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Biomedical subjects

J F Dreyfus

Publications and source records attributed to J F Dreyfus.

At least 19 recordsLinked to original sources
PubMed1991

Glycosaminoglycan polysulfate in the treatment of old age dementias.

1. In a multicenter, placebo-controlled, double-blind clinical trial in 155 elderly patients with cognitive decline, glycosaminoglycan polysulfate was found to be a therapeutically effective agent in the treatment of old age dementias. 2. Treatment with glycosaminoglycan polysulfate in the daily dosage of 600 LRU, administered on the basis of a divided dosage schedule for 12 weeks, was significantly superior to an inactive placebo on several outcome measures including the Wechsler Memory Scale-Russell Revision (Easy Paired Associates Learning and Immediate Visual Reproduction), Mini Mental State Examination, the Sandoz Clinical Assessment Geriatric (Cognitive Dysfunction and Depression), Hachinski Dementia Scale, Brief Psychiatric Rating Scale (Confusion and Depressive Withdrawal) and Global Improvement Scale of the Clinical Global Impression. 3. Adverse effects with glycosaminoglycan polysulfate were few and mild. The drug was equally well tolerated and equally effective in the two major dementias of old age, i.e., primary degenerative and multi-infarct. The number of abnormal laboratory test readings remained essentially unchanged from pre-treatment to post-treatment.

Activities of Daily Living↗
PubMed1990

Psychophysiological effects and dose equivalence of zopiclone and triazolam administered to healthy volunteers. Methodological considerations.

1. Dose-equivalence studies of zopiclone and triazolam were carried out. 2. Zopiclone (6.25, 8.75 and 11.25 mg), triazolam (0.1875, 0.375 and 0.5 mg) and placebo were given in the morning to 14 healthy male volunteers aged 20-25 years under double-blind conditions according to an incomplete block design. Each patient received three of the seven possible treatments at intervals of at least 1 week. Subjects were evaluated using physiological measures, rating scales and memory tasks before and 1.5 and 4.5 h after drug administration. 3. The sedative and amnestic effects of zopiclone were qualitatively similar to those of triazolam, with the highest dose of each having the greatest effect. 4. On the basis of the digit symbol substitution test, 10 mg of zopiclone is equivalent to 0.5 mg of triazolam. Methodological problems of the experimental design of dose-equivalence studies are discussed.

Adult↗
PubMed1989

Efficacy of tianeptine in anxious-depressed patients: results of a controlled multicenter trial versus amitriptyline.

265 adult outpatients with dysthymic disorder (DSM-III) associated with clinically manifest anxiety (according to FDA criteria) were included in a multicenter, randomized double-blind study. The trial consisted of three phases: placebo pretreatment phase and inclusion in the trial, treatment phase, placebo posttreatment phase. Patients were treated in monotherapy for 42 days with a mean dosage of 3 tablets per day corresponding to 37.5 mg/day of tianeptine or 75 mg/day of amitriptyline respectively. The following assessment instruments were used: the Montgomery and Asberg Depression Rating Scale (MADRS), the Hamilton Anxiety Rating Scale (HARS), and the Check-List for the Evaluation of Somatic Symptoms of J.D. Guelfi and C.B. Pull (CHESS 82). Analysis of MADRS total scores showed an important and rapid improvement in tianeptine and amitriptyline groups, reaching statistical significance as soon as D7. At the end of the 6-week treatment period the tianeptine group reached a decrease of 64% in the initial MADRS total score versus 69% in the amitriptyline group. 78% of patients treated with tianeptine and 83% of patients treated with amitriptyline were considered as treatment responders. There was no difference in drop-out rates between the two groups. HARS scores showed a decrease in psychic as well as somatic anxiety in both groups. The action of tianeptine on anxious-depressive symptomatology was confirmed by the concomitant improvement of global clinical rating and patients' self-rating (HSCL). Statistical comparison of all clinical rating-scale scores in patients having completed the trial failed to show any significant group differences.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1987

Zopiclone versus nitrazepam: a double-blind comparative study of efficacy and tolerance in elderly patients with chronic insomnia.

