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Is paroxetine in post-stroke depression useful?
0-4 Psychoimmunology
7
Telephone interviews were performed by lay interviewers using the knowledge based system Eval which is a previously validated computerized system designed to guide the interviewers. The sample was divided into four age groups: 15 to 44 years old (56.4%); 45 to 64 years old (25.6%); 65 to 74 years old (10.8%) and 75 years old or more (7.2%). Earlier bedtime, long sleep latency, spending more time in bed with a reduction of nocturnal sleep time, nocturnal awakenings and daytime naps were found more frequently in "young old" (65 to 74 years old) and "old old" subjects (75 years old or more). Daytime naps and spending more time in bed with a reduction of nocturnal sleep time also distinguished "old old" subjects from "young old" subjects. The rate of psychotropic drug consumption dramatically increased with age: 4.8% between 15 to 44 years old; 15.6% between 45 to 64 years old; 24.3% in "young old" subjects and 32.8% in "old old" subjects. The chronic use (at least one year) of hypnotic or anxiolytic drugs was frequent in "old old" subjects (92.6% and 80.2%, respectively) and "young old" subjects (74% and 78%, respectively). The assessment of sleep by the physician should be made part of the routine clinical examination of older subjects. Review of the etiology of insomnia complaints is crucial in the choice of treatment. These data underline the importance of educating physicians about consequences of long-term utilization of these drugs and on the need for sleep hygiene measures as alternative solutions for treating insomnia complaints.
I0-3-91
(more than 50%), in comparison with the non depressed patients, so is essential that such patients should have the opportunity to recover from the affective pathology early and accurately. Since early nineties, our group very largely used SSRI in patients with heart intracardiac conduction problems and specifically we prescribed paroxetine for its better compliance. In our cases, paroxetine has been employed in 12 patients, recently struck by infarctus, who developed a post-stroke depressive episode. Five of them showed a lengthening of the QRS interval and 7 a normal ECG. The mean daily dosage employed was 30 mg (10 mg t.i.d.). The patients with heart arrythmias ameliorate in few weeks and all recovered from depression in 4-8 weeks of treatment. No one of them showed a minimal cardiac abnormality.
10-41 Psychoimmunology I0-4-1 I Natural Killer Cell Activity andIn Vitro Responsiveness to Glucocorticoids and Cytokines in the Elderly andin Alzheimer's Disease L. Ravizza, G. Griot I , R.G. Masera I, P. Prolo, M. Mantovan I, A. Staurenghi I, L. Tarenzi 2, A. Lazzero I, A. Angeli I. Institute of
Pharmacological Profile of GV150526A a Novel Glycine Antagonist for Stroke
E. Ratti, G. Gaviraghi, C. Pietra, D. Trist, A. Reggiani. Glaxo Research
Laboratories, 37100 Verona, Italy It is now believed that the glycine site of the NMDA receptor is an attractive target for new antistroke compounds. In line with this, in the present paper the pharmacological profile ofGVI50526A (GV), a novel and very promising glycine antagonist, is described. GV has a very high affinity and selectivity for rat and human glycine receptors (pKi 8.5) and additional in vitro studies confirmed its mode of action on the glycine site. In fact, a truly competitive antagonism was observed with GV if NMDA receptor was stimulated by glycine (depolarization in cultured hippocampal cells and the increase of 3H_TCP binding in rat cortex), but a non-competitive effect was seen if stimulation was due to NMDA itself (depolarization of intact rat cortical wedges). The neuroprotective activity of GV was tested as single IV bolus, in the permanent and transient MCA occlusion models in rats (p-MCAo and t-MCAo). When given PRE-ISCHAEMIA (0.3-3 mg/kg) a dose-dependent reduction of neuronal damage was seen in both models. Maximal protection was at 3 mg/kg: in the p-MCAo was 78% (p < 0.05), in the t-MCAo was 56% (p < 0.05). A very wide POST-ISCHAEMIA window was observed in both models. Significant neuroprotection (p < 0.05) was detected at 3 mg/kg IV, as single bolus, even when administration was delayed up to 6 hrs from occlusion (53% and 37% protection in the p-MCAo and t-MCAo respectively). In our data base none of the reference compound tested so far, including other NMDA antagonists (MK 801, Eliprodil and ACEA 1021), showed a similar wide window of effectiveness. In view of these results and due to the lack of side-effects even at doses above the neuroprotective doses, GVI50526A is a very promising candidate as antistroke agent in man.
