factors explain most of the variance. There are no consistent findings of a correlation between any serum hormone level and severity or presence of mood symptoms. Neurobiological studies show, with regard to an antidepressant effect, promising effects of estradiol on serotonergic, noradrenergic, cholinergic, dopaminergic and GABAergic functions. Progestogens seem to oppose some of these effects. The role of adrenergic hormones and DHEA(S) is less clear. Most clinical trials showed a modest effect on symptoms of depression. However, the predominantly poor methodological quality does not allow generalisation and recommendations. A "tonic" effect on well-being in non- or mild depressed women should not be regarded as true antidepressant effect. Results yielded in studies of surgically menopausal women may not be applicable to women with natural menopause. There is a great potential for exploring various types, doses, and routes of administration of both antidepressants and sex hormones. With regard to the domino theory, future studies should also focus on the mediation of treatment effects through alleviation of vasomotor symptoms or sleep quality.     

Stinging insect allergy: Natural history and modification with venom immunotherapy

The natural history of stinging insect allergy and its modification by venom immunotherapy was investigated by follow-up observations of patients with histories of venom anaphylaxis and detectable venom-specific IgE. The patients were divided into three categories: (1) receiving venom immunotherapy, (2) declined venom immunotherapy, and (3) terminated venom immunotherapy. One hundred twenty-seven patients were evaluated after 6 mo to 9 yr of venom immunotherapy. Most received top venom doses of 50 μg of yellow jacket and/or honeybee venoms every 4 wk. There were 87 restings in 48 patients resulting in two systemic reactions, only one of which could be considered a treatment failure (1%). Fifty-six patients never received venom immunotherapy. In this group there were 40 restings in 28 patients with 14 systemic reactions (35%). In 88 patients who stopped venom immunotherapy, 61 restings in 41 patients led to 11 systemic reactions (17%). Patients with cardiovascular/or respiratory symptoms with initial sting anaphylaxis were at risk for subsequent reactions. With one exception, patients with hives and edema only as the initial reaction either had a similar or no reaction when they were restung. These results confirm the efficacy of venom immunotherapy but also suggest that there are factors other than the presence of venom-specific IgE modulating the occurrence of clinical anaphylaxis.     

Adverse reactions during drug challenges: a single US institution's experience

BackgroundDrug challenge is a useful tool when diagnostic testing lacks predictive value for a questionable history of drug allergy. Placebo-controlled drug challenge studies demonstrate that a significant number of patients report purely subjective symptoms to placebo.ObjectiveTo evaluate the safety and rate of adverse effects when performing drug challenges and to identify predictive factors for occurrences of subjective symptoms during drug challenges.MethodsWe performed a 6-year, retrospective medical record review of patients who underwent drug challenges by members of the Allergy and Immunology Division after consultation deemed drug challenges to be appropriate. Statistical analysis was performed to compare the proportion of patients with subjective symptoms based on certain factors, including sex, age, number of listed drug allergies, interval from historical drug reaction to the drug challenge, and types of historical reaction.ResultsA total of 114 patients underwent 123 drug challenges. Only 1 patient was deemed to have a true positive drug challenge result. Twenty patients reported subjective symptoms during graded challenge, all of which were not deemed a positive challenge. There was a significantly higher proportion of patients who reported subjective symptoms in females, those with a higher number of listed drug allergies, and those whose historical reactions were primarily subjective in nature.ConclusionDrug challenges are safe procedures in appropriately selected patients. A number of patients report subjective symptoms during drug challenges. Identifying patients at high risk for subjective symptoms may assist in determining whether placebo-controlled drug challenges should be performed.     

The treatment of depression in patients with epilepsy. A double-blind trial

Forty-two patients with depression and epilepsy were entered into an antidepressant trial of amitriptyline, nomifensine and placebo. The dose of the active drug was 25 mg tid, which was doubled in non-responders on the active drug after 6 weeks. At that point a further 6 week follow-up was carried out. Serum antidepressant and anticonvulsant levels were assessed. The results indicated that at 6 weeks all patients showed a decline in their depression scores but at 12 weeks nomifensine was superior to amitriptyline. The possible reasons for this and the clinical implications of this are discussed.     

