flupenthixol-decanoate and Chronic-Disease

Eighteen chronic schizophrenic patients who had shown improvement from increased maintenance dosages of cis(z)-flupenthixol decanoate were entered into a double-blind study in which half of the patients were randomly allocated to be maintained on 50% of their pre-trial dosage. During the 44 week study the reduced dosage group showed increased morbidity and one-third of these patients had a schizophrenic relapse. The greatest deterioration occurred in patients reduced from above to below 200 mg cis(z)-flupenthixol decanoate biweekly. A review of all the patients entered into the study showed a relationship between deterioration of schizophrenic and depressive features and cis(z)-flupenthixol plasma levels which reflected the administered dosage. Prolactin levels in general did not reflect control of schizophrenic symptoms. Side-effects were few, and there was no emergence of tardive dyskinesia. A multicentre trial is needed for further evaluation.

Topics: Adult; Chronic Disease; Clinical Trials as Topic; Dose-Response Relationship, Drug; Double-Blind Method; Female; Flupenthixol; Humans; Male; Middle Aged; Psychiatric Status Rating Scales; Schizophrenia; Schizophrenic Psychology; Thioxanthenes

Topics: Adolescent; Adult; Aged; Chronic Disease; Clinical Trials as Topic; Delayed-Action Preparations; Female; Flupenthixol; Humans; Length of Stay; Male; Middle Aged; Schizophrenia; Thioxanthenes; Tranquilizing Agents

Thirty-two chronic schizophrenics who had relapsed entered a double-blind randomised study and were followed-up for 2 years with the intention of measuring any difference in therapeutic effect and side effects between flupenthixol decanoate and fluphenazine decanoate. No differences could be seen as regards the global effect or the effect on the schizophrenic symptomatology during the first 6 months. After 1 year of treatment flupenthixol decanoate showed a trend towards a better effect on schizophrenic symptomatology. A corresponding result was seen for the depressive symptoms. There were no differences in the appearance of side effects. The need for additional neuroleptics in the initial phase seemed to be identical for both drugs. A possible slow antipsychotic effect with flupenthixol decanoate is probably due to the administered dose being somewhat low (in the present study approximately 31 mg flupenthixol corresponding to 27 mg fluphenazine). This suggests that flupenthixol should have been given in a somewhat higher dose (25 mg fluphenazine decanoate corresponding to 40 mg flupenthixol decanoate).

Topics: Adult; Aged; Chronic Disease; Clinical Trials as Topic; Depression; Double-Blind Method; Flupenthixol; Fluphenazine; Humans; Middle Aged; Random Allocation; Recurrence; Schizophrenia; Thioxanthenes; Time Factors

Attitude towards treatment, side-effects, mental state and quality of life was assessed in 53 chronic schizophrenic out-patients on maintenance treatment with depot neuroleptics. It was found that 60% of the patients viewed depot medication positively, while only 8% viewed it negatively. Only 70% of patients complained about side-effects, even though 94% had scored as having them. Hypokinesia and hyperkinesis were the side-effects least noticed by the patients, but most noticed by the treating physician, while the opposite was the case with psychic side-effects. Only 49% of patients thought they had a psychotic illness, and there was no correlation between the patients' own evaluation of the severity of their illness and their score on the Positive and Negative Symptom Scale (PANSS) or the treating physician's evaluation. Quality of life did not correlate with either side-effect score or PANSS score. The schizophrenic patients' assessment of their condition was therefore in general different both from that of the treating physician and from that determined using rating scales.

Topics: Adult; Aged; Antipsychotic Agents; Chronic Disease; Clopenthixol; Delayed-Action Preparations; Dyskinesia, Drug-Induced; Female; Flupenthixol; Humans; Male; Middle Aged; Neurologic Examination; Perphenazine; Psychiatric Status Rating Scales; Quality of Life; Schizophrenia; Sick Role

This study investigated the effects of transferring patients on combined depot and oral neuroleptics to a single depot preparation; a secondary objective was to assess the effects of transferring patients from one depot neuroleptic to another. It was found that, whereas transferring from one depot preparation (flupenthixol) to another (fluphenazine) had no clear disadvantage for the patients, changing over from a combined oral and depot (fluphenazine) regimen to equivalent doses of depot alone resulted in an unacceptably high rate of relapse. The reasons for this may relate to either the unique pharmacokinetics of these drugs or subtle qualitative differences between them. It is suggested that caution is necessary whenever attempts are made to rationalize polypharmacy in schizophrenic patients.

