Deep Brain Stimulation of the Nucleus Accumbens/Ventral Capsule for Severe and Intractable Opioid and Benzodiazepine Use Disorder
Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed for those who are treatment refractory. The objective of this study was to evaluate the safety of deep brain stimulation (DBS) for SUD and the effects of DBS on su...
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Veröffentlicht in: | Experimental and clinical psychopharmacology 2021-04, Vol.29 (2), p.210-215 |
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creator | Mahoney, James J. Haut, Marc W. Hodder, Sally L. Zheng, Wanhong Lander, Laura R. Berry, James H. Farmer, Daniel L. Marton, Jennifer L. Ranjan, Manish Brandmeir, Nicholas J. Finomore, Victor S. Hensley, Jeremy L. Aklin, Will M. Wang, Gene-Jack Tomasi, Dardo Shokri-Kojori, Ehsan Rezai, Ali R. |
description | Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed for those who are treatment refractory. The objective of this study was to evaluate the safety of deep brain stimulation (DBS) for SUD and the effects of DBS on substance use, substance craving, emotional symptoms, and frontal/executive functions. DBS electrodes were implanted bilaterally within the Nucleus Accumbens/Ventral anterior internal capsule (NAc/VC) of a man in his early 30s with >10-year history of severe treatment refractory opioid and benzodiazepine use disorders. DBS of the NAc/VC was found to be safe with no serious adverse events noted and the participant remained abstinent and engaged in comprehensive treatment at the 12-week endpoint (and 12-month extended follow-up). Using a 0-100 visual analog scale, substance cravings decreased post-DBS implantation; most substantially in benzodiazepine craving following the final DBS titration (1.0 ± 2.2) compared to baseline (53.4 ± 29.5; p < .001). A trend toward improvement in frontal/executive function was observed on the balloon analog risk task performance following the final titration (217.7 ± 76.2) compared to baseline (131.3 ± 28.1, p = .066). FDG PET demonstrated an increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices at the 12-week endpoint compared to post-surgery/pre-DBS titration. Heart Rate Variability (HRV) improved following the final titration (rMSSD = 56.0 ± 11.7) compared to baseline (19.2 ± 8.2; p < .001). In a participant with severe, treatment refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC was safe, reduced substance use and craving, and improved frontal and executive functions. Confirmation of these findings with future studies is needed.
Public Significance Statement
Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed. In an individual with severe, treatment refractory opioid and benzodiazepine use disorder, deep brain stimulation (DBS) of the Nucleus Accumbens/Ventral Capsule was found to be safe and this participant remained entirely abstinent from illicit substance use throughout the 12-month follow-up. These findings must be replicated so that more substantive conclusions regarding the utility of DBS for SUD can be made. |
doi_str_mv | 10.1037/pha0000453 |
format | Article |
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Public Significance Statement
Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed. In an individual with severe, treatment refractory opioid and benzodiazepine use disorder, deep brain stimulation (DBS) of the Nucleus Accumbens/Ventral Capsule was found to be safe and this participant remained entirely abstinent from illicit substance use throughout the 12-month follow-up. These findings must be replicated so that more substantive conclusions regarding the utility of DBS for SUD can be made.