Disodium cromoglycate in ragweed-allergic rhinitis.

This study was designed to test the effectiveness of disodium cromoglycate when compared to placebo in a double-blind study in patients with ragweed allergic rhinitis. Patients were selected on the basis of a clinical history and a 4+ reaction to the intradermal injection of water-soluble ragweed, 0.02 c.c. of 500 PNU/c.c. Active agent/placebo groups were selected at random and were on the drug for approximately 8 wk, commencing 1 wk prior to the onset of the ragweed pollen season. Patient response was evaluated using patient diary cards, number of antihistamine tablets taken, and patient interviews. In the Toronto study, of 17 patients on the active drug, 15 were graded as improved, compared to only 6 of 21 placebo-treated patients who were improved. However, in the Hamilton study, results were less impressive. Nonetheless, it appears that intranasal insufflation of disodium cromoglycate was more effective in reducing ragweed hay fever symptoms than placebo.     

How accurate are patients in reporting their antidepressant treatment history?

BACKGROUND: A patient's report of their antidepressant treatment history is one of the most important pieces of information used in selecting an antidepressant regimen. It is currently unknown how accurate patients are in describing and characterizing their antidepressant treatment history. METHODS: Seventy-three patients receiving treatment for depression at our outpatient psychiatric practice were interviewed by an independent evaluator who was blind to each patient's treatment history. Information was obtained regarding which antidepressant and augmentation regimens patients had undergone, antidepressant doses, duration of trials, and the nature of response to each trial. The results of these interviews were then compared with patients' actual treatment history as elicited from an independent chart review. RESULTS: Patients recalled 85 of the 104 (81.7%) monotherapy trials they had undergone in the past 5 years, but only recalled 12 of 46 (26.1%) augmentation trials (P<0.001). Patients were found to be very reliable in distinguishing between those trials that were of adequate dose and duration and those that were not. Patients were also generally reliable in depicting the quality of response to past trials, though patient report of a past negative trial was significantly more reliable than a report of a past positive trial. The presence of current depressive symptomatology did not adversely affect patients' ability to recall past trials or accurately describe their responses to past regimens. LIMITATIONS: All patients were treated by a single psychiatrist, and all trials occurred within the last 5 years. CONCLUSION: Patients are able to recall the majority of monotherapy trials they have undergone, but have great difficulty remembering when two medications were taken concurrently, i.e. augmentation trials. Patient report appears to be a satisfactory method to obtain information regarding trial adequacy and response in most, but not all instances.     

Dexamethasone suppression test in masked depression

The dexamethasone suppression test (DST), family history, response to antidepressant medication and short-term course were investigated in 16 female patients with masked depression. Twelve patients showed abnormal DST results, 3 patients had positive family history of affective illness in first-degree relatives, 11 responded well to antidepressant drug treatment and 3 showed definite hypomanic episodes during follow-up. The results suggest that masked depression is a special form of primary (endogenous) depressive illness, and that the DST is a good diagnostic aid not only in the 'classical' but also in masked forms of depressive disorders.     

Attrition in maintenance therapy for recurrent depression. A preliminary report

All maintenance treatment programs are complicated by the issue of patient noncompliance. This report investigates factors contributing to noncompliance during a 2-year study designed to evaluate the efficacy of long-term antidepressant medication in patients with recurrent unipolar depression. Only 21 of 51 patients (49%) who entered maintenance treatment successfully completed this phase of the study. Fifteen patients (8 completers and 7 dropouts) were randomly selected for an interview which focused on their previous psychiatric treatment history and attitudes towards the maintenance treatment program. In addition, these patients also completed a comprehensive personality battery. Results indicate that, while both groups had similar attitudes about the treatment program, they differed significantly along personality and psychiatric treatment history variables. Dropouts scored higher than completers on a measure of hysterical personality style. They were also more likely to have received psychotherapy in previous treatment experiences and to rate it as beneficial, while completers consistently rated prior treatment, which did not include antidepressant medication, as being of no benefit whatsoever. In order to enhance patient compliance, it is important to obtain information early in treatment about patients' treatment histories and their expectations about effective treatment for depression.     

