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Original article
peer-reviewed

A Randomized Blinded Trial of Nucleus Accumbens Ablation to Treat Opiate Dependence in Humans: Location Correlates with Outcome



Abstract

Background: Opiate addiction remains intractable in a large percentage of patients. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. In China, ablation of the NAc was common before November 2004, though it was poorly regulated. This study, a prospective randomized double-blinded trial carried out from January 2004 to November 2004, investigates the effect of different stereotactic lesions within NAc on opiate addiction to maximize benefit and minimize risk.

Methods: Seventy-eight opiate-dependent patients were treated at the Tangdu Hospital Fourth Military Medical University during Jan. 2004 to Nov. 2004 with bilateral stereotactic radiofrequency lesioning of the posteromedial one-third of NAc. Patients were randomly divided into four groups (A, B,C, and D). Relative to the initial target, the lesion in Group A was enlarged laterally and superiorly, in Group B anteriorly and superiorly, and in Group C laterally and anteriorly. Among these three groups, the lesion volume was identical. In Group D, the lesion extended laterally and anteriorly and superiorly. Using opiate abstinence as the primary endpoint, four years of follow-up data for all patients regarding relapse and complications were collected. This trial is supplementarily registered with Current Controlled Trials, number ISRCTN33954423.

Results:  Four patients were withdrawn at the fourth year post-operation. For convenience of interpretation, this article appointed these patients as relapses. The overall abstinence rate was 53.8% (42/78). The abstinence rates of Group C (75.0%) and Group D (76.2%) were higher than Groups A (31.3%) and B (28.6%) (p≤0.005). The neuropsychological adverse event rate was 24.3% (18/74) and did not differ statistically between the four groups.

Conclusions: Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location significantly impacts treatment efficacy.



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Original article
peer-reviewed

A Randomized Blinded Trial of Nucleus Accumbens Ablation to Treat Opiate Dependence in Humans: Location Correlates with Outcome


Author Information

Xuelian Wang Corresponding Author

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Chongwang Chang

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

John R. Adler

Department of Neurosurgery, Stanford University School of Medicine

Department of Radiation Oncology, Stanford University Medical Center

Nan Li

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Shunnan Ge

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Ning Geng

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Jing Wang

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Xin Wang

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Guodong Gao

Department of Neurosurgery, Tangdu Hospital, Xi'an, China, Department of Neurosurgery, Tangdu Hospital, Xi'an, China


Ethics Statement and Conflict of Interest Disclosures

Human subjects: Consent was obtained by all participants in this study. The Ethics Committee of Fourth Military Medical University issued approval N/A. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Funding sources: (1) China National “11th five years” scientific support plan project 《Clinical reevaluation of current prevention of relapse》(No.2007BAI0703) (2) Scientific and technological achievements popularizing plan project supported by China, Shaanxi Province Government in the year 2005 (No.2005KT-027) (3) Major clinical high-technique program 《Clinical and experimental research on stereotactic neurosurgery for treating addiction》granted by the health subdepartment of General Logistics Department of Peoples Liberation Army (No.200218) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Trials registered number ISRCTN33954423. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

Acknowledgements

Acknowledgements: We express our gratitude to every patient for participating in this study. Furthermore, we thank Xingsuo Wang and Tian Luo for their close follow-up with all patients. Moreover, Drs. Qing Li and Wei Wang deserve our thanks for obtaining and processing all patient MRIs. Lastly, we wish to express our sincere appreciation to Dr. Paul Kalanithi for his immensely helpful conversations voicing his sincere ethical concerns, his encouragement to present complications, and advice on appropriate data analysis and interpretation. Contributions: Xuelian Wang and Guodong Gao are responsible for the design of this study. Chongwang Chang, Shunnan Ge, Nan Li, Ning Geng, Jing Wang, and Xin Wang devoted themselves to data collection and paper writing. John R Adler is in charge of data handling and polishing the language.


Original article
peer-reviewed

A Randomized Blinded Trial of Nucleus Accumbens Ablation to Treat Opiate Dependence in Humans: Location Correlates with Outcome


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Original article
peer-reviewed

A Randomized Blinded Trial of Nucleus Accumbens Ablation to Treat Opiate Dependence in Humans: Location Correlates with Outcome

  • Author Information
    Xuelian Wang Corresponding Author

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China

    Chongwang Chang

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China

    John R. Adler

    Department of Neurosurgery, Stanford University School of Medicine

    Department of Radiation Oncology, Stanford University Medical Center

    Nan Li

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China

    Shunnan Ge

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China

    Ning Geng

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China

    Jing Wang

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China

    Xin Wang

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China

    Guodong Gao

    Department of Neurosurgery, Tangdu Hospital, Xi'an, China, Department of Neurosurgery, Tangdu Hospital, Xi'an, China


