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Blunted reaction to the citalopram challenge test in patients with major depression
P.I Affective disorders andantidepressants
S4-80
In conclusion we found significantly low central 5-HT concentrations in subjects with acute suicidal ideations. whereas anamnestic suicidal behavior revealed no 5-HT abnormalities. We see thus a reduced central 5-HT metabolism rather as a state marker for acute suicidal ideations. than as a trait markerfor anamnestic suicidal or autoaggressive behavior.
IP.1.056I Blunted reaction to thecitalopram challenge test in patients with major depression
T. Kapitany, S.D. Schindler. B. Hesselrnann, M. Schindl, C. Barnas, W. Sieghart, S. Kasper. University Hospital of Psychiatry. Clinical Department ofGeneral Psychiatry Wiihringer GiirteI18-20. A-109O Vienna, Austria The serotonergic neurotransmission in the limbic system is discussed as a major part in the pathophysiology of depression and is a major point of action for pharmacological antidepressant treatment. In depressed patients neuroendocrine challenge tests have revealed a blunted reaction to serotonergic stimuli in terms of a significantly reduced hormonal response of prolactin and cortisol secretion. As a selective serotonergic neuroendocrine challenge the Citalopram Challenge Test was shown to be effective in healthy volunteers. In the present study 15 patients suffering from an acute episode of majordepression underwent neuroendocrinological stimulation with 20 mg citalopram and with placebo. The results were compared with those of an age- and sex-matched group of controls. In the group of the depressed patients prolactin and cortisol secretion was compared with the stimulation procedure with 20 mg citalopram and placebo stimulation. For both hormones no differences were found between the two conditions, neither for the area under the curve (AUC) as measurement of total hormonesecretion nor for the peak of hormone secretion. Significant differences of hormone secretion were shown between depressed patients and controls (AUC of prolactin: 742.8 nglml x 90 min vs. 114.9 nglml x 90 min; p < 0.05). These results support the hypothesis of serotonergic hypofunction in depressed patients. In conclusion the Citalopram Challenge Test with 20 mg is thought to be a promising tool for further investigation of serotonergic function in psychiatric illness. 1 P.1.057!
Neuroendocrine challenge of serotonergic function with citalopram in healthy volunteers
T. Kapitany, B. Hesselmann, S.D. Schindler, M. Schindl, C. Barnas. W. Sieghart,S. Kasper. University Hospital of Psychiatry, Clinical Department ofGeneral Psychiatry Wiihringer GiirteI18-20, A-I090 Vienna, Austria Neuroendocrinological reactions to psychopharmacological stimulies are used as a sensitive clinical method to study neurotransmitter systems. In the present study citalopram , a selective serotonergic agent, is used for neuroendocrine challenge. It combinesthe advantage of goodtolerability with the possibility of intravenous administration. and therefore avoides interindividual differences throughenteral absorbtion. 12 healthyvolunteers underwent the stimulation procedure underthree different conditions with 10 mg citalopram, 20 mg citalopram and with placebo. After a short infusion with the challenging agent blood samples were drawn at 15-minutes intervals over a period of 90 minutes to determine levelsof prolactinand cortisol. Overall, the procedure waswell tolerated. Side effects occurredespecially during stimulation with 20 mg citalopram, mostly in terms of nausea. Mean values of hormone bloodlevels were higher after citalopram challenge than after placebo and showed to be dose-dependent. A maximum of hormone secretion was detected 30 minutes after the beginning of the challenge. ANOVAs revealed significant differences between the three stimulating conditions for the variables "area under the curve" (AUC) of prolactinmeasurement, peak of prolactin secretion and AUCof cortisolmeasurement. Group comparisons only becamesignificant for the variables AUC of prolactin and AUCof cortisol betweenthe stimulation condition of 20 mg citalopram and the placebo condition (p < 0.05). It is concluded that the Citalopram Challenge Test with 20 mg showed a clear-cut neuroendocrine reaction to serotonergic stimulation and will
be a promising 1001 for further clinical investigation of the serotonergic neurotransmitter system.
