- Email: [email protected]
Depression in primary care patients: Improvement during long-term escitalopram treatment
P1. Affective disorders and antidepressants
$232
Using a repeated measures, mixed-model analysis, subjects treated with sertraline demonstrated a significantly greater mean change in the CDRS-R total score (p=0.007), CGI-I (p=0.009), and CGI-S (p=0.005). In the treatment by visit week analysis, significantly greater improvement was seen at Week 1 for the CGI-I (p=0.043) and Week 3 for the CGI-S (p=0.032) and CDRS-R total score (p=0.014). A significantly greater percentage of subjects treated with sertraline met criteria for response based on the CDRS-R (69 vs. 59%, p=0.050) and CGI-I (63 vs. 53%, p=0.049). No significant difference between treatment groups was seen for the MASC or CGAS. The change in PQ-LES-Q score was of borderline significance (p=0.066) in favor of sertraline. Sertraline was generally well-tolerated, though a greater number of children (13.9%) than adolescents (3.8%) discontinued from the study due to adverse events. Adverse events occurring in greater than 5% of sertraline-treated subjects and twice that of placebo-treated subjects included diarrhea, vomiting, agitation, and anorexia. No clinically meaningful differences in laboratory data, electrocardiograms, or vital signs were noted between treatment groups. A small but statistically significant decrease in body weight was noted in sertraline subjects compared to placebo. These data support the efficacy and safety of sertraline in the treatment of pediatric MDD and contribute to the knowledge base of sertraline in the treatment of pediatric mood and anxiety disorders.
References [1] Wagner, K.D. and Ambrosini, P.J. (2001) Childhood depression: pharmacological therapy/treatment (pharmacotherapy of childhood depression). J. Clin. Child Psychol. 30, 88-97. [2] Emslie, G.J. et al. (1997) A double-blind, randomized, placebocontrolled trial of fluoxetine in children and adolescents with depression. Arch. Gen. Psychiatry 54, 1031-1037. [3] Rynn MA et al. (2001) Placebo-controlled trial of sertraline in the treatment of children with GAD. Am. J. Psychiatry 158, 2008-2014.
•
Remission rates in elderly depressed patients treated with sertraline
J. Sheikh 1, P. Newhouse 2, T. Burt 3, C. Clary 3. 1Stanford
University School of Medicine, Department of Psychiatry & Behavioral Sciences, Stanford, U.S,A.; 2University of Vermont, College of Medicine, Department of Psychiatry, Burlington, U.S.A., 3Pfizer Pharmaceuticals, New York, U.S.A. Purpose: Depression in older adults is common, under-diagnosed, disabling, and treatable. Although increasingly recognized as an important indicator of antidepressant efficacy, little data is available on remission rates from placebo-controlled trials in the elderly. We report on remission rates based on analyses performed on the largest placebo-controlled trial conducted in elderly patients with depression. Methods: Outpatients (N=752) 60 years or older (mean age 69.9), with DSM-IV diagnosis of major depression, and a 17-item Hamilton Rating Scale for Depression (HAM-D) total score ~>18, were randomized to receive sertraline or placebo for 8 weeks. Remission was defined as endpoint HAM-D<10 or CGI-S of 1 or 2 (normal, not at all ill, or borderline mentally ill). Remission rates were calculated using Cochran-Mantel-Haenszel test. Results: There were significantly more remitters in the sertraline group compared to those in the placebo group. Specifically, HAM-D remitters were 34°,5 on sertraline and 24% on placebo (completers), and 29% on sertraline and 23% on placebo (LOCF at endpoint). CGI-S remitters were 37% on sertraline and 25% on
placebo (completers), and 33% on sertraline and 23% on placebo (LOCF at endpoint). Discussion: These results suggest that sertraline is efficacious in achieving complete remission of symptoms in elderly patients with major depression. The 8 week duration of the study should be taken into account when interpreting these findings as longer antidepressant treatment periods, particularly in the elderly, may be associated with higher remission rates. Future studies are needed to confirm these observations.
