Thomas Baghai - Academia.edu (original) (raw)

Papers by Thomas Baghai

European Psychiatry, 2014

Background: In this study, the impact of quetiapine fumarate extended release (QXR) and escitalop... more Background: In this study, the impact of quetiapine fumarate extended release (QXR) and escitalopram (ESC) on HPA axis activity was investigated in depressed patients in relationship to antidepressant efficacy. Methods: In a randomized, open-label 5-week trial 60 inpatients suffering from major depression (DSM-IV criteria) were treated for 5 weeks with either QXR (300 mg/day) or ESC (10 mg/day). The dexamethasone/CRH (DEX/CRH) test was performed before treatment, after 1, and after 5 weeks of treatment. Cortisol (COR) AUC values were used to assess HPA axis function. The Hamilton Depression Rating Scale was used weekly to estimate antidepressant efficacy. Results: QXR and ESC showed comparable antidepressant effects but strongly differed in their impact on HPA axis activity. In the QXR group, a marked inhibition of COR AUC levels was observed which was most pronounced after one week of treatment but showed a partial re-increase after 5 weeks of treatment. In contrast, ESC transiently stimulated COR AUC values (week 1) whereas COR AUC levels at week 0 and week 5 were comparable. COR improvement at week 1 (defined as COR peak value reduction between DEX/CRH test 1 and 2) was significantly associated with better clinical outcome. Conclusion: Apparently, different effects on HPA axis activity reflect distinct pharmacoendocrinological properties of psychotropic drugs. (clinicaltrials.gov Identifier: NCT00953108).

Journal of Psychiatric Research, May 1, 2014

The hypothalamicepituitaryeadrenocortical (HPA) system is believed to play an important role in t... more The hypothalamicepituitaryeadrenocortical (HPA) system is believed to play an important role in the pathophysiology of major depressive disorder. In this context, the atypical antipsychotic quetiapine (QUE) has been shown to inhibit HPA system activity in healthy subjects. In this study we investigated whether the putative inhibitory effects of QUE on HPA system activity may contribute to its antidepressant efficacy. We analyzed the effects of QUE as an augmentation to the selective serotonin reuptake inhibitor (SSRI) escitalopram (ESC) on HPA system activity in comparison to a monotherapy with ESC in relation to the antidepressant effectiveness. HPA axis activity (cortisol and ACTH) was measured by means of the dexamethasone/corticotropin-releasing hormone (DEX/CRH) test which was performed before (week 0) and during (week 1, week 5) antidepressant psychopharmacotherapy. The combination therapy, but not the ESC monotherapy showed significantly inhibiting effects on HPA system activity leading to stepwise down-regulation. ACTH concentrations were reduced in the ESC/QUE group during five weeks of treatment. The inhibitory effect of QUE maybe involved in its antidepressant effects as an augmentation strategy.

Psychoneuroendocrinology, 2014

In this study, the impact of quetiapine fumarate extended release (QXR) and escitalopram (ESC) on... more In this study, the impact of quetiapine fumarate extended release (QXR) and escitalopram (ESC) on HPA axis activity was investigated in depressed patients in relationship to antidepressant efficacy. In a randomized, open-label 5-week trial 60 inpatients suffering from major depression (DSM-IV criteria) were treated for 5 weeks with either QXR (300 mg/day) or ESC (10mg/day). The dexamethasone/CRH (DEX/CRH) test was performed before treatment, after 1, and after 5 weeks of treatment. Cortisol (COR) AUC values were used to assess HPA axis function. The Hamilton Depression Rating Scale was used weekly to estimate antidepressant efficacy. QXR and ESC showed comparable antidepressant effects but strongly differed in their impact on HPA axis activity. In the QXR group, a marked inhibition of COR AUC levels was observed which was most pronounced after one week of treatment but showed a partial re-increase after 5 weeks of treatment. In contrast, ESC transiently stimulated COR AUC values (week 1) whereas COR AUC levels at week 0 and week 5 were comparable. COR improvement at week 1 (defined as COR peak value reduction between DEX/CRH test 1 and 2) was significantly associated with better clinical outcome. Apparently, different effects on HPA axis activity reflect distinct pharmacoendocrinological properties of psychotropic drugs.

Journal of Psychiatric Research, 2014

Psychiatrische Praxis, 2011

Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimm... more Dieses Dokument wurde zum persönlichen Gebrauch heruntergeladen. Vervielfältigung nur mit Zustimmung des Verlages.

Journal fur Neurologie, Neurochirurgie und Psychiatrie

Recent research contributed to an enhancement of the knowledge of possible mechanisms of action o... more Recent research contributed to an enhancement of the knowledge of possible mechanisms of action of ECT and to a safer and well tolerable treatment. The final clarification of the underlying crucial mechanisms still remains unresolved. Nevertheless, this highly effective therapeutic option should not kept back especially from patients who are resistant to other treatments such as combined pharmaco-and psychotherapies. ECT still represents an important option in the treatment of therapy resistant depressions. Other nonpharmacological treatments like repetitive transcranial magnetic stimulation, magnetic seizure therapy and vagus nerve stimulation are currently still under development. Comprehensive information in hospitals but also the growing objective and unbiased information in the press and other media could contribute to fight prejudice and stigma of psychiatric disorders and specific therapies such as ECT.