Flupenthixol in depression. A study of serum levels and prolactin response

The relationship between improvement in symptomatology and changes in prolactin and serum cis-flupenthixol levels has been evaluated in 16 patients with a clinical diagnosis of depression, who were treated with 1 or 2 mg of flupenthixol in a once daily morning dose. No significant differences in clinical response were noted between those on 1 and 2 mg, and side effects were few. The presentation of some side effects, in particular extrapyramidal symptoms, were related to higher serum levels and prolactin levels particularly in the early stages of the study. Improvements in depressive symptoms were unrelated to serum levels, but at day 56 of the trial were positively correlated to changes in prolactin levels. Improvements in anxiety symptoms were positively related to serum levels at day 3 but negatively related at day 56. These results are discussed in the light of possible influences of dopamine antagonism in relation to an antidepressant effect.     

Subject-own-control design in evaluating clinical antidepressant effects

This study tested the use of a subject-own-control, multiple crossover design for evaluating the clinical effects of an established tricyclic antidepressant drug, imipramine. Although significant physiological and cognitive performance effects were demonstrated, only one clinical measure, target symptom change rated by the patients, showed a statistically significant drug-placebo difference. This result is in considerable contrast to the sensitivity of similar designs in detecting the clinical effects of antianxiety drugs in studies employing less than 20 patients. Crossover designs appear to be most successful when the treated condition is continuous, rather than episodic, and the treatment effects have a rapid onset and offset.     

S—腺苷蛋氨酸治疗抑郁症

目的：观察新型天然抗抑郁药Ｓ－腺苷蛋氨酸的抗抑郁作用及其不良反应。方法：采用该药开放性治疗各种抑郁性障碍３１例。采用Ｈａｍｉｌｔｏｎ抑郁量表和临床总体印象评定临床疗效。结果：全部病人（包括脱落病人）的有效率为７２．４％。疗程分析发现该药起效较快，在治疗第四天量表评分业已有显著下降。第二周时已较基线分下降了５２％。因子分析发现，该药对主观焦虑因子效果不佳，对其它各因子均有显著效果。该药不良反应轻微，无一例因药物不良反应导致治疗中断。结论：Ｓ－腺苷蛋氨酸是一种安全有效的天然抗抑郁药物     

Paracoccidioidomycosis associated with human immunodeficiency virus infection. Report of 10 cases.

We describe here the epidemiological and clinical characteristics of 10 HIV-infected patients with paracoccidioidomycosis. All patients were adult males from small towns in Brazil and had a previous history of work or residence in a rural area. The two infections were diagnosed concomitantly in six of the ten patients, and for six of the patients, the mycosis was the first clinical manifestation of HIV infection. Risk factors for HIV infection were injection drug use in some patients and multiple sexual partners in others. Six patients died and autopsy revealed severe disseminated paracoccidioidomycosis in three. Exuberant and severe clinical pictures suggest an alteration in the natural history of this mycosis as a result of HIV immunosuppression. The frequency of paracoccidioidomycosis in the HIV-infected population is not known to differ from that reported for this mycosis in non-HIV patients.     

Anticonvulsant hypersensitivity syndrome: cross-reactivity with tricyclic antidepressant agents.

BACKGROUND: Aromatic anticonvulsant agents such as carbamazepine and phenytoin can induce anticonvulsant hypersensitivity syndrome (AHS) at a frequency of 1 in 10,000 to 1 in 1,000 treated patients. The hypersensitivity syndrome is a potentially life-threatening adverse drug reaction with multiorgan involvement, and incidental reexposure must be strictly avoided. Patients and treating physicians must be informed and educated about the causal drug and its potential immunologic or toxicologic cross-reactivity with other compounds. It has been well established that for future antiepileptic drug therapy, carboxamides (carbamazepine and oxcarbazepine), phenytoin, and barbiturates (phenobarbital and primidone) have to be avoided owing to their high degree of cross-reactivity. Other anticonvulsant agents, such as valproic acid, benzodiazepines, and gabapentin, may be prescribed. OBJECTIVES: To present the clinical data for and to describe the potential cross-reactivity between aromatic anticonvulsant and tricyclic antidepressant agents in patients with carbamazepine- and phenytoin-induced AHS. METHODS: The knowledge of cross-reactivity among aromatic anticonvulsant agents mainly emerged from clinical experience and observations because diagnostic challenge tests are not advisable. Thirty-six patients with the diagnosis of AHS were instructed to contact our unit if the symptoms relapsed. RESULTS: Despite better knowledge of AHS, one third of the patients had avoidable recurrences after exposure to cross-reactive drugs. Besides the known cross-reactivity among aromatic anticonvulsant agents, we observed a recurrence of the hypersensitivity syndrome in 5 patients after the administration of tricyclic antidepressant agents. CONCLUSION: The important potential cross-reactivity between aromatic anticonvulsant and tricyclic antidepressant drugs should be brought to the attention of treating physicians.     

