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Biomedical subjects

S J Dencker

Publications and source records attributed to S J Dencker.

At least 55 records · Page 3Linked to original sources

Late (4-8 years) outcome of treatment with megadoses of fluphenazine enanthate in drug-refractory schizophrenics.

Fourteen schizophrenics who did not respond to standard doses of neuroleptics have been treated with megadoses of fluphenazine enanthate during a period of 4-8 years. Repeated attempts have been made to reduce the dose to the standard dosage. Some of the patients have gradually been transferred to maintenance treatment with standard doses, with megadoses given only during psychotic relapse. The megadose treatment has led to substantial reduction in social disablement, enabling the patients, for instance, to leave the hospital or live in an open ward. These patients have been evaluated with rating scales for psychopathology and side effects, and subjected to EEG, ECG, chest X-ray, and examinations for skin and eye changes and local infiltrations. Laboratory tests, including anti-DNA examination, have also been performed. These patients, treated with high total doses of different oral neuroleptics and fluphenazine depot, showed some EEG and ECG abnormalities, eye changes, slight leucopenia, a low number of staff nuclei neutrophils and infiltrations at the injection site, but these reactions did not result in any practical handicaps. The rating scales showed dyskinetic movements, usually slight, in six out of the 14 patients studied.

Adult↗

Flupenthixol decanoate in recurrent manic-depressive illness. A comparison with lithium.

The hypothesis that flupenthixol decanoate may serve as an alternative to prophylactically administered lithium in recurrent manic-depressive illness, bipolar and unipolar type, was tested in two groups of patients. In Group I the patients were allocated randomly to maintenance treatment with either lithium or flupenthixol decanoate. The patients in Group II had previously been given lithium and were switched to flupenthixol decanoate because of unsatisfactory prophylactic effect of lithium, doubtful tablet compliance, troublesome side effects, or fear of later harmful effects. The flupenthixol decanoate dosage was 20 mg every 2-3 weeks. The study was not blind. In Group I neither lithium treatment (14 patients) nor treatment with flupenthixol decanoate (19 patients) led to a significant fall of mean episode frequency or mean per cent time ill. The reasons for this lack of response are not clear, but prognostically negative selection of the patients presumably took place before and possibly also during the hospitalization. Since absent effects cannot be compared, this part of the trial remains inconclusive. In Group II (93 patients) treatment with flupenthixol decanoate was associated with significant falls of the frequency of manic episodes and per cent time ill in mania and with significant rises of the frequency of depressive episodes and per cent time ill in depression. Increase of depressive morbidity was seen only in patients who had been given lithium during the pre-trial period and was presumably a result of the discontinuation of lithium. It is not known whether flupenthixol decanoate is of value in the prophylactic treatment of recurrent manic-depressive illness, but the drug may be worth trying in patients whose disease is dominated more by manic than by depressive recurrences and who do not respond to lithium or do not tolerate it or do not take it.

Bipolar Disorder↗

The need for long-term neuroleptic treatment in schizophrenia.

The need for long-term neuroleptic treatment in nuclear schizophrenia depends on several factors, including the type of chronic schizophrenia, the phase of the disease, and the patient's total social situation. A neuroleptic drug withdrawal study demonstrated a need for further neuroleptic treatment for survival in the community even when the most symptom-free and socially best adapted chronic schizophrenics were considered. Prevention of relapse can apparently be achieved with lower neuroleptic doses than those necessary for optimal symptom suppression. Moreover, the patient's evaluation of his total social situation, including some quality-of-life aspects, must be considered as well as measures to avoid the patient becoming a burden on his family and his friends. Neuroleptic treatment in adequate antipsychotic doses usually means a risk of early, immediate and possibly late side effects. In striking a balance between benefit and risk it seems preferable to keep the benefit strategy, which means that the main point will be to monitor neuroleptic and antiparkinsonian drugs with regard to optimal symptom suppression not accepting any possible late side effects as a guideline.

Antipsychotic Agents↗

A double-blind study of dothiepin hydrochloride (Prothiaden) and amitriptyline in out-patients with masked depression.

A group of forty patients who presented to their general practitioner with depression or somatic complaints, which were considered to be due to depression, were included in a double-blind trial of dothiepin and amitriptyline. Patient improvement as judged by the Hamilton Rating Scale (HRS) and the Comprehensive Psychopathological Rating Scale (CPRS) indicated that both groups significantly improved over the 6 week period. Only in one comparison, CPRS after 1 week, was there any statistical difference between the groups and in this case dothiepin produced a better response than amitriptyline (p less than 0.05). Statistical analysis of side-effects indicated that the frequency and severity of certain individual side-effects, hypotension, tiredness/sleepiness and dry mouth were significantly less with dothiepin than with amitriptyline at Week 1 (p less than 0.05). The overall incidence and severity of side-effects was also less with dothiepin at all assessments during the trial.

Adult↗

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.

Adult↗

Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. I. A one year double-blind study of clopenthixol decanoate and flupenthixol palmitate.

