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Survival analysis (Kaplan-Meier; Stassen) and pattern analysis to assess the onset of action of mirtazapine versus other new antidepressants
P.1. Affectiue disorders and antidepressants
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Early onset of action of mirtazapine versus other new-generation antidepressants for patients in remission
I. Van Hensbeek, H. Van Oers, A.J. Schutte. N. V. Organon, Oss,
The Netherlands New-generation antidepressants have favorable risk/benefit characteristics that result in remission of depressive symptoms. A successful antidepressant treatment should be measured by both remission and by onset of response. The clinical use of antidepressants is seriously impaired by the delay in the onset of their therapeutic action. This study evaluated the speed of onset of mirtazapine compared to the other newer antidepressants in a subset of those patients who were defined as HAMD-17 or MADRS remitter after 6 weeks of treatment. The efficacy data of six double-blind, randomized, parallel group trials comparing mirtazapine with SSRIs (fluoxetine, paroxetine, citalopram or setraline) or SNRI (venlafaxine) were pooled and reanalyzed. Remission was defined as total score on HAMD-17<8 or MADRS<13. Comparing mirtazapine and SSRIs, 501 subjects (mirtazapine 263, SSRIs 238) were considered 'remitter' at week 6. Comparing mirtazapine and SSRI/SNRI, 548 subjects (mirtazapine 289, SSRI/SNRI 259) fulfilled the criterion of remitter at week 6. Changes from baseline on total score and responder rates (at least 50% reduction in HAMD17 or MADRS total score) were assessed for these patients. The mean HAMD/MADRS total score in the mirtazapine treatment group decreased from baseline faster than in the SSRIs treatment group at all assessments. This difference reached significance at week 1, 2 and 4 (p<0.05). Including data from the venlafaxine study gave the same results. The difference in responder rate between the mirtazapine and SSRIs was in favor of mirtazapine at all assessments. The difference was statistically significant at weeks 2 and 4. Including the venlafaxine data showed significance at weeks 1, 2 and 4. These results provide evidence that in patients who achieved remission, mirtazapine showed a faster onset of therapeutic action.
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Mirtazapine versus other new-generation antidepressants: Pooled analysis on the onset of action
H. Van Oers, A.J. Schutte, I. Van Hensbeek. N.V. Organon, Oss,
The Netherlands Efficacy data on six double-blind, randomized, parallel group trials with mirtazapine were included in this pooled analysis. Data on mirtazapine were pooled (619 patients) and data on the SSRIs fluoxetine, paroxetine, citalopram and sertraline (607 patients) were pooled. In addition, analyses were done with addition of the SNRI venlafaxine to the SSRI group (n=682) versus mirtazapine (n=696). All studies were comparable in design. Data from assessments which occurred in all trials were used, i.e. week 1, 2, 4 and 6. Changes from baseline (HAMD-17) and responder rates (at least 50% reduction in HAMD-17 or MADRS) were assessed as well as the proportion of remitters (HAMD-17<8 or MADRS<13). Furthermore, the antidepressant response at week 1 on HAMD item 1 (depressed mood)(item 1=0) and the Bech Depression Factor (at least 50% reduction) were evaluated. Statistical analyses were performed on the basis of the IntentionTo-Treat group(s). The results were similar with and without inclusion of the SNRI. Decrease from baseline was significantly
S187
greater with mirtazapine at all assessment points (p<0.05). The proportion of responders as well as the proportion of remitters was higher on mirtazapine than the other "newer" antidepressants. The differences achieved significance for the responders at weeks 1, 2 and 4 and for the remitters at weeks 2 and 4 (p<0.05). Looking at HAMD item 1 and the Bech Depression Factor at week 1, a significant difference in favor of mirtazapine was seen. In conclusion, these results provide evidence for mirtazapine to have a faster onset of therapeutic effect compared to the other new generation antidepressants.
