The original publication is available at http://www.samj.org.za / Medical practitioners in South Africa are increasingly confronted with requests to treat patients with opioid use disorders. Many do not possess the required knowledge and skills to deal with these patients effectively. This overview of the medical treatment of opioid dependence was compiled by an elected working group of doctors working in the field of substance dependence. Recommendations are based on current best practice derived from scientific evidence and consensus of the working group, but should never replace individual clinical judgement. / Publishers' version

Thesis (M.A.)--Boston University / Cocaine use among opioid dependent persons is common, with an estimated 40 to 70% of those seeking treatment for opioid dependence, also using cocaine (Sullivan et al., 2011 ). The effects of cocaine use on treatment outcomes for those seeking medication assisted treatment (MAT) for opioid dependence are not well understood. Buprenorphine, prescribed under the brand name Suboxone, has recently emerged as a convenient, effective method of MAT. The Facilitated Access to Substance Abuse Treatment with Prevention And Treatment of HIV (FAST PATH) program at Boston Medical Center, is a research study to provide substance abuse treatment along with primary care and HIV risk-reduction counseling to those afflicted with these epidemics. The objective of this study was to determine the association of cocaine use with treatment retention and opioid abstinence at six months for patients receiving buprenorphine in the FAST PATH program. A prospective cohort study was conducted on 116 patients enrolled in the FAST PATH program through 02/01/2012. Assessments were conducted at baseline and six months to evaluate the association between baseline cocaine use and treatment retention as well as opioid abstinence at six months. Baseline cocaine use was measured by either any urine toxicology screen positive for cocaine prior to study enrollment or 30 day self-reported cocaine use on the initial assessment. Of the 116 participants, 39% were positive for cocaine use at baseline and 52% were HIV positive. Baseline cocaine use had no effect significant on treatment retention or opioid abstinence at six months. Among all the participant characteristics measured, there were no significant differences between the cocaine positive (n=45) and cocaine negative (n=71) groups. In adjusted analysis, age was the only covariate which was significant at predicting the odds of treatment retention or opioid abstinence with a 1.11 (p-value = 0.0003) and 1.08 (p-value = 0.02) greater odds of each, respectively. Although cocaine use did not affect the dependent variables, integrated substance abuse and primary care clinics utilizing buprenorphine are a rich area of future research. Specifically, subsequent studies should determine how varied groups of opioid dependent persons perform within this framework, and the underlying characteristics moderating their outcomes.

Class of 2014 Abstract / Specific Aims: To show that Suboxone is more effective than no MAT (Medically Assisted Treatment) in opioid dependence. Additionally, that Suboxone is as effective as methadone in MAT. Methods: This study was a retrospective chart review of probationer’s case files at The Pima County Adult Probation Office. Treatment groups included: Suboxone (n=16), methadone (n=15), and no MAT control group (n=15). The total sample size was 46 probationers. The primary dependent variables were the number of negative events and time to a negative event (i.e. missed/positive urinalysis, violation of terms of probation). The secondary outcome variables were the number of positive events and time to a positive event (i.e. finding employment, documented social/family improvement). Data analysis utilized chi-square for categorical data while t-tests were used for continuous data. Main Results: 46 probationers of Pima County with violations related to possession or use of an opioid substance were analyzed. No significant differences were found between Suboxone and placebo (no MAT) for any of the four outcomes (number of negative events p=0.82; time to first negative event p=0.41; number of positive events p=0.93; time to first positive event p=0.45). No significant differences were found between Suboxone and methadone as well (number of negative events p=0.34; time to first negative event p=0.52; number of positive events p=0.93; time to first positive event p=0.56). Conclusion: This study found no statistically significant differences between no MAT and Suboxone nor Suboxone and methadone. Differences in baseline characteristics between groups were found that could characterize the Suboxone group as being more severely ill.

Suicide attempts and opioid dependence are important clinical issues, as both are associated with a high degree of psychiatric morbidity and elevated risk of mortality. Research has identified a number of risk factors for suicide attempts among the general population, and to a lesser extent, among heroin users. Due to a lack of case-control studies, however, it is still not known to what extent opioid dependence per se is a risk factor for suicide attempts. This thesis comprised the first study to directly examine whether opioid dependence is a unique risk factor of suicide attempts. This thesis examined suicide attempts, associated risk factors, and related comorbidity among an opioid-dependent case group and a non-opioid-dependent control group. A structured interview was used to collect data from 726 opioid-dependent cases and 399 non-opioid-dependent controls. This thesis identified a number of important findings. Firstly, although opioid-dependent individuals were more likely to report lifetime suicide attempts compared to controls, the risk factors were largely the same for both groups. It appeared that opioid-dependent individuals were characterised by a higher likelihood of the same risk factors for suicide attempts, rather than having different risks. Cases appeared to be at increased risk of suicide attempts because of increased levels of multiple risk factors. Secondly, borderline personality disorder (BPD) and impulsivity were identified as important risk markers for suicidal behaviour, especially among opioid-dependent individuals. The study concluded that the treatment of BPD should be prioritised among this group. Third, self-mutilation was identified as a clinically significant problem in its own right, however, when combined with a history of attempted suicide, the psychological dysfunction observed was found to be very high. Fourth, non-fatal opioid overdose and suicide attempts were found to be distinct behaviours. The risk factors for each were completely different. While drug-related risks were associated with non-fatal overdose, the risk markers for suicide attempts were related to the presence of psychological disorders. This thesis has highlighted important areas of concern for clinical interventions as well as for future research to explore. Considering this is the first study of its kind, future research should focus on its replication.