Sexual dysfunction before antidepressant therapy in major depression

BACKGROUND: Decreased sexual interest and function both occur as a consequence of antidepressant medication use, and are especially associated with serotonin reuptake inhibitors (SRIs). However, few investigators have reported the base rate for disturbances in sexual desire, arousal and orgasm or ejaculation in patients with major depression (MD) prior to antidepressant treatment. The purpose of this report is to define the frequency of sexual dysfunction (SD) in 134 patients with MD and examine the relationship between SD and demographic, clinical and personality variables. METHOD: A consecutive series of 55 male and 79 female MD patients diagnosed by SCID-DSM IV assessment completed a series of psychometric measures including a Sexual Function Questionnaire, which asked about change in sexual interest and function as well as sexual activity during the preceding month. RESULTS: Only 50% of women and 75% of men reported sexual activity during the preceding month. Over 40% of men and 50% of women reported decreased sexual interest. Reduced levels of arousal were more common in both men and women (40-50%) than ejaculatory or orgasm difficulties (15-20%). In women, problems with arousal and orgasm correlated with higher neuroticism and lower extraversion. There was no relationship between SD and personality measures in men. While age at onset of depression and number of prior episodes showed a modest correlation with SD measures, there were no correlations with severity of depression or specific symptoms clusters. LIMITATIONS AND CONCLUSIONS: Although limited by a relatively small sample of drug free patients with MD, and by the absence of a non-depressed comparison sample, these results emphasize the importance of factors beyond specific drug effects in the assessment of antidepressant related sexual dysfunction.     

Association of race and gender with HIV-1 RNA levels and immunologic progression

CONTEXT: HIV-1 RNA and lymphocyte subset levels are the principal indications for antiretroviral treatment. Past reports have differed with regard to the effect of gender and race on these measures and in measures of disease progression. OBJECTIVE: To assess racial and gender differences in HIV-1 RNA levels and CD4+ lymphocyte decline. DESIGN: A longitudinal study based in the two largest HIV natural history cohort studies conducted in 7 metropolitan areas of the United States. RESULTS: In all, 1256 adult women and 1603 adult men for whom multiple data points were available prior to initiation of antiretroviral therapy were included. Women were more likely to be nonwhite, to have a history of injection drug use, and to have HIV-associated symptoms. After adjustment for differences in measurement method, baseline CD4+ cell count, age, and clinical symptoms, HIV-1 RNA levels were 32% to 50% lower in women than in men at CD4+ counts >200 cells/mm3 (p <.001) but not at CD4+ cell counts <200 cells/mm3. HIV-1 RNA levels were also 41% lower in nonwhites than in whites (p <.001) and 21% lower in persons reporting a prior history of injection drug use (p <.001). Women had more rapid declines in CD4+ cell counts over time than men (difference in slope of 46 cells/year) and nonwhite individuals had slower decline in CD4 cell counts than whites (difference of 39 cells/year). CONCLUSIONS: Both race and gender influence the values of HIV-1 RNA and the rate of HIV-1 disease progression as indicated by decline in CD4 cell counts over time. These effects could provide clues regarding the factors that influence HIV-disease progression and may indicate that guidelines for therapy should be adjusted for demographic characteristics.     