</description><identifier>ISSN: 1064-1297</identifier><identifier>EISSN: 1936-2293</identifier><identifier>DOI: 10.1037/pha0000453</identifier><identifier>PMID: 34043402</identifier><language>eng</language><publisher>United States: American Psychological Association</publisher><subject>Addiction ; Adult ; Analgesics, Opioid - adverse effects ; Benzodiazepines ; Benzodiazepines - adverse effects ; Deep Brain Stimulation ; Drug Overdoses ; Human ; Humans ; Internal Capsule ; Male ; Neuromodulation ; Nucleus Accumbens ; Opiates ; Pilot Projects ; Relapse (Disorders) ; Substance Use Disorder ; Substance-Related Disorders - therapy</subject><ispartof>Experimental and clinical psychopharmacology, 2021-04, Vol.29 (2), p.210-215</ispartof><rights>2021 American Psychological Association</rights><rights>2021, American Psychological Association</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a508t-411bcc0c5b5f1c8773a63fd234c928c7c56f43ae933cc1494a849e9496f453193</citedby><orcidid>0000-0002-3338-8676 ; 0000-0003-0235-362X ; 0000-0002-1854-5856 ; 0000-0003-1491-8480 ; 0000-0002-5017-9905 ; 0000-0002-9884-1152 ; 0000-0002-0728-5550 ; 0000-0001-6846-3173 ; 0000-0003-0824-1776 ; 0000-0003-0183-5678 ; 0000-0003-3262-2720 ; 0000-0002-1132-8787 ; 0000-0002-6223-721X</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34043402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Stoops, William W</contributor><creatorcontrib>Mahoney, James J.</creatorcontrib><creatorcontrib>Haut, Marc W.</creatorcontrib><creatorcontrib>Hodder, Sally L.</creatorcontrib><creatorcontrib>Zheng, Wanhong</creatorcontrib><creatorcontrib>Lander, Laura R.</creatorcontrib><creatorcontrib>Berry, James H.</creatorcontrib><creatorcontrib>Farmer, Daniel L.</creatorcontrib><creatorcontrib>Marton, Jennifer L.</creatorcontrib><creatorcontrib>Ranjan, Manish</creatorcontrib><creatorcontrib>Brandmeir, Nicholas J.</creatorcontrib><creatorcontrib>Finomore, Victor S.</creatorcontrib><creatorcontrib>Hensley, Jeremy L.</creatorcontrib><creatorcontrib>Aklin, Will M.</creatorcontrib><creatorcontrib>Wang, Gene-Jack</creatorcontrib><creatorcontrib>Tomasi, Dardo</creatorcontrib><creatorcontrib>Shokri-Kojori, Ehsan</creatorcontrib><creatorcontrib>Rezai, Ali R.</creatorcontrib><title>Deep Brain Stimulation of the Nucleus Accumbens/Ventral Capsule for Severe and Intractable Opioid and Benzodiazepine Use Disorder</title><title>Experimental and clinical psychopharmacology</title><addtitle>Exp Clin Psychopharmacol</addtitle><description>Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed for those who are treatment refractory. The objective of this study was to evaluate the safety of deep brain stimulation (DBS) for SUD and the effects of DBS on substance use, substance craving, emotional symptoms, and frontal/executive functions. DBS electrodes were implanted bilaterally within the Nucleus Accumbens/Ventral anterior internal capsule (NAc/VC) of a man in his early 30s with >10-year history of severe treatment refractory opioid and benzodiazepine use disorders. DBS of the NAc/VC was found to be safe with no serious adverse events noted and the participant remained abstinent and engaged in comprehensive treatment at the 12-week endpoint (and 12-month extended follow-up). Using a 0-100 visual analog scale, substance cravings decreased post-DBS implantation; most substantially in benzodiazepine craving following the final DBS titration (1.0 ± 2.2) compared to baseline (53.4 ± 29.5; p < .001). A trend toward improvement in frontal/executive function was observed on the balloon analog risk task performance following the final titration (217.7 ± 76.2) compared to baseline (131.3 ± 28.1, p = .066). FDG PET demonstrated an increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices at the 12-week endpoint compared to post-surgery/pre-DBS titration. Heart Rate Variability (HRV) improved following the final titration (rMSSD = 56.0 ± 11.7) compared to baseline (19.2 ± 8.2; p < .001). In a participant with severe, treatment refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC was safe, reduced substance use and craving, and improved frontal and executive functions. Confirmation of these findings with future studies is needed.
