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Escitalopram has potent and rapid effect in a chronic mild stress model of depression in rats
PI. Aflective disorders and antidepressants
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Escitalopram has potent and rapid effect in a chronic mild stress model of depression in rats
M. Papp', C. Sanchez* *. ‘Institute of Pharmacology, Polish Academy of Sciences, Krakow, 12 Smetna St, 31-343 Krakow, Poland; 2Neuropharmacology Department, H. Lundbeck A/S, Ottiliavej 9, 2500 Copenhagen- Valby, Denmark
The rat chronic mild stress (CMS) model of depression is a behavioural procedure, with high predictive validity, for determining the efficacy of antidepressant compounds (Willner 1997). It consists of sequential exposures to a variety of mild stressors for a prolonged period and results in behavioural hedonic deficits (in the present study decreased consumption of 1% sucrose solution). This condition is suggested to model a key symptom of depressive disorder; loss of interest or pleasure. Chronic treatment with antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors) over several weeks has consistently produced a gradual normalisation of the sucrose intake. The efficacy and time to onset was explored for treatment with escitalopram (5 and 10 mg/kg per day), citalopram (10 mgkg per day) and R-fluoxetine (5 and 10 mgkg per day). Male Wistar rats that had been trained to drink sucrose solution were subjected to CMS for 3 weeks. The weekly stress regimen consisted of two IO-14-hr periods of: food or water deprivation, 45” cage tilt, intermittent illumination (lights on and off every 2 hrs), wetted bedding, paired housing, low intensity stroboscopic illumination, and no stress. Control rats were separately housed. For the following 5 weeks, stressed and control rats received IP injections of vehicle or drug. Sucrose tests were carried out 24 hrs after the last injection. Stress was continued throughout the treatment period. CMS caused a decrease in sucrose consumption to approximately 8 g compared to 15 g in non-stressed controls. Drug treatment did not affect sucrose consumption in unstressed controls. In the stressed groups, escitalopram (5 and 10 mgkg per day) normalised the consumption of sucrose solution by week 1. A similar effect was observed in the citalopram group by week 2 and in the R-fluoxetine groups 5 and 10 mgkg per day by weeks 5 and 4, respectively. The results for citalopram are consistent with those of previous studies where sucrose consumption was normalised by week 2 (Przegalinski et al. 1995, Sanchez & Papp 2000). In conclusion, these results indicate potential for an improved time to onset of efficacy of escitalopram compared to citalopram. R-fluoxetine also showed efficacy in the CMS model. However, the onset to efficacy of R-fluoxetine was within the range usually observed following administration of tricyclic antidepressants (e.g., imipramine).
References [l] Przegalinski, E., Moryl E., Papp M. (199.5) The effect of 5-HTlA receptor ligands in chronic mild stress model of depression. Neumpharm., 35,3%310. [2] SLnchez, C., Papp M. (2000) The selective 6 2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression. Behau. Pharmacol., 11,117-l 24. [3] Willner I? (1997) Validity, reliability and utility of the chronic mild stress model of depression: a lo-year review and evaluation. Psychopharmacology, 134, 3 19-329.
