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Biomedical subjects

S J Dencker

Publications and source records attributed to S J Dencker.

At least 37 records · Page 2Linked to original sources

Pharmacokinetic and pharmacodynamic studies on high doses of fluphenazine.

Six chronic schizophrenics--earlier refractory to recommended doses of neuroleptic drugs but eventually responding to 250 mg fluphenazine heptanoate weekly--participated in a pharmacokinetic study. Five out of the six patients showed rather constant steady state plasma fluphenazine values on a 250 mg depot weekly. After depot drug withdrawal, the single oral dose pharmacokinetics on 400 mg fluphenazine showed the same variations in Cmax, tmax, t 1/2 and AUC as are observed when recommended doses of fluphenazine are used. We thus could not demonstrate any dose-dependent pharmacokinetics on high oral fluphenazine doses. In half the patients, a biphasic decay in the plasma concentration curve indicated at least two compartments. The patients were then studied for up to 2 years on 200-500 mg fluphenazine as a single daily dose. The fluphenazine plasma levels were rather constant in the individual patients during this period. The plasma prolactin values were related to the fluphenazine values even in the high value area, thus showing a persistent pharmacodynamic variation capacity. The clinical part of the study did not show any relevant findings.

Adult↗

Zuclopenthixol acetate in Viscoleo--a new drug formulation. An open Nordic multicentre study of zuclopenthixol acetate in Viscoleo in patients with acute psychoses including mania and exacerbation of chronic psychoses.

Eighty-three acutely disturbed, psychotic patients were included in an open multicentre study. The aim of the study was to evaluate the clinical effect of zuclopenthixol acetate in Viscoleo (CPT-A). Each patient received from one to four intramuscular injections of CPT-A during the 6-day study period. The duration of action after one injection was between 2 and 3 days and doses from 50 mg to 150 mg were sufficient for most patients. Treatment with CPT-A caused a pronounced and rapid reduction of the psychotic symptoms. At the end of the 6-day test period the mean total score on BPRS in acute non-manic and exacerbated chronic patients was reduced by more than 50 per cent. In acute manic patients the mean total score on BRMS was reduced by 57 per cent already 1 day after injection. Rapidly after the injection of CPT-A a useful short-acting sedation can be expected, but the risk for oversedation even after a second injection is low. The frequency of unwanted effects, including extrapyramidal reactions, was low and the severity of symptoms was most often mild. With a rapid onset of action, a duration of effect of 2 to 3 days, and few and mild side effects, CPT-A offers advantages over the neuroleptic preparations conventionally used in the initial treatment of acutely disturbed, psychotic patients.

Acute Disease↗

Combination of psychotherapy and drugs in the treatment of neurosis. A controlled comparison of bromazepam and thioridazine.

Eighty out-patients with neurotic disorders were studied in an integrated treatment model combining psychotherapy and psychotropics in a "conjoint marital therapy" setting. The spouses, who seemed a healthy group, were used as reporters, as controls and as participants in the psychotherapy. The pharmacological trial was a double-blind, cross-over study, comparing bromazepam and thioridazine after a placebo period. Bromazepam was more effective in controlling different anxiety symptoms and demonstrated more potent activating properties than thioridazine. Hostility symptoms, however, responded better to thioridazine. These findings were confirmed by ratings performed by patients, spouses and the investigator. Differences in drug preference and drop-out rate showed the same tendency. Nine weeks' continuous treatment did not change the differences found in the cross-over study. No pharmacological rebound symptoms were observed after drug withdrawal. The personality of the spouses was related to the outcome in the patients. Moreover, there was an obvious positive interaction between the psychotherapy given and the drug treatment.

Adult↗

Schizophrenic relapse after drug withdrawal is predictable.

Thirty-two patients in remission were followed by regular ratings during a prospective neuroleptic withdrawal study. They were outpatients who fulfilled the DSM-III criteria of schizophrenia and who were motivated for drug withdrawal. The relapse rate was 81%. The results from the rating scales confirm the hypothesis that a symptom increase occurs before psychotic relapse. In the order statistical differences occurred, the factors predicting relapse were those concerned with positive psychopathology, motor dysfunction, impaired affects and sleep disturbances. The corresponding symptoms and signs were mainly concerned with thought disorders, paranoid ideation, overactivity, depression and insomnia middle, all of nonpsychotic degree of severity. If prodromes appear, the patient should resume his neuroleptic treatment, or other preventive measures should be taken. By such therapeutic interactions, psychotic relapse may be prevented, or can be dealt with in an outpatient setting.