•
Survival analysis (Kaplan-Meier; Stassen) and pattern analysis to assess the onset of action of mirtazapine versus other new antidepressants
A.J. Schutte, H. Van Oers, I. Van Hensbeek. N.V. Organon, Oss,
The Netherlands A limitation of all antidepressants is the delay in onset of effect. This study evaluated the speed of onset of mirtazapine compared to the newer antidepressants using the widely accepted survival analytical approach and the concept of persistent response described as part of pattern analysis. The efficacy data of six double-blind, randomized, parallel group trials comparing mirtazapine with SSRIs (fluoxetine, paroxetine, citalopram or setraline) or SNRI (venlafaxine) were pooled in this analysis to determine if 'time to first response' (Kaplan-Meier), 'time to sustained response' (Stassen) and onset of persistent response could be detected earlier with mirtazapine. Response, defined as >50% reduction in HAMD-17 or MADRS, was determined according to the KaplanMeier method. Patients were judged as persistent responder if they achieved a 50% response on the HAMD/MADRS within 14 days without subsequent deterioration. The data showed no differences in result with or without the inclusion of the SNRI. There was a significant advantage for mirtazapine in the overall survival function. A highly statistically significant difference in 'time to first response' was found in favor of mirtazapine (p<0.001). The same was found for the 'time to first sustained response' (p<0.001) indicating a faster onset of action with mirtazapine. In the patteren analysis the proportion of patients with onset of a persistent response with mirtazapine was 27.4% (113/413), whereas for all the SSRIs, it was 17.8% (74/416) [p=0.001]. With the inclusion of venlafaxine it was 28.7% (137/477) for mirtazapine vs. 18.9% (89/472) for the SSRI/SNRI group (p<0.001). These highly consistent findings support the hypothesis that not only is the onset of a therapeutic response faster, but also that the time to get a sustained response is shorter with mirtazapine than with treatment of the other new antidepressants.
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Comparison of MMPI-2 profiles of the first degree relatives of bipolar patients and normal controls
A. Sutcu Yildirim 1, E. Kabakci 2, A. Ulusahin 2 *. IPrivate Practice, Bartin, Turkey," 2Hacettepe University, Faculty of Medicine, Department of Psychiatry, Ankara, Turkey Background: Since Kraepelin the relation of temperament and affective disorders have been emphasized. Clinical genetics research indicates that temperament and major affective disorders
•
Early onset of action of mirtazapine versus other new-generation antidepressants for patients in remission
I. Van Hensbeek, H. Van Oers, A.J. Schutte. N. V. Organon, Oss,
The Netherlands New-generation antidepressants have favorable risk/benefit characteristics that result in remission of depressive symptoms. A successful antidepressant treatment should be measured by both remission and by onset of response. The clinical use of antidepressants is seriously impaired by the delay in the onset of their therapeutic action. This study evaluated the speed of onset of mirtazapine compared to the other newer antidepressants in a subset of those patients who were defined as HAMD-17 or MADRS remitter after 6 weeks of treatment. The efficacy data of six double-blind, randomized, parallel group trials comparing mirtazapine with SSRIs (fluoxetine, paroxetine, citalopram or setraline) or SNRI (venlafaxine) were pooled and reanalyzed. Remission was defined as total score on HAMD-17<8 or MADRS<13. Comparing mirtazapine and SSRIs, 501 subjects (mirtazapine 263, SSRIs 238) were considered 'remitter' at week 6. Comparing mirtazapine and SSRI/SNRI, 548 subjects (mirtazapine 289, SSRI/SNRI 259) fulfilled the criterion of remitter at week 6. Changes from baseline on total score and responder rates (at least 50% reduction in HAMD17 or MADRS total score) were assessed for these patients. The mean HAMD/MADRS total score in the mirtazapine treatment group decreased from baseline faster than in the SSRIs treatment group at all assessments. This difference reached significance at week 1, 2 and 4 (p<0.05). Including data from the venlafaxine study gave the same results. The difference in responder rate between the mirtazapine and SSRIs was in favor of mirtazapine at all assessments. The difference was statistically significant at weeks 2 and 4. Including the venlafaxine data showed significance at weeks 1, 2 and 4. These results provide evidence that in patients who achieved remission, mirtazapine showed a faster onset of therapeutic action.
