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Mirtazapine vs SSRIs: Onset of therapeutic effect using a survival analysis approach (Kaplan-Meier analysis)
S186
Rl. Affective disorders and antidepressants
after the tirst injection. Escape failures during avoidance training were recorded and compared to vehicle control by ANOVA. Results: DRL. Following vehicle administration, pigeons earned an average of 1.7-3.5 reinforcers. Amitriptyline (3 m&g), fluoxetine (10 mgikg) and AR-A2XX (1 mg/kg) evoked roughly 4fold increases in the number of reinforcers earned, consistent with antidepressant activity. All compounds did so without altering the number of responses emitted, indicating specificity of drug action. In guinea pigs, fluoxetine (10 mgikg) desipramine (10 mg/kg) and AR-A2XX (30 m&g) produced increases in reinforcers earned. RDD. In guinea pigs, amitriptyline (5.6 mgkg), fluoxetine (10 mg/kg) and AR-A2XX (0.3 mg/kg) produced increases in mean response duration, consistent with antidepressant action. Both fluoxetine and AR-A2XX did so in a manner suggesting specificity of drug action. Learned Helplessness. And average of 16.8 & 7 escape failures were noted in the vehicle control group. AR-A2XX (1 mg/kg) significantly reduced escape failures, as did imipramine (ANOVA, F = 4.29, P < 0.002, Dunnett’s p < 0.05). AR-A2XX (0.3 mgkg) tended toward efficacy (P = 0.06) whereas 5 mg/kg AR-AZXX was without effect on escape failures. Conclusion: These data agree with the suggestion that antagonists at the 5-HTlB receptor have a preclinical profile that is consistent with antidepressant activity.
Method: Data from four double-blind, controlled studies of mirtazapine vs. fluoxetine (2), paroxetine or citalopram in depressed patients were analyzed with regard to efficacy parameters and inter-treatment differences in the onset of anti-depressive action. Response, defined as time to first 2 50% reduction in HAMD-17 or MADRS total score, was determined according to the Kaplan-Meier method. Remission, defined as time to first 17 total score on HAMD-17 or < 12 total score on the MADRS was also determined according this method. Results: In the combined analysis of mirtazapine versus the 4 SSRI studies, there was a significant advantage for mirtazapine in the overall survival function (p = 0.0104). The largest difference was observed during the first two weeks of treatment. The survival analysis on the time to first remission on total HAMD or MADRS score reached also significance (p = 0.0354). The statistically significant differences between the response functions of mirtazapine and the SSRI group was found indicative for a faster onset of action with mirtazapine. Conclusion: The highly consistent findings in the studies support the hypothesis that the time to get a response is shorter with mirtazapine than with SSRI treatment.
Ip.1.010)
Ip.1.0081
Mirtazapine’s onset of action compared with SSRls: Response and remission rates
A naturalistic study of mirtaxapine in depressed patients with comorbidities
D. Dieterle’, H. Van Oers*, A.J. Schutte**. ‘Organon GmbH, 85764 OberschleiJheim, Germany; ‘N. K Organon, Oss, The Netherlands
H.J.J. Van Oers, A.J. Schutte. N r Organon, Oss, The Netherlands Objective: A pooled analysis was performed to compare the efficacy of mirtazapine with SSRIs Method: Data from four double-blind controlled studies of mirtazapine vs. fluoxetine (2), paroxetine or citalopram in depressed patients were pooled and reanalyzed. Data from the fluoxetine and the paroxetine studies (using HAMD-17) were combined (665 patients) and data from the fluoxetine with the citalopram study (using MADRS) (561 patients). Changes from baseline and responder rates (250% reduction in HAMD-17 or MADRS) were assessed, as well as the proportion of remitters (HAMD 5 7 or MADRS < 12). Results: Decrease from baseline was greater with mirtazapine, reaching significance on the HAMD-17 at weeks 1, 2, 4, 6 and endpoint and on the MADRS at weeks 1,2 and 4. The proportion of responders as well as the proportion of remitters was higher on mirtazapine than SSRIs. The differences achieved significance for the responders at weeks 1, 2, 4 and 6 and for the remitters at weeks 2 and 4. Conclusion: These results provide strong evidence that mirtazapine has a faster onset of antidepressant effect compared to the SSRIs.