Adult↗

Zuclopenthixol decanoate in schizophrenia: serum levels and clinical state.

Serum concentrations of zuclopenthixol were determined in a group of 20 patients treated with a depot preparation, zuclopenthixol decanoate in Viscoleo. Clinical assessments according to a Clinical Global Impression (CGI) scale, Comprehensive Psychological Rating Scale (CPRS), 16-item subscale for schizophrenia, and the UKU side effect scale were performed on 3 consecutive days of injection. The serum concentrations showed a limited individual variation and a high and significant correlation between dose and serum concentration. One patient had a particularly high serum concentration of zuclopenthixol. This patient also had an elevated concentration of the N-dealkyl metabolite, but a low concentration of the sulphoxide. For serum concentrations versus clinical state and side effects some significant correlations were found. All correlations were positive, which means that the higher the serum concentration the poorer the clinical state of the patient. We think that this probably reflects a common clinical pattern of increasing the dose, when the antipsychotic response is unsatisfactory. The study also showed that for moderately ill patients, who were given the optimum dose of drug, the subgroup of patients not experiencing side effects had significantly lower serum concentrations than the subgroup with side effects.

Adult↗

Patients admitted for compulsory treatment to selected psychiatric units in Italy and in Sweden.

Eighty-five Italian and forty-nine Swedish patients consecutively admitted for compulsory treatment to either an Italian or a Swedish psychiatric unit in selected areas of the two countries have participated in an exploratory study aimed at assessing the main characteristics of compulsory admitted patients, and in particular, the immediate reason for admission. The two series proved to be quite similar as concerns most sociodemographic variables, and as concerns clinical diagnosis and severity of the morbid condition at admission as measured by means of a rating scale. More Swedish than Italian patients lived alone when admitted to hospital, and for more of them the request for admission was made by other people than relatives, and a larger proportion of them was accompanied to the hospital by medical or social welfare personnel. In both series the largest proportion had a low educational level and belonged to the lower social groups. The same proportion in the two series had previous admissions. The most common reason for admission was "odd or improper behaviour" for the Swedish patients, and "feared or manifest dangerousness" for the Italian patients. The Italian patients remained at hospital on average half the time than the Swedish patients.

Adolescent↗

The risk/benefit ratio of depot neuroleptics: a Scandinavian perspective.

The three developmental phases in the acceptance and use of depot neuroleptics are described. The practical advantages of these drugs are considered, as well as the extrapyramidal side effects that may result from oral or depot administration. Local (injection site) and other side effects of depot neuroleptics are discussed. Typical plasma drug concentration curves and receptor responses of depot neuroleptics are illustrated. Alternative use of oral drugs and strategies to increase the effectiveness of depot forms are presented. The depot neuroleptics used in Scandinavia today are discussed, and predictions are made regarding their use in the future.

Administration, Oral↗

Serum concentrations of cis(Z)-flupentixol and prolactin in chronic schizophrenic patients treated with flupentixol and cis(Z)-flupentixol decanoate.

Nine chronic schizophrenic patients selected from three hospital departments were treated with flupentixol (orally and IV) and cis(Z)-flupentixol decanoate in Viscoleo (IM) in a three-phase pharmacokinetic study. Oral administration (single and repeated dosage) showed a relatively slow absorption with maximum serum concentration around 4 h after administration. Intravenous injection indicated multicompartment kinetics for cis(Z)-flupentixol. The biological half-lives calculated after the different doses were the same, indicating that the pharmacokinetics of cis(Z)-flupentixol does not differ between single and repeated administration and does not change when moderately higher doses are given. The bioavailability of orally administered cis(Z)-flupentixol was calculated to be about 40% with IV injection as reference. After IM administration maximum serum concentration was seen between 4 and 10 days in most patients. Calculation of a disappearance half-life gave very variable results, indicating that the release of the drug from the oil depot is not a monoexponential process. The intramuscular depot had a much lower bioavailability than IV injection, which means that steady state has not been obtained after 8 weeks of depot treatment. Serum prolactin concentrations were elevated during neuroleptic treatment, but no correlation was found between prolactin concentrations and the serum concentrations of cis(Z)-flupentixol. A correlation between the changes in clinical ratings and concentrations of cis(Z)-flupentixol or prolactin was not found.