Clopenthixol decanoate and flupenthixol palmitate, both depot neuroleptics belonging to the thioxanthene group, were studied during double-blind conditions for 12 months using four week intervals between injections. The 60 patients included in the study were chronic schizophrenics and treated as outpatients after earlier admission to hospital and rehabilitation training periods. They had all been treated with depot neuroleptics in the last three years and they had been free from relapse for at least 15 months. The main aim with this trial was to study the two depot drugs during maintenance treatment conditions in an outpatient setting. Ten patients dropped out, 7 because of unsatisfactory effect, mainly because only limited dose levels were accepted according to the design. In spite of the earlier long lasting neuroleptic treatment and the good social adaptation in this schizophrenic subgroup there was observed a symptom decrease in all the rating scales even in these symptom poor patients. This improvement in psychopathology with optimal results after half a year seems to be a combined result of the efficient neuroleptics tested and careful monitoring of the drug.

Adult↗

Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. II. Factor analysis of the CPRS sub-scale for schizophrenia.

Eleven factors were obtained by factor analysing the CPRS results from a longitudinal treatment process study in chronic schizophrenics during maintenance phase. Such factors may give more reliable information than the single item. Two factors--"anxiety-depression-asthenia" and "psychotic" (psychotic schizophrenic symptoms and signs)--nonpsychotic rating of anxiety and depressive symptoms as well as definite psychotic-schizophrenic symptoms, respectively--demonstrated special value for the clinical work, i.e. being relevant instrument for monitoring a treatment process.

Adult↗

Clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. IV. Serum levels and clinical outcome.

Two pharmacolkinetic parameters viz. the minimum serum concentration in the dosage interval and the sera under the serum concentration curve have been correlated to 14 parameters for clinical outcome, viz. total points and factor points from the three rating scales, BPRS, CPRS, and side effects scale, in a double blind clinical trial of clopenthixol and flupenthixol depot preparations in outpatient schizophrenics. No statistically significant correlations were observed. It is of some interest, however, that the results suggest that the treatment of individual patients with neurleptics may be adjusted by means of repeated ratings, residual percentage, changes in psychopathology, and determinations of serum concentrations. Our results do not indicate any optimal concentration range for these depot neuroleptics in the maintenance phase of schizophrenia. The so-called therapeutic window as to neuroleptics obviously varies with regard to the phase of the disease as well as the patients' social situation.

Ambulatory Care↗

Do schizophrenics well adapted in the community need neuroleptics? A depot neuroleptic withdrawal study.

Two depot neuroleptics (flupenthixol plamitate and clopenthixol decanoate) used for at least 15 months were withdrawn in 32 schizophrenic outpatients belonging to the most symptom-free and social cohort of a total patient population. They all had only slight schizophrenic symptoms, were well adapted in the community, and had been free from relapse for at least 2 years before the study. They were assessed by means of rating scales every month during the first six months and then after 9 and 12 months. After the one-year trial 26 patients had relapsed. Moreover, after the control period further 4 out of 6 patients relapsed during the following drug-free year. These results indicate the necessity of a long follow-up period after withdrawal of depot neuroleptics. Moreover, the results suggest that periodical drug-free periods of about 3 months are appropriate in symptom-poor patients during long-term treatment with long-acting antipsychotic drugs.

Ambulatory Care↗

Clopenthixol decanoate and perphenazine enanthate in schizophrenic patients. A double-blind Nordic multicentre trial.

The clinical properties of clopenthixol decanoate has been investigated versus perphenazine enanthate in a double-blind clinical multicentre trial including 14 psychiatric hospitals in Finland, Sweden, Norway, and Denmark. Test treatment was initiated in 172 chronic schizophrenic patients and the planned 6 months test period was completed by 57 patients receiving clopenthixol decanoate and 48 receiving perphenazine enanthate. The therapeutic effect was assessed by means of CGI, BPRS, and NOSIE-30 and was found significant with both test drugs. Significant differences in the effect were seen only in "Hostile-suspiciousness" (BPRS) and "Social interest" (NOSIE-30). For these items clopenthixol decanoate was found superior to perphenazine enanthate. The influence of side effects on the patients' functioning was found to be slightly, but not significantly more troublesome in the perphenazine enanthate patients.

Adult↗

Symptom reduction in depression after treatment with L-tryptophan or imipramine. Item analysis of Hamilton rating scale for depression.

Thirty-eight in-patients with endogenous- and 20 in-patients with non-endogenous depression, took part in a multi-centre 3-week double-blind trial where patients were randomly allocated to treatment with either 6 g L-tryptophan or 150 mg imipramine daily. Item analysis of Hamilton ratings, before the investigation and weekly during the trial period demonstrated few statistically different mean scores on individual items between the two treatment groups. After 3 weeks' treatment a statistically significant item mean reduction on the 0.1% level was found in the item Agitation in favour of imipramine-treated, and in the item Work and Activities in favour of L-tryptophan-treated endogenously depressed patients. After 3 weeks' treatment a statistically significant item mean reduction on the 5% level was found in the item Suicide in favour of imipramine-treated non-endogenously depressed patients. The present study has shown that, after 3 weeks' treatment, imipramine and L-tryptophan has decreased the mean score on individual items of HRS in about the same degree.

Adolescent↗

Single versus divided daily dosages of clomipramine. Plasma concentration and clinical effect.

Sixteen depressed patients have been treated with a daily dose of 150 mg clomipramine for 20 days. Every patient received the total dose at night for 10 days and three times daily for 10 days according to a double-blind, cross-over design. No differences were noted between the two dose regimens, either regarding the clinical effect or the side effects. The plasma level ratio of parent drug to demethylated metabolite was higher on single than multiple doses.

Adolescent↗