Acceptability of Extended-Release Naltrexone by Heroin-Dependent Patients and Addiction Treatment Providers in the Netherlands.

BACKGROUND: Extended-release naltrexone (XRNT) was developed to overcome poor treatment compliance with oral naltrexone in alcohol and opioid-dependent patients. XRNT injections are registered in the United States and Russia, but not in The Netherlands. However, XRNT can be obtained for individual patients, but it is expensive and not reimbursed by the health insurance. OBJECTIVES: This study evaluates the support for abstinence oriented treatment among heroin-dependent patients and the acceptability of XRNT injections by heroin-dependent patients and treatment providers in The Netherlands. METHODS: A sample of 261 patients in methadone maintenance treatment or heroin assisted treatment and a sample of 188 addiction treatment providers completed specially designed questionnaires. RESULTS: The current study shows that many patients in opioid maintenance treatment (58%) report a desire to become abstinent from opioids and that 83% of the patients with a desire for abstinence are interested in XRNT. The majority of treatment providers (81%) are willing to support the prescription of XRNT injections in opioid-dependent patients to prevent relapse after detoxification. CONCLUSIONS: The current practice of automatic and indefinite continuation of opioid substitution should therefore be reconsidered. However, XRNT injections are very expensive and currently not reimbursed by the health insurance agencies in The Netherlands and thus not really available to most patients.

Hemodynamic predictors of aortic dilatation in bicuspid aortic valve by velocity-encoded cardiovascular magnetic resonance.

BACKGROUND: Congenital bicuspid aortic valve (BAV) is a significant risk factor for serious complications including valve dysfunction, aortic dilatation, dissection, and sudden death. Clinical tools for identification and monitoring of BAV patients at high risk for development of aortic dilatation, an early complication, are not available. METHODS: This paper reports an investigation in 18 pediatric BAV patients and 10 normal controls of links between abnormal blood flow patterns in the ascending aorta and aortic dilatation using velocity-encoded cardiovascular magnetic resonance. Blood flow patterns were quantitatively expressed in the angle between systolic left ventricular outflow and the aortic root channel axis, and also correlated with known biochemical markers of vessel wall disease. RESULTS: The data confirm larger ascending aortas in BAV patients than in controls, and show more angled LV outflow in BAV (17.54 +/- 0.87 degrees) than controls (10.01 +/- 1.29) (p = 0.01). Significant correlation of systolic LV outflow jet angles with dilatation was found at different levels of the aorta in BAV patients STJ: r = 0.386 (N = 18, p = 0.048), AAO: r = 0.536 (N = 18, p = 0.022), and stronger correlation was found with patients and controls combined into one population: SOV: r = 0.405 (N = 28, p = 0.033), STJ: r = 0.562 (N = 28, p = 0.002), and AAO r = 0.645 (N = 28, p < 0.001). Dilatation and the flow jet angle were also found to correlate with plasma levels of matrix metallo-proteinase 2. CONCLUSIONS: The results of this study provide new insights into the pathophysiological processes underlying aortic dilatation in BAV patients. These results show a possible path towards the development of clinical risk stratification protocols in order to reduce morbidity and mortality for this common congenital heart defect.

Subchronic administration of short-acting naltrexone has no effect on striatal dopamine transporter availability, food intake or body weight gain in rats.

The opioid receptor antagonist naltrexone is successfully used in the treatment of opioid and alcohol dependence. However, questions have been raised about possible anhedonic side effects, because the opioid system is directly involved in hedonic responses to natural rewarding activities, possibly due to its indirect effects on the striatal dopamine transporter (DAT). In order to test this hypothesis, 30 rats were randomized to either a 10-day treatment with 3 mg/kg short-acting naltrexone or vehicle. No significant differences between the groups were found in striatal DAT availability, cumulative food intake (for 48 or 72 h), body weight gain and abdominal fatpad weight. Thus, the results of this study suggest that (sub)chronic treatment with short-acting naltrexone does not induce possible anhedonic effects. However, it cannot be ruled out the anhedonic effect of naltrexone is only short-lived and thus not detected in the current study. Therefore, future studies are needed to study possible acute anhedonic effects at several time points shortly after short-acting naltrexone administration and to directly compare the possible anhedonic effects of long-acting with those of short-acting opioid antagonists.