A randomized, double-blind, comparative trial of zopiclone versus nitrazepam was conducted in 74 geriatric chronic insomniac patients. Following a 7-day wash-out period, two parallel groups, successively received a placebo for 7 days, then either 7.5 mg zopiclone or 5 mg nitrazepam for another 7-day period. Efficacy on sleep was assessed by a sleep analogue scale and the Spiegel Sleep Questionnaire, residual effects by psychometric tests and tolerance by a standardized question, as well as by clinical and laboratory tests. Zopiclone and nitrazepam were more active than placebo on all tests of efficacy. In contrast with nitrazepam, zopiclone was devoid of effect on neurological function. In addition, the condition on awakening was better with zopiclone.

Aged↗
PubMed1987

Fluvoxamine and imipramine: results of a long-term controlled trial.

Following a multicentre double-blind controlled trial comparing the effects of fluvoxamine and imipramine in depressed inpatients (M.D.E.) 39 patients continued on longer term treatment with maintenance of double-blind conditions (17 on fluvoxamine, 22 on imipramine). The results regarding the reasons for premature interruption of treatment show a slight advantage in favour of fluvoxamine. There were several significant differences in favour of fluvoxamine at the 20th week. The most common side-effects were hot flushes with imipramine and dizziness with fluvoxamine. Overall, despite the small number of patients, the results show a greater clinical tolerance to fluvoxamine than to imipramine.

Antidepressive Agents↗
PubMed1987

Critical factors for pharmacokinetics of zopiclone in the elderly and in patients with liver and renal insufficiency.

Zopiclone, a new hypnotic cyclopyrrolone, undergoes extensive hepatic metabolism. The carrier of hypnotic activity is the parent compound; however, knowledge of its metabolic profile is essential for the understanding of pharmacokinetic changes in various pathophysiological conditions. In 45 healthy young volunteers, zopiclone had a Tmax of 0.5. A first-pass effect of 20% resulted in an absolute bioavailability, F, of 77%. The volume of distribution ratio Vdc/Vdt was 3.2. The plasma half-life (t1/2) was 5.1 h. A metabolic ratio of 3.7 and 4.6 was found for the two main urinary metabolites, N-oxide and N-desmethyl derivatives. No modifications of kinetics were seen after chronic treatment. In eight patients with liver insufficiency, the main changes (delayed Tmax, 3.5 h, higher plasma concentrations with an increased F of 97%, prolonged t1/2 of 8.4 h) were essentially due to a reduced hepatic metabolic clearance, as shown by a decreased metabolic ratio for the two main metabolites. In 18 patients with renal insufficiency, the only major modification was an increased bioavailability (F of 115%) probably due to a relative decrease of the Vdc. In 19 elderly subjects, the main findings were a decreased metabolic clearance, as shown by decreased metabolic ratios, and an inversion of the Vdc/Vdt ratio, evoking the changes seen in renal insufficiency. The increase in F (168%) and the age-dependent increase in plasma t1/2 (8.1 h) in the oldest subjects (over 74 years of age) can be explained by this double mechanism. On the basis of these findings, a reduction of the initial zopiclone dose from 7.5 to 3.5 mg/day is recommended for patients with severe liver insufficiency and patients over 70 years of age with liver insufficiency.

Adult↗
PubMed1985

Pharmacological and clinical studies of cyclopyrrolones: zopiclone and suriclone.

Among the non-benzodiazepine compounds which have been found to interact with the "GABA receptor-BZ receptor-chloride channel complex," the very chemically original cyclopyrrolone family has a special place. This has been demonstrated using selected pharmacological, biochemical and clinical data obtained with two cyclopyrrolones, zopiclone and suriclone, which, in addition to their capacity of displacing BZ from their sites, simultaneously possess the main pharmacological properties of BZ and well established therapeutic activities, as hypnotic and anxiolytic, respectively. However, although cyclopyrrolones recognize BZ receptor sites, their mechanism of action might not exactly fit with that of BZ. Indeed, using tritiated zopiclone and suriclone, it has been shown that they could act on sites distinct from those of BZ or could induce receptor conformational changes different from those induced by BZ.

