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P.1.078 Chronic imipramine treatment reversesolfactory bulbectomized-induced hyperactivity species in three rodent species
P1. Affection disorders and ant~depre~saut~ Results: In patients treated with pegylated IFN-A, platelet MAC-activity increased more than 80% (95% CI: 53-127%) at all time-points compared to non-treated controls. Compared to baseline, the platelet MAO-activily increased more than 60% (95% CI: 45-92%). In the control group, platelet MAC-activity did not change significantly. As expected, decreases in platelet counts were observed in the treated group compared to controls. No significant changes were found between the two groups in whole blood MAC-activity. Conclmions-" Immunotherapy with pegylated IFN-A significantly increased platelet MAC-activity. If platelet MAC-activity is a reflection of the capacity of the central serotonergic system, then treatment with this cytokine may also increase central serotonergic neurotransmission. Future studies in patients treated with pegylated IFN-A should also focus on the relationship between the development of nenropwchiatric side effects and the activity of platelet MAC).
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Escitalopram vs venlafaxine XR treatment of major depressive disorder
S.A. Montgomery. Imperial College, Department of Psy&iatry, London, United Kingdom Escitalopram is a highly sdective serotonin reuptake inhibitor (SRI) antidepressant, Venlafaxine is a non-selective SRI that also inhibits noradrenergic reuptake. Two randomised, doubleblind, g-week trials compared the efficacy and tolerability of escitalopram with that of venlafaxine in major depressive disorder (MDD). The primary efficacy variable was the mean change from baseline in Montgomery A_sberg Depression Rating Scale (MADRS) scores. In the study in primary care in Europe, 10-20 my/day escitalopram (N=148) was at least as effective as 75-150 my/day venlafaxine (N=145), with a better side effect profile. Survival analysis of sustained response and sustained remission, showed escitalopram to be significantly superior to venlafaxine @<0.05). In the study in depressed outpatients in specialist settings in the US, 20 my/day escitalopram (N=97) appeared to be more effective than 225 my/day venlafaxine (N=98). In the subpopulation of severely depressed patients (N_&DRS,,->30, N=121), escitalopram was more effective than venlafaxine. The venlafaxine group had a higher overall incidence of treatment-emergent adverse events than the escitalopram group (85% vs. 68%), and more patients withdrew due to adverse events from the venlafaxine group than from the escitalopram group (16% vs. 4%; p<0.01). These results demonstrate that escitalopram has a better risk/benefit profile than venlafaxine in the treatment of MDD.
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Chronic imipramine treatment reverses olfactory bulbectomized-induced hyperactivity in three rodent species
M. Roche, E. Shanahan, A. Harkin, J.R Kelly. National Unioersity
of Ireland, Galway, Dept, _Pharmacology, Galway, Ireland Attenuation of novelty-induced hyperactivity following olfactory bulbectomy (OB) by chronic antidepressant treatment has been proposed as an animal model of antidepressant actionl. Although this feature of the model has been extensively examined in rats, it has only occasionally been used in other rodent species, such as mice and hamsters. It highly desirable to develop animal
$207
models in these species on the grounds of cost, space, amount of compound required and genomic similarities to the human. The objective of the present study was to assess chronic antidepressant trea~nent, using the tricyclic antidepressant imipramine (IMI), on Oh-induced hyperactivity in three rodent species, namely the male rat (S'prague-Dawley), mouse (C57/BL6j) and Golden Syrian hamster. Pollowing OB surgery animals were allowed two weeks recovery prior to commencement of chronic drug treatment (rat: 10 mg/kg/day s.c; mouse: 40 mg/kg/day i.p; hamster: 10 mg/kg/day s.c). Animals were placed in a brightly lit "open field" for 5 minutes and distance moved (cm) and velocity (cm/sec) were determined using the Ethovision video tracking system. Data were analysed by two-way ANOVA followed by Fisher's LSD post-hoe test where appropriate. Values of p<0.05 were considered as statistically significant. A significant increase in OB distance moved and velocity in the "open field" was observed in all three species when compared to their sham-operated controls. In the rat and hamster, IMI attenuated the OB-induced hyperactivity after 2 weeks of treatment. However, in the mouse, OB-induced increase in activity was reversed only after 5 weeks of IMI treatment. In conclusion, Ethovision provides an objective measure of novelty-induced hyperactivity in OB rats, mice and hamsters. This study demonstrates that OB related hyperactivity generalises to these rodent species and that chronic treatment with the tricyclic antidepressant, imipramine, attenuated this increase in activity. Finally, this study allows for the expansion of the model and the possibility for pre-clinical detection of antidepressant activity in situations where the rat is unsuitable.