NeuroImage, 2009

204 F-PM The modulating effect of repetitive transcranial magnetic stimulation (rTMS) on brain ac... more 204 F-PM The modulating effect of repetitive transcranial magnetic stimulation (rTMS) on brain activity evoked by word generation in depressive patients

International Journal of Molecular Sciences

Background: Cardiovascular disorders (CVD) and major depressive disorder (MDD) are the most frequ... more Background: Cardiovascular disorders (CVD) and major depressive disorder (MDD) are the most frequent diseases worldwide responsible for premature death and disability. Behavioral and immunological variables influence the pathophysiology of both disorders. We therefore determined frequency and severity of MDD in CVD and studied whether MDD without CVD or other somatic diseases influences classical and inflammatory biomarkers of cardiovascular risk. In addition, we investigated the influence of proinflammatory cytokines on antidepressant treatment outcome. Methods: In a case-control design, 310 adults (MDD patients without CVD, CVD patients, and cardiologically and psychiatrically healthy matched controls) were investigated. MDD patients were recruited after admission in a psychiatric university hospital. Primary outcome criteria were clinical depression ratings (HAM-D scale), vital signs, classical cardiovascular risk factors and inflammatory biomarkers which were compared between MDD patients and healthy controls. Results: We detected an enhanced cardiovascular risk in MDD. Untreated prehypertension and signs directing to a metabolic syndrome were detected in MDD. Significantly higher inflammatory biomarkers such as the high sensitivity C-reaktive protein (hsCRP) and proinflammatory acute phase cytokines interleukine-1β (IL-1β) and interleukine-6 (IL-6) underlined the higher cardiovascular risk in physically healthy MDD patients. Surprisingly, high inflammation markers before treatment were associated with better clinical outcome and faster remission. The rate of MDD in CVD patients was high. Conclusions: Patients suffering from MDD are at specific risk for CVD. Precise detection of cardiovascular risks in MDD beyond classical risk factors is warranted to allow effective prophylaxis and treatment of both conditions. Future studies of prophylactic interventions may help to provide a basis for prophylactic treatment of both MDD and CVD. In addition, the high risk for MDD in CVD patients was confirmed and underlines the requirement for clinical attention.

American Journal of Respiratory and Critical Care Medicine, 1997

It has recently been shown that an insertion (I)/deletion (D) polymorphism exists in the angioten... more It has recently been shown that an insertion (I)/deletion (D) polymorphism exists in the angiotensin-converting enzyme (ACE) gene that can affect the serum ACE level. There are three genotypes: DD, DI, and II, with the ACE level being highest in DD, intermediate in DI, and lowest in II. The DD genotype has been reported as a genetic risk factor for diabetes mellitus. In the present investigation, 170 patients with type 2 diabetes mellitus (T2DM) and 144 control subjects were studied. The ACE I/D polymorphism was determined by polymerase chain reaction (PCR) utilizing specific primers. ACE activity was determined spectrophotometrically. Distribution of ACE gene (I/D) polymorphism and allele frequencies in patients with T2DM were significantly different from those in control (P < 0.001); D allele frequency was 51% in T2DM vs. 48% in controls. The level of ACE activity was significantly higher in the DD genotype (91.1 ± 23.18) than those in ID (60.6 ± 22.8) and in II genotypes (36.8 ± 6.9). There was a significant difference in genotype distribution between the two groups (P < 0.001). New normal ranges of serum ACE level were determined for each genotype. Moreover, we found test sensitivity to be 62.3%. Serum ACE activity was significantly associated with ACE (I/D) gene polymorphism.

MMW - Fortschritte der Medizin, 2014

ABSTRACT Die 48-jährige Frau S. berichtet, dass sie sich wie ein Baum fühlt, der im Sturm schwank... more ABSTRACT Die 48-jährige Frau S. berichtet, dass sie sich wie ein Baum fühlt, der im Sturm schwankt. Sie hat zu nichts Lust, massive Entscheidungs- und Konzentrationsprobleme sowie Insuffizienzgefühle. Sie hat in den letzten Wochen fünf Kilogramm abgenommen und ist ständig nervös. Sie spürt „Stresskribbeln“ am Haaransatz und klagt über Verspannungen im Rücken. Sie fühlt sich leer und langsam.

