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Tolerability of a once-daily formulation of venlafaxine
244S
1997;42: 1S-297S
190-481
Comparison of the efficacy and safety of venlafaxlne and fluoxetine In GP patients with moderate to severe depression
I. Stevens. Royal Australian College of GPs, Research and Health Promotion Unit. St. Peters. Australia
ObJective: Compare the efficacy and safety venlafaxine and f1uoxetine In outpatients treated in a general practice setting with moderate to severe depression. Methods: This was a double-blind, randomized, multicenter study of the efficacy and safety 01 venlalaxine and lIuoxetine In patients attending their general practitioner In Australia. Outpatients satisfying DSM-IV criteria lor major depression with symptoms of depression lor at least 14 days, and with a baseline MADRS score 01 at least 20 were eligible. Following baseline evaluations, patients were assigned to treatment with venlalaxine 75 mglday or lIuoxetine 20 mglday. If clinically Indicated the doses could be increased to 150 mglday lor venlalaxine and 40 mglday for lIuoxetlne. Treatment was continued lor 12 weeks. The primary efficacy variables were the 12·week on-therapy total scores lrom the HAM-D, MADRS, and CGI severity scales, which were compared between treatment arms. An Intent·tOotreat analysis and a last observation carried forward method were used. Results: Baseline demographics and clinical characteristics will be pre• sented. Comparisons between groups lor the primary efficacy variables will be examined. The salety and tolerability prolile will be discussed lor each treatment group. Conclusion: These results support the efficacy and tolerability 01 ven• lafaxine lor the treatment 01 moderate to severe depression in a general practice setting and provide comparisons with Iluoxetine.
190-491
Once-dally extended release (XR) venlafaxlne versus paroxetlne in outpatients with major depression
E. Saflnas Ipr the Venlalaxlne XR 367 Study Group. Wyeth-Ayerst Research, Paris, France ObJective: Evaluate the efficacy and tolerability 01 onclHlaily venlalaxlne XR and paroxetine In outpatients with major depression. Methods: This was a randomized, double-blind, placebo-controlled com• parison of onclHlaily venlalaxine extended release (XR) and paroxetine. Outpatients with DSM-Iil-R major depression were randomly assigned to venlalaxlne XR 75 mg or 150 mg once daily, paroxetine 20 mg once daily or placebo lor a maximum 018 weeks. Results: Three hundred twenty-three patients were evaluated lor efficacy. Because 01 a high placebo response, there were no signilicant differences between active drugs and placebo. However, in pairwise comparisons, venlalaxine XR 75 mg was slgnillcantly superior (p < 0.05) to paroxetine on the HAM-D and MADRS at weeks 1, 2, 4, 6, and 8 and on the CGI severity scale at weeks 2, 4, 6, and 8. Venlafaxine XR 150 mg was signilicantly superior (p < 0.05) to paroxetine on the HAM-D at weeks 4, 6, and 8, on the MADRS at weeks 4 and 6, and on the CGI severity scale at weeks 4 and 6. The most common treatment-emergent adverse event with venlafaxlne XR and paroxetine was nausea. Discontinuations due to nausea were similar lor venlalaxine XR 75 mg (1%) and placebo (1%), and higher lorvenlafaxlne XR 150 mg (6%) and paroxetine (4%). Discontinuations overall were less with venlalaxlne XR 75 mg (20%) than lor paroxetine (35%). Conclusion: These results Indicate that onclHlaily venlalaxine XR 75 mg is more effective and well tolerated than paroxetine 20 mg daily lor treating major depression.