新冠肺炎患者焦虑症状及相关因素

目的:调查新冠肺炎患者的焦虑症状并分析相关因素。方法:新冠肺炎患者108例,采用自编一般资料调查表、广泛性焦虑量表(GAD-7)、简易应对方式量表(SCSQ)进行调查。结果:GAD-7总分(10.3±4.5)分。对GAD-7各条目进行秩和检验发现,有焦虑症状患者的GAD-7得分大于无焦虑症状患者(P<0.05)。GAD-7总分与积极应对得分呈负相关(r=-0.44,P<0.001),与消极应对得分呈正相.关(r=0.31,P<0.01)。二分类logistic回归分析显示,有发热症状、有接触史是焦虑症状的危险因素(OR=33.40、18.13),男性、积极应对是焦虑症状的保护因素(OR=0.02、0.03)。结论:新冠肺炎患者为女性、出现发热、有接触史时其焦虑症状越严重。     

Effects of antidepressant drugs on the behavior of olfactory bulbectomized and sham-operated rats

Removal of the main olfactory bulbs in rats has been shown to alter neuronal function in brain areas involved in emotional regulation and homeostasis. These neuronal alterations result in maladaptive behavioral patterns and elevated plasma corticosterone that are suggestive of the symptom profile of patients with primary unipolar depression. Moreover, the endocrine and behavioral deficits of bulbectomized rats are reversed by the chronic administration of drugs that reverse the symptoms of depression in people when given chronically. However, the therapeutic improvements seen in patients with depression are not directly due to molecules of the antidepressant drug but rather to some relatively long-lasting compensatory change induced in the neuronal substrate by the drug. The present research demonstrates that the reversal of the olfactory bulb lesion deficits following chronic antidepressant drug administration in rats is not due to molecules of the drug per se but rather to some drug-induced change in the neuronal substrate that continues for at least 5 days after the last dose of drug. These endocrine, behavioral, and pharmacological similarities suggest that the study of rats with olfactory bulb ablation may make significant contributions to the understanding of the neuroscience of primary unipolar depression in humans.     

Cross-sector sponsorship of research in eosinophilic esophagitis: A collaborative model for rational drug development in rare diseases

Like many rare diseases, eosinophilic esophagitis (EoE) is a poorly understood disorder, and assessment tools to accurately determine disease activity, remission, and natural history have long been inadequate. Clinical outcome end points able to assess the effectiveness of candidate therapeutic agents in clinical trials have been a particular deficiency and are urgently needed. With no approved therapy available to patients and with the prevalence of EoE on the increase, collaborative approaches to drug development are becoming ever more important. We describe a collaborative effort mobilized across institutions, including both the public and private sectors, that was initiated within the past 18 months expressly to address the need for further clinical research into the cause and treatment of EoE. Collaborators include the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition; the International Gastrointestinal Eosinophilic Researchers; and the US Food and Drug Administration. This effort has resulted in the elucidation of several parameters essential for effective EoE registration trials, including the need for clinically meaningful end points that measure changes in clinical symptoms in addition to the assessment of intraepithelial mucosal eosinophilia. The development and use of biomarkers, particularly in early-phase drug development, have become an important focus for investigations that might reduce clinical reliance on serial invasive monitoring. The concerted efforts described here to develop rational therapeutics and drug development paradigms in EoE also appear to provide a model for effective collaboration in the context of drug development for rare diseases and perhaps more generally for public health initiatives.     

Cortical evoked potentials and clinical rating scales as measures of depressive illness

Relationships between clinical ratings and cortical evoked potentials were examined before and during antidepressant drug treatment in 32 patients with major depressive disorder (DSM-III). Clinical rating scales included Hamilton Rating Scale for Depression, Beck Depression Inventory, Present State Examination (PSE) and Newcastle Scale. Evoked potentials included contingent negative variation (CNV), post-imperative negative variation (PINV) and auditory evoked potential (AEP) There were close correlations between all rating scales, and factor analysis produced only one component, suggesting that the common variance between them related to severity of depression. CNV magnitude before treatment correlated negatively with severity of depression regardless of diagnostic category. Depressed patients had a prominent PINV which persisted during antidepressant treatment. The amplitude of late components (N1P2) of the AEP was reduced strikingly in patients with a history of suicide attempts.