References [1] Andrew Harkin, John Kelly, Brian E. Leonard, A review of thereinvance and validity of olfactory bulbectomy as a model of depression. Clinical Neurosoienoe Research, 2003. 3:2,53-262
~Data
from r e Vienna Transdanube Aging (V1TA) Study do not support the concept of vascular depression
M . K Rainer11, H.A.M. Mucke2" , T. Kuse~bauerl, S. We~ssgram 1, S. Jungwirth , W. Krampla , K.H. Tragl , P. Fischer . Ludwig
Bo#zmann Institute for Ageing Research and Donau Hospital, gozialmedizinisches Ze~rum Oat,, Dept. for Psychiatry and Memory Giuio, Vienna, Austria; 21t3/~ Dharma Cohen#ahoy, Vienna, Austria; SLudwig Boltzmann Institute for Ageing Research and Vienna C~ueral Hosp#al, 2sychiatric Unioers#y Clinic, Unioereity of Vienna, Vienna, Austria Background and objective: The vascular depression hypothesis, which postulates that geriatric depression can be caused, exacerbated or perpetuated by cerebrovascular disease (1) has been discussed since 1997, Data presented during this ongoing debate have been confounded by the fact that depression and cerebrovascular neuroimaging anomalies are both correlated with age as the most significant risk factor. In elderly individuals, brain MRI frequently reveals quite significant deviations from the norm in the absence of psychiatric or neurological signs and symptoms (2) while most patients with major depression have scans that are completely normal for their respective age. As a result of this extensive breadth of variation, studies with larger patient numbers and/or much more homogenous populations than have been reported so far are needed to evaluate the concept of vascular depression.
•
Escitalopram vs venlafaxine XR treatment of major depressive disorder
S.A. Montgomery. Imperial College, Department of Psy&iatry, London, United Kingdom Escitalopram is a highly sdective serotonin reuptake inhibitor (SRI) antidepressant, Venlafaxine is a non-selective SRI that also inhibits noradrenergic reuptake. Two randomised, doubleblind, g-week trials compared the efficacy and tolerability of escitalopram with that of venlafaxine in major depressive disorder (MDD). The primary efficacy variable was the mean change from baseline in Montgomery A_sberg Depression Rating Scale (MADRS) scores. In the study in primary care in Europe, 10-20 my/day escitalopram (N=148) was at least as effective as 75-150 my/day venlafaxine (N=145), with a better side effect profile. Survival analysis of sustained response and sustained remission, showed escitalopram to be significantly superior to venlafaxine @<0.05). In the study in depressed outpatients in specialist settings in the US, 20 my/day escitalopram (N=97) appeared to be more effective than 225 my/day venlafaxine (N=98). In the subpopulation of severely depressed patients (N_&DRS,,->30, N=121), escitalopram was more effective than venlafaxine. The venlafaxine group had a higher overall incidence of treatment-emergent adverse events than the escitalopram group (85% vs. 68%), and more patients withdrew due to adverse events from the venlafaxine group than from the escitalopram group (16% vs. 4%; p<0.01). These results demonstrate that escitalopram has a better risk/benefit profile than venlafaxine in the treatment of MDD.