Aggression↗
PubMed1984

[Computer program for the processing of data collected during therapeutic trials in psychiatry].

A computer program is described which has been developed over several years and allows for the easy processing of psychiatric data gathered in clinical trials. It provides user-defined parametrization of a computer-aided data entry system, the use of the program created to input data to the computer and the data processing of the data collected either through modifications of the file created or by statistical analysis, the procedures of which have been simplified to enable its performance even by lay people.

Clinical Trials as Topic↗
PubMed1983

A double-blind controlled clinical trial comparing fluvoxamine with imipramine.

1 The effects of fluvoxamine to a maximum of 300 mg daily were compared with those of imipramine to a maximum of 200 mg daily, in 151 patients with primary major depression. 2 Four weeks of treatment with fluvoxamine resulted in 67.2% improvement (+/- s.d. 21.6) on the Hamilton Rating Scale for Depression (26 items). Treatment with imipramine showed 62.1% improvement (+/- s.d. 29.5) on this scale. 3 Fluvoxamine had no untoward effects on the cardiovascular system, while imipramine produced systematic increases in the postural fall in blood pressure. Dry mouth, nausea, daytime somnolence and tremor were seen with fluvoxamine treatment, while imipramine was associated with dry mouth, daytime somnolence, dizziness and tremor. 4 We conclude that fluvoxamine seems to have the same general antidepressant efficacy as imipramine. It was not associated with any safety problems and was generally well tolerated.

Antidepressive Agents↗
PubMed1983

Placebo use in clinical trials on psychotropic drugs in France.

The use of placebos is often justified in therapeutic drug testing. They may be employed in order to compare their effects with those of a so-called active treatment, to compare two active medications, in double-blind comparisons of two drugs of different appearance (double-dummy technique) or to carry through initial washout periods. Although the scientific justification for this procedure is hardly contestable, the methodological difficulties and demands must be considered. The clinical use of placebo comparison poses a true ethical dilemma which increases with the effectiveness of psychotropic drugs. Placebos were used relatively rarely in France before 1978 as a general review of 120 controlled psychotropic drug trials published in French shows. Various precautions undertaken in drug testing designs respond, nevertheless, to both ethical and methodological demands in the majority of the cases. Examples are given regarding the testing of major or minor tranquilizers and antidepressive drugs.

Anxiety Disorders↗
PubMed1983

A double-blind controlled multicenter trial comparing butriptyline with amitriptyline.

77 primary depressive in-patients aged 18-70 years (mean = 46/47 years) were assigned randomly to experimental and control groups and treated in double-blind conditions in ten centers. Butriptyline and amitriptyline were both administered with an identical increasing schedule, up to 150 mg daily in the first week and a flexible schedule for the last 3 weeks of trial. Mean daily doses were 145 mg butriptyline and 142 mg amitriptyline after 2 weeks, and 77.5 mg amitriptyline and butriptyline after 4 weeks. Nitrazepam (5-10 mg) and haldol (5 mg) were also allowed, only if necessary. Symptomatology and antidepressant efficacy were assessed using the rating scales of Hamilton, Overall, BPRS, CGI and a side effect checklist. After initial comparison of the two treatment groups, the results showed that the antidepressant effects were significantly better with butriptyline on the number of dropouts, on the total score and on the following factors of the Overall Depression Scale: depression, guilt, anxiety, somatization and somatic complaints. Frequency of haldol prescription was significantly lower with butriptyline than with amitriptyline. The overall frequency of side effects and of autonomic symptoms did not differ in the two groups. The effects on other parameters (hematological and biochemical variables, ECG and EEG) were similar for both drugs. In conclusion, butriptyline has the same indications as amitriptyline but shows a better antidepressant efficacy at the same dosage.

Adolescent↗
PubMed1983

Pharmacokinetics and metabolism of zopiclone.