Suicide attempts and opioid dependence are important clinical issues, as both are associated with a high degree of psychiatric morbidity and elevated risk of mortality. Research has identified a number of risk factors for suicide attempts among the general population, and to a lesser extent, among heroin users. Due to a lack of case-control studies, however, it is still not known to what extent opioid dependence per se is a risk factor for suicide attempts. This thesis comprised the first study to directly examine whether opioid dependence is a unique risk factor of suicide attempts. This thesis examined suicide attempts, associated risk factors, and related comorbidity among an opioid-dependent case group and a non-opioid-dependent control group. A structured interview was used to collect data from 726 opioid-dependent cases and 399 non-opioid-dependent controls. This thesis identified a number of important findings. Firstly, although opioid-dependent individuals were more likely to report lifetime suicide attempts compared to controls, the risk factors were largely the same for both groups. It appeared that opioid-dependent individuals were characterised by a higher likelihood of the same risk factors for suicide attempts, rather than having different risks. Cases appeared to be at increased risk of suicide attempts because of increased levels of multiple risk factors. Secondly, borderline personality disorder (BPD) and impulsivity were identified as important risk markers for suicidal behaviour, especially among opioid-dependent individuals. The study concluded that the treatment of BPD should be prioritised among this group. Third, self-mutilation was identified as a clinically significant problem in its own right, however, when combined with a history of attempted suicide, the psychological dysfunction observed was found to be very high. Fourth, non-fatal opioid overdose and suicide attempts were found to be distinct behaviours. The risk factors for each were completely different. While drug-related risks were associated with non-fatal overdose, the risk markers for suicide attempts were related to the presence of psychological disorders. This thesis has highlighted important areas of concern for clinical interventions as well as for future research to explore. Considering this is the first study of its kind, future research should focus on its replication.

Opioid dependence is a complex and persistent disorder with a high mortality rate and severe impact on health and social situation. It is associated with much harm, including the transmission of blood-borne bacterial and viral infections, self-harm, traumatic injury and drug overdose. All of these harms carry a risk of death, and accordingly, mortality rates in opioid-dependent people are many times higher than those in the general population of the same age and sex. One of the more commonly used strategies for reducing the risks of opioid dependence is the provision of maintenance treatment. In Australia, available maintenance treatments include methadone, buprenorphine, oral naltrexone, and the unregistered sustained-release formulation of naltrexone, naltrexone implants. This thesis reports on a range of data collections and study designs to investigate the levels, predictors and causes of mortality in opioid-dependent persons entering methadone, buprenorphine and naltrexone maintenance treatment in Australia. The studies used data linkage to examine mortality rates and causes of death in a longitudinal cohort of the early entrants to the NSW methadone program, examined the predictors of mortality (particularly the impact of methadone and buprenorphine treatment) using survival analysis in a longitudinal cohort study, compared national mortality rates between methadone, buprenorphine and naltrexone maintenance treatments in a cross-sectional analytic study, and used a small case series of coronial cases to examine whether death from opioid overdose was possible in a recipient of a naltrexone implant. This thesis demonstrates that mortality rates as a whole and from particular causes of death are many times higher in Australian opioid-dependent subjects than the general population, exposure to methadone or buprenorphine maintenance treatment significantly reduced mortality in a sample of opioid-dependent subjects, naltrexone treatment appears to have higher mortality than both methadone and buprenorphine maintenance treatments, and fatal opioid overdose while in receipt of sustained-release naltrexone treatment is possible. These results support longer retention in and repeated access to methadone and buprenorphine maintenance treatments in order to reduce mortality in opioid-dependent people, and greater regulation of the access to and more rigorous monitoring of the mortality associated with oral and sustained-release naltrexone maintenance treatments.