IP.1.058! Comparative efficacy of moclobemide and
imipramine onanxiety features in major depression- a meta-analysls of double blind comparative studies against placebo
Alexandra Delini-Stula I, Anne Cameron2. Jules Angst 2. I CNSMed. Research Councel. Basel, Hoffmann -]A Roche, Basel; Switzerland; 2 Psychiatric University Hospital, Zurich, Switzerland Antianxiety effects of conventional inhibitors of MAO (MAOI) have been observed and described as early as in 1959 and there is empirical evidence suggesting that these effects are genuineand not only secondary 10 antidepressant efficacy (Tyrer and Shawcross 1988).Due, however, to therestrictions of the use and almostcompleteabandonof MAOI in many countries, untilpresenttheir anxiolytic properties havenot beenrigorously investigated. Moclobemide is a recently developed reversible inhibitor of MAO-A. Recent meta-analysis of a subpopulation of depressedpatients, defined according to the severity of agitation/anxiety symptomsby means of the Factor score of the Hamilton (HAMD-17 items) agitation/anxiety subscale (Angst et al. 1993), indicated that moclobemide is as effective as sedative antidepressants (amitriptyline, maprotiline, mianserin) and clearly superior to placebo even in patients with severe agitation/anxiety subscores at baseline (Delini-Stula et al. 1995). These results indirectly suggested that anxiety symptoms in patients with Major Depression are favourably affected by moclobemide. In the present study we have re-analysed the effects of moclobemide separately on features of psychic and somatic anxiety in patients with MajorDepression. The data for the meta-analysis were providedby Hoffmann-La Roche. Patients population consistedof a total of 950 patients (moclobemide n = 346. imipramine n = 266, placebon = 338) from 5 double-blind, placebo controlled studies. All patients fulfilled the intention-to treat criteria for efficacy analysis and DSM-ill and ill-R criteria for MajorDepression. All study protocols weresimilar. Treatment durationwas minimally 4 weeks. Psychic andsomaticanxiety were defined by RAMO items scores IO and 11 and by scores derived from arbitrarycomposed psychic and somatic HAMO subscales (ANXP and SOMS subscales). Broader definitions of anxiety permitted more equal distribution of patients into subgroups with a larger proportion of more severe e.g, high score anxiety patients. Treatment efficacy and the outcome were evaluated by considering the regression of scores by comparison to the baseline and by percentage of responders at the end of the treatment (> 50% reduction of HAMD total scoreand subsscalescores and CGI very good and good responses). Analysis of variance for repeated measures (MANOYA), the Chi square statistics and the maximum likelihood, multivariate statisticswere applied for the assessment of the significance of the results. The results showed significant regression of psychic and somatic anxiety over time in all treatment groups and significantly larger effect of active drugs than of placebo with all anxiety criteria. The effects of moclobemide and imipramine were comparable and not significantly different. Table 1 exemplifies the results. Table I. Changes of psychic (HAMD-item 10)and somatic (HAMO-item II ) anxiety during moclobemide treatment in patients with majordepression comparison withimipramine and placebo Treatment Meanscore Meanscore 6Psychic score Somatic score Baseline Endpoint Baseline Endpoint Placebo 2.5 1.8 0,7 1.9 1.4 0.5 Imipramine 1.4 2.5 2.0 1.1' 1.1 0.9" Moclobemide 2.5 1.9 1.2' 1.3 0.98 0.9" 'p < 0.0237vs placebo, '*p < 0.007vs placebo
Comparison of the response rates in relation to the severity of anxiety symptoms showed significant and considerably higher responses (55-75%) in active drug groups than in the placebo-group (25-35%), irrespectively of howthe anxiety featuresweredefined, or whichoutcome measures were applied. The response to active drugs was independent of initial severity of anxiety. In contrast, clear-cut negative correlation
S4-80
In conclusion we found significantly low central 5-HT concentrations in subjects with acute suicidal ideations. whereas anamnestic suicidal behavior revealed no 5-HT abnormalities. We see thus a reduced central 5-HT metabolism rather as a state marker for acute suicidal ideations. than as a trait markerfor anamnestic suicidal or autoaggressive behavior.
