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Biomedical subjects

M Deuschle

Publications and source records attributed to M Deuschle.

At least 19 recordsLinked to original sources
PubMed2006

[Lengthening of QT interval by antipsychotic drugs].

Prolongation of myocardial repolarisation, i.e. lengthening of the QT interval on surface electrocardiogram, has been recognised as a side effect of many drugs, including antipsychotics. In predisposed individuals, abnormal excessive QT prolongation and severe ventricular arrhythmias (the ventricular tachycardia type 'torsade de pointes', or TdP) may occur. In almost all cases, additional factors are present that increase the propensity of patients to develop TdP, such as serum hypokalemia, the combination of drugs prolonging repolarisation, overdosing, intoxication, and factors interfering with drug metabolism and excretion. Serum hypokalemia and/or bradycardia may induce TdP alone, in the absence of drugs prolonging the QT interval. Experimental studies demonstrate that prolongation of myocardial repolarisation is a class effect of neuroleptics. Clinically, the extent to which individual drugs prolong the QT interval varies. Among the antipsychotics, thioridazine has the greatest propensity to induce abnormal QT prolongations and TdP. Case reports of TdP with other antipsychotics have been published. Physicians prescribing physicians these drugs must be aware that they can induce proarrhythmia in individual cases. They should also be aware of the circumstances which are necessary for abnormal QT prolongation and TdP to develop. Patients should be monitored with regard to these risk factors before and during drug treatment.

Antipsychotic Agents↗
PubMed2006

Duloxetine treatment of major depressive episodes in the course of psychotic disorders.

During the course of psychotic disorders, patients often suffer from intercurrent major depressive episodes (MDEs), and suicides frequently occur. This constellation challenges further improvements in psychopharmacological therapy. The antidepressant duloxetine was recently introduced as a novel reuptake inhibitor of serotonin and noradrenaline. We provide the first reports on duloxetine treatment of MDEs in the course of psychotic disorders. In two cases this substance was successfully involved as an add-on to antipsychotic treatment consisting of clozapine or amisulpride. We achieved a response of the MDEs, as reflected by psychopathological rating scales. A significant rise in the clozapine serum level was detected, most likely because of pharmacokinetic interactions. Overall, the application of duloxetine was well tolerated; therefore, further investigations in prospective studies seem to be recommendable.

Adult↗
PubMed2005

Paroxetine serum concentrations in depressed patients and response to treatment.

INTRODUCTION: There is no established relationship between the serum concentration of selective serotonin reuptake inhibitors (SSRIs) and clinical response in depressed patients. METHODS: We analyzed paroxetine concentrations in serum of 46 depressed patients during treatment with a fixed dosage of 40 mg paroxetine. RESULTS: After 5 weeks 29 patients responded to treatment, while 17 did not. Analysis of variance with repeated measures (ANOVA-rm) revealed a significant effect of "response" with responders having lower serum concentrations throughout the treatment period, when compared to non-responders. After 2, 3, and 4 weeks of treatment, we could define an upper threshold of paroxetine serum concentrations (week 1 : 22.7 ng/mL; week 2 : 43 ng/mL; week 3 : 53.4 ng/mL; week 4 : 39.1 ng/mL) above which response to treatment was unlikely. CONCLUSION: We conclude that -- in contrast to other pharmacological approaches -- high rather than low drug serum concentrations may be associated with non-response in paroxetine treatment of depressed patients.

Adult↗
PubMed2004

No major effect of orciprenaline and propranolol upon ACTH-induced cortisol secretion.

Preclinical research suggests adrenal beta-adrenergic receptors to be involved in the regulation of steroid synthesis. In a group of healthy male volunteers, we compared ACTH-induced cortisol and dehydroepiandrosterone (DHEA) secretion after pre-treatment with orciprenaline, propranolol or placebo. Neither baseline nor ACTH-induced steroid secretion differed between these conditions. Our data do not support the hypothesis that the adrenal beta-receptor plays a major role in steroid secretion in humans.

Adrenergic beta-Agonists↗
PubMed2004

Impaired declarative memory in depressed patients is slow to recover: clinical experience.

INTRODUCTION: The temporal course of recovery of depressed patients' cognitive impairment is not fully understood. METHODS: We used the California Verbal Learning Test (CVLT) to test declarative memory in 24 depressed patients before and after 35 days of antidepressive treatment as well as after long-term follow-up (> 12 months) in order to relate improvement of depression to recovery of cognitive impairment. RESULTS: Patients with complete remission after 35 days had generally been less impaired at baseline. The disturbance of declarative memory in treatment responders as well as in non-responders did not change from baseline to end of treatment (day 35). However, our results revealed normal values in the CVLT sum score as well as in measures of short- and long-delay free-recall measures in both groups after long-term full remission. DISCUSSION: We conclude that clinical response to antidepressive treatment precedes improvement of declarative memory. A low degree of impairment of declarative memory is associated with early complete remission of depression.