Opioid dependence is a complex and persistent disorder with a high mortality rate and severe impact on health and social situation. It is associated with much harm, including the transmission of blood-borne bacterial and viral infections, self-harm, traumatic injury and drug overdose. All of these harms carry a risk of death, and accordingly, mortality rates in opioid-dependent people are many times higher than those in the general population of the same age and sex. One of the more commonly used strategies for reducing the risks of opioid dependence is the provision of maintenance treatment. In Australia, available maintenance treatments include methadone, buprenorphine, oral naltrexone, and the unregistered sustained-release formulation of naltrexone, naltrexone implants. This thesis reports on a range of data collections and study designs to investigate the levels, predictors and causes of mortality in opioid-dependent persons entering methadone, buprenorphine and naltrexone maintenance treatment in Australia. The studies used data linkage to examine mortality rates and causes of death in a longitudinal cohort of the early entrants to the NSW methadone program, examined the predictors of mortality (particularly the impact of methadone and buprenorphine treatment) using survival analysis in a longitudinal cohort study, compared national mortality rates between methadone, buprenorphine and naltrexone maintenance treatments in a cross-sectional analytic study, and used a small case series of coronial cases to examine whether death from opioid overdose was possible in a recipient of a naltrexone implant. This thesis demonstrates that mortality rates as a whole and from particular causes of death are many times higher in Australian opioid-dependent subjects than the general population, exposure to methadone or buprenorphine maintenance treatment significantly reduced mortality in a sample of opioid-dependent subjects, naltrexone treatment appears to have higher mortality than both methadone and buprenorphine maintenance treatments, and fatal opioid overdose while in receipt of sustained-release naltrexone treatment is possible. These results support longer retention in and repeated access to methadone and buprenorphine maintenance treatments in order to reduce mortality in opioid-dependent people, and greater regulation of the access to and more rigorous monitoring of the mortality associated with oral and sustained-release naltrexone maintenance treatments.

Prescription opioid (PO) abuse is a growing public health concern worldwide as evidenced by an increasing number of opioid-related hospital admissions with a striking lack of research examining the neural basis underlying cognitive symptomatology. Drugs of abuse, through their impact on the dopaminergic system, are thought to disrupt the cognitive network regulating impulse control and incentive salience through inhibition of goal-oriented behaviour and drug-induced attentional biases. The objective of the present study is to examine neurocognitive processes in PO abusers (vs. healthy controls) by relying on the enhanced temporal resolution (1ms) of event-related potentials (ERPs) to track information processing abnormalities associated with cognitive control. In a naturalistic clinical study, 16 patients actively using prescription opioids and 16 healthy controls (matched for age, gender, educational level and smoking status) were assessed using a Go/NoGo and cue reactivity paradigm. Analysis revealed no significant differences in N2 or P3 amplitude, measures of inhibitory control, between groups after successful NoGo trials and no significant differences in ERN or Pe amplitude, measures of error processing, between groups after unsuccessful NoGo trials. Cue reactivity analysis of attention-related ERP components in patients demonstrated significantly (p<0.005) smaller P2 amplitudes, indexing the commencement of attentional processing, for drug pictures compared to neutral and affective pictures. Furthermore, stimulus type did not significantly modulate LPP amplitudes, indexing sustained attention, in patients however arousal ratings for drug pictures were positively correlated with LPP amplitudes in patients. These ERP results of altered cognitive control and incentive salience suggest the neural mechanisms underlying these cognitions are affected by chronic opioid abuse. Investigating the cognitive abnormalities experienced by PO abusers is an important factor in understanding the neural correlates of substance abuse and in predicting successful outcomes to ensure the best chance at long-term recovery for addicted individuals.

Previous research on college students has found that cooperation in iterated prisoner's dilemma game is correlated with preference for delayed rewards in studies of temporal discounting. The present study attempted to replicate this finding in a drug-dependent population. Thirty-one individuals who intranasally abuse prescription opioids participated in temporal discounting and iterated prisoner's dilemma game procedures during intake for a treatment study. Rate of temporal discounting was determined for each participant at two hypothetical reward magnitudes, as well as proportion of cooperation in a 60-trial iterated prisoner's dilemma game versus a tit-for-tat strategy. Cooperation in the prisoner's dilemma game and temporal discounting rates were significantly correlated in the predicted direction: individuals who preferred delayed rewards in the temporal discounting task were more likely to cooperate in the prisoner's dilemma game.

National rates of chronic non-cancer pain (CNCP) are rising alongside increasing reports of prescription opioid abuse and mortality. Associations between the rise in CNCP and in opioid abuse seem logical, yet research on CNCP among individuals with opioid dependence is currently limited due to the complicated nature of comorbid conditions in research and treatment. This study aims to expand the CNCP knowledge base by responding to the question: Do individuals with CNCP participating in an opiate treatment program have better or worse treatment outcomes than individuals without CNCP? This study used a secondary dataset including 483 adults from Kentucky’s Opiate Recovery Treatment Outcome Study. Individuals in the sample met DSM-IV-TR criteria for opioid dependence and were in treatment at a licensed opiate treatment program (OTP). Analysis compared cases with and without CNCP on national treatment outcome measures including substance use, recovery support, education, employment, mental health symptoms, and criminal justice system involvement. Results indicated no differences at follow-up between the CNCP (n=163) and non-CNCP (n=320) individuals on substance abstinence, recovery supports, education level, or criminal justice system involvement. At baseline and follow-up there were more unemployed individuals and individuals receiving disability benefits in the CNCP group than the non-CNCP group. Reported anxiety and depression symptoms increased at follow-up, while use of prescription medicine for mental health symptoms declined for both groups (non-significant differences). The only predictors for CNCP cases in this sample were tobacco use and presence of a chronic medical condition. Recommendations include expansion of smoking cessation programs in substance abuse treatment settings. Future research might examine integrated treatment and medical home health models to better address biopsychosocial components of clients with comorbid conditions like opioid dependence and CNCP.