Biomedical subjects

Harald Murck

Publications and source records attributed to Harald Murck.

23 records · Page 2Linked to original sources

PubMed2003

Clinical and neurobiological effects of tianeptine and paroxetine in major depression.

Selective serotonin reuptake inhibitors (SSRIs) are widely used as effective pharmacological agents to treat depressive disorders. In contrast to the SSRIs, which block the presynaptic serotonin (5-HT) transporter and by this route increase the concentration of serotonin in the synaptic cleft, the antidepressant tianeptine enhances the presynaptic neuronal reuptake of 5-HT and thus decreases serotonergic neurotransmission. Both SSRIs and tianeptine are clinically effective; however, their opposite modes of action challenge the prevailing concepts on the need of enhancement of serotonergic neurotransmission. To better understand the differences between these two opposite pharmacological modes of action, we compared the changes induced by tianeptine and paroxetine on psychopathology, the hypothalamic-pituitary-adrenocortical (HPA) system, and cognitive functions in a double-blind, randomized, controlled trial including 44 depressed inpatients over a period of 42 days. Depressive symptomatology significantly improved in all efficacy measures, with no significant differences between tianeptine and paroxetine. There was a trend toward better response to the SSRI among women. Assessment of the HPA system showed marked hyperactivity before the beginning of treatment, which then normalized in most of the patients, without significant differences between the two antidepressants. Cognitive assessments showed no significant differences between the two drugs investigated. The results of the current study suggest that the initial effect, i.e., enhancement or decrease of 5-HT release, is only indirectly responsible for antidepressant efficacy, and they support the notion that downstream adaptations within and between nerve cells are crucial. The normalization of the HPA system as a common mode of action of different antidepressants seems to be of special interest.

Adult↗

PubMed2002

St John's wort extract (LI 160) in somatoform disorders: results of a placebo-controlled trial.

RATIONALE AND OBJECTIVE: Preliminary data have shown that St John's wort might possess some specific efficacy in patients with somatoform complaints. Therefore, the efficacy of the Hypericum extract LI 160 in patients with somatoform disorders should be studied in a double-blind placebo-controlled fashion. METHODS: This was a multicentre, randomised, placebo controlled, 6-week trial comparing the efficacy of LI 160 (600 mg/day) and placebo in 151 out-patients suffering from somatization disorder (ICD-10: F45.0), undifferentiated somatoform disorder (F45.1), or somatoform autonomic dysfunctions (F45.3). The primary outcome measure was the decrease of the Hamilton Anxiety Scale, subfactor somatic anxiety (HAMA-SOM), during the trial period. RESULTS: LI 160 was superior effective concerning the primary outcome criterion HAMA-SOM [decrease from 15.39 (SD 2.68) to 6.64 (4.32) in the Hypericum group and from 15.55 (2.94) to 11.97 (5.58) in the placebo group (statistically significant difference, P=0.001)]. This was corroborated by the result of a statistically significant superior efficacy in the outcome criteria additionally used such as Clinical Global Impression, HAMA-total score, HAMA, subscore psychic anxiety, Hamilton Depression Scale, Self-Report Symptom Inventory 90 items - revised (SCL-90-R), and SCL-90-R, subscore somatic anxiety. The efficacy of LI 160 was preserved after splitting the population in those with and those without mild depressive symptoms [corrected]. Tolerability of LI 160 was excellent. CONCLUSION: The data from this trial show excellent efficacy and tolerability for LI 160 in somatoform disorders. The efficacy is independent of an existing depressive mood. This is the first study showing the efficacy of a drug in patients with somatisation disorder independent of depressive symptomatology.

Adolescent↗

PubMed2002

Increase in amino acids in the pons after sleep deprivation: a pilot study using proton magnetic resonance spectroscopy.