IF?I.0091
Mirtaxapine VI SSRls: Onset of therapeutic effect using a survival analysis approach (Kaplan-Meier analysis)
A.J. Schutte, H.J.J. Van Oers. N. r Organon, Oss, The Netherlands Objective: To compare the ‘time to fhst response’ between mirtazapine and various SSRIs, using the widely accepted survival analytical approach (Kaplan-Meier).
Objective: To assess the efficacy and tolerability of mirtazapine in patients with comorbidities in everyday clinical practice in Germany. Method: A total of 21,891 depressed patients were treated with mirtazapine for six weeks. The patients were divided in different groups on the basis of comorbidities and reanalyzed (i.e. hypertension, diabetes mellitus, heart insufficiency, disturbances in heart rhythm, myocard infarct, angina pectoris, etc.). Clinical efficacy and tolerability were both rated by the physicians and the patients. Results: ‘Very good’ or ‘good’ efficacy was seen in a vast majority (80%) in these groups of patients by the treating physicians, while patients rated rnirtazapine’s efficacy ‘very good’ or ‘good’ in about 75% of the cases. The treating physicians rated tolerability ‘very good’ or ‘good’ in 95% of the patients and again the patients rated a little lower (90%). Conclusion: These results show that mirtazapine is a very efficacious and well-tolerated antidepressant in patients with comorbidities. m
Mirtazapine has similar short- and long-term efficacy compared to venlafaxine
E.J.A.M. Van Hensbeek, H.J.J. Van Oers, A.J. Schutte. N.I! Organon, Oss, The Netherlands Objective: To compare the onset of antidepressant activity and the efficacy and tolerability of two dual-acting antidepressants, mirtazapine and venlafaxine, in the long-term treatment of severely depressed patients with melancholia. Method: This was a multicenter, randomized, double blind 8week study with a 16-week extension phase. Patients with DSMIV Major Depressive Disorder with melancholic features and
Rl. Affective disorders and antidepressants
after the tirst injection. Escape failures during avoidance training were recorded and compared to vehicle control by ANOVA. Results: DRL. Following vehicle administration, pigeons earned an average of 1.7-3.5 reinforcers. Amitriptyline (3 m&g), fluoxetine (10 mgikg) and AR-A2XX (1 mg/kg) evoked roughly 4fold increases in the number of reinforcers earned, consistent with antidepressant activity. All compounds did so without altering the number of responses emitted, indicating specificity of drug action. In guinea pigs, fluoxetine (10 mgikg) desipramine (10 mg/kg) and AR-A2XX (30 m&g) produced increases in reinforcers earned. RDD. In guinea pigs, amitriptyline (5.6 mgkg), fluoxetine (10 mg/kg) and AR-A2XX (0.3 mg/kg) produced increases in mean response duration, consistent with antidepressant action. Both fluoxetine and AR-A2XX did so in a manner suggesting specificity of drug action. Learned Helplessness. And average of 16.8 & 7 escape failures were noted in the vehicle control group. AR-A2XX (1 mg/kg) significantly reduced escape failures, as did imipramine (ANOVA, F = 4.29, P < 0.002, Dunnett’s p < 0.05). AR-A2XX (0.3 mgkg) tended toward efficacy (P = 0.06) whereas 5 mg/kg AR-AZXX was without effect on escape failures. Conclusion: These data agree with the suggestion that antagonists at the 5-HTlB receptor have a preclinical profile that is consistent with antidepressant activity.
