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Biomedical subjects

P C Baastrup

Publications and source records attributed to P C Baastrup.

At least 19 recordsLinked to original sources

A controlled Nordic multicentre study of zuclopenthixol acetate in oil solution, haloperidol and zuclopenthixol in the treatment of acute psychosis.

Zuclopenthixol acetate--a new injectable formulation with a duration of action of 2-3 days--was compared with conventional intramuscular and oral formulations of haloperidol and zuclopenthixol in the initial treatment of acutely disturbed, psychotic patients. The patients were stratified into 3 diagnostic categories: acute psychoses (48 patients), mania (22 patients), and exacerbation of chronic psychoses (73 patients). The patients were rated on the Brief Psychiatric Rating Scale (BPRS), the Bech-Rafaelsen Mania Rating Scale (BRMAS) (only manic patients) and globally on the Clinical Global Impression (CGI). The study was an open, randomized multicentre trial with a 6-day treatment period. The zuclopenthixol acetate patients received 1-4 doses, the haloperidol patients 1-26 and the zuclopenthixol patients 1-22 doses. The assessments on the CGI showed that all 3 treatments caused a clear reduction of the severity of illness scores in all 3 diagnostic categories, with no differences between treatments. The ratings of the acute and chronic psychotic patients on the BPRS also showed significant reductions in scores with no differences between treatments. All 3 treatments caused a rapid remission of symptoms on the BRMAS. Haloperidol induced hypokinesia in significantly more patients than zuclopenthixol acetate after 24 h. Later there were no significant differences between treatments. Zuclopenthixol acetate fulfils many desires for an amended neuroleptic formulation for the initial treatment of acutely disturbed psychotic patients.

Acute Disease

Thyroid function and ultrasonically determined thyroid size in patients receiving long-term lithium treatment.

Thyroid function was investigated in 100 manic-depressive patients. Goiter was more common in patients treated with lithium for 1-5 years (44%) or more than 10 years (50%) than in patients who never received lithium (16%). Smoking contributed significantly to thyroid size and goiter. In nonsmoking patients, ultrasonically determined thyroid volume was significantly related to treatment duration. The mechanism behind this increased thyroid volume is unclear, as most patients had normal serum thyrotropin levels and no thyroid autoimmunity. Subclinical or overt hypothyroidism was found in 4% and 21% of patients treated for 1-5 and more than 10 years, respectively. Since few hypothyroid patients had autoimmunity or goiter, lithium may affect the thyroid gland directly.

Adult

Psychotropic medication in the elderly. A survey of prescribing and clinical outcome.

Due to the increasing elderly population, an increased number of elderly patients requires treatment for mental and behavioural disorders. There are relatively few clinical studies of the prescribing of psychotropic drugs in patients over 65 years of age. A prospective study was undertaken at three centres caring for the elderly, encompassing patients from general nursing homes and a psychiatric department. Entry of patients into the survey was determined by the clinical decision to prescribe psychotropic medication and an age of 65 years or older. Included in the study were 160 patients. The main reasons for initiating psychotropic medication were indicated, and anamnestic data were collected. Initial and continuing dosages of psychotropic medication were recorded. The clinical condition was assessed at the start of treatment and after four and eight weeks, utilising the Clinical Global Impressions (CGI) scale. The patient's daily activity using an abbreviated Stockton Geriatric Rating Scale (SGRS) was assessed. Side effects were recorded using the UKU Scale. Clinical improvement was seen in about half of the patients with the best effect in patients with mainly psychotic symptoms. Patients with chronic dementia-related problems responded less well. Side effects were few and generally mild. This situation may relate to cautious introduction of the medication and adoption of low-dose regimens. All centres avoided, if possible, psychotropic polypharmacy.

Adjustment Disorders

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

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

Renal function in 153 manic-depressive patients treated with lithium for more than five years.

Renal function was examined in 153 manic-depressive patients treated with lithium for more than 5 years, mean 10 years. No significant change was detectable in plasma creatinine. Glomerular filtration rate (GFR) decreased slightly, but significantly, and not until after 17 years of treatment did the regression line reach the lower confidence limit in the reference material. GFR was generally only moderately decreased. Renal concentrating capacity was significantly reduced during the whole investigation period and did not change with time. GFR was independent of the dosage pattern. The diuresis did not differ markedly in patients given one or three daily doses. In a two-dose group predominantly treated with slow-release tablets, the diuresis was somewhat higher in 75% of the patients but much higher for the rest of the group. Since the prophylactic effect of lithium was the same in the one-dose group (mean dosage 21 mmol/day) as in the two-dose and three-dose groups (mean dosage 27-28 mmol/day), our data indicate that generally employed lithium doses may be reduced somewhat without loss of prophylactic efficacy.