Effect of extended-release naltrexone on striatal dopamine transporter availability, depression and anhedonia in heroin-dependent patients.

RATIONALE: Extended-release naltrexone (XRNT), an opioid receptor antagonist, is successfully used in the treatment of opioid dependence. However, naltrexone treatment of opioid-dependent patients may reduce striatal dopamine transporter (DAT) availability and cause depression and anhedonia. OBJECTIVES: The aim of this study is to investigate changes in striatal DAT availability and symptoms of depression (Beck Depression Inventory (BDI)) and anhedonia (Snaith Hamilton Pleasure Scale (SHAPS)) before and during XRNT treatment. METHODS: At baseline, ten detoxified heroin-dependent patients and 11 matched healthy controls underwent [(123)I]FP-CIT single photon emission computed tomography (SPECT) imaging to assess striatal DAT binding. Patients underwent a second SPECT scan 2 weeks after an intramuscular injection with XRNT. RESULTS: At baseline, the mean binding potential (BPND) in the putamen was at a trend level lower and the mean BDI score was significantly higher in heroin patients (n = 10) than in controls (n = 11) (3.45 ± 0.88 vs. 3.80 ± 0.61, p = 0.067, d = -0.48 and 12.75 ± 7.40 vs. 5.20 ± 4.83, p = 0.019, d = 1.24, respectively). Post hoc analyses in subgroups with negative urine analyses for opioids and cocaine showed significantly lower baseline putamen BPND in heroin patients (n = 8) than controls (n = 10) (3.19 ± 0.43 vs. 3.80 ± 0.64, p = 0.049, d = -1.03). XRNT treatment in heroin patients was not significantly associated with changes in striatal DAT availability (p = 0.348, d = 0.48), but the mean BDI score after XRNT treatment was significantly lower than before treatment (7.75 ± 7.21 vs. 12.75 ± 7.40, p = 0.004, d = -0.68). CONCLUSIONS: The results of this study suggest that XRNT treatment does not reduce striatal DAT availability and has no significant effect on anhedonia, but is associated with a significant reduction of depressive symptoms.

Personality as a risk factor for illicit opioid use and a protective factor for illicit opioid dependence.

BACKGROUND: Most studies investigating the role of personality as a risk factor for the development of opioid dependence compare dependent opioid users with healthy controls who never used heroin. In order to understand the potential protective role of personality, it is crucial to compare illicit opioid users who never became dependent with dependent opioid users. AIMS: This study aims to examine the role of personality as a risk factor for opioid use and as a protective factor for the development of opioid dependence. METHODS: Comparing personality factors between three groups: (1) 161 never-dependent illicit opioid users who have been using illicit opioids but never became opioid dependent; (2) 402 dependent opioid users in methadone maintenance treatment or heroin-assisted treatment; and (3) 135 healthy controls who never used heroin. Personality was assessed with a short version of Cloninger's Temperament and Character Inventory. RESULTS: Never-dependent opioid users reported more Novelty Seeking and Harm Avoidance and less Self-Directedness and Cooperativeness than healthy controls and more Reward Dependence and Self-Directedness, and less Harm Avoidance than dependent opioid users. Furthermore, never-dependent opioid users reported more Self-Transcendence than both dependent opioid users and healthy controls. CONCLUSIONS: Never-dependent opioid users may have started to use opioids partly due to their tendency to seek novel and/or spiritual experiences (high Novelty Seeking, high Self-Transcendence) and their tendency to avoid aversive stimuli (high Harm Avoidance), whereas they may have been protected against the development of dependence by their need for social approval (high Reward Dependence) and their self-efficacy (high Self-Directedness).