•
Symptom pattern analysis of premenstrual dysphoric disorder (PMDD)
T. Pearlstein 1, J.A. Gillespie2. 1 Women & Infants and Brown
University, Providence, U S.A.; 2Pfizer Inc., Depression & Anxie~ Disease Management Team, New York, U.S.A. Background: The advent of intermittent dosing strategies for the treatment of Premenstrual Dysphoric Disorder (PMDD) has highlighted the need for more detailed empirical data on the onset, duration and pattern of PMDD symptoms. Method: Data was analyzed from 276 women who met DSM-IV criteria for PMDD and who prospectively charted 2 menstrual cycles off medication. The presence and severity of PMDD symptoms were rated using the Daily Rating of Severity of Problems (DRSP). Results: The top PMDD symptoms (moderate-to-severe for>3 days) included anger/irritability (76%), anxiety/tension (71%), and mood swings (58%). DRSP scores peaked at day -2, but the day of onset of PMDD-level symptom severity was highly variable, differing from cycle-to-cycle by 3 or more days in>60% of women. Similarly, the duration of PMDD-Ievel symptoms varied by 3 or more days in>50% of women. One day after the onset of menstruation, 34% of women continued to report PMDD-level of symptoms (> moderate severity of >5 out of 11 DSM-IV symptoms). The DRSP anger/irritability/conflict factor showed the earliest rise in symptom severity, and the slowest tail-off after the onset of bleeding. Conclusion: The variable onset/offset pattern of PMDD symptoms suggests that care must be taken when utilizing luteal phase dosing to ensure adequate pharmacologic coverage of cycle-tocycle episodes.
References [1] Hurt SW, Schnurr PP, Severino SK, Freeman EW, Gise LH, RiveraTovar A, Steege JE Late luteal phase dysphoric disorder in 670 women evaluated for premenstrual complaints. Am J Psychiatry 1992; 149:525-530. [2] Soares CN, Cohen LS, Otto MW, Harlow BL. Characteristics of Women with Premenstrual Dysphoric Disorder (PMDD) Who Did or Did Not Report History of Depression: A Preliminary Report from the Harvard Study of Moods and Cycles. J Womens Health Gend Based Med 2001;10:873 878.
•
Depression in primary care patients: Improvement during long-term escitalopram treatment
A. Wade 1, N. Despiegel 2, E.H. Reines 2. 1CPS Clinical Research
Centre, Glasgow, United Kingdom," 2H. Lundbeck A/S, ICR, Copenhagen, Denmark Escitalopram is a highly selective and potent SSRI that has been proven safe and effective in the treatment of Major Depressive
P.1. Affectiue disorders and antidepressants Disorder (MDD) in recently completed short-term phase III studies. Long-term clinical efficacy results have now been evaluated from a study with a total exposure time to escitalopram of 486 patient years. Escitalopram was administered at doses of 10 or 20 mg/day (dose increase based on physician's clinical judgement) in an open-label, 12-month safety, follow-up study conducted in outpatients (n=588) who fulfilled the DSM-IV criteria for MDD. Patients entered the study after completing one of two 8-week, double-blind, placebo-controlled, lead-in studies. The primary efficacy parameter was the MADRS total score. At baseline (entry into the 12-month study), patients had a mean MADRS total score of 14.2, which decreased to 10.5 after 8 weeks and 5.8 after 52 weeks. The percentage of patients in remission (defined here as MADRS total score ~<12) increased from 46% at baseline to 65% by Week 8 and 86% by Week 52. There was a corresponding decrease in the number of moderately to severely ill patients (MADRS total score ) 2 2 ) from 22% at baseline to 8% by Week 8 and 2% by Week 52. A total of 437 patients completed the study, with an average exposure to escitalopram of 315 days. The robustness of these long-term efficacy results is confirmed by the results from the secondary efficacy parameter - the CGISeverity (CGI-S) scale. At baseline, 55% of patients had a CGI-S score of 3 or more (mildly ill, or worse), decreasing to 37% by Week 8, and 14% by Week 52. In conclusion, moderately to severely depressed patients in primary care treated with escitalopram (10 to 20 mg/day) showed continued improvement throughout this long-term study.
