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- [Neuroleptic malignant syndrome after cardiac surgery]. [English Abstract, Journal Article]
- Kyobu Geka 2013 Nov; 66(12):1052-5.
A 64-year-old man without any phychiatric disease, including Parkinson's disease underwent aortic valve replacement and mitral valve replacement for rheumatic valvular disease. One day after the cardiac surgery, he developed hyperthermina, muscle rigidity, coma and delirium, and his serum creatine kinase (CK) level was elevated. In spite of his negative brain computed tomography(CT), his consciousness remained unclear. He had received diazepam, flunitrazepam and buprenorphine after the cardiac surgery because of his hyper-reactivity. Although these drugs were not typical antipsychotics' causing neuroleptic malignant syndrome (NMS), NMS was strongly suspected because of his clinical appearance. Dantrolene was administered in a dose of 60 mg per day and he recovered consciousness and his CK level began to decrease. We reported a case of neuroleptic malignant syndrome after cardiac surgery.
- Prenatal buprenorphine exposure decreases neurogenesis in rats. [JOURNAL ARTICLE]
- Toxicol Lett 2013 Dec 6.
Perinatal opioid exposure has a negative effect on neurogenesis and produces neurological consequences. However, its mechanisms of action are incompletely understood. Buprenorphine, a mixed opioid agonist/antagonist, is an alternative medication for managing pregnant opioid addicts. This study provides evidence of decreased neurogenesis and depression-like consequences following prenatal exposure to buprenorphine and sheds light on mechanisms of action in a rat model involving administration of intraperitoneal injection to pregnant rats starting from gestation day 7 and lasting for 14 days and a cultured neurosphere model. Results of forced swimming test and tail suspension test showed that pups at postnatal day 21 had worse parameters of depression-like neurobehaviors, independent of gender. Neurobehavioral changes were accompanied by reduction of neuronal composition, biochemical parameters of neural stem/progenitor cells, brain-derived neurotrophic factor (BDNF) expression, tropomyosin-related kinase receptor type B phosphorylation, protein kinase A (PKA) activity, and cAMP response element-binding protein phosphorylation. Results of parallel cell studies further demonstrated a negative impact of buprenorphine on cultured neurospheres, including proliferation, differentiation, BDNF expression and signaling, and PKA activity. Taken together, our results suggest that prenatal exposure to buprenorphine might result in depression-like phenotypes associated with impaired BDNF action and decreased neurogenesis in the developing brain of weanlings.
- Is buprenorphine transdermal patch equally safe and effective in younger and elderly patients with osteoarthritis-related pain? Results of an age-group controlled study. [JOURNAL ARTICLE]
- Curr Med Res Opin 2013 Dec 10.
Abstract Objective A recent pharmacokinetic study with buprenorphine transdermal patches showed similar systemic exposures of buprenorphine in subjects aged ≥75 and 50-60 years. The current prospective, open-label study aimed to verify this in a clinical setting by evaluating efficacy and safety of buprenorphine patches in patients with chronic osteoarthritis (OA) pain. Methods Patients with chronic, moderate to severe osteoarthritic pain (hip and/or knee) were enrolled: 50-60 years (younger group, N=65) and ≥75 years (elderly group, N=57). After 2 weeks on paracetamol only, patients received buprenorphine patches (5-40 µg/h) for 12 weeks. Paracetamol rescue was provided. Primary endpoint was the Box-Scale-11 (BS-11) score for pain on average over the last week. WOMAC OA Index, EQ-5D, Patients' and Investigators' Global Assessment of Pain Relief, rescue medication use, sleep disturbance and quality of sleep were secondary efficacy endpoints. Results Both groups showed a statistically significant (p<0.001) and clinically relevant change from baseline to last visit in BS-11 score, with no significant difference between groups. The least squares (LS) mean change from baseline was 2.20 in elderly and 1.87 in younger patients, with an age group difference of 0.33 (95% CIs: -0.42, 1.07). Non-inferiority of the elderly versus the younger group was shown. Both age groups showed a significant improvement in WOMAC total score, patients' overall health state (EQ-5D visual analogue scale) and sleep quality, and a significant reduction in rescue use and nights woken due to pain, with no significant differences between groups. Elderly patients tolerated buprenorphine patches at least as well as younger patients. Conclusions Efficacy and tolerability of buprenorphine patches was demonstrated in chronic pain patients, regardless of age, supporting the conclusion that no age-related dose adjustment of transdermal buprenorphine is needed. A study limitation is lack of active control but no other opioid was appropriate in elderly patients or this indication.