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(p.1.125) Sexual dysfunction among patients treated with antidepressants - A Hungarian retrospective study I? Osv&l~’ , S. Fekete’ , V. Vorijs’ , T. Tenyi’ , J.Vitra? . ’UniversiQ of Pets, Department of Psychiatry, Pets; ‘Ministry of Health, Budapest, Hungary Objective: The presence of sexual function impairment in patients with psychiatric disorders -especially depression - is very common. Sexual dysfunctions (SD) are often perpetuated by the majority of antidepressive drugs used in the treatment. This may occur up to 75% of the patients. The nature and frequency of SD caused by antidepressive medication have not been systematically characterised, nor has the specific drug effects on sexual function been adequately studied in a larger population of patients. Thus the purpose of our study was to investigate the incidence and several aspects of sexual problems in Hungarian outpatients treated with antidepressive medication. Material and Method: This multicenne epidemiological survey involved 52 psychiatrists working in psychiatric outpatient centres in Hungary. The study population comprised 637 randomly selected patients (males: 262/41%/, females: 375/59%/, mean age: 42, SD: 10.75, 17-76) who were diagnosed depressive (73%) and anxiety disorders (27%) (by ICD 10) and treated with antidepressants in a setting of routine clinical practice. SD (decreased libido, problems with erection and ejaculation, delayed orgasm or anorgasmia,) was assessed by psychiatrists using structured interviews. Results: In our sample two-third of the patients were taking an SSRI compound while 25% were under RIMA and 7% under tri/tetracyclic (TCA) antidepressant medication, The rate of SD was 78% (N = 494) (male: 79.4%, female: 76.5%) in our sample. Prior to the current illness 17% of the patients had already some sexual problems in their life. Following the development of the present psychiatric disorder, but before taking any medication, 27% experienced some sexual dysfunction, while 56% mentioned SD after starting antidepressive medication. Among sexual dysfunctions the frequency of decreased libido was 25% (m/f: 16/33), diminishing sexual desire was 30% (m/f: 22/36), while erectile problems in 32%, ejaculation problems in 18% of males, and problems with orgasm or anorgasmia in 22% (m/f: 12131) were found. Almost one-third of the patients had sexual intercourse weekly or more frequently, 39% monthly, and 21% more rarely, while 8% of them had no sexual acts at all. Overall 16% valued his/her sexual functioning good, 25% satisfactory and 59% insufficient. In the group of patients with SD the frequency of sexual intercourse was significantly lower, but the rate of unsatisfactory sexual functioning was much higher (75% vs. 3%). In the group of patients with SD almost 40 percent consider their problem to have been caused by psychiatric disorder (especially depression), while others think that the antidepressants (30%), other medication (So/,), problems with his/her partners (18%) resulted in the sexual dysfunction. Comparing patients who reported SD after starting antidepressants to those who did not, we found that the frequency of SD was very high in the TCA (75%) and SSRI (79%) groups, while in the RIMA group it was much lower (29%). Conclusion: In the Hungarian out-patient population treated with antidepressants a high rate of sexual dysfunction was found. In addition, to mood disorder antidepressive medication was considered as the most important causative factor in generating sexual dysfunction. Comparing various groups of antidepressants,
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Escitalopram has potent and rapid effect in a chronic mild stress model of depression in rats
M. Papp', C. Sanchez* *. ‘Institute of Pharmacology, Polish Academy of Sciences, Krakow, 12 Smetna St, 31-343 Krakow, Poland; 2Neuropharmacology Department, H. Lundbeck A/S, Ottiliavej 9, 2500 Copenhagen- Valby, Denmark
The rat chronic mild stress (CMS) model of depression is a behavioural procedure, with high predictive validity, for determining the efficacy of antidepressant compounds (Willner 1997). It consists of sequential exposures to a variety of mild stressors for a prolonged period and results in behavioural hedonic deficits (in the present study decreased consumption of 1% sucrose solution). This condition is suggested to model a key symptom of depressive disorder; loss of interest or pleasure. Chronic treatment with antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, and monoamine oxidase inhibitors) over several weeks has consistently produced a gradual normalisation of the sucrose intake. The efficacy and time to onset was explored for treatment with escitalopram (5 and 10 mg/kg per day), citalopram (10 mgkg per day) and R-fluoxetine (5 and 10 mgkg per day). Male Wistar rats that had been trained to drink sucrose solution were subjected to CMS for 3 weeks. The weekly stress regimen consisted of two IO-14-hr periods of: food or water deprivation, 45” cage tilt, intermittent illumination (lights on and off every 2 hrs), wetted bedding, paired housing, low intensity stroboscopic illumination, and no stress. Control rats were separately housed. For the following 5 weeks, stressed and control rats received IP injections of vehicle or drug. Sucrose tests were carried out 24 hrs after the last injection. Stress was continued throughout the treatment period. CMS caused a decrease in sucrose consumption to approximately 8 g compared to 15 g in non-stressed controls. Drug treatment did not affect sucrose consumption in unstressed controls. In the stressed groups, escitalopram (5 and 10 mgkg per day) normalised the consumption of sucrose solution by week 1. A similar effect was observed in the citalopram group by week 2 and in the R-fluoxetine groups 5 and 10 mgkg per day by weeks 5 and 4, respectively. The results for citalopram are consistent with those of previous studies where sucrose consumption was normalised by week 2 (Przegalinski et al. 1995, Sanchez & Papp 2000). In conclusion, these results indicate potential for an improved time to onset of efficacy of escitalopram compared to citalopram. R-fluoxetine also showed efficacy in the CMS model. However, the onset to efficacy of R-fluoxetine was within the range usually observed following administration of tricyclic antidepressants (e.g., imipramine).