•
Onset of action of NaSSA Mirtazapine: Results from an antidepressant-naive group
$233
Statistical analysis: For normal variables, classical one-way ANOVA can be used for assessing significant differences between groups (previous checking homogeneity of variances). In the other cases, a non-parametric Kruskall-Wallis test was used. Onset of action was measured by persistent reduction of more than 50 % from the base line HAM-D17. Four groups: faster response (onset persistent response at 7th day), fast response (onset persistent response at 14th day), traditional response (onset persistent response at 28th day), and delayed or non-response (partial or non-response on the 28th day). Results: - CGI-Severity distribution: 26 mild depressed patients (4.5%), 258 patients with moderate depression (44.3%), 243 markedly depressed patients (41.8%), 54 severely depressed patients (9.3%) and one patients suffered an extreme depression (0.2%). - Onset of action: 93 patients (16.0%) showed a faster response, 245 patients (42.1%) showed a fast response, 154 patients (26.5 %) showed a traditional response, and 90 patients (15.5 %) showed delayed or no response. - There were no significant differences between groups as to demographic and medical characteristics. - he CGI-Severity at base line did not show differences among groups. Basal scores in the HAM-D17 were different between groups: 23.02!6.26 ( 9 4 2 ) for all groups, but 21.49 for the faster one (p<0.051). Conclusion: Onset of action is a variable condition. In our study, Mirtazapine shows a majority of faster or fast response (58.1% for both groups). Neither demographic or medical conditions are related to this response. Faster response is related to severity in HAMD-17 scores at the base line, but not to CGISeverity.
References J. Cobo 1, J.E. Rojo 2, K. Gibert 3, E. Rodrlguez4. ~Corporaci6
Parc Tauli, Parc Taull, s.n., Sabadell, Spain; 2Belluitge Hospital, Psychiatry Department, Llobregat, Spain; 3Uniuersitat Politkcnica de Barcelona, Statistic Department, Barcelona, Spain; 4Benito Menni Mental Health Institute, Psychiatry Out-patient Department, Sant Boi de Llobregat, Spain It is generally thought that there is a delay of 2 weeks between the initiation of an antidepressant therapy and the appearance of response, but some patients show a faster response. Mirtazapine is the first noradrenergic and serotoninergic antidepressant (NaSSA). In order to assess the onset of activity of Mirtazapine several approaches were applied in several studies. This paper show some of the results of our further analysis. Objectives: we study the onset of response of Mirtazapine in the general depressive population of our psychiatric outpatients, but especially in a group of patients, the antidepressant-naive. Method: 1262 patients were included in the MAR study. This study was a multi-centre, prospective, open-label, noncomparative naturalistic study made among depressive outpatients. A total of 582 were included. Patients accomplishing the DSM-IV criteria for a Major Depressive Episode and with a base line score >8 on the 17-item Hamilton Depression Rating Scale (HAM-D17) were included. Reasons for exclusion: previous or concomitant use of any psychotropic drugs, except for benzodiacepines and sedative drugs in previous and continuous stabilised dose. Patients were assessed at screening, after 1 week, 2 weeks and 4 weeks. Symptom severity and clinical efficacy were assessed by HAM-D17 and Clinical Global Impression-Severity (CGI) at the base line on the 7th, 14th and 28th day.
[1] Rojo JE et al. Estudio MAR: mirtazapina acci6n r~ipida. Caracteristicas y resultados. Psiquiatria Biolrgica 2000; 7: 12-19. [2] Early Onset of Antidepressant Action. Journal of Clinical Psychiatry 2001; 62 (suppl. 4).