Amitriptyline↗
PubMed2004

Open-label non-randomized versus double-blind randomized antidepressive treatment: what are the advantages of clinical decision over randomization?

OBJECTIVE: To study, whether and how the results from open and double-blind randomized trials on antidepressants differ. METHODS: Seventy-one patients were included in a study comparing open, non-randomized, standardized treatment with paroxetine (PAROX) and amitriptyline (AMI) after a minimum of six drug-free days (OPEN). A second group of 56 patients received the same treatment under blind-randomized conditions (BLIND-RANDOM). The course of psychopathology as assessed by the Hamilton Depression Rating Scale was compared using repeated measurements ANOVA-(rm). RESULTS: While the rate of adverse events was higher in the BLIND-RANDOM compared to the OPEN condition, completer-analyses revealed no differences in psychopathological outcome. CONCLUSIONS: With similar clinical outcome BLIND-RANDOM trials of antidepressants may expose depressed patients to an increased risk of adverse events, when compared to OPEN conditions. However, the clinical outcome in study completers did not differ between the BLIND-RANDOM and the OPEN condition. Thus, the psychiatrist's choice may have impact on adverse events rather than on clinical outcome of antidepressant treatment.

Adult↗
PubMed2003

Platelet counts in depressed patients treated with amitriptyline or paroxetine.

OBJECTIVE: To assess whether therapy with two widely used antidepressants influences platelet counts. SUBJECTS AND METHODS: In 90 patients hospitalized for treatment of a major depressive episode according to DSM-IV, platelet counts were performed after a 6 d antidepressant-free run-in period and again after 35 d of active standardized treatment with amitriptyline (n = 40) or paroxetine (n = 50). RESULTS: There was a trend for platelet counts to increase during treatment with amitriptyline (from 245.5 +/- 68.6 to 256.8 +/- 69 cells x 10(9) L(-1), P < 0.06); no change was observed during treatment with paroxetine (from 232.6 +/- 58.3 to 234.6 +/- 68.9 cells x 10(9) L(-1), n.s). CONCLUSION: Treatment with amitriptyline tends to be associated with elevated platelet counts. The cause for this increase is not known, but may be relevant in terms of patients' long-term thromboembolic risk.

Amitriptyline↗
PubMed2002

[Depression and cardiovascular disease: pathogenetic factors of the stress concept].

To date cardiovascular disorders still represent the most frequent cause of death in our western hemisphere. A number of prospective studies have now been able to show that patients with no prior history of heart disease run a higher risk of developing cardiovascular problems, if they either suffered a number of depressive symptoms or showed a depressive syndrome. Similarly, in patients who have suffered a myocardial infarction the presence of a depressive syndrome is frequently associated with poor clinical prognosis and outcome. Within this context the knowledge of the pathophysiological relationship between affective and cardiovascular disorders constitutes an essential element for instituting effective preventive measures for protecting depressed patients against the risk of suffering cardiovascular problems. The activation of stress-responsive systems during depressive episodes may contribute to metabolic risk factors and dysbalance of the autonomic heart regulation. The present overview provides a summary of current knowledge and findings within this area of research.

Antidepressive Agents↗
PubMed2001

Increased platelet aggregability in major depression?

There is compelling evidence that depression constitutes an independent risk factor for cardiovascular morbidity and mortality. As exaggerated platelet reactivity is associated with an increased risk of intra-arterial thrombus formation, we studied platelet aggregability in patients with major depression both before and after 5 weeks of anti-depressant therapy as well as in healthy control subjects. Twenty-two depressed patients and 24 healthy control subjects participated in the study. Washed and rediluted platelets were stimulated with the agonists collagen and thrombin in three concentration steps. Depression was associated with a higher aggregability after stimulation with thrombin in the intermediate concentration and with collagen at the low concentration, with ceiling effects for the other concentrations. After 5 weeks of anti-depressant therapy, aggregability was somewhat less exaggerated, although this effect did not reach statistical significance. We thus conclude that major depression is associated with increased platelet aggregability, which seems to persist even under a marked improvement in depressive symptomatology. This effect may contribute to the increased cardiovascular morbidity in depressed patients.

