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Biomedical subjects

M Asberg

Publications and source records attributed to M Asberg.

At least 109 records · Page 6Linked to original sources
PubMed1980

Clomipramine treatment of obsessive-compulsive disorder. II. Biochemical aspects.

Concentrations of the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), the dopamine metabolite homovanillic acid, and the noradrenaline metabolite 4-hydroxy-3-methoxyphenyl glycol were measured in CSF before and after three weeks' treatment of severe obsessive-compulsive disorder with clomipramine hydrochloride. Patients who responded to clomipramine treatment had significantly higher CSF levels of 5-HIAA before treatment. The amelioration of obsessive-compulsive symptoms was positively correlated to the reduction of CSF concentrations of 5-HIAA during clomipramine treatment but negatively correlated to plasma concentrations of clomipramine. Reduction of CSF concentrations of 5-HIAA, which probably reflects drug action on central serotonin neurons, was maximal at a plasma clomipramine concentration of about 300 nmole/L. At higher levels, the reduction of CSF levels of 5-HIAA was smaller. The antiobsessive effect of clomipramine may be connected to its capacity to inhibit serotonin uptake.

Adult↗
PubMed1980

Monitoring tricyclic antidepressants.

As a result of their slow onset of action, the difficulty of assessing dose-effect, and the marked interindividual variability of steady-state plasma concentration, tricyclic antidepressants present a special challenge, as well as opportunity, for therapeutic drug monitoring. As shown particularly by the twin studies of Alexanderson, the most important factor responsible for interindividual variation is metabolism; in comparison, differences in binding to plasma proteins are much less significant. Despite the problems posed by the complexity of action of tricyclic antidepressants and their active metabolites on noradrenaline and serotonin metabolism and on monoaminergic receptor sites--as well as the heuristic difficulty calling for a combination of analytical, clinical, pharmacological, and psychiatric expertise--some headway is being made in our understanding the responses of patient populations to this family of drugs. The following conclusions are drawn: (a) monitoring of the plasma concentration of some tricyclics in some types of depressives may improve the clinical use of these drugs; (b) such measurements are valuable mainly in non-responders to normal therapeutic doses; and (c) there seem to exist biochemical subgroups of depressive patients for whom drug choice must be tailored.

Antidepressive Agents, Tricyclic↗
PubMed1979

Construction of a new psychiatric rating instrument, the Comprehensive Psychopathological Rating Scale (CPRS).

1. The CPRS (the Comprehensive Psychopathological Rating Scale) is a recently constructed rating instrument consisting of 65 scaled items, covering a wide range of psychiatric symptoms. Explicit definitions in a non-technical language are provided for items as well as scale steps. 2. The CPRS is mainly intended for evaluation of treatment effects, but due to the explicit descriptions, it has also been found useful for teaching purposes. It can be used in full, or as an item pool for which subscales for different psychiatric syndromes can be designed. Subscales exist, inter al., for depression, schizophrenia, obsessive-compulsive disorder, neurasthenic syndromes and mental distress in connection with severe physical illness. 3. The CPRS is available in parallel Swedish and English versions. It has been translated into all Scandinavian languages, and into German, Italian and Spanish. French and Russian versions are in preparation. 4. The rating is based on an interview which will require less than an hour in most cases if the scale is used in full. Due to the non-technical language used, raters without formal training in psychiatry (i.e. nurses, psychologists, general practitioners) can use the scale without reduction in reliability.

Humans↗
PubMed1979

Intraindividual similarity in the metabolism of amitriptyline and chlorimipramine in depressed patients.

The two structurally similar tricyclic antidepressant drugs amitriptyline (AT) and chlorimipramine (CI) were administered to 15 patients in a cross-over study. Approximately equimolar daily doses of the two drugs (5 mumol/kg body weight) were given as commercial tablets. Steady state plasma levels of the parent drugs and the demethyl metabolites were determined by high performance liquid chromatography. An about 5-fold interindividual variation was found in plasma levels of all four compounds. As the reciprocal plasma level during multiple dosing is proportional to the clearance of a compound, this parameter was used for linear regression analysis. In the 15 patients there was a significant correlation between the reciprocal plasma levels of CI and its metabolite demethylchlorimipramine (r = 0.76; p less than 0.001) and also between AT and its metabolite nortriptyline (r = 0.52; p less than 0.05). The reciprocal plasma levels of the parent compounds AT and CI were closely correlated (r = 0.87; p less than 0.001). A similar correlation was found for the demethyl metabolites (r = 0.77; p less than 0.001). The results indicate that similar factors control the plasma levels of AT and CI during treatment and that similar enzymes may be involved in the metabolism of the two drugs.

Amitriptyline↗
PubMed1979

A new depression scale designed to be sensitive to change.

The construction of a depression rating scale designed to be particularly sensitive to treatment effects is described. Ratings of 54 English and 52 Swedish patients on a 65 item comprehensive psychopathology scale were used to identify the 17 most commonly occurring symptoms in primary depressive illness in the combined sample. Ratings on these 17 items for 64 patients participating in studies of four different antidepressant drugs were used to create a depression scale consisting of the 10 items which showed the largest changes with treatment and the highest correlation to overall change. The inner-rater reliability of the new depression scale was high. Scores on the scale correlated significantly with scores on a standard rating scale for depression, the Hamilton Rating Scale (HRS), indicating its validity as a general severity estimate. Its capacity to differentiate between responders and non-responders to antidepressant treatment was better than the HRS, indicating greater sensitivity to change. The practical and ethical implications in terms of smaller sample sizes in clinical trials are discussed.

