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- [Mental health service utilization among borderline personality disorder patients inpatient.] [JOURNAL ARTICLE]
- Encephale 2014 Dec 16.
Borderline personality disorder (BPD) is characterized by a pervasive pattern of instability and impulsivity. Several North American prospective studies support the high level of mental health care utilization in this population. There is little data in other systems of health organization, such as France. Furthermore, little is known on the variables associated with the mental health service utilization among BPD patients.The main objective was to compare the utilization of mental health care among BPD patients, to the general population and patients with another personality disorder (PD) and to describe the demographic and clinical factors associated with the group of patients who use the most health care.A multi-center (5 public and private centers), epidemiological study. Data were collected prospectively (database of an insurance fund covering 80% of the population) and viewed, retrospectively. We used the data collected during the five years previously to the inclusion. Inclusion criteria were age (18-60 years) and membership in the health insurance fund targeted. Patients on legal protection, forced hospitalization, with a chronic psychotic disorder, manic, mental retardation, or not reading French were excluded. First, four groups were composed: BPD, other PD, control groups for PD and other PD. The first two groups were recruited from a screening of inpatients including a self-administered questionnaire (Personality Disorder Questionnaire 4+). Assessment by a psychologist including the Structured Interview for DSM-IV Personality Disorders (SIDP-IV) was given straight to those who had a score above 28. This questionnaire allowed us to distinguish one group of subjects with BPD and a group with other PD (without BPD). Clinical evaluation included Axis I (MINI), Axis II (SIDP-IV), psychopathological features (YSQ-I, DSQ-40), demographic variables and therapeutic alliance (Haq-II). Matched controls (age, sex) composed the 3rd and 4th group (BPD control and other PD control). They were randomly chosen in the health database insurance previously used.One hundred and thirty-seven (95.8%) screened patients agreed to answer the psychological assessment. In this sample, 44 (32.1%) had BPD, 39 (28.5%) other PD and another 39 (28.5%) did not have PD. The BPD group was compared to a sample of 165 matched subjects and the other group PD to a sample of 123 matched controls. There was no difference between BPD and other PD groups regarding the mental health utilization. However, there was an increased use of hospitalizations and deliverances of nervous system drugs in both clinical groups compared to their controls. The analysis of drugs supplied in pharmacies for BPD patients showed that the first two drugs were opiate substitutes (12.3% methadone, buprenorphine 6.7%). No anticonvulsants or atypical antipsychotics appear in the top 20 of treatments delivered. A composite variable (hospitalization for more than 6 months during previous five years and 500 supplied drugs) allowed the discrimination of two groups among patients with BPD: heavy users of care and low care users. No variables (demographics, Axis I, Axis II, self-aggressiveness, DSQ-40, Haq-II, YSQ-I) could discriminate the two groups except the number of previous psychotherapies (heavy users: n=0.4 (SD 0.5) vs low users: n=1.8 (SD 2.1) P=0.0054).This study confirms the important use of the service of BPD patients in France, as well as the possible moderating role of psychotherapy. We found a mismatch between these uses and recommendations.
- Spontaneous Pain-Like Behaviors Are More Sensitive to Morphine and Buprenorphine Than Mechanically Evoked Behaviors in a Rat Model of Acute Postoperative Pain. [JOURNAL ARTICLE]
- Anesth Analg 2014 Dec 18.