- Predictive factors for relapse in patients on buprenorphine maintenance. [Journal Article]
- Am J Addict 2014 Jan; 23(1):62-7.
Despite the dramatic increase in the use of buprenorphine for the treatment of opioid dependence, clinical outcomes of this treatment approach continue to need evaluation. This study examines factors associated with relapse and retention during buprenorphine treatment in a sample of opioid dependent outpatients.In a retrospective chart review of 62 patients with opioid dependence, relapse was determined by self-report, urine toxicology screens, and by checking the state controlled substance monitoring database. Data was analyzed using two-way tests of association and logistic regression.Patients with comorbid anxiety disorders, active benzodiazepine use (contrary to clinic policy), or active alcohol abuse, were significantly more likely to relapse. Patients who relapsed were also more likely to be on a higher buprenorphine maintenance dose.This study identifies relapse risk factors during buprenorphine treatment for opioid dependence. Future research is needed to determine whether modifying these factors may lead to improved treatment outcomes. (Am J Addict 2014;23:62-67).
- Effects of HCV seropositive status on buprenorphine pharmacokinetics in opioid-dependent individuals. [Journal Article]
- Am J Addict 2014 Jan; 23(1):34-40.
The purpose of this study was to examine the effect of hepatitis C virus (HCV) infection on buprenorphine pharmacokinetics in opioid-dependent, buprenorphine/naloxone-maintained adults.A retrospective analysis of buprenorphine pharmacokinetics in HCV seropositive and seronegative buprenorphine/naloxone-maintained individuals (N = 49) was undertaken.Relative to HCV seronegative subjects, HCV seropositive subjects had higher buprenorphine exposure, as demonstrated by elevated buprenorphine AUC and Cmax values (p = .03 and .02, respectively) and corresponding elevations in the metabolites, buprenorphine-3-glucuronide AUC values (p = .03) and norbuprenorphine-3-glucuronide AUC and C24 values (p = .05 and .03, respectively).HCV infection was associated with higher plasma concentrations of buprenorphine and buprenorphine metabolites.Findings suggest the potential for opioid toxicity among HCV-infected patients treated with buprenorphine/naloxone, and possible hepatotoxic effects related to increased buprenorphine exposure. HCV-infected patients receiving buprenorphine may need lower doses to maintain therapeutic plasma concentrations. (Am J Addict 2014;23:34-40).
- Perioperative Pain Management for Patients on Chronic Buprenorphine: A Case Report. [JOURNAL ARTICLE]
- J Anesth Clin Res 2013 Oct 30; 3(250)
Here we present a patient with a Type I Chiari malformation who was receiving buprenorphine for chronic pain who underwent two separate urogynecologic procedures for removal of vaginal mesh with two different pain management regimens. For the first procedure at an outside hospital, the patient's usual dose of buprenorphine (8 mg sublingual every 8 hours) was continued up through her surgery and then a full opioid receptor agonist was used for postoperative pain management. The patient complained that this resulted in very poor pain control for her in the postoperative period. Prior to her second procedure, which was performed at our institution, buprenorphine was switched to a full opioid agonist (oral hydromorphone 4 mg every 4 to 6 hours, maximum 20 mg per day) for 5 days prior to surgery; postoperative pain was managed with full opioid receptor agonists. The patient again reported suboptimal pain control in spite of substantially increased doses of opioids. This case report highlights the difficulty of perioperative pain management for patients on chronic buprenorphine and emphasizes the need for additional investigation.
- Neonatal outcomes and their relationship to maternal buprenorphine dose during pregnancy. [JOURNAL ARTICLE]
- Drug Alcohol Depend 2013 Nov 16.