IP.1.056I Blunted reaction to thecitalopram challenge test in patients with major depression
T. Kapitany, S.D. Schindler. B. Hesselrnann, M. Schindl, C. Barnas, W. Sieghart, S. Kasper. University Hospital of Psychiatry. Clinical Department ofGeneral Psychiatry Wiihringer GiirteI18-20. A-109O Vienna, Austria The serotonergic neurotransmission in the limbic system is discussed as a major part in the pathophysiology of depression and is a major point of action for pharmacological antidepressant treatment. In depressed patients neuroendocrine challenge tests have revealed a blunted reaction to serotonergic stimuli in terms of a significantly reduced hormonal response of prolactin and cortisol secretion. As a selective serotonergic neuroendocrine challenge the Citalopram Challenge Test was shown to be effective in healthy volunteers. In the present study 15 patients suffering from an acute episode of majordepression underwent neuroendocrinological stimulation with 20 mg citalopram and with placebo. The results were compared with those of an age- and sex-matched group of controls. In the group of the depressed patients prolactin and cortisol secretion was compared with the stimulation procedure with 20 mg citalopram and placebo stimulation. For both hormones no differences were found between the two conditions, neither for the area under the curve (AUC) as measurement of total hormonesecretion nor for the peak of hormone secretion. Significant differences of hormone secretion were shown between depressed patients and controls (AUC of prolactin: 742.8 nglml x 90 min vs. 114.9 nglml x 90 min; p < 0.05). These results support the hypothesis of serotonergic hypofunction in depressed patients. In conclusion the Citalopram Challenge Test with 20 mg is thought to be a promising tool for further investigation of serotonergic function in psychiatric illness. 1 P.1.057!
Neuroendocrine challenge of serotonergic function with citalopram in healthy volunteers
T. Kapitany, B. Hesselmann, S.D. Schindler, M. Schindl, C. Barnas. W. Sieghart,S. Kasper. University Hospital of Psychiatry, Clinical Department ofGeneral Psychiatry Wiihringer GiirteI18-20, A-I090 Vienna, Austria Neuroendocrinological reactions to psychopharmacological stimulies are used as a sensitive clinical method to study neurotransmitter systems. In the present study citalopram , a selective serotonergic agent, is used for neuroendocrine challenge. It combinesthe advantage of goodtolerability with the possibility of intravenous administration. and therefore avoides interindividual differences throughenteral absorbtion. 12 healthyvolunteers underwent the stimulation procedure underthree different conditions with 10 mg citalopram, 20 mg citalopram and with placebo. After a short infusion with the challenging agent blood samples were drawn at 15-minutes intervals over a period of 90 minutes to determine levelsof prolactinand cortisol. Overall, the procedure waswell tolerated. Side effects occurredespecially during stimulation with 20 mg citalopram, mostly in terms of nausea. Mean values of hormone bloodlevels were higher after citalopram challenge than after placebo and showed to be dose-dependent. A maximum of hormone secretion was detected 30 minutes after the beginning of the challenge. ANOVAs revealed significant differences between the three stimulating conditions for the variables "area under the curve" (AUC) of prolactinmeasurement, peak of prolactin secretion and AUCof cortisolmeasurement. Group comparisons only becamesignificant for the variables AUC of prolactin and AUCof cortisol betweenthe stimulation condition of 20 mg citalopram and the placebo condition (p < 0.05). It is concluded that the Citalopram Challenge Test with 20 mg showed a clear-cut neuroendocrine reaction to serotonergic stimulation and will
be a promising 1001 for further clinical investigation of the serotonergic neurotransmitter system.