=
I0-3-10 lis Paroxetine In Post·Stroke Depression Useful? G. Rutigliano, F. Vadruccio. Center of Psychopharmacotherapy,
University of Bari, Italy Several data suggest that patients with abnormalities of intraventricular conduction are at increased risk if they assume tryciclic antidepressant drugs (TCA) for the treatment of the frequently correlated depressive pathology. Cardiologist mandatorily prohibits TCA for the treatment of hearts ischaemia-correlated depressive pathology, because of the likelihood of an impairment of intra-cardiac conduction, namely in the left bundle branch. It is, by on the other hand, very important remember that the infarctuated patients which suffer from a concomitant depressive disease are exposed to a greater risk of a fatal outcome of their ischaemic cardiopathy
Psychiatry, University of Turin, Turin, Italy; I Internal Medicine, Dept. of Clinicaland BiologicalSciences, University of Turin, Turin, Italy; 2 Institute of Neurology, University of Turin, Turin, Italy Natural Killer (NK) cells are a CD3-CDI6+CD56+ lymphocyte subset involved in immunosurveillance. Both cytokines and hormones have been reported to be influential on differentiation and activity of these cells. Among cytokines, interferons (IFNs) and interleukin 2 (IL-2) enhance NK cytotoxicity; among hormones, glucocorticoids are well known inhibitors. In patients with Alzheimer's Disease (AD), reduced sensitivity of pituitary secretion to glucocorticoid feed-back is relevant. We evaluated the spontaneous NK cell activity on pheripheral blood mononuclear cells (PBMe) and responsiveness in vitro to positive (IFN-y, IL-2) or negative (cortisol, F) modulators in 21 AD patients (age: 58-78; mean duration of illness: 38 months; diagnosis according to DSM IV criteria; Mini Mental Test Examination, MMSE: 20.2 ± 0.83; Hashinski Test: 3.5 ± 0.22), in 15 age and sex-matched healthy controls and in 20 young volunteers (age: 23-32). PBMC preparations were incubated in presence or absence of F (10- 6 M) or IFN-y (650 IV/ml) or IL-2 (100 IV/ml). Cytotoxicity was assayed by a direct 4-h non radiometric assay, using K562 cells as a target. Levels of spontaneous NK cell activity did not differ between patients and age-matched controls while they were significantly higher in AD vs. young subjects (p < 0.01). Cytokine-inducible enhancement of cytotoxicity was similar in AD and young volunteers and significantly higher in AD vs. elderly controls (p < 0.05 for both IFN- and IL-2). F-dependent inhibition was lower in the elderly vs. young volunteers. In AD F-dependent inhibition appeared to be even lower (p < 0.05). The results are compatible with abnormal susceptibility to modifiers of NK effectors drawn from AD patients. In particular, excess boosting by physiological cytokines and less inhibition by F lend support to the view that AD patients have glucocorticoids resistence at different target levels.