Pharmacokinetics and metabolism of a new hypnotic, zopiclone (ZD), were studied under the following conditions: (1) rats and dogs were given oral doses of the molecule, 14C-labeled either on the side chain or on the pyrrolopyrazine nucleus; (2) rats, rabbits and dogs were given increasing oral doses of the cold compound; (3) human subjects in various physiopathological situations--young and elderly healthy volunteers, patients with liver or renal impairments, nursing mothers--were given single or repeated doses, p.o. or i.v. (range 3.5-15 mg). ZD is rapidly and efficiently absorbed: its oral bioavailability was greater than 75% in all species except rats, where a first-pass effect of about 65% was recorded. Plasma protein binding is about 45%. The radioactive material rapidly diffuses from the vascular compartment, with a marked affinity for the brain. Plasma kinetics of ZD are generally well described by a two-compartment open model; in man, terminal half-life is 4-5 h; total body clearance is large (300 ml/mn), renal clearance very low (10 ml/min). The relationship between doses and concentrations, doses and urinary excretion of unchanged compound and major metabolites was linear in all species, except rabbits. The major metabolic routes involve decarboxylation affecting more than 50% of dose (rats and dogs), N-demethylation and N-oxidation--more than 30% as N-desmethyl and N-oxide derivatives in urine (humans). Due to intensive metabolism, only 7-10% of the dose is recovered in urine and feces as unchanged compounds (all species). In nursing mothers, milk and plasma kinetics of ZD are similar with a milk/plasma ratio around 0.80. In human volunteers, plasma half-life of ZD increases with age, while patients with liver or renal impairments show little or no modification of pharmacokinetic parameters.

Administration, Oral↗
PubMed1983

Effects of hypnotics on memory.

The influence on memory of 7.5 mg zopiclone, given in single and repeated doses was compared with that of 2 mg flunitrazepam, 5 mg nitrazepam and placebo. Compared with placebo, all three drugs induced some impairment of memory especially after the first day of administration. Effects were more pronounced for the two benzodiazepines and more marked for flunitrazepam. There was one report of an anterograde amnestic episode after flunitrazepam.

Adult↗
PubMed1983

Drug-alcohol interactions on psychomotor skills: zopiclone and flunitrazepam.

Interaction between alcohol and zopiclone or flunitrazepam as well as the residual effects of both these hypnotics were studied in 20 normal male volunteers who received each 3 of 6 different drug and drink combinations according to a balanced incomplete block design as follows: placebo, zopiclone (7.5 mg), or flunitrazepam (2 mg) was administered double-blind in identical capsules at 23.00 h, and 0.5 g/kg body weight of alcohol or placebo alcohol was given at 08.30 h the following morning. Psychomotor skills of the volunteers were measured before drinking and 30 min, 1.5 h and 2.5 h after it. As compared with placebo, zopiclone had no residual effects, while flunitrazepam had some effects on standing steadiness, tracking, and flicker recognition. Alcohol alone had a non-significant effect on skills, and the combination zopiclone plus alcohol behaved as alcohol alone. Flunitrazepam plus alcohol impaired significantly standing steadiness, tracking, and reactive skills when compared with all other treatments. Time anticipation and hand and foot proprioception were not affected by any treatment. The results suggest that flunitrazepam, unlike zopiclone, has residual effects and interacts with alcohol in the morning following overnight ingestion of the drug.

Adult↗
PubMed1983

Polygraphical sleep recordings in insomniac patients under zopiclone or nitrazepam.

Zopiclone, a new hypnotic with an original chemical structure, was compared in a sleep laboratory study with nitrazepam according to a double-blind, parallel group randomized design. Zopiclone (7.5 mg) and nitrazepam (5 mg) were each given for 14 nights to 5 insomniacs; a placebo washout period of 4 nights and a placebo withdrawal period of 10 nights were included in the design. Both drugs were found to be immediately and lastingly effective. Some slight insomnia rebound was found with nitrazepam, but not with zopiclone. Stage 2 was decreased, slow wave sleep (SWS) increased, and rapid eye movement unchanged by both drugs: however, only nitrazepam increased rapid eye movement latency. The differences between the effects of the drugs were quite limited. However, 3 out of 50 comparisons favoured zopiclone and none nitrazepam.

Adult↗