Akute und therapieresistente Depressionen, 2005

Die junge Disziplin der Algorithmusforschung hat in den letzten Jahren gezeigt, dass Therapiealgo... more Die junge Disziplin der Algorithmusforschung hat in den letzten Jahren gezeigt, dass Therapiealgorithmen Mittel zur Optimierung der Behandlung depressiver Erkrankungen sind. Sie stellen wichtige Werkzeuge zur Vermeidung und Überwindung therapieresistenter Depression dar. Therapiealgorithmen sind explizite Behandlungsprotokolle, die standardisierte Handlungsanweisungen für therapeutische Entscheidungen, die Diagnosestellung, Definition des Therapieziels, Definition der Kontrollinstrumente und Kontrolle des Therapieerfolgs in einem zeitlich festgelegten Rahmen enthalten.

Psychoneuroendocrinology, 2006

... In contrast, up-regulation of BDNF has been suggested to mediate the action of antidepressant... more ... In contrast, up-regulation of BDNF has been suggested to mediate the action of antidepressant treatment (Saarelainen et al., 2003). ... Depressive disorder has been demonstrated to be associated with hippocampal atrophy (Sheline et al., 1996; Sapolsky, 2000). ...

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MMW Fortschritte der Medizin

Psychopharmacology, 2003

It has been suggested that hypothalamic-pituitary-adrenocortical (HPA) system dysregulation plays... more It has been suggested that hypothalamic-pituitary-adrenocortical (HPA) system dysregulation plays an important role in the pathophysiology of depression and that normalization of HPA axis hyperactivity precedes successful treatment with antidepressants. Mirtazapine acts as an antagonist at presynaptic alpha(2)-receptors and at postsynaptic 5-hydroxytryptamine (5-HT)(2), 5-HT(3) and histamine H(1) receptors. It has been shown acutely to inhibit cortisol secretion in healthy subjects. In this study, we investigated whether mirtazapine may downtune HPA axis hyperactivity in depressed patients and whether this is related to treatment outcome. Forty patients suffering from a major depressive episode (DSM-IV criteria) were treated with mirtazapine for 5 weeks. The combined dexamethasone suppression/CRH stimulation test (DEX/CRH test) was performed before and after 1 week of mirtazapine treatment (45 mg daily). Mirtazapine effectively reduced the overshoot of cortisol and ACTH during the D...

Neurophysiologie clinique = Clinical neurophysiology, 1993

Twenty-six untreated schizophrenic inpatients and 34 control persons were investigated using 16-c... more Twenty-six untreated schizophrenic inpatients and 34 control persons were investigated using 16-channel EEG mapping during resting, manumotor and music perception tasks. Power values of activation tasks were each referenced to a separate, immediately preceding resting condition, using conventional delta, theta, alpha and 2 beta frequency bands. Results in delta and alpha bands, which maximally separated the two groups, are reported only for space reasons. Results indicated a "nonreactivity" (in all frequency bands) on the two activation paradigms in schizophrenic patients as a group. Major gender effects were obtained in normal persons, but not signs of nonreactivity comparable to patients. Subdividing patients exclusively by means of their EEG changes on activation produced meaningful clinical subgroups of "positive/negative" schizophrenics. This latter finding could contribute towards clinical utility of EEG mapping in psychiatry.

Objective: Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephr... more Objective: Unlike other antidepressants, mirtazapine does not inhibit the reuptake of norepinephrine or serotonin (5-HT) but acts as an antagonist at presynaptic a 2 -receptors and at postsynaptic 5-HT 2 , 5-HT 3 and histamine H 1 -receptors. In the present investigation, the influence of acute oral administration of 15-mg mirtazapine on the cortisol (COR), adrenocorticotropin (ACTH), growth hormone (GH) and prolactin (PRL) secretion was examined in 12 healthy male subjects, compared to placebo. Methods: After insertion of an intravenous catheter, both the mean arterial blood pressure (MAP) and the heart rate were recorded and blood samples were drawn 1 h prior to the administration of mirtazapine or placebo (7:00 a.m.), at time of administration (8:00 a.m.) and during 5 h thereafter in periods of 30 min. Concentrations of COR, ACTH, GH and PRL were measured in each blood sample by double antibody radioimmunoassay and chemiluminescence immunoassay methods. The area under the curve (AUC; 0 -300 min after mirtazapine or placebo administration) was used as parameter for the COR, ACTH, GH and PRL response. Furthermore, the urinary free cortisol excretion (UFC) was determined beginning at 8:00 a.m. (time of administration of placebo or mirtazapine) up to 8:00 a.m. the day after. Results: Two-sided t-tests for paired samples revealed significantly lower COR AUC, ACTH AUC, UFC and PRL AUC values after 15-mg mirtazapine compared to placebo, whereas no significant differences were found with respect to GH AUC, MAP and heart rate. Conclusions: Since the acute inhibition of COR secretion in the healthy volunteers was paralleled by a simultaneous decrease of ACTH release, central mechanisms (e.g., inhibition of hypothalamic corticotropin releasing hormone (CRH) output) are suggested to be responsible for the inhibitory effects of mirtazapine on COR secretion. Our results are of particular interest in the light of the hypercortisolism observed in depressed patients and new pharmacological approaches such as CRH 1 receptor antagonists. D

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