Topics: Administration, Oral; Antipsychotic Agents; Chronic Disease; Drug Therapy, Combination; Dyskinesia, Drug-Induced; Female; Flupenthixol; Fluphenazine; Humans; Injections, Intramuscular; Male; Middle Aged; Neurologic Examination; Psychiatric Status Rating Scales; Recurrence; Schizophrenia; Schizophrenic Psychology

Two groups of schizophrenic outpatients were treated with perphenazine decanoate (N = 20) and cis(z)-flupentixol decanoate (N = 24) respectively. Every 3 months the dose was gradually reduced until symptoms appeared that were suggestive of a prodromal phase of a psychotic episode. A slightly higher dose was then promptly reinstituted (the minimum effective dose). At each dose level, two blood samples were drawn for determination of serum concentration. The mean minimum effective dose of perphenazine decanoate was 99.3 mg/2 weeks (range 21.6-270.5), while the mean minimum effective dose of cis(z)-flupentixol decanoate was 60 mg/2 weeks (range 20-250). The corresponding mean serum level of perphenazine decanoate was 7.3 nmol/l (range 2.0-18.1) and of cis(z)-flupentixol decanoate 7.8 nmol/l (range 1.2-37.0). There was a significant correlation between the administered doses and the corresponding serum levels for both drugs (r = 0.87, P less than 0.01). A weak positive correlation was found between serum levels at the minimum effective dose and symptom intensity (BPRS total score) (r = 0.53, P less than 0.02) for perphenazine, but not cis(z)-flupentixol. No correlation was found between serum levels and side effects or length of neuroleptic treatment. It is concluded that the serum drug concentrations corresponding to the lowest effective dose are so variable that routine serum level monitoring may be of limited value in the long-term maintenance treatment of schizophrenia.

Topics: Adult; Chronic Disease; Dose-Response Relationship, Drug; Female; Flupenthixol; Humans; Male; Middle Aged; Outpatients; Perphenazine; Psychiatric Status Rating Scales; Schizophrenia

Ninety-one schizophrenics (mean age 34 years) were examined for tardive dyskinesia (TD) during chronic neuroleptic treatment. Dyskinesia was found in 23 (25.3%). The only variable that showed an association with TD was the current doses of neuroleptics: in none of the TD patients did the dose of fluphenazine decanoate (or equivalent) exceed 45 mg/week, whereas it was higher in 23 of the 68 without TD (p less than 0.01). When these 23 "high-dose" patients were disregarded, the TD group differed significantly from the 45 dose-matched non-TD subjects in that it had more common anticholinergic drugs, more common parkinsonian symptoms, and less instances of good remission (p less than 0.05 in each case). There was no association between TD and other considered variables (drug history, age, sex, clinical characteristics, size of the lateral brain ventricles, neurological "soft" signs, cognitive impairment). The results illustrate a relationship between TD prevalence and current doses of neuroleptics and indicate that differences in doses between the groups with and without TD may obscure associations between dyskinesia and other factors.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Dose-Response Relationship, Drug; Dyskinesia, Drug-Induced; Female; Flupenthixol; Fluphenazine; Humans; Male; Prognosis; Schizophrenia

Topics: Adult; Chronic Disease; Female; Flupenthixol; Fluphenazine; Humans; Male; Middle Aged; Schizophrenia; Thioxanthenes

In a prospective follow-up the outcome of 60 chronic schizophrenic patients who discontinued neuroleptic therapy after remaining stable 12-48 months was compared with controls continuing medication. Not only did the drug-discontinued patients have more relapses (P less than 0.001), but the form of relapse was both more severe and acute, resulting in differences of self-injury (P less than 0.05), anti-social behaviour (P less than 0.01), inpatient admissions (P less than 0.001), and the use of compulsory powers (P less than 0.01). In patients who relapsed, both social and work function was affected adversely for some months. Patients who remained relapse-free without drugs (20%) had a level of work and social function similar to medicated patients. At the end of 18 months the patients who discontinued depot maintenance therapy were found to have been prescribed one-third more neuroleptic drugs than controls, with a possible increase in the risk of long-term tardive dyskinesia.

Topics: Adult; Antipsychotic Agents; Chronic Disease; Drug Administration Schedule; Female; Flupenthixol; Fluphenazine; Humans; Male; Psychiatric Status Rating Scales; Recurrence; Schizophrenia; Schizophrenic Psychology; Social Adjustment; Thioxanthenes

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.

Topics: Administration, Oral; Adult; Chronic Disease; Female; Flupenthixol; Half-Life; Humans; Injections, Intravenous; Male; Middle Aged; Prolactin; Schizophrenia; Thioxanthenes