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

Calcium metabolism in schizophrenic patients on long-term neuroleptic therapy.

The bone mineral content (BMC) in both forearms (highly related to total body calcium) was measured in a large group of schizophrenic patients receiving neuroleptic drugs. The mean BMC value was 86% of normal (p less than 0.001), and the decrease was independent of type of neuroleptic treatment. In contrast, the biochemical variables (serum calcium, magnesium, phosphate, and alkaline phosphatases) were virtually normal. This combination of osteopenia and normal biochemical variables suggests that schizophrenics have osteoporosis, be it due to the disease or the treatment given.

Adolescent

Development of 'primary' hyperparathyroidism during lithium therapy: longitudinal study.

The bone mineral content and the serum levels of immunoreactive parathyroid hormone (iPTH), and protein-corrected calcium and magnesium were measured in 13 manic depressive patients before and during treatment with lithium. Initially all four parameters were normal. During the treatment the bone mineral decreased and the serum levels of iPTH, calcium, and magnesium increased. Although altered metabolism of parathyroid hormone cannot be ruled out, these data, together with other observations, suggest that a mild 'primary' hyperparathyroidism sets in quite early after institution of lithium therapy.

Adult

Calcium metabolism in lithium-treated patients. Relation to uni-bipolar dichotomy.

The bone mineral content (BMC) together with biochemical indices of calcium metabolism were measured in 83 manic-depressive patients on long-term lithium therapy. The patients were diagnosed and divided into a unipolar and a bipolar group according to strict symptomatic course criteria. The patients with bipolar course had a significantly decreased BMC (88% of normal, P is less than 0.001), while the unipolar patients had normal BMC. Both groups had biochemical changes consistent with primary hyperparathyroidism.

Adult

Endocrine effects of lithium: II. 'Primary' hyperparathyroidism.

Ninety-six manic-depressive patients were studied during long-term lithium treatment. Highly significant elevations were observed respecting the levels of serum immunoreactive parathyroid hormone (P less than 0.001) as well as the protein-corrected levels of serum calcium (P less than 0.001) and serum magnesium (P less than 0.001), thus indicating a state of 'primary' hyperparathyroidism. The patients as a group had normophosphataemia and normophosphatasia supporting the impression of a rather mild state of biochemical hyperparathyroidism.

Adult

Endocrine effects of lithium. III. Hypermagnesaemia and activation of the renin-aldosterone system.

Hypermagnesaemia is a well-known but as yet unexplained concomitant of lithium treatment. Prior suggestions implicating a role for aldosterone in magnesium homoeostasis prompted this study of plasma renin, plasma aldosterone and serum magnesium in 17 maniodepressive patients on long-term lithium treatment. In addition to hypermagnesaemia (P less than 0.001), this group of patients had raised plasma levels of aldosterone (P less than 0.001) and increased plasma renin concentration (P less than 0.05). Serum magnesium was positively correlated to plasma aldosterone (r = 0.58, P less than 0.02). The relation between activation of the renin-aldosterone system and the presence of hypermagnesaemia during chronic lithium treatment could conceivably be mediated through a lithium-induced hypovolaemic state.

Adult

Lithium treatment of Huntington's chorea. A placebo-controlled clinical trial.

The therapeutic effect of lithium in Huntington's chorea was tested in six patients through a double-blind cross-over comparison of lithium and placebo, each administered for 6 weeks. Four of the patients received neuroleptic drugs at the same time. Lithium and placebo periods did not differ as regards motor skills, hyperkinesias, or total ward situation, all rated quantitatively with the use of scales. Lithium does not seem to be of therapeutic value in Huntington's chorea.

Adult

Adverse reactions in treatment with lithium carbonate and haloperidol.

Hospital records of 425 patients who had been treated simultaneously with lithium carbonate and haloperidol were examined. Adverse reactions in these patients were the same as in patients given lithium alone or haloperidol alone. None of the patients developed a syndrome resembling that described by others in patients treated with a lithium and haloperidol combination.

Affective Symptoms