Markus Gastpar - Academia.edu (original) (raw)

Papers by Markus Gastpar

Eur Arch Psychiat Clin Neuros, 1980

Eur Arch Psychiat Clin Neuros, 1980

Diurnal variations during the depressive phase and healthy periods were investigated in 84 hospit... more Diurnal variations during the depressive phase and healthy periods were investigated in 84 hospitalised depressive patients of different nosological diagnosis. The occurrence of different rhythm-types in this population led to the conclusion that depression induces rhythmicity: those belonging to the arhythmic group when healthy showed significant increase in rhythmicity when depressed, predominantly the classical form of diurnal variation (morning with improvement toward evening). Age and sex were found to be important factors determining diurnal variation. In the course of hospitalisation, the type of diurnal rhythm remained individually constant.

Int Clin Psychopharmacol, 1990

Psychiatry Research, 1985

The density of platelet 3H-imipramine binding sites has been proposed as a biological marker in p... more The density of platelet 3H-imipramine binding sites has been proposed as a biological marker in psychiatry. We report the range of platelet 3H-imipramine binding in 55 psychiatric patients and 11 control subjects. All blood samples were withdrawn at 2300 h (on the day of hospital admission for patients). With the use of a slight modification of a previously described 3H-imipramine binding method, a mean B max of 1,510 fmole/mg protein (range: 390-5,560; median: 1,450) and a mean Kd of 2.0 nM (range: 0.6-17.0; median: 1.4) were determined for psychiatric patients. For the controls, a mean B max of 1,590 fmole/mg protein (range: 870-2,570; median: 1,440) and a mean Kd of 1.4 nM (range 0.8-2.4; median 1.4) were determined. When patients were subdivided based on ICD-9 psychiatric diagnoses, no significant differences between distinct subgroups of psychiatric patients with respect to B max or Kd values for platelet 3H-imipramine binding could be established. Similarly, no significant difference between psychiatric patients and controls was obtained.

Nordic Journal of Psychiatry, 1984

Clinical Chemistry and Laboratory Medicine, 2000

The compliance of 581 drug addicts attending six methadone substitution outpatient clinics was de... more The compliance of 581 drug addicts attending six methadone substitution outpatient clinics was determined over a period of 18 months. Urine from these patients was labeled following oral administration of low molecular weight polyethylene glycols as marker substances. These substances were measured in approx. 5800 urine samples. A protocol for applying marker substances and ways to prevent substitution of urine samples were evaluated. Normal values for marker substances in urine were determined. The results suggest that this labeling procedure is a new diagnostic tool to prevent manipulation of urine samples by drug addicts receiving substitution therapy.

Pharmacopsychiatry, 1996

ABSTRACT

The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intraveno... more The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intravenous heroin users were measured before and, respectively, 1, 2 or 4 hours after oral routine administration and related to the individual additional drug usage (detected by urine drug screening), liver function, side-effects and withdrawal symptoms. In general, accelerated levomethadone metabolism induced by additional misuse of benzodiazepines, barbiturates and opiates resulted in significantly lower plasma levels of the substitute. In particular, high gamma-glutamyltransferase activity was related to benzodiazepine consumption. On the other hand, an impaired liver function reflected by increased beta-globulins resulted in an insufficient body clearance and drug accumulation. Major side effects, such as sweating, were not related to plasma levels whereas withdrawal symptoms like diarrhoea or "feeling cold" correlate with lower plasma concentrations. It is concluded that polydrug misuse in the methadone maintenance therapy creates a vicious circle of enzyme induction, thus increasing "instrumental drug utilization". However, underestimated maintenance dosage may lead to additional drug consumption resulting, finally, in therapeutic failure.