Adult↗
PubMed2001

The glutamate antagonist riluzole and its effects upon basal and stress-induced activity of the human hypothalamus-pituitary-adrenocortical system in elderly subjects.

There is preclinical evidence that CRH is released in response to a glutamatergic stimulation. However, it is not clear, whether glutamate plays a role in the physiological stress response. We tested whether the antiglutamatergic drug riluzole dampens the response of the hypothalamus-pituitary-adrenocortical (HPA) system to both a mental and a physical stressor. Nine male elderly healthy subjects received placebo and 150 mg riluzole for 2 days in a randomized balanced order. Blood was withdrawn every 15 min for estimation of cortisol and ACTH from 14.00 to 20.00 h. Between 16.00 and 16.45 h, the subjects were subjected to a cognitive challenge paradigm. Further, between 19.02 and 19.15 an individually adapted physical stress test was performed. After riluzole treatment, baseline ACTH and cortisol concentrations were unchanged when compared to placebo treatment. Also, after the mental stressor, there was no difference between both treatment conditions. In contrast, the cortisol (riluzole vs. placebo: 148 +/- 60 vs. 183 +/- 98 nmol/l) and ACTH response (20.2 +/- 11.9 vs. 40.7 +/- 61.9 pmol/l) to the physical stressor tended to be lower after riluzole pretreatment. In conclusion, the antiglutamatergic drug riluzole did not have any effects upon HPA system activity under baseline and cognitive-stress-induced conditions in elderly subjects. However, a trend for dampening the endocrine response to physical stress emerged.

Adrenocorticotropic Hormone↗
PubMed2000

Effect of coadministration of clozapine and fluvoxamine versus clozapine monotherapy on blood cell counts, plasma levels of cytokines and body weight.

RATIONALE: Clozapine treatment is associated with side-effects such as blood cell dyscrasias and weight gain. Increased plasma levels of the cytokines and soluble cytokine receptors leptin, tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors p55 and p75, as well as toxic metabolites of clozapine, have been suggested as the basis for these side-effects, OBJECTIVES: This study examined whether the coadministration of the selective serotonine reuptake inhibitor fluvoxamine, which interferes with clozapine's hepatic metabolism, affects the immunomodulation by clozapine and some of its side-effects. METHODS: The following parameters were measured: circulating levels of the cytokines and soluble receptors, plasma concentrations of clozapine and its metabolite N-desmethylclozapine, body weight and blood cell counts in 11 and 12 schizophrenic inpatients on combined and monotherapy, respectively, before and during the first 6 weeks of medication. RESULTS: On the basis of comparable plasma levels of clozapine and N-desmethylclozapine, the coadministration of fluvoxamine 1) attenuated and delayed the clozapine-induced increase in TNF-alpha plasma levels, 2) enhanced and accelerated the clozapine-induced increase in leptin plasma levels without significant effect on clozapine-induced weight gain, and 3) decreased granulocyte counts. CONCLUSIONS: As clozapine, its metabolite N-desmethylclozapine and fluvoxamine are unlikely to make these differences, other metabolites might be responsible. The coadministration of clozapine and fluvoxamine offers the opportunity to investigate further the putative associations between certain metabolites, immunomodulation and these side-effects.

Adolescent↗
PubMed2000

Increased activity of the hypothalamus-pituitary-adrenal system after treatment with the mineralocorticoid receptor antagonist spironolactone.

The hippocampal mineralocorticoid receptor (MR) is critical for the regulation of the basal activity of the hypothalamus-pituitary-adrenocortical (HPA) system. It has been hypothesized that reduced capacity of the hippocampal MR is involved in the HPA-system dysregulation found in depression and aging. We applied the combined dexamethasone suppression/corticotropin releasing hormone stimulation (DEX/CRH) test to six healthy young females both before and after 12 days of treatment with the MR antagonist spironolactone to assess HPA regulation. Treatment with spironolactone caused a significant increase in post-dexamethasone cortisol concentrations (75.1+/-56.7 vs. 36.6+/-24.6 nmol/l, p<0.05). Furthermore, we observed a significant rise in peak cortisol concentration after additional human CRH (hCRH) application (223. 6+/-139.1 vs. 126.7+/-73.3 nmol/l, p<0.02). There was no change in ACTH plasma concentrations. We thus conclude that (1) the MR antagonist spironolactone affects HPA system regulation as reflected in the DEX/CRH test and (2) these findings are in accordance with the assumption that MR dysfunction may underlie HPA-system dysfunction in depression and/or aging.

Adrenal Glands↗