•
Mirtazapine versus other new-generation antidepressants: Pooled analysis on the onset of action
H. Van Oers, A.J. Schutte, I. Van Hensbeek. N.V. Organon, Oss,
The Netherlands Efficacy data on six double-blind, randomized, parallel group trials with mirtazapine were included in this pooled analysis. Data on mirtazapine were pooled (619 patients) and data on the SSRIs fluoxetine, paroxetine, citalopram and sertraline (607 patients) were pooled. In addition, analyses were done with addition of the SNRI venlafaxine to the SSRI group (n=682) versus mirtazapine (n=696). All studies were comparable in design. Data from assessments which occurred in all trials were used, i.e. week 1, 2, 4 and 6. Changes from baseline (HAMD-17) and responder rates (at least 50% reduction in HAMD-17 or MADRS) were assessed as well as the proportion of remitters (HAMD-17<8 or MADRS<13). Furthermore, the antidepressant response at week 1 on HAMD item 1 (depressed mood)(item 1=0) and the Bech Depression Factor (at least 50% reduction) were evaluated. Statistical analyses were performed on the basis of the IntentionTo-Treat group(s). The results were similar with and without inclusion of the SNRI. Decrease from baseline was significantly
S187
greater with mirtazapine at all assessment points (p<0.05). The proportion of responders as well as the proportion of remitters was higher on mirtazapine than the other "newer" antidepressants. The differences achieved significance for the responders at weeks 1, 2 and 4 and for the remitters at weeks 2 and 4 (p<0.05). Looking at HAMD item 1 and the Bech Depression Factor at week 1, a significant difference in favor of mirtazapine was seen. In conclusion, these results provide evidence for mirtazapine to have a faster onset of therapeutic effect compared to the other new generation antidepressants.
•
Survival analysis (Kaplan-Meier; Stassen) and pattern analysis to assess the onset of action of mirtazapine versus other new antidepressants
A.J. Schutte, H. Van Oers, I. Van Hensbeek. N.V. Organon, Oss,
The Netherlands A limitation of all antidepressants is the delay in onset of effect. This study evaluated the speed of onset of mirtazapine compared to the newer antidepressants using the widely accepted survival analytical approach and the concept of persistent response described as part of pattern analysis. The efficacy data of six double-blind, randomized, parallel group trials comparing mirtazapine with SSRIs (fluoxetine, paroxetine, citalopram or setraline) or SNRI (venlafaxine) were pooled in this analysis to determine if 'time to first response' (Kaplan-Meier), 'time to sustained response' (Stassen) and onset of persistent response could be detected earlier with mirtazapine. Response, defined as >50% reduction in HAMD-17 or MADRS, was determined according to the KaplanMeier method. Patients were judged as persistent responder if they achieved a 50% response on the HAMD/MADRS within 14 days without subsequent deterioration. The data showed no differences in result with or without the inclusion of the SNRI. There was a significant advantage for mirtazapine in the overall survival function. A highly statistically significant difference in 'time to first response' was found in favor of mirtazapine (p<0.001). The same was found for the 'time to first sustained response' (p<0.001) indicating a faster onset of action with mirtazapine. In the patteren analysis the proportion of patients with onset of a persistent response with mirtazapine was 27.4% (113/413), whereas for all the SSRIs, it was 17.8% (74/416) [p=0.001]. With the inclusion of venlafaxine it was 28.7% (137/477) for mirtazapine vs. 18.9% (89/472) for the SSRI/SNRI group (p<0.001). These highly consistent findings support the hypothesis that not only is the onset of a therapeutic response faster, but also that the time to get a sustained response is shorter with mirtazapine than with treatment of the other new antidepressants.
•
Comparison of MMPI-2 profiles of the first degree relatives of bipolar patients and normal controls
A. Sutcu Yildirim 1, E. Kabakci 2, A. Ulusahin 2 *. IPrivate Practice, Bartin, Turkey," 2Hacettepe University, Faculty of Medicine, Department of Psychiatry, Ankara, Turkey Background: Since Kraepelin the relation of temperament and affective disorders have been emphasized. Clinical genetics research indicates that temperament and major affective disorders