I
0-4-2 1 Longitudinal Course of Immune Changes In Severe Depression
I. Hickie, D. Silove, D. Wakefield, A. Lloyd, B. Bennett. Universityof
New South Wales Australia, School of Psychiatry; Department of Inflammation Research While severe depression produces immunological changes, recent research [Il suggests that not all depression syndromes result in immune dysfunction. Epidemiological data [2] confirms an increased risk of physical morbidity and mortality in patients with major depression. A longitudinal perspective however, is essential if the scientific relationships between depressed mood, immune dysfunction, treatment effects and medical outcomes are to be established. We have followed a cohort of 67 adults with major depression at monthly intervals for a period
7
Telephone interviews were performed by lay interviewers using the knowledge based system Eval which is a previously validated computerized system designed to guide the interviewers. The sample was divided into four age groups: 15 to 44 years old (56.4%); 45 to 64 years old (25.6%); 65 to 74 years old (10.8%) and 75 years old or more (7.2%). Earlier bedtime, long sleep latency, spending more time in bed with a reduction of nocturnal sleep time, nocturnal awakenings and daytime naps were found more frequently in "young old" (65 to 74 years old) and "old old" subjects (75 years old or more). Daytime naps and spending more time in bed with a reduction of nocturnal sleep time also distinguished "old old" subjects from "young old" subjects. The rate of psychotropic drug consumption dramatically increased with age: 4.8% between 15 to 44 years old; 15.6% between 45 to 64 years old; 24.3% in "young old" subjects and 32.8% in "old old" subjects. The chronic use (at least one year) of hypnotic or anxiolytic drugs was frequent in "old old" subjects (92.6% and 80.2%, respectively) and "young old" subjects (74% and 78%, respectively). The assessment of sleep by the physician should be made part of the routine clinical examination of older subjects. Review of the etiology of insomnia complaints is crucial in the choice of treatment. These data underline the importance of educating physicians about consequences of long-term utilization of these drugs and on the need for sleep hygiene measures as alternative solutions for treating insomnia complaints.
I0-3-91
(more than 50%), in comparison with the non depressed patients, so is essential that such patients should have the opportunity to recover from the affective pathology early and accurately. Since early nineties, our group very largely used SSRI in patients with heart intracardiac conduction problems and specifically we prescribed paroxetine for its better compliance. In our cases, paroxetine has been employed in 12 patients, recently struck by infarctus, who developed a post-stroke depressive episode. Five of them showed a lengthening of the QRS interval and 7 a normal ECG. The mean daily dosage employed was 30 mg (10 mg t.i.d.). The patients with heart arrythmias ameliorate in few weeks and all recovered from depression in 4-8 weeks of treatment. No one of them showed a minimal cardiac abnormality.
10-41 Psychoimmunology I0-4-1 I Natural Killer Cell Activity andIn Vitro Responsiveness to Glucocorticoids and Cytokines in the Elderly andin Alzheimer's Disease L. Ravizza, G. Griot I , R.G. Masera I, P. Prolo, M. Mantovan I, A. Staurenghi I, L. Tarenzi 2, A. Lazzero I, A. Angeli I. Institute of
Pharmacological Profile of GV150526A a Novel Glycine Antagonist for Stroke
E. Ratti, G. Gaviraghi, C. Pietra, D. Trist, A. Reggiani. Glaxo Research
Laboratories, 37100 Verona, Italy It is now believed that the glycine site of the NMDA receptor is an attractive target for new antistroke compounds. In line with this, in the present paper the pharmacological profile ofGVI50526A (GV), a novel and very promising glycine antagonist, is described. GV has a very high affinity and selectivity for rat and human glycine receptors (pKi 8.5) and additional in vitro studies confirmed its mode of action on the glycine site. In fact, a truly competitive antagonism was observed with GV if NMDA receptor was stimulated by glycine (depolarization in cultured hippocampal cells and the increase of 3H_TCP binding in rat cortex), but a non-competitive effect was seen if stimulation was due to NMDA itself (depolarization of intact rat cortical wedges). The neuroprotective activity of GV was tested as single IV bolus, in the permanent and transient MCA occlusion models in rats (p-MCAo and t-MCAo). When given PRE-ISCHAEMIA (0.3-3 mg/kg) a dose-dependent reduction of neuronal damage was seen in both models. Maximal protection was at 3 mg/kg: in the p-MCAo was 78% (p < 0.05), in the t-MCAo was 56% (p < 0.05). A very wide POST-ISCHAEMIA window was observed in both models. Significant neuroprotection (p < 0.05) was detected at 3 mg/kg IV, as single bolus, even when administration was delayed up to 6 hrs from occlusion (53% and 37% protection in the p-MCAo and t-MCAo respectively). In our data base none of the reference compound tested so far, including other NMDA antagonists (MK 801, Eliprodil and ACEA 1021), showed a similar wide window of effectiveness. In view of these results and due to the lack of side-effects even at doses above the neuroprotective doses, GVI50526A is a very promising candidate as antistroke agent in man.
