Aniracetam tested in chronic psychosyndrome after long-term exposure to organic solvents. A randomized, double-blind, placebo-controlled cross-over study with neuropsychological tests.

In order to examine if the nootropic drug, aniracetam, was capable of improving cognitive performance, 44 subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents were included in a randomized, double-blind, placebo-controlled, cross-over study. The treatment periods were 3 months with aniracetam 1 g daily and 3 months with placebo. Neuropsychological tests as well as a physical and neurological examination were performed at entry into the study and after each treatment period, together with an evaluation of the subjects' overall condition. Neither the doctors' nor the subjects' own assessment of the overall condition indicated that the trial medication had had any effect. No significant changes in neuropsychological symptoms were observed. A statistically significant difference in favour of antiracetam was found in only 1 of the 19 neuropsychological test measures, namely a test for constructional ability. However, in another test on visuo-spatial function, a statistically significant result was found in favour of placebo. Thus, aniracetam was found to be ineffective in the treatment of subjects suffering from chronic psychosyndrome after long-term exposure to organic solvents.

A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia. I. Mothers.

In a randomized blind trial midazolam (0.3 mg kg-1) was compared with thiopental (4 mg kg-1), both combined with meperidine-nitrous oxide, for elective cesarean section anesthesia in 40 women. We found no statistically significant differences between thiopental and midazolam at induction, during operation or recovery with regard to maintenance doses, change in maternal neurologic status based on a modified Glasgow Coma Scale, systolic blood pressure, and heart rate. Induction time was 120 seconds with midazolam and 111 seconds with thiopental. There were significant differences with regard to diastolic blood pressure. Side effects occurred with approximately equal frequencies, but vomiting was significantly more frequent after thiopental. Perivenous tenderness and erythema occurred in four patients, all after thiopental. Midazolam appears to be a suitable alternative to thiopental for the induction and maintenance of anesthesia for elective cesarean section.

A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: II. Neonates.

In a randomized blind trial, the general condition of 40 neonates was assessed following midazolam- or thiopental-based general anesthesia for elective cesarean section. Among 19 neonatal neurobehavioral observations and tests, statistically significant differences between the midazolam and the thiopental groups were rare. However, a statistically significant interaction with regard to body temperature, general body tone, and arm recoil was observed where results were inferior for midazolam, although only within the first 2 hours. It was concluded that midazolam is as safe as thiopental for the induction and maintenance of elective cesarean section anesthesia in neonates.

A randomized comparison between midazolam and thiopental for elective cesarean section anesthesia: III. Placental transfer and elimination in neonates.

Forty neonates delivered by cesarean section were studied, half being delivered of mothers in whom anesthesia was induced with midazolam (0.3 mg/kg intravenously) and half of mothers given thiopental (4 mg/kg). At delivery, blood samples from mother and the umbilical vein were drawn for determination of plasma concentrations of thiopental, midazolam, and alpha-hydroxymidazolam. Over the next 60 hours, three blood samples were drawn using a randomized procedure of two blood samples at 30 different times. Placental transfer, expressed as the umbilical/maternal concentration ratio, was 0.96, 0.66, and 0.28, respectively, for thiopental, midazolam, and alpha-hydroxymidazolam. The transfer of thiopental was significantly more rapid than the transfer of midazolam and alpha-hydroxymidazolam. The population average of elimination half-life in neonates was 6.3 hours for midazolam and 14.7 hours for thiopental. Both values are substantially larger than those found in previous studies in adults.

Reversal of flunitrazepam sedation with flumazenil. A randomized clinical trial.

Fifty-nine male patients scheduled for transurethral resection of the prostate under flunitrazepam sedation and spinal analgesia were randomized in a double-blind trial to reversal of sedation with either the benzodiazepine antagonist flumazenil or placebo. Judged by degree of sedation, comprehension and cooperation as well as by estimation of orientation in time and space, flumazenil was superior to placebo (P less than 0.001). The median duration of anterograde amnesia was 16 min after flumazenil and 75 min after placebo (P less than 0.001). Adverse events were more frequent with placebo (P greater than 0.05), while no differences were evident with regard to laboratory data or cardiorespiratory function.

A controlled release form of madopar in parkinsonian patients with advanced disease and marked fluctuations in motor performance.

Flucuations in motor performance is a major problem in long-term levodopa treatment of Parkinsonian patients. A slow release preparation of levodopa with benserazide, Madopar HBS, has been developed in an attempt to decrease this problem. Eleven of 22 Parkinsonian patients with advanced disease and marked fluctuations experienced long-lasting benefit with reduction of their fluctuations in motor performance on treatment with Madopar HBS; 11 dropped out within the first 5 months of the trial. This was probably due to lack of experience with the effect of this new slow-release formulation. Nine patients (82%) required an additional dose of standard Madopar, especially in the morning. Significant improvements were found for akinetic phenomenon and dystonic cramps, and with the global evaluation of motor fluctuations. The occurrence of peak dose dyskinesia remained unchanged. No abnormalities in laboratory values were found.

Madopar HBS: slow-release levodopa and benserazide in parkinsonian patients presenting marked fluctuations in symptoms on standard L-dopa treatment.

In this open study patients with advanced Parkinson's disease, who experienced pronounced fluctuations in symptoms while on standard L-dopa, were switched from Madopar/Sinemet to Madopar HBS. The dosage was adjusted until optimal response was obtained. The effect was unsatisfactory in 4 cases and side effects intervened in another 2. The remaining 16 patients exhibited substantial and frequently significant improvements with regard to both akinetic and dyskinetic phenomena. L-Dopa dosage was increased in all cases, and addition of standard L-dopa was required in one third of the cases. These benefits continued in the majority of patients.