IP.1.058! Comparative efficacy of moclobemide and
imipramine onanxiety features in major depression- a meta-analysls of double blind comparative studies against placebo
Alexandra Delini-Stula I, Anne Cameron2. Jules Angst 2. I CNSMed. Research Councel. Basel, Hoffmann -]A Roche, Basel; Switzerland; 2 Psychiatric University Hospital, Zurich, Switzerland Antianxiety effects of conventional inhibitors of MAO (MAOI) have been observed and described as early as in 1959 and there is empirical evidence suggesting that these effects are genuineand not only secondary 10 antidepressant efficacy (Tyrer and Shawcross 1988).Due, however, to therestrictions of the use and almostcompleteabandonof MAOI in many countries, untilpresenttheir anxiolytic properties havenot beenrigorously investigated. Moclobemide is a recently developed reversible inhibitor of MAO-A. Recent meta-analysis of a subpopulation of depressedpatients, defined according to the severity of agitation/anxiety symptomsby means of the Factor score of the Hamilton (HAMD-17 items) agitation/anxiety subscale (Angst et al. 1993), indicated that moclobemide is as effective as sedative antidepressants (amitriptyline, maprotiline, mianserin) and clearly superior to placebo even in patients with severe agitation/anxiety subscores at baseline (Delini-Stula et al. 1995). These results indirectly suggested that anxiety symptoms in patients with Major Depression are favourably affected by moclobemide. In the present study we have re-analysed the effects of moclobemide separately on features of psychic and somatic anxiety in patients with MajorDepression. The data for the meta-analysis were providedby Hoffmann-La Roche. Patients population consistedof a total of 950 patients (moclobemide n = 346. imipramine n = 266, placebon = 338) from 5 double-blind, placebo controlled studies. All patients fulfilled the intention-to treat criteria for efficacy analysis and DSM-ill and ill-R criteria for MajorDepression. All study protocols weresimilar. Treatment durationwas minimally 4 weeks. Psychic andsomaticanxiety were defined by RAMO items scores IO and 11 and by scores derived from arbitrarycomposed psychic and somatic HAMO subscales (ANXP and SOMS subscales). Broader definitions of anxiety permitted more equal distribution of patients into subgroups with a larger proportion of more severe e.g, high score anxiety patients. Treatment efficacy and the outcome were evaluated by considering the regression of scores by comparison to the baseline and by percentage of responders at the end of the treatment (> 50% reduction of HAMD total scoreand subsscalescores and CGI very good and good responses). Analysis of variance for repeated measures (MANOYA), the Chi square statistics and the maximum likelihood, multivariate statisticswere applied for the assessment of the significance of the results. The results showed significant regression of psychic and somatic anxiety over time in all treatment groups and significantly larger effect of active drugs than of placebo with all anxiety criteria. The effects of moclobemide and imipramine were comparable and not significantly different. Table 1 exemplifies the results. Table I. Changes of psychic (HAMD-item 10)and somatic (HAMO-item II ) anxiety during moclobemide treatment in patients with majordepression comparison withimipramine and placebo Treatment Meanscore Meanscore 6Psychic score Somatic score Baseline Endpoint Baseline Endpoint Placebo 2.5 1.8 0,7 1.9 1.4 0.5 Imipramine 1.4 2.5 2.0 1.1' 1.1 0.9" Moclobemide 2.5 1.9 1.2' 1.3 0.98 0.9" 'p < 0.0237vs placebo, '*p < 0.007vs placebo
Comparison of the response rates in relation to the severity of anxiety symptoms showed significant and considerably higher responses (55-75%) in active drug groups than in the placebo-group (25-35%), irrespectively of howthe anxiety featuresweredefined, or whichoutcome measures were applied. The response to active drugs was independent of initial severity of anxiety. In contrast, clear-cut negative correlation