Susan G Kornstein1, Carl Gommoll2, Changzheng Chen2, Kenneth Kramer2. 1. Department of Psychiatry and Institute for Women's Health, Virginia Commonwealth University School of Medicine, Richmond, VA, United States. Electronic address: susan.kornstein@vcuhealth.org. 2. Forest Research Institute (an Allergan affiliate), Jersey City, NJ, United States.
Abstract
BACKGROUND:Major depressive disorder (MDD) can be challenging to manage due its variable and episodic nature. Post hoc analyses were conducted on five studies (NCT00969709, NCT01377194, NCT00969150, NCT01034462, EudraCT:2006-002404-34) to evaluate the efficacy of levomilnacipran extended-release (ER) in patients with different MDD episode histories. METHODS:Adults with MDD were randomized to double-blind treatment with levomilnacipran ER (40-120mg/d) or placebo. Three subgroups were identified: first-episode (n=494); highly recurrent (≥3 major depressive episodes; n=1954); and chronic (current episode duration ≥2 years; n=218). Mean changes from baseline to end of study (Week 8 [US studies], Week 10 [non-US study]) in Montgomery-Åsberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating Scale (HAMD17), and Sheehan Disability Scale (SDS) total scores were analyzed in each subgroup. MADRS response, defined as ≥50% total score improvement from baseline to Week 8/10, was also analyzed. RESULTS: Least squares mean differences (LSMDs) between treatment groups indicated significantly greater improvements with levomilnacipran ER versus placebo in MADRS (first-episode, -2.5; highly recurrent, -3.0; chronic, -4.9; all P<.05) and HAMD17 (first-episode, -2.1; highly recurrent, -1.6; chronic, -2.6; all P<.05) total scores. LSMDs for SDS total score were statistically significant in the first-episode and highly recurrent MDD subgroups (both subgroups, -2.3; P<.01). MADRS response rate was significantly higher with levomilnacipran ER versus placebo in all three subgroups (first-episode, 44.5% versus 35.0%; highly recurrent, 44.3% versus 33.5%; 36.8% versus 22.0%; all P<.05). LIMITATIONS: MDD subgroups were defined post hoc; none of the studies were prospectively designed to evaluate outcomes in these subgroups. Other limitations include lack of active comparators and variability of dose/duration due to data being pooled from multiple clinical trials. CONCLUSIONS: Results suggest that levomilnacipran ER improves depression symptoms and functional impairment in adult patients with different histories of MDD episodes.
RCT Entities:
BACKGROUND: Major depressive disorder (MDD) can be challenging to manage due its variable and episodic nature. Post hoc analyses were conducted on five studies (NCT00969709, NCT01377194, NCT00969150, NCT01034462, EudraCT:2006-002404-34) to evaluate the efficacy of levomilnacipran extended-release (ER) in patients with different MDD episode histories. METHODS: Adults with MDD were randomized to double-blind treatment with levomilnacipran ER (40-120mg/d) or placebo. Three subgroups were identified: first-episode (n=494); highly recurrent (≥3 major depressive episodes; n=1954); and chronic (current episode duration ≥2 years; n=218). Mean changes from baseline to end of study (Week 8 [US studies], Week 10 [non-US study]) in Montgomery-Åsberg Depression Rating Scale (MADRS), 17-item Hamilton Depression Rating Scale (HAMD17), and Sheehan Disability Scale (SDS) total scores were analyzed in each subgroup. MADRS response, defined as ≥50% total score improvement from baseline to Week 8/10, was also analyzed. RESULTS: Least squares mean differences (LSMDs) between treatment groups indicated significantly greater improvements with levomilnacipran ER versus placebo in MADRS (first-episode, -2.5; highly recurrent, -3.0; chronic, -4.9; all P<.05) and HAMD17 (first-episode, -2.1; highly recurrent, -1.6; chronic, -2.6; all P<.05) total scores. LSMDs for SDS total score were statistically significant in the first-episode and highly recurrent MDD subgroups (both subgroups, -2.3; P<.01). MADRS response rate was significantly higher with levomilnacipran ER versus placebo in all three subgroups (first-episode, 44.5% versus 35.0%; highly recurrent, 44.3% versus 33.5%; 36.8% versus 22.0%; all P<.05). LIMITATIONS: MDD subgroups were defined post hoc; none of the studies were prospectively designed to evaluate outcomes in these subgroups. Other limitations include lack of active comparators and variability of dose/duration due to data being pooled from multiple clinical trials. CONCLUSIONS: Results suggest that levomilnacipran ER improves depression symptoms and functional impairment in adult patients with different histories of MDD episodes.