Nonevoked spontaneous pain is most problematic for postoperative patients. Physicians assess this form of pain using the human visual analog scale or verbal numeric rating scale. Recent studies have proposed that spontaneous foot-lifting (SFL) behaviors are an expression of spontaneous pain in animals after spinal nerve injury or adjuvant-induced inflammation. In the current study, we characterize SFL behaviors in a rat model of acute postoperative pain, which includes comparisons with evoked behaviors to analgesic treatments.SFL was manually recorded over four 5-minute periods with 10-minute intervals between each testing session. Paw-withdrawal thresholds were subsequently measured with an electronic von Frey esthesiometer. To evaluate the effects of age, rats were tested in different age groups: 2, 7, and >26 months. The effects of buprenorphine and morphine were tested in a separate group of animals, which received intraperitoneal injections of saline, morphine (0.01, 0.1, 1, or 2 mg/kg), or buprenorphine (0.001, 0.01, or 0.1 mg/kg) before testing.SFL behaviors peaked at 3 hours after incision and significantly recovered by the 3rd or 4th postoperative day (P < 0.0001). The presentation of these behaviors did not significantly vary with animal age (2, 7, and >26 months old; P = 0.30). SFL behaviors, with the exception of rapid SFL at 3 hours after incision, did not show significant correlation with paw-withdrawal threshold behaviors. The median effective dose of buprenorphine for reversal of mechanical hyperalgesia (0.0452 mg/kg; 95% CI, 0.0259-0.0787) was significantly larger than for reversing rapid (0.0027 mg/kg; 95% CI, 0.0009-0.0083; P < 0.0001) and prolonged (0.0004 mg/kg, 95% CI, 0.0000, 0.0035; P = 0.001) SFL at 3 hours after incision. Similarly, the median effective dose of morphine for reversal of mechanical hypersensitivity behaviors (2.901 mg/kg; 95% CI, 1.132-7.436) was larger than for SFL count (0.4044 mg/kg; 95% CI, 0.1048-1.561; P = 0.0103) and SFL duration (0.0309 mg/kg; 95% CI, 0.0095-0.0998; P < 0.0001) at 3 hours after incision.The present study demonstrates that a hindpaw plantar incision induces SFL behaviors in rats and that these behaviors have higher bioassay sensitivity to analgesic interventions with morphine and buprenorphine compared with mechanically evoked behaviors.
- Buprenorphine transdermal system compared with placebo reduces interference in functioning for chronic low back pain. [JOURNAL ARTICLE]
- Postgrad Med 2014 Dec 15.:1-8.
Abstract Objective: This study examines the efficacy of the buprenorphine transdermal system (BTDS) for reducing the interference of pain on physical and emotional functioning associated with chronic low back pain (CLBP). Methods: A post-hoc analysis used data from a randomized, placebo-controlled, double-blind trial of patients with moderate-to-severe CLBP. The Brief Pain Inventory (BPI) measured pain interference at screening, following a run-in period, and during the 12-week double-blind treatment phase. Statistical analyses examined treatment arm differences (BTDS vs placebo) for the following: BPI Interference subscale items and subscale scores at the trial end point (week 12); patterns of change in the Interference subscale scores over time; proportions of patients indicating mild or no interference following treatment; and proportions of patients showing improvement (30%, 50%, 2-point, or 4-point change in score from screening to week 12) for each item and subscale. Results: Mean scores for BPI Interference items and Interference subscale were significantly lower (ie, indicated less interference) for BTDS than for placebo (all P < 0.001). Treatment arm differences in Interference subscale scores emerged within 4 weeks of treatment. The BTDS patients were significantly more likely to indicate mild/no interference on 5 of 7 Interference subscale items following treatment (P < 0.05). For most comparisons, BTDS patients were significantly more likely to show criterion-level improvements in Interference item and subscale scores (P < 0.05 for differences). Discussion: Results indicate the efficacy of BTDS treatment, compared with placebo, for reducing the interference of pain on physical and emotional functioning in patients with moderate-to-severe CLBP. The advantage of BTDS was observed within 4 weeks of treatment, and was maintained throughout the 12-week treatment phase.
- The Prescription of Addiction Medications After Implementation of Chronic Care Management for Substance Dependence in Primary Care. [JOURNAL ARTICLE]
- J Subst Abuse Treat 2014 Dec 2.
