Original Article Factors Affecting Norbuprenorphine Level in Monitoring Clinical Outcome for Buprenorphine-maintained Patients Ayman Fareed, MD,*w Kelly Scheinberg, MD,* Sreedevi Vayalapalli, MD,*w Steven Stout, MD, PhD,wz Robin Gale, RN, MSN, ARNP, GNP, PMHNP-BC,w Aalok Chandora, MD,* and Karen Drexler, MD,*w Abstract Background: We conducted an observational retrospective chart review to determine whether buprenorphine or norbu- prenorphine levels could predict treatment outcomes. Methods: Of the 174 patients treated in the clinic between 2006 and 2012, 123 were excluded from the study because they did not have a buprenorphine/norbuprenor- phine level done at the time of data collection. Thus, 51 patient charts were selected for review. Results: The multiple regression analysis of the predictable variables for positive urine drug screen (UDS) before and after the level showed that norbuprenorphine level (P = 0.018 before and P = 0.02 after the level) and the primary drug of addiction (P = 0.047 before and P = 0.01 after the level) are significantly associ- ated with positive UDS for opiates before and after the level (R 2 = 0.06 and R 2 = 0.09, respectively). The multiple regression analysis of the predictable vari- ables for norbuprenorphine level showed that age (P = 0.01), race (P = 0.006), hepatitis C status, (P = 0.006), primary drug of addiction (P = 0.0001), and buprenorphine dose (P = 0.0003) are signifi- cantly associated with higher levels of norbuprenor- phine (R 2 = 0.70). The positive UDS for cocaine (P = 0.02) before the level is significantly associated with lower norbuprenorphine level (R 2 = 0.70). Conclusions and Scientific Significance: This study suggests that norbuprenorphine levels could be used to guide dosing of buprenorphine, as well as determining whether taking buprenorphine would continue to be beneficial or whether a full agonist may be needed. This study opens the door for further studies on how buprenorphine levels may be used to guide treatment in the clinical setting. Key Words: norbuprenorphine, outcome, buprenor- phine maintenance (Addict Disord Their Treatment 2013;12:167–174) B uprenorphine is a partial m-opioid receptor agonist that has been ap- proved by the Food and Drug Admin- istration for office-based treatment of opioid dependence since 2002. 1 Several studies reported that buprenorphine is a safe and effective medication for treat- ment of opioid dependence in both the inpatient and outpatient setting. 2–6 It has several pharmacological properties that make it particularly advantageous in the outpatient setting, where the safety profile of a medication is of great con- cern. Buprenorphine has a ceiling effect that reduces its risk for overdose as compared with full agonists such as mor- phine or methadone. 7–10 Doses >24 to 32 mg daily would not increase its respi- ratory-depressant effect. 8–10 The ceiling effect also lowers the abuse potential of buprenorphine by limiting the subjective euphoric effect with escalating doses. 11 The drug has a strong affinity and slow dissociation from m-receptors, which re- sult in a milder withdrawal syndrome upon discontinuation as well. Buprenorphine has been shown in several studies to have positive treat- ment outcomes including lowering illic- it use of opioids, reducing cravings, and maintaining retention in treat- ment. 3–5,12–15 More recently, studies have shown that higher ranges of bu- prenorphine (16 to 32 mg daily) are more effective in reducing illicit use [as measured by positive urine drug screen (UDS)] and cravings for opioids than lower doses. 16–20 Concentrations of buprenorphine and its major metabolite, norbuprenor- phine, can be measured both in serum and in urine. 21,22 International guide- lines on buprenorphine advise prescrib- ers to routinely use objective methods to validate compliance with treatment, ADDICTIVE DISORDERS & THEIR TREATMENT Volume 12, Number 4 December 2013 167 From the *Department of Psychiatry, School of Medicine, Emory University; zDepartment of Psychiatry, Morehouse School of Medicine, Atlanta; wAtlanta VA Medical Center, Decatur, GA A.F. and K.S. contributed equally and both are considered first authors. The authors declare no conflict of interest. Reprints: Ayman Fareed, MD, Atlanta VA Medical Center 116A, 1670 Clairmont Rd, Decatur, GA 30033 (e-mail: ayman.fareed@va.gov). Copyright r 2012 by Lippincott Williams & Wilkins www.addictiondisorders.com DOI: 10.1097/ADT.0b013e31826d1dda