=
I0-3-10 lis Paroxetine In Post·Stroke Depression Useful? G. Rutigliano, F. Vadruccio. Center of Psychopharmacotherapy,
University of Bari, Italy Several data suggest that patients with abnormalities of intraventricular conduction are at increased risk if they assume tryciclic antidepressant drugs (TCA) for the treatment of the frequently correlated depressive pathology. Cardiologist mandatorily prohibits TCA for the treatment of hearts ischaemia-correlated depressive pathology, because of the likelihood of an impairment of intra-cardiac conduction, namely in the left bundle branch. It is, by on the other hand, very important remember that the infarctuated patients which suffer from a concomitant depressive disease are exposed to a greater risk of a fatal outcome of their ischaemic cardiopathy
Psychiatry, University of Turin, Turin, Italy; I Internal Medicine, Dept. of Clinicaland BiologicalSciences, University of Turin, Turin, Italy; 2 Institute of Neurology, University of Turin, Turin, Italy Natural Killer (NK) cells are a CD3-CDI6+CD56+ lymphocyte subset involved in immunosurveillance. Both cytokines and hormones have been reported to be influential on differentiation and activity of these cells. Among cytokines, interferons (IFNs) and interleukin 2 (IL-2) enhance NK cytotoxicity; among hormones, glucocorticoids are well known inhibitors. In patients with Alzheimer's Disease (AD), reduced sensitivity of pituitary secretion to glucocorticoid feed-back is relevant. We evaluated the spontaneous NK cell activity on pheripheral blood mononuclear cells (PBMe) and responsiveness in vitro to positive (IFN-y, IL-2) or negative (cortisol, F) modulators in 21 AD patients (age: 58-78; mean duration of illness: 38 months; diagnosis according to DSM IV criteria; Mini Mental Test Examination, MMSE: 20.2 ± 0.83; Hashinski Test: 3.5 ± 0.22), in 15 age and sex-matched healthy controls and in 20 young volunteers (age: 23-32). PBMC preparations were incubated in presence or absence of F (10- 6 M) or IFN-y (650 IV/ml) or IL-2 (100 IV/ml). Cytotoxicity was assayed by a direct 4-h non radiometric assay, using K562 cells as a target. Levels of spontaneous NK cell activity did not differ between patients and age-matched controls while they were significantly higher in AD vs. young subjects (p < 0.01). Cytokine-inducible enhancement of cytotoxicity was similar in AD and young volunteers and significantly higher in AD vs. elderly controls (p < 0.05 for both IFN- and IL-2). F-dependent inhibition was lower in the elderly vs. young volunteers. In AD F-dependent inhibition appeared to be even lower (p < 0.05). The results are compatible with abnormal susceptibility to modifiers of NK effectors drawn from AD patients. In particular, excess boosting by physiological cytokines and less inhibition by F lend support to the view that AD patients have glucocorticoids resistence at different target levels.
I
0-4-2 1 Longitudinal Course of Immune Changes In Severe Depression
I. Hickie, D. Silove, D. Wakefield, A. Lloyd, B. Bennett. Universityof
New South Wales Australia, School of Psychiatry; Department of Inflammation Research While severe depression produces immunological changes, recent research [Il suggests that not all depression syndromes result in immune dysfunction. Epidemiological data [2] confirms an increased risk of physical morbidity and mortality in patients with major depression. A longitudinal perspective however, is essential if the scientific relationships between depressed mood, immune dysfunction, treatment effects and medical outcomes are to be established. We have followed a cohort of 67 adults with major depression at monthly intervals for a period