Adverse experiences during licensed treatment with the antidepressant serotonin (5-HT) reuptake inhibitor zimeldine in Sweden are presented. Data were obtained from a written inquiry of 694 patients and 67 reports to the Medical Products Agency. The spectrum of adverse symptoms was in agreement with those reported in previous studies on zimeldine. The most frequent adverse experiences were headache, nausea, myalgia, signs of liver function disturbance, arthralgia, neurological symptoms, fever and insomnia. No new case of the Guillain-Barré syndrome was found. The estimated frequency of the zimeldine-induced hypersensitivity syndrome (HSS), comprising fever, myalgia and/or arthralgia and signs of liver function disturbance, ranged from 1.4% to 13% in the inquiry and from 0.63% to 3.4% in the report part of the study. Adverse experiences usually had a considerably higher incidence during the first 6 weeks of zimeldine treatment than thereafter. This is in agreement with the clinical experience that most of the adverse reactions occur early during zimeldine treatment. However, a number of adverse experiences did occur with a later onset. This may justify a prolongation of the compulsory 4 weeks' testing of liver function that is required during licensed treatment. There were significantly fewer patients who developed fever among the patients who had experienced previous zimeldine treatment than among those who had not. Otherwise there was no statistically significant difference in frequency of adverse symptoms between these two groups. Consequently zimeldine treatment per se does not seem to predispose to development of an HSS or other types of adverse reactions during subsequent therapy.
In the period from October 1990 to December 1991, 23 patients with acute ischemic stroke were treated with recombinant tissue plasminogen activator (rt-PA) at a median of 205 min (range 78-355 min) after symptom onset. In this open pilot study rt-PA was given intravenously after an acute CT scan had not shown acute changes. In 12 patients regional cerebral blood flow was measured intravenously using 99mTc-HMPAO before and within 24 h after thrombolytic therapy. Reperfusion of the ischemic area was obtained in 10 patients. In these patients clinical improvement was greater the shorter the delay from symptom onset to initiation of treatment. Three of the 23 patients died, one of a parenchymatous hematoma, one of a large middle cerebral artery infarct, and one of acute myocardial infarction.
Physiological dependence on benzodiazepines is accompanied by a withdrawal syndrome which is typically characterized by sleep disturbance, irritability, increased tension and anxiety, panic attacks, hand tremor, sweating, difficulty in concentration, dry wretching and nausea, some weight loss, palpitations, headache, muscular pain and stiffness and a host of perceptual changes. Instances are also reported within the high-dosage category of more serious developments such as seizures and psychotic reactions. Withdrawal from normal dosage benzodiazepine treatment can result in a number of symptomatic patterns. The most common is a short-lived "rebound" anxiety and insomnia, coming on within 1-4 days of discontinuation, depending on the half-life of the particular drug. The second pattern is the full-blown withdrawal syndrome, usually lasting 10-14 days; finally, a third pattern may represent the return of anxiety symptoms which then persist until some form of treatment is instituted. Physiological dependence on benzodiazepines can occur following prolonged treatment with therapeutic doses, but it is not clear what proportion of patients are likely to experience a withdrawal syndrome. It is also unknown to what extent the risk of physiological dependence is dependent upon a minimum duration of exposure or dosage of these drugs. Withdrawal phenomena appear to be more severe following withdrawal from high doses or short-acting benzodiazepines. Dependence on alcohol or other sedatives may increase the risk of benzodiazepine dependence, but it has proved difficult to demonstrate unequivocally differences in the relative abuse potential of individual benzodiazepines.
This paper is intended to help American clinicians and investigators further their understanding of the clinical use of clozapine by reviewing experience with the drug in Russia, where it was introduced 17 years before it became available in the United States.
Key articles on clozapine from the Russian clinical research literature were reviewed by the first two authors, former Russian clinical investigators. The third author comments briefly about the implications of this work from a contemporary American perspective.
The review found that although clozapine was not widely distributed in Russia, it was investigated at several large psychiatric research institutions and hospitals. It was not reserved for neuroleptic-resistant disorders but instead was used with some success as a first-line treatment in acute disorders. Although no controlled clinical trials were conducted, results of long-term outcome studies of treatment-resistant schizophrenia were largely in agreement with those of controlled trials and clinical follow-up studies in the U.S. The studies found short-term gains for previously refractory patients as well as improvements in social functioning that continued for extended periods in some cases. Russian investigators described clozapine as an effective antipsychotic agent that lacked the extrapyramidal side effects of other neuroleptics.
To compare preference assessments that were made by using the EuroQol EQ-5D and the Health Utilities Index Mark II.
561 patients in a randomized trial of tirilazad mesylate for aneurysmal subarachnoid hemorrhage.
Three preference assessments (a value score for the EuroQol instrument and value and utility scores for the Health Utilities Index) made three months after randomization. The averages for each of the three scores, stratified by clinical outcomes and attributes of the Health Utilities Index health status classification system, were compared. To evaluate potential sources of difference between the instruments, the authors estimated two alternative Health Utilities Index scoring rules that were based on patient responses to the EuroQol instrument.
Patients' ratings of their current health made by using the 100-point visual analog scale from the EuroQol instrument were more similar to the utility scores for the Health Utilities Index than they were to the value scores for the Health Utilities Index. The biggest differences between the visual analog scores for the EuroQol instrument and the utility scores for the Health Utilities index were seen at higher levels of functioning.