Administration, Oral↗

Comparison of nitrazepam with triazolam in insomniac outpatients.

The short-acting hypnotic, triazolam 0.5 mg, was compared in a 7-day double-blind study with the longer acting drug, nitrazepam 5 mg. Of the 60 patients enrolled, 29 in each drug treatment group completed the study and were evaluated. All significant differences found favoured triazolam. On the first night, triazolam was found to be significantly more effective than nitrazepam in inducing and maintaining sleep and in increasing its overall duration. The patients' subjective preference, reflecting the depth of sleep experienced and the effect of the medication, reached highly significant levels in favour of triazolam. Later in the study the differences between the drugs disappeared although the depth of sleep as judged in the study was better with triazolam.

Adult↗

Antidepressant effect of femoxetine and desipramine and relationship to the concentration of amine metabolites in cerebrospinal fluid. A double-blind evaluation.

The antidepressant and biochemical effects of femoxetine, a selective serotonin uptake inhibitor, and desipramine, a selective nor-adrenaline uptake inhibitor, have been compared in a double-blind study in 42 outpatients with depressive illness. The patients were allocated at random to treatment with either 600 mg femoxetine or 150 mg desipramine daily for 6 weeks. The total depression score showed a significant decrease in both groups, indicating an overall improvement in depressive symptoms. The patients treated with femoxetine reported significantly less severe anticholinergic effects during the whole treatment period than the desipramine patients. Both drugs, decreased the level of 5-HIAA in CSF, whereas no consistent changes were found in the MHPG and HVA levels. The pretreatment level of the metabolites had no predictive value for the outcome of the treatment with either drug. No significant correlation was found between therapeutic effect and the plasma concentration of the active compounds.

Adult↗

Pharmacokinetics of toloxatone in man following intravenous and oral administrations.

Pharmacokinetics of the antidepressant drug toloxatone were investigated in man following intravenous and oral administration. Five healthy adult volunteers received a single 1 mg/kg dose given as a gelatin capsule (p.o.) and an i.v. infusion. After p.o. administration toloxatone was rapidly absorbed, peak plasma concentrations (Cmax) ranging from 0.384 to 0.640 mg/l occurred between 0.53 and 1.00 h. Plasma curves were fitted according to a one-compartment open model. After absorption, toloxatone was cleared from plasma with a half-life (t 1/2 beta) of 0.96-1.81 h. Following i.v. administration Cmax values from 0.623 to 0.840 mg/l were reached at the end of the 0.5-h infusion. As observed for the capsule form, the elimination of the drug from the plasma was monophasic with t 1/2 beta of 0.88-2.46 h. Plasma clearance of toloxatone was high (0.462 to 0.860 l/h . kg) and the apparent volume of distribution ranged between 1.09 and 1.64 l/kg. Protein binding to plasma proteins is near 50% and appears almost exclusively due to albumin. Free fatty acids do not modify substantially the degree of binding which is constant over the range of concentrations from 0.05 to 100 mg/l. The availability of the gelatin capsule was 50-62% of the i.v. infusion. Since toloxatone is extensively eliminated in urine as metabolites, the reduced availability of the drug appears to be related mainly to first pass metabolism.

Administration, Oral↗

Evaluation of the quality of life of the schizophrenic outpatient: a checklist.

The quality of life of schizophrenic patients has become an important issue, both in the community and in the hospital. Treatment programs should be individualized to improve patients' quality of life, which calls for both flexibility and detailed assessment of patients' patterns of existence. Described is the Quality of Life Checklist for recording judgments of the patient's situation in a systematic way, to make sure that important areas are not overlooked. It is simple, easy to use, and potentially a useful tool for evaluation, and for planning relevant and individualized interventions. A pilot study in 40 schizophrenic patients demonstrated its utility. The troubles of schizophrenia are not exclusively a medical and psychiatric rehabilitation problem. Other agencies and other professionals have a responsibility for our patient's quality of life and to deal with social problems that are beyond the usual scope of our own capabilities and expertise.

Adolescent↗