Browsing by Author "Peindl, Kathleen S"
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Item Open Access Buprenorphine-mediated transition from opioid agonist to antagonist treatment: state of the art and new perspectives.(Current drug abuse reviews, 2012-03) Mannelli, Paolo; Peindl, Kathleen S; Lee, Tong; Bhatia, Kamal S; Wu, Li-TzyConstant refinement of opioid dependence (OD) therapies is a condition to promote treatment access and delivery. Among other applications, the partial opioid agonist buprenorphine has been studied to improve evidence-based interventions for the transfer of patients from opioid agonist to antagonist medications. This paper summarizes PubMed-searched clinical investigations and conference papers on the transition from methadone maintenance to buprenorphine and from buprenorphine to naltrexone, discussing challenges and advances. The majority of the 26 studies we examined were uncontrolled investigations. Many small clinical trials have demonstrated the feasibility of in- or outpatient transfer to buprenorphine from low to moderate methadone doses (up to 60-70 mg). Results on the conversion from higher methadone doses, on the other hand, indicate significant withdrawal discomfort, and need for ancillary medications and inpatient treatment. Tapering high methadone doses before the transfer to buprenorphine is not without discomfort and the risk of relapse. The transition buprenorphine-naltrexone has been explored in several pilot studies, and a number of treatment methods to reduce withdrawal intensity warrant further investigation, including the co-administration of buprenorphine and naltrexone. Outpatient transfer protocols using buprenorphine, and direct comparisons with other modalities of transitioning from opioid agonist to antagonist medications are limited. Given its potential salience, the information gathered should be used in larger clinical trials on short and long-term outcomes of opioid agonist-antagonist transition treatments. Future studies should also test new pharmacological mechanisms to help reduce physical dependence, and identify individualized approaches, including the use of pharmacogenetics and long-acting opioid agonist and antagonist formulations.Item Open Access Extended release naltrexone injection is performed in the majority of opioid dependent patients receiving outpatient induction: a very low dose naltrexone and buprenorphine open label trial.(Drug and alcohol dependence, 2014-05) Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S; Swartz, Marvin S; Woody, George EThe approval of extended release injectable naltrexone (XR-NTX; Vivitrol(®)) has introduced a new option for treating opioid addiction, but studies are needed to identify its place within the spectrum of available therapies. The absence of physiological opioid dependence is a necessary and challenging first step for starting XR-NTX. Outpatient detoxification gives poor results and inpatient detoxification is either unavailable or too brief for the physiological effects of opioids to resolve. Here we present findings from an open label study that tested whether the transition from opioid addiction to XR-NTX can be safely and effectively performed in an outpatient setting using very low dose naltrexone and buprenorphine.Twenty treatment seeking opioid addicted individuals were given increasing doses of naltrexone starting at 0.25mg with decreasing doses of buprenorphine starting at 4 mg during a 7-day outpatient XR-NTX induction procedure. Withdrawal discomfort, craving, drug use, and adverse events were assessed daily until the XR-NTX injection, then weekly over the next month.Fourteen of the 20 participants received XR-NTX and 13 completed weekly assessments. Withdrawal, craving, and opioid or other drug use were significantly lower during induction and after XR-NTX administration compared with baseline, and no serious adverse events were recorded.Outpatient transition to XR-NTX combining upward titration of very low dose naltrexone with downward titration of low dose buprenorphine was safe, well tolerated, and completed by most participants. Further studies with larger numbers of subjects are needed to see if this approach is useful for naltrexone induction.Item Open Access Pharmacological enhancement of naltrexone treatment for opioid dependence: a review.(Subst Abuse Rehabil, 2011-06) Mannelli, Paolo; Peindl, Kathleen S; Wu, Li-TzyPURPOSE: Opioid dependence (OD) is a serious and growing clinical condition with increasing social costs that requires expanding treatment beyond opioid agonist substitution. The opioid antagonist naltrexone has displayed a remarkable association of theoretical effectiveness and poor clinical utility in treating OD due to noncompliant behavior and low acceptability among patients, only partly modified by psychosocial interventions. We reviewed pharmacological studies, including naltrexone depot formulations and combination treatments. METHOD: We searched PubMed for clinical studies on the use of naltrexone implants and slow-release injections in OD, and investigations using adjunct medications to improve naltrexone maintenance therapy of OD. We discussed the results in view of their application to the clinical practice. RESULTS: Significant reduction in opioid use and improved retention in treatment have been found in several studies using depot naltrexone formulations, some of which are controlled clinical trials. Pilot investigations have gathered initial positive results on the use of naltrexone in combination with serotonin reuptake inhibitors, α-2 adrenergic, opioid, and γ-aminobutyric acid agonist medications. CONCLUSION: Current evidence suggests that more research on effectiveness and safety is needed in support of depot naltrexone treatment for OD. Further research comparing slow-release with oral naltrexone and opioid agonist medications will help characterize the role of opioid antagonist-mediated treatment of OD. Preliminary investigations on naltrexone combination treatments suggest the opportunity to continue study of new mixed receptor activities for the treatment of OD and other drug addictions.Item Open Access Smoking and opioid detoxification: behavioral changes and response to treatment.(Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco, 2013-10) Mannelli, Paolo; Wu, Li-Tzy; Peindl, Kathleen S; Gorelick, David AThe relevance of tobacco use in opioid addiction (OA) has generated a demand for available and more effective interventions. Thus, further analysis of less explored nicotine-opioid clinical interactions is warranted.A post-hoc analysis of OA participants in a double-blind, randomized very low dose naltrexone (VLNTX) inpatient detoxification trial evaluated measures of opioid withdrawal and tobacco use. Intreatment smokers were compared with nonsmokers, or smokers who were not allowed to smoke.A total of 141 (81%) of 174 OA participants were smokers, all nicotine-dependent. Inpatient smoking was a predictor of opioid withdrawal discomfort. Intreatment smokers (n = 96) showed significantly higher opioid craving (F = 3.7, p < .001) and lower detoxification completion rate (χ(2) = 7.9, p < .02) compared with smokers who were not allowed to smoke (n = 45) or nonsmokers (n = 33). Smoking during treatment was associated with more elevated cigarette craving during detoxification (F = 4.1, p < .001) and a higher number of cigarettes smoked at follow-up (F = 3.6, p < .02). Among intreatment smokers, VLNTX addition to methadone taper was effective in easing opioid withdrawal and craving more than other treatments, whereas the combination VLNTX-clonidine was associated with significantly reduced cigarette craving and smoking during detoxification.Failure to address tobacco use may negatively affect pharmacologically managed opioid discontinuation. Opioid detoxification may offer a window of opportunity to expand smoking cessation treatment, hence improving OA outcomes. The observed effects support testing of VLNTX-clonidine in smoking cessation trials among individuals with or without substance abuse.