For states representing higher levels of functioning, differences were seen between patients' self-ratings obtained by using the EuroQol instrument and the patients' utility scores on the Health Utilities Index; for states representing lower levels of functioning, substantial agreement was observed between these two scores. Differences observed at the higher levels of functioning suggest that further research is needed to determine whether the Health Utility Index's assignment of a score of 1.0 to the reference state representing being healthy is appropriate.
Erratum In: Med Decis Making 1999 Oct-Dec;19(4):511
The recovery of 16 infants born by elective caesarean section with spinal anaesthesia, in which either ephedrine or fluid load was used to prevent maternal hypotension, were studied using Scanlon's neurobehavioural tests and a computerized EEG. Neurobehavioural testing showed no differences between the ephedrine and the non-ephedrine groups of infants at ages of 3 h, 1 day, 2 days and 4-5 days, whereas the spectral EEG showed significant differences between the two groups during the first 2 h after delivery, which had disappeared 24 h later. It is suggested that small doses of ephedrine given to the mother i.v. to prevent hypotension during spinal anaesthesia have short-lived effects on the neonate's central nervous system, which will be detected in the spectral EEG, but not in neurobehavioural tests.
In this study, we investigated the effects of selegiline on levodopa treatment and parkinsonian disability over several years of treatment in patients with early Parkinson's disease (PD). The 163 patients were randomized to receive either selegiline or placebo in addition to levodopa in a double-blind, parallel-group study design, and the patients were to be followed up until a defined termination point or for 5 years. All patients had previously either never (two thirds) or for or = 3 years. Nine patients were excluded from the study because of protocol violations or because the patients were diagnosed as unlikely PD. At the time of interim analysis, 39 patients had been withdrawn from the study because of adverse effects or their own wish. Eighteen patients had reached the termination point, and 97 patients (observation time, 30-54 months) were still in the study. Among the patients receiving selegiline, we found a rather stable daily levodopa dose during 54 months of therapy, compared with an anticipated increase among patients with levodopa monotherapy. Concurrently, patients in the selegiline group showed a trend to develop less severe parkinsonian disability and a lower frequency of motor fluctuations and need for additional antiparkinsonian medication. The results of this study indicate that early combination therapy of selegiline and levodopa compared with levodopa monotherapy has an increasingly favorable impact on the long-term daily levodopa dose and may possibly delay the development of disability in PD.
The aim of this study was to estimate the association between moderate alcohol consumption in pregnancy and child development to the age of 3.5 years. Furthermore, the aim was to compare development indices at 18 and 42 months of age. This study is an extension of the Danish participation in the EuroMac study. In a two-stage sampling, pregnant women in a well-defined region (Odense, Denmark) were recruited to a follow-up study according to their reported drinking habits in the first trimester of pregnancy. All among 2880 pregnant women who reported an alcohol consumption early in pregnancy (12th week of gestation) of at least 5 drinks/week were ascertained (164 women). A similar age and expected time of delivery matched group was selected from the remaining group of pregnant women. Alcohol consumption data were based on self-reported data, and child development recording was done blindly by two psychologists at 18 and 42 months after birth. Two hundred fifty-one mother-child pairs participated in all follow-up studies. None of the reported levels of alcohol intake was statistically significantly associated with any of the child development indices (including measures of binge drinking). Comparing child development indices at 18 and 42 months did, however, reveal a rather large variation over time for alcohol exposures, as well as nonexposures. A large variation in the outcome measure will tend to mask effects of any exposures, but nevertheless it is unlikely that a low alcohol intake in pregnancy has any substantial impact on child development.
An international, multicenter trial was conducted in 331 patients to determine the effect of a large dose of flunarizine (a calcium entry blocker) in the treatment of acute ischemic stroke in the territory of the Middle cerebral artery.
The administration of the trial medication should start within 24 h after the initial symptoms of stroke. According to a random schedule, the patients were assigned to a 4-weeks double-blind treatment with either flunarizine (n = 166) or placebo (n = 165): one week intravenous administration (50 mg daily), followed by 3 weeks oral treatment (week 2, 21 mg daily; week 3-4, 7 mg daily). All patients had to be investigated by computerized tomography (CT) within 7 days after stroke onset; 36 patients were secundarily excluded because the CT showed another pathology. During the treatment period, other "stroke therapies" were not allowed. Patients were followed up for 24 weeks.
After the 24 weeks trial period, the percentage of patients who were dead or pendent (modified Rankin score 3-5) was similar in both treatment groups (flunarizine 67%, placebo 65%). During the trial, the scores for handicap severity (modified Rankin scale), neurological status (Orgogozo) and activities of daily living (modified Barthel index) strongly improved in both treatment groups, but no differences were found between the treatment groups. In this trial, the administration of trial treatment started relatively late after stroke onset (flunarizine group: mean time interval 13.5 h; placebo 12.3 h). A subgroup of patients received trial medication within 6 h after stroke onset (flunarizine n = 31; placebo n = 29). Also in this subgroup, no differences were found between the flunarizine and placebo group.
Flunarizine did not improve neurologic and functional outcome in patients with acute ischemic stroke.
A 10-year-old boy with subacute sclerosing panencephalitis was treated with intravenous gamma-globulin and inosiplex and followed for 18 months. Clinical improvement, demonstrated by decreasing scores on the Neurologic Disability Index, was observed. There were no side effects. We recommend intravenous immune globulin as an alternative therapy in the treatment of subacute sclerosing panencephalitis.