•
Chronic imipramine treatment reverses olfactory bulbectomized-induced hyperactivity in three rodent species
M. Roche, E. Shanahan, A. Harkin, J.R Kelly. National Unioersity
of Ireland, Galway, Dept, _Pharmacology, Galway, Ireland Attenuation of novelty-induced hyperactivity following olfactory bulbectomy (OB) by chronic antidepressant treatment has been proposed as an animal model of antidepressant actionl. Although this feature of the model has been extensively examined in rats, it has only occasionally been used in other rodent species, such as mice and hamsters. It highly desirable to develop animal
$207
models in these species on the grounds of cost, space, amount of compound required and genomic similarities to the human. The objective of the present study was to assess chronic antidepressant trea~nent, using the tricyclic antidepressant imipramine (IMI), on Oh-induced hyperactivity in three rodent species, namely the male rat (S'prague-Dawley), mouse (C57/BL6j) and Golden Syrian hamster. Pollowing OB surgery animals were allowed two weeks recovery prior to commencement of chronic drug treatment (rat: 10 mg/kg/day s.c; mouse: 40 mg/kg/day i.p; hamster: 10 mg/kg/day s.c). Animals were placed in a brightly lit "open field" for 5 minutes and distance moved (cm) and velocity (cm/sec) were determined using the Ethovision video tracking system. Data were analysed by two-way ANOVA followed by Fisher's LSD post-hoe test where appropriate. Values of p<0.05 were considered as statistically significant. A significant increase in OB distance moved and velocity in the "open field" was observed in all three species when compared to their sham-operated controls. In the rat and hamster, IMI attenuated the OB-induced hyperactivity after 2 weeks of treatment. However, in the mouse, OB-induced increase in activity was reversed only after 5 weeks of IMI treatment. In conclusion, Ethovision provides an objective measure of novelty-induced hyperactivity in OB rats, mice and hamsters. This study demonstrates that OB related hyperactivity generalises to these rodent species and that chronic treatment with the tricyclic antidepressant, imipramine, attenuated this increase in activity. Finally, this study allows for the expansion of the model and the possibility for pre-clinical detection of antidepressant activity in situations where the rat is unsuitable.
References [1] Andrew Harkin, John Kelly, Brian E. Leonard, A review of thereinvance and validity of olfactory bulbectomy as a model of depression. Clinical Neurosoienoe Research, 2003. 3:2,53-262
~Data
from r e Vienna Transdanube Aging (V1TA) Study do not support the concept of vascular depression
M . K Rainer11, H.A.M. Mucke2" , T. Kuse~bauerl, S. We~ssgram 1, S. Jungwirth , W. Krampla , K.H. Tragl , P. Fischer . Ludwig
Bo#zmann Institute for Ageing Research and Donau Hospital, gozialmedizinisches Ze~rum Oat,, Dept. for Psychiatry and Memory Giuio, Vienna, Austria; 21t3/~ Dharma Cohen#ahoy, Vienna, Austria; SLudwig Boltzmann Institute for Ageing Research and Vienna C~ueral Hosp#al, 2sychiatric Unioers#y Clinic, Unioereity of Vienna, Vienna, Austria Background and objective: The vascular depression hypothesis, which postulates that geriatric depression can be caused, exacerbated or perpetuated by cerebrovascular disease (1) has been discussed since 1997, Data presented during this ongoing debate have been confounded by the fact that depression and cerebrovascular neuroimaging anomalies are both correlated with age as the most significant risk factor. In elderly individuals, brain MRI frequently reveals quite significant deviations from the norm in the absence of psychiatric or neurological signs and symptoms (2) while most patients with major depression have scans that are completely normal for their respective age. As a result of this extensive breadth of variation, studies with larger patient numbers and/or much more homogenous populations than have been reported so far are needed to evaluate the concept of vascular depression.