Public Significance Statement
Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed. In an individual with severe, treatment refractory opioid and benzodiazepine use disorder, deep brain stimulation (DBS) of the Nucleus Accumbens/Ventral Capsule was found to be safe and this participant remained entirely abstinent from illicit substance use throughout the 12-month follow-up. These findings must be replicated so that more substantive conclusions regarding the utility of DBS for SUD can be made.</description><subject>Addiction</subject><subject>Adult</subject><subject>Analgesics, Opioid - adverse effects</subject><subject>Benzodiazepines</subject><subject>Benzodiazepines - adverse effects</subject><subject>Deep Brain Stimulation</subject><subject>Drug Overdoses</subject><subject>Human</subject><subject>Humans</subject><subject>Internal Capsule</subject><subject>Male</subject><subject>Neuromodulation</subject><subject>Nucleus Accumbens</subject><subject>Opiates</subject><subject>Pilot Projects</subject><subject>Relapse (Disorders)</subject><subject>Substance Use Disorder</subject><subject>Substance-Related Disorders - therapy</subject><issn>1064-1297</issn><issn>1936-2293</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpdkV1rFTEQhhex2Fq98QdIwBtRts3XfuRGaE_VFoq9qPU2zGZnPSm7yZpsCu2d_9wcT63VQMgw8_Ayb96ieMXoAaOiOZzXQPORlXhS7DEl6pJzJZ7mmtayZFw1u8XzGK8pZVIo_qzYFZLKfPle8fMEcSbHAawjl4ud0giL9Y74gSxrJF-SGTFFcmRMmjp08fAbuiXASFYwxzQiGXwgl3iDAQm4npxtpmaBLo8uZutt_7t9jO7O9xbucLYOyVVEcmKjDz2GF8XOAGPEl_fvfnH16ePX1Wl5fvH5bHV0XkJF26WUjHXGUFN11cBM2zQCajH0XEijeGsaU9WDFIBKCGOYVBJaqVBJlduVyL-yX3zY6s6pm7A3Wx96DnaCcKs9WP3vxNm1_u5vdCs5522VBd7eCwT_I2Fc9GSjwXEEhz5FzSsha8YpbzP65j_02qfgsr0NxRve1A3L1LstZYKPMeDwsAyjepOs_ptshl8_Xv8B_RNlBt5vAZhBz_HWQFhsTi-aFEK2tBHTXGmuedb-BeC3rx0</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Mahoney, James J.</creator><creator>Haut, Marc W.</creator><creator>Hodder, Sally L.</creator><creator>Zheng, Wanhong</creator><creator>Lander, Laura R.</creator><creator>Berry, James H.</creator><creator>Farmer, Daniel L.</creator><creator>Marton, Jennifer L.</creator><creator>Ranjan, Manish</creator><creator>Brandmeir, Nicholas J.</creator><creator>Finomore, Victor S.</creator><creator>Hensley, Jeremy L.</creator><creator>Aklin, Will M.</creator><creator>Wang, Gene-Jack</creator><creator>Tomasi, Dardo</creator><creator>Shokri-Kojori, Ehsan</creator><creator>Rezai, Ali R.</creator><general>American Psychological Association</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7RZ</scope><scope>PSYQQ</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-3338-8676</orcidid><orcidid>https://orcid.org/0000-0003-0235-362X</orcidid><orcidid>https://orcid.org/0000-0002-1854-5856</orcidid><orcidid>https://orcid.org/0000-0003-1491-8480</orcidid><orcidid>https://orcid.org/0000-0002-5017-9905</orcidid><orcidid>https://orcid.org/0000-0002-9884-1152</orcidid><orcidid>https://orcid.org/0000-0002-0728-5550</orcidid><orcidid>https://orcid.org/0000-0001-6846-3173</orcidid><orcidid>https://orcid.org/0000-0003-0824-1776</orcidid><orcidid>https://orcid.org/0000-0003-0183-5678</orcidid><orcidid>https://orcid.org/0000-0003-3262-2720</orcidid><orcidid>https://orcid.org/0000-0002-1132-8787</orcidid><orcidid>https://orcid.org/0000-0002-6223-721X</orcidid></search><sort><creationdate>20210401</creationdate><title>Deep Brain Stimulation of the Nucleus Accumbens/Ventral Capsule for Severe and Intractable Opioid and Benzodiazepine Use Disorder</title><author>Mahoney, James J. ; Haut, Marc W. ; Hodder, Sally L. ; Zheng, Wanhong ; Lander, Laura R. ; Berry, James H. ; Farmer, Daniel L. ; Marton, Jennifer L. ; Ranjan, Manish ; Brandmeir, Nicholas J. ; Finomore, Victor S. ; Hensley, Jeremy L. ; Aklin, Will M. ; Wang, Gene-Jack ; Tomasi, Dardo ; Shokri-Kojori, Ehsan ; Rezai, Ali R.