Ro 15-1788 for postoperative recovery. A randomised clinical trial in patients undergoing minor surgical procedures under midazolam anaesthesia.

In a double-blind randomised study, 100 women who underwent induced abortion under midazolam anaesthesia were given the benzodiazepine antagonist Ro 15-1788 or placebo after termination of anaesthesia. Recovery was assessed by means of a modified Steward coma scale. Following incremental doses of Ro 15-1788, 56% of the patients were fully awake within 3 minutes and 92% after 5 minutes, which was significant compared to the placebo group. The median duration of amnesia was 91 minutes after Ro 15-1788 compared to 121 minutes in the placebo group (p less than 0.001). The median dose of Ro 15-1788 was 0.4 mg. A slight positive correlation between total dose of Ro 15-1788 and total amount of midazolam was found. Nausea and/or vomiting were found to be more frequent in the Ro 15-1788 group, but otherwise we found no differences between groups with regard to either side effects or cardiorespiratory function. Ro 15-1788 is evidently an effective antagonist to the sedation induced by midazolam.

Comparison between midazolam and thiopentone-based balanced anaesthesia for day-case surgery.

In a randomized study of 100 women (ASA 1-2) undergoing termination of pregnancy as outpatients, the combination of midazolam-fentanyl-nitrous oxide was compared with thiopentone-fentanyl-nitrous oxide. The induction time (the time recorded until disappearance of the palpebral reflex) was significantly longer in the midazolam group (40 s) than in the thiopentone group (31 s). There were no significant differences in heart rate or arterial pressure between the two groups. Thirty minutes after the termination of surgery the degree of awareness, estimated by means of Glasgow Coma Scale, was lower in the midazolam group. After 60 and 180 min the scores were equal. During recovery more patients experienced side-effects in the thiopentone group than in the midazolam group, the difference being statistically significant 72 h after discharge when 66% and 34% of the patients complained of side-effects, respectively. Midazolam is as suitable as thiopentone for the induction of anaesthesia in day-case surgery.

PIP: In a randomized study of 100 women (ASA 1-2) undergoing pregnancy termination as outpatients, the combination of midazolam-fentanyl-nitrous oxide was compared with thiopentone-fentanyl-nitrous oxide. The induction time (time recorded until disappearance of the palpebral reflex) was significantly longer in the midazolam group (40 seconds) than in the thiopentone group (31 seconds). There were no significant differences in heartrate or arterial pressure between the 2 groups. 30 minutes after termination of the surgery, the degree of awareness, estimated by means of Glasgow Coma Scale, was lower in the midazolam group. After 60 and 180 minutes, the scores were equal. During recovery, more patients experienced side effects in the thiopentone group than in the midazolam group, the difference being statistically significant 72 hours after discharge when 66% and 34% of the patients complained of side effects, respectively. Midazolam is as suitable as thiopentone for the induction of anesthesia in day-case surgery. (author's modified)

Tolerance of tetrabenazine during long-term treatment.

Side-effects, haematological, hepatic and renal changes during long-term treatment with tetrabenazine (Nitoman) were assessed in a multicentre trial of 124 patients with various hyperkinetic syndromes. Side-effects were infrequent and usually mild. They necessitated discontinuation of therapy in 5 cases. Changes in clinico-chemical tests during 12 months on tetrabenazine were always minor, nearly always unsystematic and, on the whole, tended more towards a normalization of values than the opposite. Even recognizing the limitations inherent in a uncontrolled trial, we conclude that long-term treatment with tetrabenazine seems to be quite safe.

Anaesthesia with flunitrazepam and ketamine.

A randomized study of 96 women undergoing hysterectomy was used to compare two anaesthetic techniques: flunitrazepam, ketamine and nitrous oxide in oxygen; and pethidine, thiopentone, nitrous oxide in oxygen and halothane. The techniques exerted small, but significantly different influences on heart rate and arterial pressure. Significantly more patients complained of nausea and vomiting on awakening after inhalation anaesthesia. Amnesia after operation lasted significantly longer after flunitrazepam combined with ketamine and nitrous oxide in oxygen.

Clonazepam (Rivotril) and carbamazepine (Tegretol) in psychomotor epilepsy: a randomized multicenter trial.

The antiepileptic properties of carbamazepine (Tegretol) and clonazepam (Rivotril) were compared in a double-blind randomized study comprising 36 patients with newly diagnosed, untreated psychomotor epilepsy (partial seizures with complex symptomatology). No significant differences were found between the two drugs during the 6 months of treatment. Measurements of concentrations in plasma confirmed that the patients exceeded the accepted lower limit for therapeutic range of the drugs.

Dopaminergic agonist Ro 8-4650 in Parkinson's disease. II. Patients not treated with dopa.

An isoquinolone derivative Ro 8-4650 (rac-4-(3,4-dichlorophenyl)-1,2,3,4-tetrahydro-7-methoxy-2-methylisoquinoline hydrochloride) with dopaminergic properties was studied in a randomized crossover trial. The group studied comprised 37 patients with idiopathic parkinsonism, not previously treated with levodopa or dopamin agonists. The trial drug was significantly more effectve than placebo, but the clinical improvement, according to the Webster rating scale, was small. No significant difference was observed as regards involuntary movements, but the trial drug led to more frequent minor side effects. It can be concluded that the trial drug, despite its proven effect in Parkinson's disease, has only limited clinical value.