190-50
Poster session IV
BIOL. PSYCHIATRY
I Dose-response effects of once-daily extended release (XR) venlafaxlne In outpatients with major depression
E. Salinas lor the Venlalaxine XR Study Group. Wyeth-Ayerst Research, Paris, France ObJective: Demonstrate the dose-flexibility 01 onclH!aily venlafaxlne ex• tended release (XR) in palients with major depression. Methods: An analysis was conducted 01 two placebo-controlled, flex!· bllHlose studies and one fixed-dose study to determine the dose-response effects 01 venlalaxine XR. In one study, outpatients received venlalaxine XR 75 mg once daily, with the option to Increase the dosage to 150 mg daily alter 2 weeks il necessary. In a second study, outpatients received venlafaxine XR 75 mg; the dosage could be Increased to 150 mg dally and
further to 225 mg daily at 2 week Intervals II necessary. In the third study, outpatients received IIXed doses 01 venlalaxine XR 75 mg or 150 mg once daily. Results: In the two f1exibllHlose studies, the results Indicate that once• daily venlalaxine XR 75 mg is an effective dose lor most patients. For more difficult to treat patients, an increase In the dose 01 venlalaxine XR after 2 weeks improves the response. In the lixed-dose study, the tolerability with venlafaxine XR 75 mglday was superior to that with 150 mglday and supports the recommendation that therepy be initiated at a dosage of 75 mglday. Conclusion: These findings are consistent with data on venlafaxine Immediate release and support a dosage regimen 01 venlalaxine XR 75 mglday Initially, with an Increase in the dosage II necessary to Improve the response.
190-51 1 Tolerability of a once-dally formulation of venlafaxlne D. Hackett lor the Venlalaxlne XR Study Group. Wyeth-Ayerst Research, Paris, France ObJective: Evaluate the tolerability 01 onclH!aily venlalaxlne extended• release (XR) in the treatment 01 major depression. Methods: A pooled analysis was conducted 01 phase II and III clinical trials to determine the saletyltolerabllity prolile 01 onclHlaily venlafaxine XA. Venlalaxine XR was administered to 728 depressed patients over the dosage range of 75 to 225 mglday including 357 patients In placebo-controlled trials. Data on patients treated with venlafaxlne XR were compared with data from 2,897 patients treated with venlalaxlne immediate release (IR) and patients treated w~h paroxetine. Results: Discontinuations lor any reason (31% vs. 52%), lack 01 efficacy. or adverse effects were lower with venlafaxine XR than with venlalaxine IR. Venlalaxine XR was associated with signilicantly lewer discontinuatlons lor all reasons (p = 0.014) and lor lack 01 efficacy (p 0.001) compared with placebo. In the fixed dose comparison 01 venlafaxlne XR and paroxetine, venlafaxine XR 75 mg was associated with marginally signillcantly (p 0.054) lewer discontinuations than paroxetine. Over the total venlalaxine XA database, the incidence 01 common adverse events was consistently lower with venlalaxlne XR than with venlalaxine IR. Adaptation to nausea and somnolence occurred with venlalaxine XR. The Incidence 01 nausea with venlalaxine XR was highest (22%) during the first week 01 therapy, and then declined rapidly to an Incidence similar to that 01 placebo during the lourth week. Conclusion: These results Indicate onclH!ally venlafaxine XR may offer advantages In tolerability over the conventional venlalaxlne lormulation.
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190-521
Once-dally venlafaxlne extended release (XR) In outpatients with major depression
L Aguiar, A.T. Derivan lor the Venlalaxine XR 209 Study Group. Wyeth-Ayerst Research. PhiladelphIa, PennsylvanIa. USA ObJective: Evaluate the efficacy and salety 01 once-daily venlafaxine ex• tended release (XR) In outpatients with major depression. Methods: This was a randomized, double-blind, placebo-controlled evalu• ation 01 the efficacy and salety 01 venlalaxine XR In outpatients with major depression. Outpatients with DSM-III major depression were randomly as• signed to venlalaxine XR 75 mg once daily or placebo for up to 8 weeks. II the response was Inadequate alter 2 weeks, the dosage 01 venlalaxine XR could be Increased to 150 mg dally and to 225 mg daily alter another 2 weeks. One hundred ninety-one patients were evaluated lor efficacy, 91 venialaxine XR·treated patients and 100 placebo-treated patients. Results: Venlalaxlne XR was superior (p < 0.05) to placebo beginning at week 4 on the HAM-D and MADRS, week 2 on the CGI severity scale, and week 3 on the HAM-D depressed mood Item and continuing through week 8. The most common adverse events with venlalaxine XR were nausea, insomnia and somnolence. The Incidence 01 nausea was highest during the first week, decreased by 50% during the second week, and was comparable to that 01 placebo from week 3 onward. Conclusions: Venlalaxlne XR administered In once daily doses 01 75 to 225 mg Is effective and well tolerated lor the treatment of major depression.