•
Onset of action of Mirtazapine: A review of comparative studies
J. Cobo 1, J.E. Rojo 2, E. Rodriguez 3, J.M. De Pedro 4. 1Corporaci6 Sanitbria Parc TaulL Parc Tauli, s.n., Sabadell, Spain; 2Bellvitge Hospital, Psychiatry Department, L'Hospitalet de Llobregat, Spain; 3Benito Menni Mental Health Institute, Psychiatry Outpatient Department, Sant Boi de Llobregat, Spain; 40rganon Espa~ola S.A., Medical Department, Barcelona, Spain Mirtazapine is the first noradrenergic and serotoninergic antidepressant (NaSSA). In order to assess the onset of activity of Mirtazapine several approaches were applied. This paper reviews the onset of action of Mirtazapine compared to placebo and different antidepressant. Objectives: Review studies about the comparative onset of action of Mirtazapine in different depressive populations and study design and with different statistical analysis and response criteria. Method: We review medical databases (MEDLINE), monographies and preliminary results of studies presented in posters not yet published in medical articles. We selected the studies that specified the onset of action of mirtazapine in comparison with other antidepressant. We analysed the Design, Population involved, Methods of Evaluation of the evolution, Efficacy, Response and Remission Criteria and Type of Onset of Action
$232
Using a repeated measures, mixed-model analysis, subjects treated with sertraline demonstrated a significantly greater mean change in the CDRS-R total score (p=0.007), CGI-I (p=0.009), and CGI-S (p=0.005). In the treatment by visit week analysis, significantly greater improvement was seen at Week 1 for the CGI-I (p=0.043) and Week 3 for the CGI-S (p=0.032) and CDRS-R total score (p=0.014). A significantly greater percentage of subjects treated with sertraline met criteria for response based on the CDRS-R (69 vs. 59%, p=0.050) and CGI-I (63 vs. 53%, p=0.049). No significant difference between treatment groups was seen for the MASC or CGAS. The change in PQ-LES-Q score was of borderline significance (p=0.066) in favor of sertraline. Sertraline was generally well-tolerated, though a greater number of children (13.9%) than adolescents (3.8%) discontinued from the study due to adverse events. Adverse events occurring in greater than 5% of sertraline-treated subjects and twice that of placebo-treated subjects included diarrhea, vomiting, agitation, and anorexia. No clinically meaningful differences in laboratory data, electrocardiograms, or vital signs were noted between treatment groups. A small but statistically significant decrease in body weight was noted in sertraline subjects compared to placebo. These data support the efficacy and safety of sertraline in the treatment of pediatric MDD and contribute to the knowledge base of sertraline in the treatment of pediatric mood and anxiety disorders.
References [1] Wagner, K.D. and Ambrosini, P.J. (2001) Childhood depression: pharmacological therapy/treatment (pharmacotherapy of childhood depression). J. Clin. Child Psychol. 30, 88-97. [2] Emslie, G.J. et al. (1997) A double-blind, randomized, placebocontrolled trial of fluoxetine in children and adolescents with depression. Arch. Gen. Psychiatry 54, 1031-1037. [3] Rynn MA et al. (2001) Placebo-controlled trial of sertraline in the treatment of children with GAD. Am. J. Psychiatry 158, 2008-2014.
•
Remission rates in elderly depressed patients treated with sertraline
J. Sheikh 1, P. Newhouse 2, T. Burt 3, C. Clary 3. 1Stanford
University School of Medicine, Department of Psychiatry & Behavioral Sciences, Stanford, U.S,A.; 2University of Vermont, College of Medicine, Department of Psychiatry, Burlington, U.S.A., 3Pfizer Pharmaceuticals, New York, U.S.A. Purpose: Depression in older adults is common, under-diagnosed, disabling, and treatable. Although increasingly recognized as an important indicator of antidepressant efficacy, little data is available on remission rates from placebo-controlled trials in the elderly. We report on remission rates based on analyses performed on the largest placebo-controlled trial conducted in elderly patients with depression. Methods: Outpatients (N=752) 60 years or older (mean age 69.9), with DSM-IV diagnosis of major depression, and a 17-item Hamilton Rating Scale for Depression (HAM-D) total score ~>18, were randomized to receive sertraline or placebo for 8 weeks. Remission was defined as endpoint HAM-D<10 or CGI-S of 1 or 2 (normal, not at all ill, or borderline mentally ill). Remission rates were calculated using Cochran-Mantel-Haenszel test. Results: There were significantly more remitters in the sertraline group compared to those in the placebo group. Specifically, HAM-D remitters were 34°,5 on sertraline and 24% on placebo (completers), and 29% on sertraline and 23% on placebo (LOCF at endpoint). CGI-S remitters were 37% on sertraline and 25% on
placebo (completers), and 33% on sertraline and 23% on placebo (LOCF at endpoint). Discussion: These results suggest that sertraline is efficacious in achieving complete remission of symptoms in elderly patients with major depression. The 8 week duration of the study should be taken into account when interpreting these findings as longer antidepressant treatment periods, particularly in the elderly, may be associated with higher remission rates. Future studies are needed to confirm these observations.