Acta Psychiatrica Scandinavica, 2010

Pharmacopsychiatry, Jun 1, 1988

International Clinical Psychopharmacology, Jun 1, 1999

DEPRES II (Depression Research in European Society II), the first in-depth, pan-European survey o... more DEPRES II (Depression Research in European Society II), the first in-depth, pan-European survey of depression in the community, provided an opportunity to identify depressed patient types and their treatment needs. Cluster analysis applied to data generated from DEPRES II interviews revealed six depressed patient types with clearly differentiated profiles. The patient type with moderately impaired depression has episodic depression and minimal disability. By contrast, severe depression associated with anxiety presents with chronic symptoms, including anxiety and panic, and causes considerable disruption to normal life and employment. Depression associated with chronic physical problems and depression associated with social problems are characterized by chronic physical illness and relationship or financial difficulties, respectively, and sufferers are pessimistic about recovery. Depression associated with sleep problems is associated with symptoms of tiredness and broken or inadequate sleep, and is commonly caused by stress. Tiredness is also a principal symptom of depression associated with tiredness or fatigue, but sufferers' ability to sleep is unaffected. All patient types would benefit from antidepressant therapy. The depressed patient types identified from the DEPRES II data make intuitive sense, but now need to be tested for face validity in the primary care setting.

International Journal of Neuropsychopharmacology, 2007

In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor an... more In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor antagonist tiapride is effective in maintaining abstinence after detoxification in alcohol-dependent patients. The rationale of the study was based on the relevance of the dopaminergic system for addictive behaviour as well as some preliminary studies. A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study was conducted. A total of 299 detoxified alcohol-dependent patients (ICD-10: F10.2) received either tiapride (300 mg/d) or placebo over a 24-wk study period. Subjects with severe comorbid psychiatric disorder such as schizophrenia or Wernicke-Korsakoff syndrome were excluded. Primary outcome variable was the time to first relapse with relapse defined as any alcohol consumption after detoxification. Data analysis was done with Kaplan-Meier estimates with log-rank test (one-sided, p<0.05). Tiapride was not superior to placebo in maintaining abstinence. The time to first relapse was 71 d in the tiapride group and 92 d in the placebo group (log-rank test, p=0.9895). Relapse rate was higher in the intervention group (54.4%) than in the control group (40.7%). Like the dopamine antagonist flupenthixol, tiapride was not effective in maintaining alcohol abstinence. Regarding the high success rate in the placebo group the influence of psychosocial treatment in studies investigating drug effects on the course of alcohol dependence has to be considered.

Eur Neuropsychopharmacol, 1999

Introduction: Olanzapine, a new atypical antipsychotic of the tbienobenzodiazepine class has a be... more Introduction: Olanzapine, a new atypical antipsychotic of the tbienobenzodiazepine class has a better risk-benefit profile with respect to efficacy and adverse events than traditional antipsychotic medication documented by preclinical and clinical findings (1, 2). The objective of the study was to assess the impact of olanzapine versus fluphenazine on patient satisfaction during acute treatment.

The Journal of Clinical Psychiatry, Sep 1, 2002

Response to antidepressant drug therapy is less than optimal for a considerable proportion of dep... more Response to antidepressant drug therapy is less than optimal for a considerable proportion of depressed patients; at present, however, few data exist to guide their rational therapeutic management. This review describes general principles for the management of such patients. This review is the result of an expert roundtable meeting convened to review published clinical data and clinical experience and provide clinicians with evidence-based principles on the management of patients who fail to respond optimally to initial antidepressant therapy. Failure to respond may be defined as a < 25% decrease on an accepted symptom rating scale such as the Montgomery-Asberg Depression Rating Scale (MADRS) or the Hamilton Rating Scale for Depression (HAM-D) in a patient who has received an adequate dosage for 4 weeks. In these patients, a neuropharmacologic rationale exists to switch to an agent with a different mode of action or a dual action. Partial response may be defined as 6 to 8 weeks at an adequate dosage and 25% to 50% decrease in MADRS or HAM-D score. In these patients, dose escalation should be considered, followed by augmentation and switching strategies. For augmentation, knowledge of neuropharmacology may allow prediction of which second agent will potentiate or complement the action of the first agent; it may also permit the prediction of potential safety concerns. On the basis of a review of the medical literature and clinical experience regarding patients with partial response or nonresponse to antidepressant drug therapy, it appears that simultaneous targeting of both the noradrenergic and serotonergic systems is one of the most effective augmentation strategies. Switching to an agent of a different class is probably optimal for those patients who fail to respond to first-line therapy.

