Abstract
Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17≤7 or CGI-S≤2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p=0.05); relapse rates were 56.1 and 64.1%, respectively (p≤0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.
| Original language | English |
|---|---|
| Pages (from-to) | 2505-2513 |
| Number of pages | 9 |
| Journal | Neuropsychopharmacology |
| Volume | 31 |
| Issue number | 11 |
| DOIs | |
| State | Published - Nov 7 2006 |
| Externally published | Yes |
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Keywords
- Citalopram
- Resistant depression
- Risperidone augmentation
ASJC Scopus subject areas
- Pharmacology
Cite this
Effects of risperidone augmentation in patients with treatment-resistant depression : Results of open-label treatment followed by double-blind continuation. / Rapaport, Mark Hyman; Gharabawi, Georges M.; Canuso, Carla M.; Mahmoud, Ramy A.; Keller, Martin B.; Bossie, Cynthia A.; Turkoz, Ibrahim; Lasser, Robert A.; Loescher, Amy; Bouhours, Philippe; Dunbar, Fiona; Nemeroff, Charles.
In: Neuropsychopharmacology, Vol. 31, No. 11, 07.11.2006, p. 2505-2513.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of risperidone augmentation in patients with treatment-resistant depression
T2 - Results of open-label treatment followed by double-blind continuation
AU - Rapaport, Mark Hyman
AU - Gharabawi, Georges M.
AU - Canuso, Carla M.
AU - Mahmoud, Ramy A.
AU - Keller, Martin B.
AU - Bossie, Cynthia A.
AU - Turkoz, Ibrahim
AU - Lasser, Robert A.
AU - Loescher, Amy
AU - Bouhours, Philippe
AU - Dunbar, Fiona
AU - Nemeroff, Charles
PY - 2006/11/7
Y1 - 2006/11/7
N2 - Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17≤7 or CGI-S≤2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p=0.05); relapse rates were 56.1 and 64.1%, respectively (p≤0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.
AB - Approximately one-third of persons with depression do not respond to antidepressant monotherapy. Studies suggest that atypical antipsychotic augmentation may benefit these patients. We investigated the longer-term efficacy of risperidone augmentation of serotonin-selective reuptake inhibitor treatment for resistant depression. In 57 in- and outpatient centers in three countries, we conducted a three-phase study with 4-6 weeks of open-label citalopram monotherapy, 4-6 weeks of open-label risperidone augmentation, and a 24-week double-blind, placebo-controlled discontinuation phase. A total of 489 patients with major depressive disorder and 1-3 documented treatment failures entered the citalopram monotherapy phase (20-60 mg/day). Patients with <50% reduction in HAM-D-17 scores entered the risperidone augmentation phase (0.25-2.0 mg/day). Patients with HAM-D-17≤7 or CGI-S≤2 were randomized to risperidone or placebo augmentation. The primary outcome was time to relapse during the double-blind phase. During citalopram monotherapy, 434 patients had <50% HAM-D-17 reduction; 299 (68.9%) were fully nonresponsive (<25% reduction) and 135 were partially nonresponsive (25-49% reduction). Of the 386 nonresponders who entered the augmentation phase, 243 remitted and 241 entered the double-blind phase. Median time to relapse was 102 days with risperidone augmentation and 85 days with placebo (NS); relapse rates were 53.3 and 54.6%, respectively. In a post hoc analysis of patients fully nonresponsive to citalopram monotherapy, median time to relapse was 97 days with risperidone augmentation and 56 with placebo (p=0.05); relapse rates were 56.1 and 64.1%, respectively (p≤0.05). Open-label risperidone augmentation substantially enhanced response in treatment-resistant patients, but the longer-term benefits of augmentation were not demonstrated in this study.
KW - Citalopram
KW - Resistant depression
KW - Risperidone augmentation
UR - http://www.scopus.com/inward/record.url?scp=33750212103&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33750212103&partnerID=8YFLogxK
U2 - 10.1038/sj.npp.1301113
DO - 10.1038/sj.npp.1301113
M3 - Article
C2 - 16760927
AN - SCOPUS:33750212103
VL - 31
SP - 2505
EP - 2513
JO - Neuropsychopharmacology
JF - Neuropsychopharmacology
SN - 0893-133X
IS - 11
ER -