TY - JOUR
T1 - Opioid modulation with buprenorphine/samidorphan as adjunctive treatment for inadequate response to antidepressants
T2 - A randomized double-blind placebo-controlled trial
AU - Fava, Maurizio
AU - Memisoglu, Asli
AU - Thase, Michael E.
AU - Bodkin, J. Alexander
AU - Trivedi, Madhukar H.
AU - De Somer, Marc
AU - Du, Yangchun
AU - Leigh-Pemberton, Richard
AU - DiPetrillo, Lauren
AU - Silverman, Bernard
AU - Ehrich, Elliot
PY - 2016/5/1
Y1 - 2016/5/1
N2 - Objective: Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a m- and k-opioid partial agonist, buprenorphine, and a m-opioid antagonist, samidorphan, would exhibit antidepressant activity in patients with major depression. Method: A multicenter, randomized, double-blind, placebocontrolled, two-stage sequential parallel comparison design study was conducted in adults with major depression who had aninadequate response tooneor twocoursesof antidepressant treatment. Participants were randomly assigned to receive adjunctive treatment with 2 mg/2 mg of buprenorphine/ samidorphan (the 2/2 dosage group), 8 mg/8 mg of buprenorphine/samidorphan (the 8/8 dosage group), or placebo. Antidepressant effect was measured based on change from baseline to the end of 4 weeks of treatment on the 17-item Hamilton Depression Rating Scale (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Clinical Global Impressions severity scale (CGI-S). Results: Compared with the placebo group, there were significantlygreater improvements inthe2/2dosagegroupacross the three depression outcome measures (HAM-D: 22.8, 95% CI=25.1,20.6;MADRS:24.9,95%CI=28.2,21.6;CGI-S:20.5, 95% CI=20.9,20.1). There was also evidence of improvement in the 8/8 dosage group, although it did not achieve statistical significance. Overall, the buprenorphine/samidorphan combinations were well tolerated, and there was no evidence of opioid withdrawal on treatment discontinuation. Conclusions: The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants.
AB - Objective: Major depressive disorder has been associated with dysregulation of the endogenous opioid system. The authors sought to determine whether opioid modulation achieved through administration of ALKS 5461, a combination of a m- and k-opioid partial agonist, buprenorphine, and a m-opioid antagonist, samidorphan, would exhibit antidepressant activity in patients with major depression. Method: A multicenter, randomized, double-blind, placebocontrolled, two-stage sequential parallel comparison design study was conducted in adults with major depression who had aninadequate response tooneor twocoursesof antidepressant treatment. Participants were randomly assigned to receive adjunctive treatment with 2 mg/2 mg of buprenorphine/ samidorphan (the 2/2 dosage group), 8 mg/8 mg of buprenorphine/samidorphan (the 8/8 dosage group), or placebo. Antidepressant effect was measured based on change from baseline to the end of 4 weeks of treatment on the 17-item Hamilton Depression Rating Scale (HAM-D), the Montgomery-Åsberg Depression Rating Scale (MADRS), and the Clinical Global Impressions severity scale (CGI-S). Results: Compared with the placebo group, there were significantlygreater improvements inthe2/2dosagegroupacross the three depression outcome measures (HAM-D: 22.8, 95% CI=25.1,20.6;MADRS:24.9,95%CI=28.2,21.6;CGI-S:20.5, 95% CI=20.9,20.1). There was also evidence of improvement in the 8/8 dosage group, although it did not achieve statistical significance. Overall, the buprenorphine/samidorphan combinations were well tolerated, and there was no evidence of opioid withdrawal on treatment discontinuation. Conclusions: The buprenorphine/samidorphan combination is a novel and promising candidate for treatment of major depressive disorder in patients who have an inadequate response to standard antidepressants.
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U2 - 10.1176/appi.ajp.2015.15070921
DO - 10.1176/appi.ajp.2015.15070921
M3 - Article
C2 - 26869247
AN - SCOPUS:84965139878
SN - 0002-953X
VL - 173
SP - 499
EP - 508
JO - American Journal of Psychiatry
JF - American Journal of Psychiatry
IS - 5
ER -