International Clinical Psychopharmacology, 1999

The first pan-European survey of depression in the community (DEPRES I) demonstrated that 17% of ... more The first pan-European survey of depression in the community (DEPRES I) demonstrated that 17% of the general population suffer from depression (major depression, minor depression, or depressive symptoms). This article describes findings from a second phase of DEPRES (DEPRES II), in which detailed interviews based on a semi-structured questionnaire (78 questions) were conducted with 1884 DEPRES I participants who had suffered from depression and who consulted a healthcare professional about their symptoms during the previous 6 months. The mean time from onset of depression was 45 months, and the most commonly experienced symptoms during the latest period were low mood (76%), tiredness (73%) and sleep problems (63%). During the previous 6 months, respondents had been unable to undertake normal activities because of their depression for a mean of 30 days, and a mean of 20 days of work had been lost to depression by those in paid employment. Approximately one-third of respondents (30%) had received an antidepressant during the latest period of depression. Significantly more respondents given a selective serotonin reputake inhibitor found that their treatment made them feel more like their normal self than those given a tricyclic antidepressant, and fewer reported treatment-related concentration lapses, weight problems, and heavy-headedness (all P < 0.05). Approximately two-thirds of respondents (70%) had received no antidepressant therapy during the latest period of depression, and prescription of benzodiazepines alone, which are not effective against depression, was widespread (17%). There is a need for education of healthcare professionals to encourage appropriate treatment of depression.

Pharmacopsychiatry, 1997

The electrocardiographic effects of high-dose hypericum extract were compared to the effects of i... more The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a randomized, double-blind, multicenter treatment study of 209 patients suffering from depression. ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine. At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings. In the first ECG analysis comparing high dose hypericum extract with imipramine, a prolongation of the conduction intervals PR, QRS and QTc was found for imipramine. In contrast, a small acceleration of conduction was seen for the high-dose hypericum extract. The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract. It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract. The reduction in pathological ECG features after treatment with hypericum extract may have resulted mainly from the change of medication, probably tricyclics, to hypericum extract. Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients, high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants.

Eur Arch Psychiat Clin Neuros, 1980

Eur Arch Psychiat Clin Neuros, 1980

Diurnal variations during the depressive phase and healthy periods were investigated in 84 hospit... more Diurnal variations during the depressive phase and healthy periods were investigated in 84 hospitalised depressive patients of different nosological diagnosis. The occurrence of different rhythm-types in this population led to the conclusion that depression induces rhythmicity: those belonging to the arhythmic group when healthy showed significant increase in rhythmicity when depressed, predominantly the classical form of diurnal variation (morning with improvement toward evening). Age and sex were found to be important factors determining diurnal variation. In the course of hospitalisation, the type of diurnal rhythm remained individually constant.

Int Clin Psychopharmacol, 1990

Psychiatry Research, 1985

The density of platelet 3H-imipramine binding sites has been proposed as a biological marker in p... more The density of platelet 3H-imipramine binding sites has been proposed as a biological marker in psychiatry. We report the range of platelet 3H-imipramine binding in 55 psychiatric patients and 11 control subjects. All blood samples were withdrawn at 2300 h (on the day of hospital admission for patients). With the use of a slight modification of a previously described 3H-imipramine binding method, a mean B max of 1,510 fmole/mg protein (range: 390-5,560; median: 1,450) and a mean Kd of 2.0 nM (range: 0.6-17.0; median: 1.4) were determined for psychiatric patients. For the controls, a mean B max of 1,590 fmole/mg protein (range: 870-2,570; median: 1,440) and a mean Kd of 1.4 nM (range 0.8-2.4; median 1.4) were determined. When patients were subdivided based on ICD-9 psychiatric diagnoses, no significant differences between distinct subgroups of psychiatric patients with respect to B max or Kd values for platelet 3H-imipramine binding could be established. Similarly, no significant difference between psychiatric patients and controls was obtained.

Nordic Journal of Psychiatry, 1984

Clinical Chemistry and Laboratory Medicine, 2000

The compliance of 581 drug addicts attending six methadone substitution outpatient clinics was de... more The compliance of 581 drug addicts attending six methadone substitution outpatient clinics was determined over a period of 18 months. Urine from these patients was labeled following oral administration of low molecular weight polyethylene glycols as marker substances. These substances were measured in approx. 5800 urine samples. A protocol for applying marker substances and ways to prevent substitution of urine samples were evaluated. Normal values for marker substances in urine were determined. The results suggest that this labeling procedure is a new diagnostic tool to prevent manipulation of urine samples by drug addicts receiving substitution therapy.