1997;42: 1S-297S
190-481
Comparison of the efficacy and safety of venlafaxlne and fluoxetine In GP patients with moderate to severe depression
I. Stevens. Royal Australian College of GPs, Research and Health Promotion Unit. St. Peters. Australia
ObJective: Compare the efficacy and safety venlafaxine and f1uoxetine In outpatients treated in a general practice setting with moderate to severe depression. Methods: This was a double-blind, randomized, multicenter study of the efficacy and safety 01 venlalaxine and lIuoxetine In patients attending their general practitioner In Australia. Outpatients satisfying DSM-IV criteria lor major depression with symptoms of depression lor at least 14 days, and with a baseline MADRS score 01 at least 20 were eligible. Following baseline evaluations, patients were assigned to treatment with venlalaxine 75 mglday or lIuoxetine 20 mglday. If clinically Indicated the doses could be increased to 150 mglday lor venlalaxine and 40 mglday for lIuoxetlne. Treatment was continued lor 12 weeks. The primary efficacy variables were the 12·week on-therapy total scores lrom the HAM-D, MADRS, and CGI severity scales, which were compared between treatment arms. An Intent·tOotreat analysis and a last observation carried forward method were used. Results: Baseline demographics and clinical characteristics will be pre• sented. Comparisons between groups lor the primary efficacy variables will be examined. The salety and tolerability prolile will be discussed lor each treatment group. Conclusion: These results support the efficacy and tolerability 01 ven• lafaxine lor the treatment 01 moderate to severe depression in a general practice setting and provide comparisons with Iluoxetine.
190-491
Once-dally extended release (XR) venlafaxlne versus paroxetlne in outpatients with major depression
E. Saflnas Ipr the Venlalaxlne XR 367 Study Group. Wyeth-Ayerst Research, Paris, France ObJective: Evaluate the efficacy and tolerability 01 onclHlaily venlalaxlne XR and paroxetine In outpatients with major depression. Methods: This was a randomized, double-blind, placebo-controlled com• parison of onclHlaily venlalaxine extended release (XR) and paroxetine. Outpatients with DSM-Iil-R major depression were randomly assigned to venlalaxlne XR 75 mg or 150 mg once daily, paroxetine 20 mg once daily or placebo lor a maximum 018 weeks. Results: Three hundred twenty-three patients were evaluated lor efficacy. Because 01 a high placebo response, there were no signilicant differences between active drugs and placebo. However, in pairwise comparisons, venlalaxine XR 75 mg was slgnillcantly superior (p < 0.05) to paroxetine on the HAM-D and MADRS at weeks 1, 2, 4, 6, and 8 and on the CGI severity scale at weeks 2, 4, 6, and 8. Venlafaxine XR 150 mg was signilicantly superior (p < 0.05) to paroxetine on the HAM-D at weeks 4, 6, and 8, on the MADRS at weeks 4 and 6, and on the CGI severity scale at weeks 4 and 6. The most common treatment-emergent adverse event with venlafaxlne XR and paroxetine was nausea. Discontinuations due to nausea were similar lor venlalaxine XR 75 mg (1%) and placebo (1%), and higher lorvenlafaxlne XR 150 mg (6%) and paroxetine (4%). Discontinuations overall were less with venlalaxlne XR 75 mg (20%) than lor paroxetine (35%). Conclusion: These results Indicate that onclHlaily venlalaxine XR 75 mg is more effective and well tolerated than paroxetine 20 mg daily lor treating major depression.