•
Symptom pattern analysis of premenstrual dysphoric disorder (PMDD)
T. Pearlstein 1, J.A. Gillespie2. 1 Women & Infants and Brown
University, Providence, U S.A.; 2Pfizer Inc., Depression & Anxie~ Disease Management Team, New York, U.S.A. Background: The advent of intermittent dosing strategies for the treatment of Premenstrual Dysphoric Disorder (PMDD) has highlighted the need for more detailed empirical data on the onset, duration and pattern of PMDD symptoms. Method: Data was analyzed from 276 women who met DSM-IV criteria for PMDD and who prospectively charted 2 menstrual cycles off medication. The presence and severity of PMDD symptoms were rated using the Daily Rating of Severity of Problems (DRSP). Results: The top PMDD symptoms (moderate-to-severe for>3 days) included anger/irritability (76%), anxiety/tension (71%), and mood swings (58%). DRSP scores peaked at day -2, but the day of onset of PMDD-level symptom severity was highly variable, differing from cycle-to-cycle by 3 or more days in>60% of women. Similarly, the duration of PMDD-Ievel symptoms varied by 3 or more days in>50% of women. One day after the onset of menstruation, 34% of women continued to report PMDD-level of symptoms (> moderate severity of >5 out of 11 DSM-IV symptoms). The DRSP anger/irritability/conflict factor showed the earliest rise in symptom severity, and the slowest tail-off after the onset of bleeding. Conclusion: The variable onset/offset pattern of PMDD symptoms suggests that care must be taken when utilizing luteal phase dosing to ensure adequate pharmacologic coverage of cycle-tocycle episodes.
References [1] Hurt SW, Schnurr PP, Severino SK, Freeman EW, Gise LH, RiveraTovar A, Steege JE Late luteal phase dysphoric disorder in 670 women evaluated for premenstrual complaints. Am J Psychiatry 1992; 149:525-530. [2] Soares CN, Cohen LS, Otto MW, Harlow BL. Characteristics of Women with Premenstrual Dysphoric Disorder (PMDD) Who Did or Did Not Report History of Depression: A Preliminary Report from the Harvard Study of Moods and Cycles. J Womens Health Gend Based Med 2001;10:873 878.
•
Depression in primary care patients: Improvement during long-term escitalopram treatment
A. Wade 1, N. Despiegel 2, E.H. Reines 2. 1CPS Clinical Research
Centre, Glasgow, United Kingdom," 2H. Lundbeck A/S, ICR, Copenhagen, Denmark Escitalopram is a highly selective and potent SSRI that has been proven safe and effective in the treatment of Major Depressive
P.1. Affectiue disorders and antidepressants Disorder (MDD) in recently completed short-term phase III studies. Long-term clinical efficacy results have now been evaluated from a study with a total exposure time to escitalopram of 486 patient years. Escitalopram was administered at doses of 10 or 20 mg/day (dose increase based on physician's clinical judgement) in an open-label, 12-month safety, follow-up study conducted in outpatients (n=588) who fulfilled the DSM-IV criteria for MDD. Patients entered the study after completing one of two 8-week, double-blind, placebo-controlled, lead-in studies. The primary efficacy parameter was the MADRS total score. At baseline (entry into the 12-month study), patients had a mean MADRS total score of 14.2, which decreased to 10.5 after 8 weeks and 5.8 after 52 weeks. The percentage of patients in remission (defined here as MADRS total score ~<12) increased from 46% at baseline to 65% by Week 8 and 86% by Week 52. There was a corresponding decrease in the number of moderately to severely ill patients (MADRS total score ) 2 2 ) from 22% at baseline to 8% by Week 8 and 2% by Week 52. A total of 437 patients completed the study, with an average exposure to escitalopram of 315 days. The robustness of these long-term efficacy results is confirmed by the results from the secondary efficacy parameter - the CGISeverity (CGI-S) scale. At baseline, 55% of patients had a CGI-S score of 3 or more (mildly ill, or worse), decreasing to 37% by Week 8, and 14% by Week 52. In conclusion, moderately to severely depressed patients in primary care treated with escitalopram (10 to 20 mg/day) showed continued improvement throughout this long-term study.