Total sleep deprivation (TSD) is an efficient method to relieve depression. An involvement of GABAergic and glutamatergic neurotransmission in the pathophysiology of depression and the mechanism of action of TSD has been suggested. To directly assess the content of GABA, glutamate (Glu) and glutamine (Gln) before and after TSD, we estimated their concentrations in four brain regions in six healthy subjects using proton magnetic resonance spectroscopy. The unresolved estimate of GABA, Glu and Gln, as well as GABA and Gln were increased in the pons after 24 h of TSD, the effect being prominent in three subjects. There were no significant changes in the hypothalamus, thalamus or parietooccipital cortex. These preliminary data support earlier animal data and indirect findings in humans suggesting that GABA and Gln, especially in the pontine structures, may play a key role in the mechanism of TSD.

Adult↗

PubMedDate not supplied

Nocturnal secretion of TSH and ACTH in male patients with depression and healthy controls.

Profound alterations of the hypothalamic-pituitary-thyroid (HPT) and the hypothalamic-pituitary-adrenal (HPA) systems at the hypophyseal level have been described in affective disorder. To precisely characterize the basal alterations of both axes during sleep, we simultaneously investigated sleep EEG and the secretion of thyrotropin, ACTH and cortisol in nine drug-free male patients with depression in comparison to 10 healthy age and sex matched controls. In depressed patients the nearly diametrical nocturnal secretion of thyrotropin and ACTH was disturbed by significantly blunted thyrotropin values (TSH AUC 51.96+/-5.68 vs. 87.23+/-13.63, P<0.05) and elevated ACTH values (ACTH AUC 1804+/-161 vs. 1538+/-130, P<0.05) compared to controls. Moreover, cross correlation analysis revealed a highly negative association of 0 lag between thyrotropin and ACTH and between thyrotropin and cortisol in the control sample, indicating a physiological nocturnal negative correlation of HPT and HPA system. In the patients sample these associations were weak and reached not statistical significance. Therefore, as a descriptive tool, the ratio TSH/ACTH revealed a significant group difference between controls and patients in the first half of the night (TSH/ACTH AUC 6.50+/-0.42 vs. 3.35+/-0.31, P<0.05). Sleep-EEG analysis showed a shortened REM latency, a decrease of stage 2 and an increase of awake time in the patients. Our data support the hypothesis that both hypophyseal hormones reflect a common dysregulation of both systems in depression probably due to impaired action of TRH-related corticotropin-release-inhibiting-factor (CRIF). The ratio TSH/ACTH might be a tool to characterize alterations of both the HPT and HPA axis in depression during the first half of the night.

Adrenocorticotropic Hormone↗

PubMedDate not supplied

Treatment of somatoform disorders with St. John's wort: a randomized, double-blind and placebo-controlled trial.

OBJECTIVE: To investigate efficacy and safety of St. John's wort (SJW) LI 160 in somatoform disorders. METHODS: In a prospective, randomized, placebo-controlled, and double-blind parallel group study, 184 outpatients with somatization disorder (ICD-10 F45.0), undifferentiated somatoform disorder (F45.1), and somatoform autonomic dysfunction (F45.3), but not major depression, received either 300 mg of SJW extract LI 160 twice daily or matching placebo for 6 weeks. Six outcome measures were evaluated as a combined measure by means of the Wei Lachin test: Somatoform Disorders Screening Instrument--7 days (SOMS-7), somatic subscore of the HAMA, somatic subscore of the SCL-90-R, subscores "improvement" and "efficacy" of the CGI, and the global judgment of efficacy by the patient. RESULTS: In the intention to treat population (N=173), for each of the six primary efficacy measures as well as for the combined test, statistically significant medium to large-sized superiority of SJW treatment over placebo was demonstrated (p <.0001). Of the SJW patients, 45.4% were classified as responders compared with 20.9% with placebo (p =.0006). Tolerability of SJW treatment was equivalent to placebo. CONCLUSIONS: Administration of 600 mg of SJW extract LI 160 daily is effective and safe in the treatment of somatoform disorders, thereby confirming results from a previous study.

Adolescent↗