People with addictive disorders commonly do not receive efficacious medications. Chronic care management (CCM) is designed to facilitate delivery of effective therapies. Using data from the CCM group in a trial testing its effectiveness for addiction (N=282), we examined factors associated with the prescription of addiction medications. Among participants with alcohol dependence, 17% (95% CI 12.0-22.1%) were prescribed alcohol dependence medications. Among those with drug dependence, 9% (95% CI 5.5-12.6%) were prescribed drug dependence medications. Among those with opioids as a substance of choice, 15% (95% CI 9.3-20.9%) were prescribed opioid agonist therapy. In contrast, psychiatric medications were prescribed to 64% (95% CI 58.2-69.4%). Absence of co-morbid drug dependence was associated with prescription of alcohol dependence medications. Lower alcohol addiction severity and recent opioid use were associated with prescription of drug dependence medications. Better understanding of infrequent prescription of addiction medications, despite a supportive clinical setting, might inform optimal approaches to delivering addiction medications.
- A conjugate vaccine attenuates morphine- and heroin-induced behavior in rats. [JOURNAL ARTICLE]
- Int J Neuropsychopharmacol 2014 Dec 7.
Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies.A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized, with 6-glutarylmorphine as the hapten and a lengthened linker of six carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed.After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse.These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin.
- The A6V polymorphism of the human μ-opioid receptor negatively impacts signalling of morphine and endogenous opioids in vitro. [JOURNAL ARTICLE]
- Br J Pharmacol 2014 Dec 17.
Polymorphisms of the μ-opioid receptor (MOPr) may contribute to the variation in responses to opioid drugs in clinical and unregulated situations. The A6V variant of MOPr (MOPr-A6V) is present in up to 20% of individuals in some populations, and may be associated with heightened susceptibility to drug abuse. There are no functional studies examining the acute signalling of MOPr-A6V in vitro, so we investigated potential functional differences between MOPr and MOPr-A6V at several signalling pathways using structurally distinct opioid ligands.CHO and AtT-20 cells stably expressing MOPr and MOPr-A6V used. Adenylyl cyclase (AC) inhibition and ERK1/2 phosphorylation assays were conducted in CHO cells, assays of K channel activation in AtT-20 cells.Buprenorphine did not inhibit AC or stimulate ERK1/2 phosphorylation in CHO cells expressing MOPr-A6V, but buprenorphine activation of K channels in AtT-20 cells was preserved. DAMGO, morphine and β-endorphin inhibition of AC was significantly reduced via MOPr-A6V, as was signalling of all opioids to ERK1/2. However, there was little effect of the A6V variant on K channel activation.This study shows that signalling to AC and ERK via MOPr-A6V is reduced for many opioids, including the clinically significant drugs morphine, buprenorphine and fentanyl, as well endogenous opioids. The MOPr-A6V variant can be common and this compromised signalling may affect individual responses to opioid therapy, while the possible disruption of the endogenous opioid system may contribute to susceptibility to substance abuse.
- Failure to identify or effectively manage prescription opioid dependence acted as a gateway to heroin use-buprenorphine/naloxone treatment and recovery in a surgical patient. [JOURNAL ARTICLE]
- BMJ Case Rep 2014.
The prescribing of opioid pain medication has increased markedly in recent years, with strong opioid dispensing increasing 18-fold in Tayside, Scotland since 1995. Despite this, little data is available to quantify the problem of opioid pain medication dependence (OPD) and until recently there was little guidance on best-practice treatment. We report the case of a young mother prescribed dihydrocodeine for postoperative pain relief who became opioid dependent. When her prescription was stopped without support, she briefly used heroin to overcome her withdrawal. After re-exposure to dihydrocodeine following surgery 9 years later and treatment with methadone for dependency, she was transferred to buprenorphine/naloxone. In our clinical experience and in agreement with Department of Health and Royal College of General Practitioner guidance, buprenorphine/naloxone is the preferred opioid substitution treatment for OPD. Our patient remains within her treatment programme and has returned to work on buprenorphine 16 mg/naloxone 4 mg in conjunction with social and psychological support.
- Evaluation of Opioid Modulation in Major Depressive Disorder. [JOURNAL ARTICLE]
- Neuropsychopharmacology 2014 Dec 18.