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a508t-411bcc0c5b5f1c8773a63fd234c928c7c56f43ae933cc1494a849e9496f453193</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Addiction</topic><topic>Adult</topic><topic>Analgesics, Opioid - adverse effects</topic><topic>Benzodiazepines</topic><topic>Benzodiazepines - adverse effects</topic><topic>Deep Brain Stimulation</topic><topic>Drug Overdoses</topic><topic>Human</topic><topic>Humans</topic><topic>Internal Capsule</topic><topic>Male</topic><topic>Neuromodulation</topic><topic>Nucleus Accumbens</topic><topic>Opiates</topic><topic>Pilot Projects</topic><topic>Relapse (Disorders)</topic><topic>Substance Use Disorder</topic><topic>Substance-Related Disorders - therapy</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Mahoney, James J.</creatorcontrib><creatorcontrib>Haut, Marc W.</creatorcontrib><creatorcontrib>Hodder, Sally L.</creatorcontrib><creatorcontrib>Zheng, Wanhong</creatorcontrib><creatorcontrib>Lander, Laura R.</creatorcontrib><creatorcontrib>Berry, James H.</creatorcontrib><creatorcontrib>Farmer, Daniel L.</creatorcontrib><creatorcontrib>Marton, Jennifer L.</creatorcontrib><creatorcontrib>Ranjan, Manish</creatorcontrib><creatorcontrib>Brandmeir, Nicholas J.</creatorcontrib><creatorcontrib>Finomore, Victor S.</creatorcontrib><creatorcontrib>Hensley, Jeremy L.</creatorcontrib><creatorcontrib>Aklin, Will M.</creatorcontrib><creatorcontrib>Wang, Gene-Jack</creatorcontrib><creatorcontrib>Tomasi, Dardo</creatorcontrib><creatorcontrib>Shokri-Kojori, Ehsan</creatorcontrib><creatorcontrib>Rezai, Ali R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>APA PsycArticles®</collection><collection>ProQuest One Psychology</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Experimental and clinical psychopharmacology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Mahoney, James J.</au><au>Haut, Marc W.</au><au>Hodder, Sally L.</au><au>Zheng, Wanhong</au><au>Lander, Laura R.</au><au>Berry, James H.</au><au>Farmer, Daniel L.</au><au>Marton, Jennifer L.</au><au>Ranjan, Manish</au><au>Brandmeir, Nicholas J.</au><au>Finomore, Victor S.</au><au>Hensley, Jeremy L.</au><au>Aklin, Will M.</au><au>Wang, Gene-Jack</au><au>Tomasi, Dardo</au><au>Shokri-Kojori, Ehsan</au><au>Rezai, Ali R.</au><au>Stoops, William W</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Deep Brain Stimulation of the Nucleus Accumbens/Ventral Capsule for Severe and Intractable Opioid and Benzodiazepine Use Disorder</atitle><jtitle>Experimental and clinical psychopharmacology</jtitle><addtitle>Exp Clin Psychopharmacol</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>29</volume><issue>2</issue><spage>210</spage><epage>215</epage><pages>210-215</pages><issn>1064-1297</issn><eissn>1936-2293</eissn><abstract>Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed for those who are treatment refractory. The objective of this study was to evaluate the safety of deep brain stimulation (DBS) for SUD and the effects of DBS on substance use, substance craving, emotional symptoms, and frontal/executive functions. DBS