Adolescent↗
PubMed1978

Reliability of the CPRS between the disciplines of psychiatry, general practice, nursing and psychology in depressed patients.

To test the reliability and robustness of the CPRS in use by different disciplines we obtained 49 pairs of ratings on depressed patients in England and Sweden during treatment. Each rater pair consisted of a psychiatrist trained as a rater plus either a psychologist, a general practitioner, or a nurse, who had not been trained as a rater. The 17 most commonly rated items in depressive illness showed good inter-rater reliability for all groups and demonstrated the robustness of the scale even in training sessions. The implications of this for future interdisciplinary research are discussed along with suggestions for the use of the CPRS for teaching purposes.

Depression↗
PubMed1978

Cross cultural studies on the use of CPRS in English and Swedish depressed patients.

54 English and 52 Swedish patients suffering from primary depressive illness were rated on the full 65 item CPRS scale to examine cross cultural differences. The correlation of the frequencies of items scored in the different patient samples was highly significant (r = 0.88). Of the most commonly scored items (occurring in more than 70% of any of the patient groups) 17 were common to both samples. The three items not in common for the two centres are compared and discussed. The inter rater reliabilities of the Swedish and English teams are compared alongside the inter rater reliabilities of a Swedish rater and an English rater on English patients and are generally good. The remarkable similarity of the psychopathology of primary depressive illness in both cultures and some of the implications are discussed.

Adolescent↗
PubMed1977

Monoamine metabolites in cerebrospinal fluid and serotonin uptake inhibition during treatment with chlorimipramine.

The effects of chlorimipramine on the concentrations of the main metabolites of serotonin (5-HT) norepinephrine (NE), and dopamine, i.e. 5-hydroxyindoleacetic acid (5-HIAA), 4-hydroxy-3-methoxyphenyl glycol (HMPG) and homovanillic acid (HVA), respectively, were studied in cerebrospinal fluid from 14 depressed patients, and related to the serotonin- and NE uptake inhibiting activity in vitro of plasma drawn from the patients. Chlorimipramine inhibited the uptake of both transmitter amines in all patients. During treatment, the levels of 5-HIAA and HMPG in cerebrospinal fluid (CSF) were significantly reduced. HVA levels were reduced in 6 patients and increased in 8 patients; there was no mean change. The decrease in 5-HIAA level in CSF was correlated to the uptake inhibition of 5-HT but there was no corresponding relationship between NE uptake and HMPG levels. The changes in HVA levels were also correlated to the uptake of 5-HT despite the absence of a unidirectional change of this metabolite.

Biogenic Amines↗
PubMed1976

"Serotonin depression"--a biochemical subgroup within the affective disorders?

The distribution of 5-hydroxyindoleacetic acid (5-HIAA) concentrations in the cerebrospinal fluid of 68 depressed patients was bimodal. Twenty-nine percent of the patients were in the lower mode, with a concentration of 5-HIAA below 15 nanograms per milliliter. Although there were no differences in overall severity of depression between the two modes, there was a significant correlation between the concnetration of 5-HIAA and severity of depression in the lower, but not in the upper, mode. The finding suggests the existence of a biochemical subgroup of depressive disorder, characterized by a disturbance of serotonin turnover.

Antidepressive Agents↗
PubMed1976

5-HIAA in the cerebrospinal fluid. A biochemical suicide predictor?

The incidence of suicidal acts was studied in 68 depressed patients and related to the level of 5-hydroxyindoleacetic acid (5-HIAA) in the cerebrospinal fluid. The distribution of 5-HIAA levels was bimodal. Patients in the low 5-HIAA mode (below 15 ng/ml) attempted suicide significantly more often than those in the high mode, and they used more violent means. Two of the 20 patients in the low mode, and none of the 48 patients in the high mode died from suicide.

Adjustment Disorders↗
PubMed1976

Treatment of depression with tricyclic drugs--pharmacokinetic and pharmacodynamic aspects.

A series of studies on the pharmacokinetic and pharmacodynamic properties of some tricyclic antidepressants is reviewed. During treatment with the same oral dose of these drugs, patients develop widely differing plasma levels. The importance of this variability for the clinical effects has been studied in detail for the monomethylated compound, nortriptyline. There is an association between side-effects and high plasma levels of this drug. In endogenously depressed patients, the relationship between plasma level and effect appears to be curvilinear. The tricyclic antidepressants differ in their capacity to inhibit transmitter uptake into noradrenaline- and serotonin neurons respectively. Nortriptyline is a preferential noradrenaline uptake inhibitor, while the dimethylated compound, chlorimipramine also has a profound influence on serotonin neurons. These differential effects are also reflected in changes in the levels of the transmitter metabolites in cerebrospinal fluid (CSF). The CSF studies have also supported the hypothesis of a biochemical heterogeneity of the depressive syndrome. The levels of the serotonin metabolite, 5-HIAA were bimodally distributed in CSF. In patients with a low level of 5-HIAA there was a significant correlation between the CSF metabolite level and the severity of the depression, and these patients also appeared to be more suicide-prone than those with higher 5-HIAA levels. These patients seemed to be less amenable to treatment with nortriptyline. The effect of chlorimipramine treatment in this subgroup of depressives is presently being explored.

Antidepressive Agents, Tricyclic↗