Pharmacopsychiatry, 1996

ABSTRACT

The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intraveno... more The plasma levels of 42 patients on a levomethadone maintenance treatment programme for intravenous heroin users were measured before and, respectively, 1, 2 or 4 hours after oral routine administration and related to the individual additional drug usage (detected by urine drug screening), liver function, side-effects and withdrawal symptoms. In general, accelerated levomethadone metabolism induced by additional misuse of benzodiazepines, barbiturates and opiates resulted in significantly lower plasma levels of the substitute. In particular, high gamma-glutamyltransferase activity was related to benzodiazepine consumption. On the other hand, an impaired liver function reflected by increased beta-globulins resulted in an insufficient body clearance and drug accumulation. Major side effects, such as sweating, were not related to plasma levels whereas withdrawal symptoms like diarrhoea or "feeling cold" correlate with lower plasma concentrations. It is concluded that polydrug misuse in the methadone maintenance therapy creates a vicious circle of enzyme induction, thus increasing "instrumental drug utilization". However, underestimated maintenance dosage may lead to additional drug consumption resulting, finally, in therapeutic failure.

Acta Psychiatrica Scandinavica, 2010

Pharmacopsychiatry, Jun 1, 1988

International Clinical Psychopharmacology, Jun 1, 1999

DEPRES II (Depression Research in European Society II), the first in-depth, pan-European survey o... more DEPRES II (Depression Research in European Society II), the first in-depth, pan-European survey of depression in the community, provided an opportunity to identify depressed patient types and their treatment needs. Cluster analysis applied to data generated from DEPRES II interviews revealed six depressed patient types with clearly differentiated profiles. The patient type with moderately impaired depression has episodic depression and minimal disability. By contrast, severe depression associated with anxiety presents with chronic symptoms, including anxiety and panic, and causes considerable disruption to normal life and employment. Depression associated with chronic physical problems and depression associated with social problems are characterized by chronic physical illness and relationship or financial difficulties, respectively, and sufferers are pessimistic about recovery. Depression associated with sleep problems is associated with symptoms of tiredness and broken or inadequate sleep, and is commonly caused by stress. Tiredness is also a principal symptom of depression associated with tiredness or fatigue, but sufferers' ability to sleep is unaffected. All patient types would benefit from antidepressant therapy. The depressed patient types identified from the DEPRES II data make intuitive sense, but now need to be tested for face validity in the primary care setting.

International Journal of Neuropsychopharmacology, 2007

In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor an... more In this investigation, the hypothesis was tested whether the selective dopamine D2/D3 receptor antagonist tiapride is effective in maintaining abstinence after detoxification in alcohol-dependent patients. The rationale of the study was based on the relevance of the dopaminergic system for addictive behaviour as well as some preliminary studies. A multi-centre, randomized, double-blind, placebo-controlled, parallel-group study was conducted. A total of 299 detoxified alcohol-dependent patients (ICD-10: F10.2) received either tiapride (300 mg/d) or placebo over a 24-wk study period. Subjects with severe comorbid psychiatric disorder such as schizophrenia or Wernicke-Korsakoff syndrome were excluded. Primary outcome variable was the time to first relapse with relapse defined as any alcohol consumption after detoxification. Data analysis was done with Kaplan-Meier estimates with log-rank test (one-sided, p<0.05). Tiapride was not superior to placebo in maintaining abstinence. The time to first relapse was 71 d in the tiapride group and 92 d in the placebo group (log-rank test, p=0.9895). Relapse rate was higher in the intervention group (54.4%) than in the control group (40.7%). Like the dopamine antagonist flupenthixol, tiapride was not effective in maintaining alcohol abstinence. Regarding the high success rate in the placebo group the influence of psychosocial treatment in studies investigating drug effects on the course of alcohol dependence has to be considered.

Eur Neuropsychopharmacol, 1999

Introduction: Olanzapine, a new atypical antipsychotic of the tbienobenzodiazepine class has a be... more Introduction: Olanzapine, a new atypical antipsychotic of the tbienobenzodiazepine class has a better risk-benefit profile with respect to efficacy and adverse events than traditional antipsychotic medication documented by preclinical and clinical findings (1, 2). The objective of the study was to assess the impact of olanzapine versus fluphenazine on patient satisfaction during acute treatment.