Method: Data from four double-blind, controlled studies of mirtazapine vs. fluoxetine (2), paroxetine or citalopram in depressed patients were analyzed with regard to efficacy parameters and inter-treatment differences in the onset of anti-depressive action. Response, defined as time to first 2 50% reduction in HAMD-17 or MADRS total score, was determined according to the Kaplan-Meier method. Remission, defined as time to first 17 total score on HAMD-17 or < 12 total score on the MADRS was also determined according this method. Results: In the combined analysis of mirtazapine versus the 4 SSRI studies, there was a significant advantage for mirtazapine in the overall survival function (p = 0.0104). The largest difference was observed during the first two weeks of treatment. The survival analysis on the time to first remission on total HAMD or MADRS score reached also significance (p = 0.0354). The statistically significant differences between the response functions of mirtazapine and the SSRI group was found indicative for a faster onset of action with mirtazapine. Conclusion: The highly consistent findings in the studies support the hypothesis that the time to get a response is shorter with mirtazapine than with SSRI treatment.
Ip.1.010)
Ip.1.0081
Mirtazapine’s onset of action compared with SSRls: Response and remission rates
A naturalistic study of mirtaxapine in depressed patients with comorbidities
D. Dieterle’, H. Van Oers*, A.J. Schutte**. ‘Organon GmbH, 85764 OberschleiJheim, Germany; ‘N. K Organon, Oss, The Netherlands
H.J.J. Van Oers, A.J. Schutte. N r Organon, Oss, The Netherlands Objective: A pooled analysis was performed to compare the efficacy of mirtazapine with SSRIs Method: Data from four double-blind controlled studies of mirtazapine vs. fluoxetine (2), paroxetine or citalopram in depressed patients were pooled and reanalyzed. Data from the fluoxetine and the paroxetine studies (using HAMD-17) were combined (665 patients) and data from the fluoxetine with the citalopram study (using MADRS) (561 patients). Changes from baseline and responder rates (250% reduction in HAMD-17 or MADRS) were assessed, as well as the proportion of remitters (HAMD 5 7 or MADRS < 12). Results: Decrease from baseline was greater with mirtazapine, reaching significance on the HAMD-17 at weeks 1, 2, 4, 6 and endpoint and on the MADRS at weeks 1,2 and 4. The proportion of responders as well as the proportion of remitters was higher on mirtazapine than SSRIs. The differences achieved significance for the responders at weeks 1, 2, 4 and 6 and for the remitters at weeks 2 and 4. Conclusion: These results provide strong evidence that mirtazapine has a faster onset of antidepressant effect compared to the SSRIs.
IF?I.0091
Mirtaxapine VI SSRls: Onset of therapeutic effect using a survival analysis approach (Kaplan-Meier analysis)
A.J. Schutte, H.J.J. Van Oers. N. r Organon, Oss, The Netherlands Objective: To compare the ‘time to fhst response’ between mirtazapine and various SSRIs, using the widely accepted survival analytical approach (Kaplan-Meier).
Objective: To assess the efficacy and tolerability of mirtazapine in patients with comorbidities in everyday clinical practice in Germany. Method: A total of 21,891 depressed patients were treated with mirtazapine for six weeks. The patients were divided in different groups on the basis of comorbidities and reanalyzed (i.e. hypertension, diabetes mellitus, heart insufficiency, disturbances in heart rhythm, myocard infarct, angina pectoris, etc.). Clinical efficacy and tolerability were both rated by the physicians and the patients. Results: ‘Very good’ or ‘good’ efficacy was seen in a vast majority (80%) in these groups of patients by the treating physicians, while patients rated rnirtazapine’s efficacy ‘very good’ or ‘good’ in about 75% of the cases. The treating physicians rated tolerability ‘very good’ or ‘good’ in 95% of the patients and again the patients rated a little lower (90%). Conclusion: These results show that mirtazapine is a very efficacious and well-tolerated antidepressant in patients with comorbidities. m
Mirtazapine has similar short- and long-term efficacy compared to venlafaxine
E.J.A.M. Van Hensbeek, H.J.J. Van Oers, A.J. Schutte. N.I! Organon, Oss, The Netherlands Objective: To compare the onset of antidepressant activity and the efficacy and tolerability of two dual-acting antidepressants, mirtazapine and venlafaxine, in the long-term treatment of severely depressed patients with melancholia. Method: This was a multicenter, randomized, double blind 8week study with a 16-week extension phase. Patients with DSMIV Major Depressive Disorder with melancholic features and