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.

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.

Plasma fluphenazine and prolactin levels in schizophrenic patients during treatment with low and high doses of fluphenazine enanthate.

The relationship between plasma prolactin (PRL) and drug levels in patients receiving neuroleptic drugs is of special interest in view of evidence that the PRL elevation induced by these drugs reaches its maximum at sub-therapeutic doses. Plasma PRL and fluphenazine (FPZ) levels were measured by radioimmunoassay (RIA) in each of 11 chronic schizophrenics (nine men, two women) during two 4-week periods of treatment with FPZ enanthate at a "High Dose' (250 mg per week) and a "Low Dose' (12.5 mg per week) given in random order. Plasma PRL levels were above normal in 9 of 11 subjects during the last week of Low Dosage. High Dosage resulted in PRL levels significantly greater than found during Low Dose treatment in 9 of 11 patients. Thus the PRL response had not reached its "ceiling" during Low Dosage in most patients. A significant correlation between PRL and FPZ levels was found in seven subjects; evidence that immunoreactive FPZ levels relate to an effect caused by blockade of dopamine receptors. The plasma FPZ pattern between injections during week 1 of Low Dosage was remarkably stable; High Doses produced an initial drug peak at 1--2 h and a secondary peak occurring on days 2--3 followed by a return to preinjection levels by day 7.

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.

Defining treatment refractoriness in schizophrenia.

Addressing the need for research on the nature of refractoriness to antipsychotic drug therapy exhibited by a substantial minority of schizophrenic patients, Philip R.A. May and Sven Jonas Dencker instigated an international study group to discuss this problem, beginning with the International Congress of Neuropsychopharmacology in Göteborg, Sweden, in 1980. The study group subsequently met in Haar, Federal Republic of Germany, in 1985; in Banff, Canada, in 1986; and again in Telfs, Austria, in 1988. The study group set three objectives: (1) to clarify the concept of treatment resistance or refractoriness; (2) to suggest criteria for defining or rating the degree of treatment refractoriness; and (3) to explore the role of psychosocial and drug therapies in increasing the responsiveness of the treatment refractory patient. This position article represents a distillation of the study group's efforts to define treatment refractoriness in schizophrenia.

Case management and assertive community treatment in Europe.

OBJECTIVE: Case management studies from Europe and the United States continue to yield conflicting results. At a symposium at the World Psychiatric Conference in Hamburg in 1999, researchers from four European countries explored the possible reasons for differences in outcome. They also examined reasons for the differing foci of case management studies across the different cultures. The authors summarize the symposium's findings. METHODS: Individual case presentations were given of studies and services from the United Kingdom (three studies), Sweden (two studies), Germany, and Italy (one each). Outcomes, methodologies, and national service context were examined. RESULTS AND CONCLUSIONS: A significant influence of national culture is evident both in the acceptability of case management and in approaches to researching it. Case management is perceived as an "Anglophone import" in Italy but is now national policy for persons with severe mental illness in the other three countries. Studies from the United Kingdom emphasized methodological rigor, with little attention to treatment content, whereas those from Sweden accepted a less disruptive research approach but with a more prescriptive stipulation of treatment content. Studies from Italy and Germany emphasized the importance of differing descriptive methodologies. Marked differences in the range of social care provision were noted across Europe. Overall, European researchers are less concerned than U.S. researchers with studying the impact of case management on hospital use.

Violence and its prediction at a psychiatric hospital.

Aggressive behaviour in psychiatric inpatients was assessed before and after a training course for staff members. The Social Dysfunction Aggression Scale (SDAS) was used to report and assess aggressive behaviour over time, and the Staff Observation Aggression Scale (SOAS) to report and assess single aggressive incidents. In addition, the numbers of nursing staff members who were on sick leave because of injuries in the periods before and after the course were recorded and compared. No statistically significant reduction was found in the number of aggressive patients or in the number of staff members on sick leave. One interesting finding was a lower reporting on the SOAS of perceived aggressive incidents after the training course in comparison with the SDAS reports. Directed verbal aggressiveness and violence towards things were found to be predictors of violence.

Consumer satisfaction in schizophrenia. A 2-year randomized controlled study of two community-based treatment programs.

Quality management and quality control of health services have become increasingly important. Central to the concept of quality of care is the consumer's (the patient's) own view of the care provided. UKU (Udvalg for Kliniske Undersøgelser), a task force within the Scandinavian Society for Psychopharmacology, has designed a brief consumer satisfaction rating scale, the UKU-ConSat. The UKU-ConSat rating scale was applied in a randomised comparative two-year study of two community-based treatment programs. The study included 84 patients with schizophrenic disorders according to DSM-IV. The major finding was a significantly increased consumer satisfaction with the new community-based program "Integrated Care" in comparison with best-established practice, called "Rational Rehabilitation." Thus, the new UKU-ConSat rating scale can detect differences, not only for in-patients as has previously been shown, but also between programs in community care settings. By per item analysis it was possible to discriminate between various elements of consumer satisfaction. There were significant correlations between the UKU-ConSat total scores and other clinical outcome domains, viz. symptoms, social function, and patient as well as carer's distress. To conclude, the UKU-ConSat rating scale is suitable for quality management and monitoring of treatment programs in mental health services.

Patient-rated versus clinician-rated side effects of drug treatment in schizophrenia. Clinical validation of a self-rating version of the UKU Side Effect Rating Scale (UKU-SERS-Pat).

A self-rating version of the UKU Side Effect Rating Scale has been developed. The present study examines the agreement between patients' self-assessment of side effects and the attending clinicians' ratings. The patient sample consisted of 63 patients with schizophrenia under maintenance treatment with risperidone, clozapine or classical antipsychotics. Approximately two thirds of the patients used concomitant medication with e.g. benzodiazepines, SSRIs, anticholinergics. Most inter-correlations between scores for single, corresponding items, subscores of Psychic, Neurological, Autonomic and Other side effects, as well as the Total Score from the patient version of the UKU Side Effect Self Rating Scale (UKU-SERS-Pat) and the clinician version (UKU-SERS-Clin) were found to be statistically significant. Patients reported side effects more frequently and or rated symptoms more severe than the clinicians. The results support the validity of the SERS-Pat and suggest that patient rated side effects may provide important clinical information not detected by clinician rated interviews. Such information can be utilised both in clinical investigations, in development of treatment programs and for individual patients in clinical practice.

Assessment of patient satisfaction with psychiatric care. Development and clinical evaluation of a brief consumer satisfaction rating scale (UKU-ConSat).

Quality management and quality control of health services has become increasingly important. Central to the concept of quality of care is the patient's (the health care consumer's) own view of the care provided and the treatment outcome. UKU (Udvalg for Kliniske Undersøgelser; that is, Committee for Clinical Trials), a working group within the Scandinavian Society for Psychopharmacology (SSP), has designed a brief consumer satisfaction rating scale, the UKU-ConSat. Based on an extensive literature review, a number of principles related to content, assessment, interview techniques, documentation and standardisation steered the design of the rating scale. UKU-ConSat consists of six items related to the structure and process of treatment care, and two items related to outcome and well-being. A manual accompanies the rating scale with guidelines for how to solicit information from the patient and how to rate each item. A first field trial of the rating scale in 135 inpatients at multiple clinical sites in Finland and Sweden showed that it could be applied to several relevant patient categories (psychotic, affective, neurotic, organic and alcohol and substance abuse disorders). According to both patients and staff the rating scale promises to become useful both for research and for improvement of routine psychiatric services.