- Email: [email protected]
Efficacy and safety of venlafaxine extended release in children and adolescents with generalised anxiety disorder
$358
•
I73. Anxiety disorders and anxiolytics Efficacy and safety of venlafaxine extended release in children and adolescents with generalised anxiety disorder
N.R. Kunz 1, A. Khan 2, L.W. Lamm 3, E. Nicolacopoulos4, L. Jenkins 5. 1Wyeth Research, Philadelpha, PA, U.S.A.,"
2Northwest Clinical Research Center, Bellvue, WA, U.S.A.; 3 Wyeth Research, Clinical Data Management, Philadelphia, PA, U.S.A.; 4Wyeth Research, Clinical Research, Philadelphia, PA, U.S.A., 5 Wyeth Research, Clinical Biostatistics, Philadelphia, PA, U.S.A. Objective: Venlafaxine extended release (XR), a selective serotonin and norepinephrine reuptake inhibitor, is an effective treatment for adults with depression or generalised anxiety disorder (GAD), but no data are available on the safety and efficacy of venlafaxine XR in paediatric patients with GAD. This abstract presents the combined results of 2 identical 8-week, multicentre, double-blind, placebo-controlled, flexible-dose studies, which evaluated the efficacy, safety, and tolerability of venlafaxine XR as a treatment for GAD in children (6-11 years old) and adolescents (12-17 years old). Methods: A total of 320 paediatric patients (175 children, 145 adolescents) were randomly assigned to receive venlafaxine XR (n=157) or placebo (n=163). The study medication was dosed by weight. The primary efficacy variable was the Columbia KIDDIESADS GAD total score for 9 delineated items (range of possible scores 9-55, with higher scores indicating greater anxiety and/or impairment) and the primary endpoint was the final on-therapy evaluation. Secondary efficacy variables were the C-KIDDIESADS GAD (complete) total score and the individual Severity (5 delineated items) and Impairment (4 delineated items) component scores of the primary efficacy variable, the Paediatric Anxiety Rating Scale (PARS) total score, the Hamilton Rating Scale for Anxiety (HAM-A) total score, the SCARED Parent and Child Forms total score, and the Clinical Global Impressions (CGI) Severity and Improvement scores. Results: Children and adolescents in the venlafaxine XR group had an adjusted mean (+SE) decrease of 17.4(:tz0.80) points on the primary efficacy variable, as compared to a 12.7(5=0.84) point decrease for patients in the placebo group (p<0.001). On the secondary measures, similar results were obtained. On the CGI Improvement scale, 106 of 154 patients in the venlafaxine XR group (69%) responded to treatment, as indicated by a score <3, as compared with 77 of 159 patients in the placebo group (48%, p= 0.004). Eight (8) of 157 patients in the venlafaxine XR group (5%) discontinued from the study because of adverse events, as compared with 9 of 163 placebo patients (5%). The most common treatment-related adverse events (=5% and incidence twice placebo) were asthenia, anorexia, pain and somnolence. Conclusion: Venlafaxine XR is an effective and well-tolerated treatment for children and adolescents with GAD.