    Ethics Statement and Conflict of Interest Disclosures

    Human subjects: Consent was obtained by all participants in this study. The Ethics Committee of Fourth Military Medical University issued approval N/A. Animal subjects: All authors have confirmed that this study did not involve animal subjects or tissue. Conflicts of interest: In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: Funding sources: (1) China National “11th five years” scientific support plan project 《Clinical reevaluation of current prevention of relapse》(No.2007BAI0703) (2) Scientific and technological achievements popularizing plan project supported by China, Shaanxi Province Government in the year 2005 (No.2005KT-027) (3) Major clinical high-technique program 《Clinical and experimental research on stereotactic neurosurgery for treating addiction》granted by the health subdepartment of General Logistics Department of Peoples Liberation Army (No.200218) The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Trials registered number ISRCTN33954423. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.

    Acknowledgements

    Acknowledgements: We express our gratitude to every patient for participating in this study. Furthermore, we thank Xingsuo Wang and Tian Luo for their close follow-up with all patients. Moreover, Drs. Qing Li and Wei Wang deserve our thanks for obtaining and processing all patient MRIs. Lastly, we wish to express our sincere appreciation to Dr. Paul Kalanithi for his immensely helpful conversations voicing his sincere ethical concerns, his encouragement to present complications, and advice on appropriate data analysis and interpretation. Contributions: Xuelian Wang and Guodong Gao are responsible for the design of this study. Chongwang Chang, Shunnan Ge, Nan Li, Ning Geng, Jing Wang, and Xin Wang devoted themselves to data collection and paper writing. John R Adler is in charge of data handling and polishing the language.


    Article Information

    Published: June 07, 2012

    DOI

    10.7759/cureus.49

    Cite this article as:

    Wang X, Chang C, Adler J R., et al. (June 07, 2012) A Randomized Blinded Trial of Nucleus Accumbens Ablation to Treat Opiate Dependence in Humans: Location Correlates with Outcome. Cureus 4(6): e49. doi:10.7759/cureus.49

    Publication history

    Published: June 07, 2012

    Copyright

    © Copyright 2012
    Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License CC-BY 3.0., which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

    License

    This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Opiate addiction remains intractable in a large percentage of patients. Multiple studies identify a central role of the nucleus accumbens (NAc) in addiction; several studies note decreased addictive behavior after interventions in this area. In China, ablation of the NAc was common before November 2004, though it was poorly regulated. This study, a prospective randomized double-blinded trial carried out from January 2004 to November 2004, investigates the effect of different stereotactic lesions within NAc on opiate addiction to maximize benefit and minimize risk.

Methods: Seventy-eight opiate-dependent patients were treated at the Tangdu Hospital Fourth Military Medical University during Jan. 2004 to Nov. 2004 with bilateral stereotactic radiofrequency lesioning of the posteromedial one-third of NAc. Patients were randomly divided into four groups (A, B,C, and D). Relative to the initial target, the lesion in Group A was enlarged laterally and superiorly, in Group B anteriorly and superiorly, and in Group C laterally and anteriorly. Among these three groups, the lesion volume was identical. In Group D, the lesion extended laterally and anteriorly and superiorly. Using opiate abstinence as the primary endpoint, four years of follow-up data for all patients regarding relapse and complications were collected. This trial is supplementarily registered with Current Controlled Trials, number ISRCTN33954423.

Results:  Four patients were withdrawn at the fourth year post-operation. For convenience of interpretation, this article appointed these patients as relapses. The overall abstinence rate was 53.8% (42/78). The abstinence rates of Group C (75.0%) and Group D (76.2%) were higher than Groups A (31.3%) and B (28.6%) (p≤0.005). The neuropsychological adverse event rate was 24.3% (18/74) and did not differ statistically between the four groups.

Conclusions: Although sometimes accompanied by neuropsychological adverse events, stereotactic ablation of NAc may effectively treat opiate addiction. Lesion location significantly impacts treatment efficacy.



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Xuelian Wang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

For correspondence:
tdwxlian@126.com

Chongwang Chang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

John R. Adler, M.D.

Department of Neurosurgery, Stanford University School of Medicine

Nan Li, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Shunnan Ge, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Ning Geng, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Jing Wang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Xin Wang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Guodong Gao, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China, Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Xuelian Wang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

For correspondence:
tdwxlian@126.com

Chongwang Chang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

John R. Adler, M.D.

Department of Neurosurgery, Stanford University School of Medicine

Nan Li, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Shunnan Ge, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Ning Geng, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Jing Wang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Xin Wang, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China

Guodong Gao, None

Department of Neurosurgery, Tangdu Hospital, Xi'an, China, Department of Neurosurgery, Tangdu Hospital, Xi'an, China