@article{ee211beae0d0489fb9e64114a198bb90,
title = "Low-dose augmentation with buprenorphine increases emotional reactivity but not reward activity in treatment resistant mid- and late-life depression",
abstract = "Buprenorphine is currently being studied for treatment-resistant depression because of its rapid effect, relative safety, and unique pharmacodynamics. To understand the neural impact of buprenorphine in depression, we examined acute limbic and reward circuit changes during an intervention with low-dose buprenorphine augmentation pharmacotherapy. Mid and late-life adults with major depression (N = 31) who did not completely respond to an adequate trial of venlafaxine were randomized to augmentation with low-dose buprenorphine or matching placebo. We investigated early neural changes using functional magnetic resonance imaging (fMRI) from pre-randomization to 3 weeks using both an emotional reactivity task and a gambling task. We tested if: 1) there were significant neural changes acutely per intervention group, and 2) if acute neural changes were associated with depressive symptom change over 8 weeks using both the total score and the dysphoria subscale of the Montgomery Asberg Depression Rating Scale. Participants in both the buprenorphine and placebo groups showed similar changes in depressive symptoms. Neither the emotional reactivity nor gambling task resulted in significant neural activation changes from pre-randomization to 3-weeks. In both groups, increases in rostral anterior cingulate (rACC) and ventromedial prefrontal cortex (vmPFC) activation during the emotional reactivity task were associated with overall symptom improvement. In the buprenorphine but not the placebo group, increased activation in left anterior insula (aINS) and bilateral middle frontal gyrus (MFG) was associated with improvement on the dysphoria subscale. Activation changes in the reward task were not associated with buprenorphine. This is the first study to show an association between acute neural changes during emotion reactivity and changes in depression severity with buprenorphine treatment.",
keywords = "Buprenorphine, Clinical trial, Geriatric, Placebo, Treatment-resistant depression, fMRI",
author = "Chemin Lin and Karim, {Helmet T.} and Marta Pecina and Aizenstein, {Howard J.} and Lenze, {Eric J.} and Blumberger, {Daniel M.} and Mulsant, {Benoit H.} and Kharasch, {Evan D.} and Reynolds, {Charles F.} and Karp, {Jordan F.}",
note = "Funding Information: JFK received medication supplies from Indivior to support this investigator initiated trial. He has also received medication supplies from Pfizer for investigator initiated work. JFK receives research funding from NIH and Patient-Centered Outcomes Research Institute and compensation for service on the editorial board of the American Journal of Geriatric Psychiatry and Journal of Clinical Psychiatry. EJL reports research funding (current/past) from Janssen, Alkermes, Acadia, Takeda, Lundbeck,Barnes Jewish Foundation, Patient-Centered Outcomes Research Institute, and Taylor Family Institute for Innovative Psychiatric Research. He receives medication supplies for an investigator-initiated trial from Indivior. BHM currently receives research funding from Brain Canada, the CAMH Foundation, the Canadian Institutes of Health Research, Patient-Centered Outcomes Research Institute, and the US National Institute of Health (NIH). During the last five years, he also received research support from Bristol-Myers Squibb (medications for a NIH-funded clinical trial), Eli-Lilly (medications for a NIH-funded clinical trial), and Pfizer (medications for a NIH-funded clinical trial). He directly own stocks of General Electric (less than $5000). DMB has received research support from the Canadian Institutes of Health Research (CIHR), National Institute of Health (NIH), Brain Canada and the Temerty Family through the Centre for Addiction and Mental Health (CAMH) Foundation and the Campbell Research Institute. He receives research support and in-kind equipment support for an investigator-initiated study from Brainsway Ltd. and he is the site principal investigator for three sponsor-initiated studies for Brainsway Ltd. He also receives in-kind equipment support from Magventure for an investigator-initiated study. He receives medication supplies for an investigator-initiated trial from Indivior. CFR has received research support from the NIH, the Patient Centered Outcomes Research Institute, the Center for Medicare and Medicaid Services, the American Foundation for Suicide Prevention, the Brain and Behavior Research Foundation, and the Commonwealth of Pennsylvania. BristolMeyerSquib and Pfizer have provided pharmaceutical supplies for his NIH sponsored research. Publisher Copyright: {\textcopyright} 2019 The Authors",
year = "2019",
month = jan,
day = "1",
doi = "10.1016/j.nicl.2019.101679",
language = "English (US)",
volume = "21",
journal = "NeuroImage: Clinical",
issn = "2213-1582",
publisher = "Elsevier BV",
}