•
Treating social anxiety disorder with venlafaxine extended release
R.M. Mangano. Wyeth Research, Collegeville, PA, U.S.A. Background: Social anxiety disorder (SAD) is characterized by the experience of anxiety in a social setting, such as speaking in public or attending a party. The fear of being judged or
criticized during public interaction causes avoidance of large gatherings and can negatively impact both personal and professional achievements. Although the neurotransmitters serotonin and noradrenaline have been implicated in SAD, to date research has only been conducted on antidepressants that selectively inhibit the reuptake of serotonin. Objective: The objective of this combined data analysis was to determine the anxiolytic efficacy of the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine extended release (VEN XR) in the treatment of generalized SAD. Method: In this analysis, data from 2 multicenter, doubleblind, placebo-controlled, parallel-group studies of outpatients with generalized SAD were pooled to evaluate efficacy in a lastobservation-carried-forward (LOCF) analysis. Both studies were preceded by a placebo lead-in period of 7+/-3 days, followed by a 12-week randomized, flexible-dose study of VEN XR (75-225 mg/day; n=259) or placebo (n=273), and concluded with a 14day optional taper period. The primary efficacy variable was the total score on the Liebowitz Social Anxiety Scale (LSAS). The secondary efficacy variables included the subscales of the LSAS, including performance, social interaction, avoidance factors, and some fear factors (eg, public speaking), in addition to the fear, avoidance, and physiologic factors of the Social Phobia Inventory (SPIN). Results: The pooled analysis indicated that the SNRI VEN XR was significantly better than placebo during weeks 3 to 12 (P=.007, week 3; P<=.001, weeks 4 to 12), based on LSAS total adjusted mean scores (LOCF Analysis) as follows:
Baseline Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 8 Week 10 Week 12
Placebo
Venlafaxine XR P
88.9 84.6 80.0 76.8 74.0 71.0 71.0 68.8 68.7 68.1
88.9 83.0 78.1 72.6 68.2 63.5 63.5 61.4 59.3 57.2
0.119 0.142 0.007 0.001 ~<0.001 ~<0.001 ~<0.001 ~<0.001 <~.001
Significant efficacy of VEN XR over placebo as early as week 3 was also demonstrated using the LSAS subscales. Similarly, early statistical separation favoring active treatment over placebo on efficacy parameters was noted on the fear, avoidance, and physiologic factors of the SPIN. Conclusions: In this analysis, the dual reuptake inhibitor VEN XR demonstrated significantly better anxiolytic activity than placebo in the short-term treatment of generalized SAD. This finding may lead to expanded options for the treatment of this disorder. Supported by funding from Wyeth Research.
References [1] Hackett, D. (2000) Venlafaxine XR in the treatment of anxiety. Acta Psychiatr Scand 102, 30-35. [2] L~pine, J.-P. and P~lissolo, A. (2000) Why take social anxiety disorder seriously? Depress Anxiety 11, 87-92. [3] Altamura, A.C., Pioli, R., Vitto, M., Mannu, E (1999):Venlafaxine in social phobia: a study in selective serotonin reuptake inhibitor nonresponders. Int Clin Psychopharmacol 14, 239-245.
•
I73. Anxiety disorders and anxiolytics Efficacy and safety of venlafaxine extended release in children and adolescents with generalised anxiety disorder
N.R. Kunz 1, A. Khan 2, L.W. Lamm 3, E. Nicolacopoulos4, L. Jenkins 5. 1Wyeth Research, Philadelpha, PA, U.S.A.,"
2Northwest Clinical Research Center, Bellvue, WA, U.S.A.; 3 Wyeth Research, Clinical Data Management, Philadelphia, PA, U.S.A.; 4Wyeth Research, Clinical Research, Philadelphia, PA, U.S.A., 5 Wyeth Research, Clinical Biostatistics, Philadelphia, PA, U.S.A. Objective: Venlafaxine extended release (XR), a selective serotonin and norepinephrine reuptake inhibitor, is an effective treatment for adults with depression or generalised anxiety disorder (GAD), but no data are available on the safety and efficacy of venlafaxine XR in paediatric patients with GAD. This abstract presents the combined results of 2 identical 8-week, multicentre, double-blind, placebo-controlled, flexible-dose studies, which evaluated the efficacy, safety, and tolerability of venlafaxine XR as a treatment for GAD in children (6-11 years old) and adolescents (12-17 years old). Methods: A total of 320 paediatric patients (175 children, 145 adolescents) were randomly assigned to receive venlafaxine XR (n=157) or placebo (n=163). The study medication was dosed by weight. The primary efficacy variable was the Columbia KIDDIESADS GAD total score for 9 delineated items (range of possible scores 9-55, with higher scores indicating greater anxiety and/or impairment) and the primary endpoint was the final on-therapy evaluation. Secondary efficacy variables were the C-KIDDIESADS GAD (complete) total score and the individual Severity (5 delineated items) and Impairment (4 delineated items) component scores of the primary efficacy variable, the Paediatric Anxiety Rating Scale (PARS) total score, the Hamilton Rating Scale for Anxiety (HAM-A) total score, the SCARED Parent and Child Forms total score, and the Clinical Global Impressions (CGI) Severity and Improvement scores. Results: Children and adolescents in the venlafaxine XR group had an adjusted mean (+SE) decrease of 17.4(:tz0.80) points on the primary efficacy variable, as compared to a 12.7(5=0.84) point decrease for patients in the placebo group (p<0.001). On the secondary measures, similar results were obtained. On the CGI Improvement scale, 106 of 154 patients in the venlafaxine XR group (69%) responded to treatment, as indicated by a score <3, as compared with 77 of 159 patients in the placebo group (48%, p= 0.004). Eight (8) of 157 patients in the venlafaxine XR group (5%) discontinued from the study because of adverse events, as compared with 9 of 163 placebo patients (5%). The most common treatment-related adverse events (=5% and incidence twice placebo) were asthenia, anorexia, pain and somnolence. Conclusion: Venlafaxine XR is an effective and well-tolerated treatment for children and adolescents with GAD.