•
Onset of action of NaSSA Mirtazapine: Results from an antidepressant-naive group
$233
Statistical analysis: For normal variables, classical one-way ANOVA can be used for assessing significant differences between groups (previous checking homogeneity of variances). In the other cases, a non-parametric Kruskall-Wallis test was used. Onset of action was measured by persistent reduction of more than 50 % from the base line HAM-D17. Four groups: faster response (onset persistent response at 7th day), fast response (onset persistent response at 14th day), traditional response (onset persistent response at 28th day), and delayed or non-response (partial or non-response on the 28th day). Results: - CGI-Severity distribution: 26 mild depressed patients (4.5%), 258 patients with moderate depression (44.3%), 243 markedly depressed patients (41.8%), 54 severely depressed patients (9.3%) and one patients suffered an extreme depression (0.2%). - Onset of action: 93 patients (16.0%) showed a faster response, 245 patients (42.1%) showed a fast response, 154 patients (26.5 %) showed a traditional response, and 90 patients (15.5 %) showed delayed or no response. - There were no significant differences between groups as to demographic and medical characteristics. - he CGI-Severity at base line did not show differences among groups. Basal scores in the HAM-D17 were different between groups: 23.02!6.26 ( 9 4 2 ) for all groups, but 21.49 for the faster one (p<0.051). Conclusion: Onset of action is a variable condition. In our study, Mirtazapine shows a majority of faster or fast response (58.1% for both groups). Neither demographic or medical conditions are related to this response. Faster response is related to severity in HAMD-17 scores at the base line, but not to CGISeverity.
References J. Cobo 1, J.E. Rojo 2, K. Gibert 3, E. Rodrlguez4. ~Corporaci6
Parc Tauli, Parc Taull, s.n., Sabadell, Spain; 2Belluitge Hospital, Psychiatry Department, Llobregat, Spain; 3Uniuersitat Politkcnica de Barcelona, Statistic Department, Barcelona, Spain; 4Benito Menni Mental Health Institute, Psychiatry Out-patient Department, Sant Boi de Llobregat, Spain It is generally thought that there is a delay of 2 weeks between the initiation of an antidepressant therapy and the appearance of response, but some patients show a faster response. Mirtazapine is the first noradrenergic and serotoninergic antidepressant (NaSSA). In order to assess the onset of activity of Mirtazapine several approaches were applied in several studies. This paper show some of the results of our further analysis. Objectives: we study the onset of response of Mirtazapine in the general depressive population of our psychiatric outpatients, but especially in a group of patients, the antidepressant-naive. Method: 1262 patients were included in the MAR study. This study was a multi-centre, prospective, open-label, noncomparative naturalistic study made among depressive outpatients. A total of 582 were included. Patients accomplishing the DSM-IV criteria for a Major Depressive Episode and with a base line score >8 on the 17-item Hamilton Depression Rating Scale (HAM-D17) were included. Reasons for exclusion: previous or concomitant use of any psychotropic drugs, except for benzodiacepines and sedative drugs in previous and continuous stabilised dose. Patients were assessed at screening, after 1 week, 2 weeks and 4 weeks. Symptom severity and clinical efficacy were assessed by HAM-D17 and Clinical Global Impression-Severity (CGI) at the base line on the 7th, 14th and 28th day.
[1] Rojo JE et al. Estudio MAR: mirtazapina acci6n r~ipida. Caracteristicas y resultados. Psiquiatria Biolrgica 2000; 7: 12-19. [2] Early Onset of Antidepressant Action. Journal of Clinical Psychiatry 2001; 62 (suppl. 4).
•
Onset of action of Mirtazapine: A review of comparative studies
J. Cobo 1, J.E. Rojo 2, E. Rodriguez 3, J.M. De Pedro 4. 1Corporaci6 Sanitbria Parc TaulL Parc Tauli, s.n., Sabadell, Spain; 2Bellvitge Hospital, Psychiatry Department, L'Hospitalet de Llobregat, Spain; 3Benito Menni Mental Health Institute, Psychiatry Outpatient Department, Sant Boi de Llobregat, Spain; 40rganon Espa~ola S.A., Medical Department, Barcelona, Spain Mirtazapine is the first noradrenergic and serotoninergic antidepressant (NaSSA). In order to assess the onset of activity of Mirtazapine several approaches were applied. This paper reviews the onset of action of Mirtazapine compared to placebo and different antidepressant. Objectives: Review studies about the comparative onset of action of Mirtazapine in different depressive populations and study design and with different statistical analysis and response criteria. Method: We review medical databases (MEDLINE), monographies and preliminary results of studies presented in posters not yet published in medical articles. We selected the studies that specified the onset of action of mirtazapine in comparison with other antidepressant. We analysed the Design, Population involved, Methods of Evaluation of the evolution, Efficacy, Response and Remission Criteria and Type of Onset of Action