electrodes were implanted bilaterally within the Nucleus Accumbens/Ventral anterior internal capsule (NAc/VC) of a man in his early 30s with >10-year history of severe treatment refractory opioid and benzodiazepine use disorders. DBS of the NAc/VC was found to be safe with no serious adverse events noted and the participant remained abstinent and engaged in comprehensive treatment at the 12-week endpoint (and 12-month extended follow-up). Using a 0-100 visual analog scale, substance cravings decreased post-DBS implantation; most substantially in benzodiazepine craving following the final DBS titration (1.0 ± 2.2) compared to baseline (53.4 ± 29.5; p < .001). A trend toward improvement in frontal/executive function was observed on the balloon analog risk task performance following the final titration (217.7 ± 76.2) compared to baseline (131.3 ± 28.1, p = .066). FDG PET demonstrated an increase in glucose metabolism in the dorsolateral prefrontal and medial premotor cortices at the 12-week endpoint compared to post-surgery/pre-DBS titration. Heart Rate Variability (HRV) improved following the final titration (rMSSD = 56.0 ± 11.7) compared to baseline (19.2 ± 8.2; p < .001). In a participant with severe, treatment refractory opioid and benzodiazepine use disorder, DBS of the NAc/VC was safe, reduced substance use and craving, and improved frontal and executive functions. Confirmation of these findings with future studies is needed.
Public Significance Statement
Given high relapse rates and the prevalence of overdose deaths, novel treatments for substance use disorder (SUD) are desperately needed. In an individual with severe, treatment refractory opioid and benzodiazepine use disorder, deep brain stimulation (DBS) of the Nucleus Accumbens/Ventral Capsule was found to be safe and this participant remained entirely abstinent from illicit substance use throughout the 12-month follow-up. These findings must be replicated so that more substantive conclusions regarding the utility of DBS for SUD can be made.</abstract><cop>United States</cop><pub>American Psychological Association</pub><pmid>34043402</pmid><doi>10.1037/pha0000453</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0002-3338-8676</orcidid><orcidid>https://orcid.org/0000-0003-0235-362X</orcidid><orcidid>https://orcid.org/0000-0002-1854-5856</orcidid><orcidid>https://orcid.org/0000-0003-1491-8480</orcidid><orcidid>https://orcid.org/0000-0002-5017-9905</orcidid><orcidid>https://orcid.org/0000-0002-9884-1152</orcidid><orcidid>https://orcid.org/0000-0002-0728-5550</orcidid><orcidid>https://orcid.org/0000-0001-6846-3173</orcidid><orcidid>https://orcid.org/0000-0003-0824-1776</orcidid><orcidid>https://orcid.org/0000-0003-0183-5678</orcidid><orcidid>https://orcid.org/0000-0003-3262-2720</orcidid><orcidid>https://orcid.org/0000-0002-1132-8787</orcidid><orcidid>https://orcid.org/0000-0002-6223-721X</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Addiction Adult Analgesics, Opioid - adverse effects Benzodiazepines Benzodiazepines - adverse effects Deep Brain Stimulation Drug Overdoses Human Humans Internal Capsule Male Neuromodulation Nucleus Accumbens Opiates Pilot Projects Relapse (Disorders) Substance Use Disorder Substance-Related Disorders - therapy |
title | Deep Brain Stimulation of the Nucleus Accumbens/Ventral Capsule for Severe and Intractable Opioid and Benzodiazepine Use Disorder |
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