•
Treating social anxiety disorder with venlafaxine extended release
R.M. Mangano. Wyeth Research, Collegeville, PA, U.S.A. Background: Social anxiety disorder (SAD) is characterized by the experience of anxiety in a social setting, such as speaking in public or attending a party. The fear of being judged or
criticized during public interaction causes avoidance of large gatherings and can negatively impact both personal and professional achievements. Although the neurotransmitters serotonin and noradrenaline have been implicated in SAD, to date research has only been conducted on antidepressants that selectively inhibit the reuptake of serotonin. Objective: The objective of this combined data analysis was to determine the anxiolytic efficacy of the serotonin-noradrenaline reuptake inhibitor (SNRI) venlafaxine extended release (VEN XR) in the treatment of generalized SAD. Method: In this analysis, data from 2 multicenter, doubleblind, placebo-controlled, parallel-group studies of outpatients with generalized SAD were pooled to evaluate efficacy in a lastobservation-carried-forward (LOCF) analysis. Both studies were preceded by a placebo lead-in period of 7+/-3 days, followed by a 12-week randomized, flexible-dose study of VEN XR (75-225 mg/day; n=259) or placebo (n=273), and concluded with a 14day optional taper period. The primary efficacy variable was the total score on the Liebowitz Social Anxiety Scale (LSAS). The secondary efficacy variables included the subscales of the LSAS, including performance, social interaction, avoidance factors, and some fear factors (eg, public speaking), in addition to the fear, avoidance, and physiologic factors of the Social Phobia Inventory (SPIN). Results: The pooled analysis indicated that the SNRI VEN XR was significantly better than placebo during weeks 3 to 12 (P=.007, week 3; P<=.001, weeks 4 to 12), based on LSAS total adjusted mean scores (LOCF Analysis) as follows:
Baseline Week 1 Week 2 Week 3 Week 4 Week 5 Week 6 Week 8 Week 10 Week 12
Placebo
Venlafaxine XR P
88.9 84.6 80.0 76.8 74.0 71.0 71.0 68.8 68.7 68.1
88.9 83.0 78.1 72.6 68.2 63.5 63.5 61.4 59.3 57.2
0.119 0.142 0.007 0.001 ~<0.001 ~<0.001 ~<0.001 ~<0.001 <~.001
Significant efficacy of VEN XR over placebo as early as week 3 was also demonstrated using the LSAS subscales. Similarly, early statistical separation favoring active treatment over placebo on efficacy parameters was noted on the fear, avoidance, and physiologic factors of the SPIN. Conclusions: In this analysis, the dual reuptake inhibitor VEN XR demonstrated significantly better anxiolytic activity than placebo in the short-term treatment of generalized SAD. This finding may lead to expanded options for the treatment of this disorder. Supported by funding from Wyeth Research.
References [1] Hackett, D. (2000) Venlafaxine XR in the treatment of anxiety. Acta Psychiatr Scand 102, 30-35. [2] L~pine, J.-P. and P~lissolo, A. (2000) Why take social anxiety disorder seriously? Depress Anxiety 11, 87-92. [3] Altamura, A.C., Pioli, R., Vitto, M., Mannu, E (1999):Venlafaxine in social phobia: a study in selective serotonin reuptake inhibitor nonresponders. Int Clin Psychopharmacol 14, 239-245.