References [l] Przegalinski, E., Moryl E., Papp M. (199.5) The effect of 5-HTlA receptor ligands in chronic mild stress model of depression. Neumpharm., 35,3%310. [2] SLnchez, C., Papp M. (2000) The selective 6 2 ligand Lu 28-179 has an antidepressant-like profile in the rat chronic mild stress model of depression. Behau. Pharmacol., 11,117-l 24. [3] Willner I? (1997) Validity, reliability and utility of the chronic mild stress model of depression: a lo-year review and evaluation. Psychopharmacology, 134, 3 19-329.
S233
(p.1.125) Sexual dysfunction among patients treated with antidepressants - A Hungarian retrospective study I? Osv&l~’ , S. Fekete’ , V. Vorijs’ , T. Tenyi’ , J.Vitra? . ’UniversiQ of Pets, Department of Psychiatry, Pets; ‘Ministry of Health, Budapest, Hungary Objective: The presence of sexual function impairment in patients with psychiatric disorders -especially depression - is very common. Sexual dysfunctions (SD) are often perpetuated by the majority of antidepressive drugs used in the treatment. This may occur up to 75% of the patients. The nature and frequency of SD caused by antidepressive medication have not been systematically characterised, nor has the specific drug effects on sexual function been adequately studied in a larger population of patients. Thus the purpose of our study was to investigate the incidence and several aspects of sexual problems in Hungarian outpatients treated with antidepressive medication. Material and Method: This multicenne epidemiological survey involved 52 psychiatrists working in psychiatric outpatient centres in Hungary. The study population comprised 637 randomly selected patients (males: 262/41%/, females: 375/59%/, mean age: 42, SD: 10.75, 17-76) who were diagnosed depressive (73%) and anxiety disorders (27%) (by ICD 10) and treated with antidepressants in a setting of routine clinical practice. SD (decreased libido, problems with erection and ejaculation, delayed orgasm or anorgasmia,) was assessed by psychiatrists using structured interviews. Results: In our sample two-third of the patients were taking an SSRI compound while 25% were under RIMA and 7% under tri/tetracyclic (TCA) antidepressant medication, The rate of SD was 78% (N = 494) (male: 79.4%, female: 76.5%) in our sample. Prior to the current illness 17% of the patients had already some sexual problems in their life. Following the development of the present psychiatric disorder, but before taking any medication, 27% experienced some sexual dysfunction, while 56% mentioned SD after starting antidepressive medication. Among sexual dysfunctions the frequency of decreased libido was 25% (m/f: 16/33), diminishing sexual desire was 30% (m/f: 22/36), while erectile problems in 32%, ejaculation problems in 18% of males, and problems with orgasm or anorgasmia in 22% (m/f: 12131) were found. Almost one-third of the patients had sexual intercourse weekly or more frequently, 39% monthly, and 21% more rarely, while 8% of them had no sexual acts at all. Overall 16% valued his/her sexual functioning good, 25% satisfactory and 59% insufficient. In the group of patients with SD the frequency of sexual intercourse was significantly lower, but the rate of unsatisfactory sexual functioning was much higher (75% vs. 3%). In the group of patients with SD almost 40 percent consider their problem to have been caused by psychiatric disorder (especially depression), while others think that the antidepressants (30%), other medication (So/,), problems with his/her partners (18%) resulted in the sexual dysfunction. Comparing patients who reported SD after starting antidepressants to those who did not, we found that the frequency of SD was very high in the TCA (75%) and SSRI (79%) groups, while in the RIMA group it was much lower (29%). Conclusion: In the Hungarian out-patient population treated with antidepressants a high rate of sexual dysfunction was found. In addition, to mood disorder antidepressive medication was considered as the most important causative factor in generating sexual dysfunction. Comparing various groups of antidepressants,