190-50
Poster session IV
BIOL. PSYCHIATRY
I Dose-response effects of once-daily extended release (XR) venlafaxlne In outpatients with major depression
E. Salinas lor the Venlalaxine XR Study Group. Wyeth-Ayerst Research, Paris, France ObJective: Demonstrate the dose-flexibility 01 onclH!aily venlafaxlne ex• tended release (XR) in palients with major depression. Methods: An analysis was conducted 01 two placebo-controlled, flex!· bllHlose studies and one fixed-dose study to determine the dose-response effects 01 venlalaxine XR. In one study, outpatients received venlalaxine XR 75 mg once daily, with the option to Increase the dosage to 150 mg daily alter 2 weeks il necessary. In a second study, outpatients received venlafaxine XR 75 mg; the dosage could be Increased to 150 mg dally and
further to 225 mg daily at 2 week Intervals II necessary. In the third study, outpatients received IIXed doses 01 venlalaxine XR 75 mg or 150 mg once daily. Results: In the two f1exibllHlose studies, the results Indicate that once• daily venlalaxine XR 75 mg is an effective dose lor most patients. For more difficult to treat patients, an increase In the dose 01 venlalaxine XR after 2 weeks improves the response. In the lixed-dose study, the tolerability with venlafaxine XR 75 mglday was superior to that with 150 mglday and supports the recommendation that therepy be initiated at a dosage of 75 mglday. Conclusion: These findings are consistent with data on venlafaxine Immediate release and support a dosage regimen 01 venlalaxine XR 75 mglday Initially, with an Increase in the dosage II necessary to Improve the response.
190-51 1 Tolerability of a once-dally formulation of venlafaxlne D. Hackett lor the Venlalaxlne XR Study Group. Wyeth-Ayerst Research, Paris, France ObJective: Evaluate the tolerability 01 onclH!aily venlalaxlne extended• release (XR) in the treatment 01 major depression. Methods: A pooled analysis was conducted 01 phase II and III clinical trials to determine the saletyltolerabllity prolile 01 onclHlaily venlafaxine XA. Venlalaxine XR was administered to 728 depressed patients over the dosage range of 75 to 225 mglday including 357 patients In placebo-controlled trials. Data on patients treated with venlafaxlne XR were compared with data from 2,897 patients treated with venlalaxlne immediate release (IR) and patients treated w~h paroxetine. Results: Discontinuations lor any reason (31% vs. 52%), lack 01 efficacy. or adverse effects were lower with venlafaxine XR than with venlalaxine IR. Venlalaxine XR was associated with signilicantly lewer discontinuatlons lor all reasons (p = 0.014) and lor lack 01 efficacy (p 0.001) compared with placebo. In the fixed dose comparison 01 venlafaxlne XR and paroxetine, venlafaxine XR 75 mg was associated with marginally signillcantly (p 0.054) lewer discontinuations than paroxetine. Over the total venlalaxine XA database, the incidence 01 common adverse events was consistently lower with venlalaxlne XR than with venlalaxine IR. Adaptation to nausea and somnolence occurred with venlalaxine XR. The Incidence 01 nausea with venlalaxine XR was highest (22%) during the first week 01 therapy, and then declined rapidly to an Incidence similar to that 01 placebo during the lourth week. Conclusion: These results Indicate onclH!ally venlafaxine XR may offer advantages In tolerability over the conventional venlalaxlne lormulation.
=
=
190-521
Once-dally venlafaxlne extended release (XR) In outpatients with major depression
L Aguiar, A.T. Derivan lor the Venlalaxine XR 209 Study Group. Wyeth-Ayerst Research. PhiladelphIa, PennsylvanIa. USA ObJective: Evaluate the efficacy and salety 01 once-daily venlafaxine ex• tended release (XR) In outpatients with major depression. Methods: This was a randomized, double-blind, placebo-controlled evalu• ation 01 the efficacy and salety 01 venlalaxine XR In outpatients with major depression. Outpatients with DSM-III major depression were randomly as• signed to venlalaxine XR 75 mg once daily or placebo for up to 8 weeks. II the response was Inadequate alter 2 weeks, the dosage 01 venlalaxine XR could be Increased to 150 mg dally and to 225 mg daily alter another 2 weeks. One hundred ninety-one patients were evaluated lor efficacy, 91 venialaxine XR·treated patients and 100 placebo-treated patients. Results: Venlalaxlne XR was superior (p < 0.05) to placebo beginning at week 4 on the HAM-D and MADRS, week 2 on the CGI severity scale, and week 3 on the HAM-D depressed mood Item and continuing through week 8. The most common adverse events with venlalaxine XR were nausea, insomnia and somnolence. The Incidence 01 nausea was highest during the first week, decreased by 50% during the second week, and was comparable to that 01 placebo from week 3 onward. Conclusions: Venlalaxlne XR administered In once daily doses 01 75 to 225 mg Is effective and well tolerated lor the treatment of major depression.