The Journal of Clinical Psychiatry, Sep 1, 2002

Response to antidepressant drug therapy is less than optimal for a considerable proportion of dep... more Response to antidepressant drug therapy is less than optimal for a considerable proportion of depressed patients; at present, however, few data exist to guide their rational therapeutic management. This review describes general principles for the management of such patients. This review is the result of an expert roundtable meeting convened to review published clinical data and clinical experience and provide clinicians with evidence-based principles on the management of patients who fail to respond optimally to initial antidepressant therapy. Failure to respond may be defined as a < 25% decrease on an accepted symptom rating scale such as the Montgomery-Asberg Depression Rating Scale (MADRS) or the Hamilton Rating Scale for Depression (HAM-D) in a patient who has received an adequate dosage for 4 weeks. In these patients, a neuropharmacologic rationale exists to switch to an agent with a different mode of action or a dual action. Partial response may be defined as 6 to 8 weeks at an adequate dosage and 25% to 50% decrease in MADRS or HAM-D score. In these patients, dose escalation should be considered, followed by augmentation and switching strategies. For augmentation, knowledge of neuropharmacology may allow prediction of which second agent will potentiate or complement the action of the first agent; it may also permit the prediction of potential safety concerns. On the basis of a review of the medical literature and clinical experience regarding patients with partial response or nonresponse to antidepressant drug therapy, it appears that simultaneous targeting of both the noradrenergic and serotonergic systems is one of the most effective augmentation strategies. Switching to an agent of a different class is probably optimal for those patients who fail to respond to first-line therapy.

International Clinical Psychopharmacology, 1999

The first pan-European survey of depression in the community (DEPRES I) demonstrated that 17% of ... more The first pan-European survey of depression in the community (DEPRES I) demonstrated that 17% of the general population suffer from depression (major depression, minor depression, or depressive symptoms). This article describes findings from a second phase of DEPRES (DEPRES II), in which detailed interviews based on a semi-structured questionnaire (78 questions) were conducted with 1884 DEPRES I participants who had suffered from depression and who consulted a healthcare professional about their symptoms during the previous 6 months. The mean time from onset of depression was 45 months, and the most commonly experienced symptoms during the latest period were low mood (76%), tiredness (73%) and sleep problems (63%). During the previous 6 months, respondents had been unable to undertake normal activities because of their depression for a mean of 30 days, and a mean of 20 days of work had been lost to depression by those in paid employment. Approximately one-third of respondents (30%) had received an antidepressant during the latest period of depression. Significantly more respondents given a selective serotonin reputake inhibitor found that their treatment made them feel more like their normal self than those given a tricyclic antidepressant, and fewer reported treatment-related concentration lapses, weight problems, and heavy-headedness (all P < 0.05). Approximately two-thirds of respondents (70%) had received no antidepressant therapy during the latest period of depression, and prescription of benzodiazepines alone, which are not effective against depression, was widespread (17%). There is a need for education of healthcare professionals to encourage appropriate treatment of depression.

Pharmacopsychiatry, 1997

The electrocardiographic effects of high-dose hypericum extract were compared to the effects of i... more The electrocardiographic effects of high-dose hypericum extract were compared to the effects of imipramine hydrochloride on ECG recordings in a randomized, double-blind, multicenter treatment study of 209 patients suffering from depression. ECGs were recorded before and after a six-week treatment period with either hypericum extract or imipramine. At the end of the study ECGs of 84 patients treated with hypericum extract and 76 patients treated with imipramine were suitable for an analysis of conduction intervals and pathological findings. In the first ECG analysis comparing high dose hypericum extract with imipramine, a prolongation of the conduction intervals PR, QRS and QTc was found for imipramine. In contrast, a small acceleration of conduction was seen for the high-dose hypericum extract. The comparison of ECGs at the beginning and after six weeks of treatment showed a significant increase in first degree AV-blocks and abnormalities of repolarization under imipramine but a significant reduction of such pathological findings under treatment with hypericum extract. It should be emphasized that this favorable feature of safe cardiac activity was achieved with 1800 mg of hypericum extract. The reduction in pathological ECG features after treatment with hypericum extract may have resulted mainly from the change of medication, probably tricyclics, to hypericum extract. Our results indicate that for the treatment of patients with a pre-existing conductive dysfunction or elderly patients, high-dose hypericum extract is safer with regard to cardiac function than tricyclic antidepressants.