Although opioids have known antidepressant activity, their use in major depressive disorder (MDD) has been greatly limited by risk of abuse and addiction. Our aim was to determine whether opioid modulation achieved through a combination of a μ opioid partial agonist, buprenorphine (BUP), and a potent μ opioid antagonist, samidorphan (SAM), would demonstrate antidepressant activity without addictive potential. A placebo-controlled crossover study assessed the opioid pharmacodynamic profile following escalating doses of SAM co-administered with BUP in opioid-experienced adults. A subsequent one-week, placebo-controlled, parallel-group study was conducted in subjects with MDD and an inadequate response to standard antidepressant therapy. This second study evaluated safety and efficacy of ratios of BUP/SAM that were associated with partial and with maximal blockade of opioid responses in the initial study. Pupillometry, visual analog scale assessments and self-report questionnaires demonstrated that increasing amounts of SAM added to a fixed dose of BUP resulted in dose-dependent reductions in objective and subjective opioid effects, including euphoria and drug liking, in opioid-experienced adults. Following 7 days of treatment in subjects with MDD, a 1 : 1 ratio of BUP and SAM, the ratio associated with maximal antagonism of opioid effects, exhibited statistically significant improvement vs. placebo in HAM-D17 total score (p=0.032) and nearly significant improvement in MADRS total score (p=0.054). Overall, BUP/SAM therapy was well tolerated. A combination of BUP and SAM showed antidepressant activity in subjects with MDD. Balanced agonist-antagonist opioid modulation represents a novel and potentially clinically important approach to the treatment of MDD and other psychiatric disorders.Neuropsychopharmacology accepted article preview online, 18 December 2014. doi:10.1038/npp.2014.330.
- A longitudinal comparison of retention in buprenorphine and methadone treatment for opioid dependence in New South Wales, Australia. [JOURNAL ARTICLE]
- Addiction 2014 Dec 16.
To examine characteristics of first-time methadone and buprenorphine clients and factors associated with risk of leaving first treatment in New South Wales (NSW), Australia.Retrospective linkage study of opioid substitution therapy (OST) treatment, court, custody and mortality data.NSW, Australia.First-time OST entrants (August 2001-December 2010).Characteristics of clients were examined. Time-dependent Cox models examined factors associated with the risk of leaving first treatment, with demographic, criminographic and treatment variables jointly considered. Interactions between medication and other variables upon risk of leaving treatment were examined.There were 15,600 treatment entrants: 7,183 (46%) commenced buprenorphine, 8,417 (54%) methadone; the proportion entering buprenorphine increased over time. Those starting buprenorphine switched medications more frequently and had more subsequent treatment episodes. Buprenorphine retention was also poorer: 44% spent 3+ months in treatment, compared with 70% of those commencing methadone; however, buprenorphine retention for first-time entrants improved over time, whereas methadone retention did not. Multivariable Cox models indicated that in addition to sex, age, treatment setting and criminographic variables, risk of leaving a first treatment episode was greater on any given day for those receiving buprenorphine, and was dependent on the year treatment was initiated There was no interaction between any demographic variables and medication received, suggesting no clear evidence of any particular groups for whom each medication might be better suited in terms of improving retention.Although retention rates for buprenorphine treatment have improved in New South Wales, Australia, individuals starting methadone treatment still show higher retention rates. This article is protected by copyright. All rights reserved.
- Buprenorphine Added to Bupivacaine Prolongs Femoral Nerve Block Duration and Improves Analgesia in Patients Undergoing Primary Total Knee Arthroplasty-A Randomised Prospective Double-Blind Study. [JOURNAL ARTICLE]
- J Arthroplasty 2014 Jul 24.
The aim of the study was to determine whether the addition the long-acting opioid buprenorphine as an adjuvant to the local anaesthetic agent would improve quality and prolong duration of femoral nerve blockade in post-operative analgesia following primary total knee arthroplasty. The study involved 48 patients. The femoral nerve was anaesthetised with a 0.25% solution of bupivacaine with adrenaline or with the addition of 0.3mg of buprenorphine. The duration of the sensory block and analgesic effect was assessed according to NRS scale at 12, 24, 36, 48, 60 and 72hours post-surgery. Patients who received buprenorphine as an adjuvant to the local anaesthetic had significantly longer sensory blockade and lower NRS-rated pain intensity with the difference reaching statistical significance at 12hours post-surgery.