Buprenorphine pharmacotherapy for opioid-dependent pregnant women is associated with maternal and neonatal outcomes superior to untreated opioid dependence. However, the literature is inconsistent regarding the possible existence of a dose-response relationship between maternal buprenorphine dose and neonatal clinical outcomes.The present secondary analysis study (1) examined the relationship between maternal buprenorphine dose at delivery and neonatal abstinence syndrome (NAS) peak score, estimated gestational age at delivery, Apgar scores at 1 and 5min, neonatal head circumference, length, and weight at birth, amount of morphine needed to treat NAS, duration of NAS treatment, and duration of neonatal hospital stay and (2) compared neonates who required pharmacotherapy for NAS to neonates who did not require such pharmacotherapy on these same outcomes, in 58 opioid-dependent pregnant women receiving buprenorphine as participants in a randomized clinical trial.(1) Analyses failed to provide evidence of a relationship between maternal buprenorphine dose at delivery and any of the 10 outcomes (all p-values>.48) and (2) significant mean differences between the untreated (n=31) and treated (n=27) for NAS groups were found for duration of neonatal hospital stay and NAS peak score (both p-values<.001).(1) Findings failed to support the existence of a dose-response relationship between maternal buprenorphine dose at delivery and any of 10 neonatal clinical outcomes, including NAS severity and (2) that infants treated for NAS had a higher mean NAS peak score and, spent a longer time in the hospital than did the group not treated for NAS is unsurprising.
- Long-term Consequences of Acute Pain for Patients under Methadone or Buprenorphine Maintenance Treatment. [Journal Article]
- Pain Physician 2013 Nov-Dec; 16(6):E739-47.
Acute and chronic pains are reported to be highly prevalent in patients under opioid maintenance treatment (OMT). Lack of knowledge concerning the complex relationship between pain, opioid use, and their impact on OMT efficacy can account for the barriers encountered for pain management.To assess the impact of acute pain exposure on long-term OMT retention in a cohort of patients under buprenorphine or methadone followed up during 12 months.Prospective, multi-center observational cohort clinical study.Emergency departments, surgery departments, and specialized addiction care centers in an outpatient setting in south-western France (Midi-Pyrenees area), from April 2008 to January 2010.Patients aged 18 or more under OMT for at least 3 months, and followed up by a physician were recruited. Acute pain was assessed using the Visual Analog Scale (VAS) or the Verbal Rating Scale (VRS). Exposed patients were those with a pain score greater than 0 at the time of admission on any of the rating scales. The OMT rate after 12 months was compared among exposed and unexposed patients. OMT retention was also investigated after 3 and 6 months follow-up.A total of 151 patients, 81 exposed and 70 unexposed, were recruited; among them, respectively, 26 (32%) and 34 (49%) completed 12-months follow-up. Acute pain exposure appeared to be significantly and negatively associated with retention in treatment (crude OR: 0.44; 95% CI [0.22 - 0.87]; adjusted OR: 0.46; 95% CI [0.23 - 0.93]). Compared to methadone users, patients under buprenorphine were less likely to have their OMT maintained after 12 months (OR 0.37; 95% CI [0.18 - 0.75]; adjusted OR 0.38; 95% CI [0.18 - 0.80]).Follow-up rate was 40% (60/151).This study demonstrates the strong negative impact of acute pain on OMT in a population mainly composed of patients under buprenorphine, as well as differential response depending on the OMT medication. The findings highlight the need to consider the characteristics of pain in the population under OMT and to develop evidence-based guidelines for pain management.The study was registered at www.clinical.trials.gov with the study identifier: NCT00738036. Ethics Committee approval was received on February 11, 2008. Participants' written consent was not required.
- Allergic Contact Dermatitis from Buprenorphine and Oral Tolerance to Other Opioid Derivatives in Three Patients. [JOURNAL ARTICLE]
- Dermatology 2013 Nov 23.
Transdermal buprenorphine (TDB) is a widely used analgesic for moderate pain. TDB is generally well tolerated, but both irritant and allergic contact dermatitis occur at patch application sites. Oral opioid tolerance in patients with allergic contact dermatitis to TDB remains controversial. Here, we describe 3 patients with allergic contact dermatitis to TDB who subsequently used oral opioid derivatives without adverse reactions. Thus, oral intolerance to opioid derivatives is not a rule in patients with allergic contact dermatitis to TDB, but the possibility should be taken into consideration. © 2013 S. Karger AG, Basel.
- Association between gene variants and response to buprenorphine maintenance treatment. [JOURNAL ARTICLE]
- Psychiatry Res 2013 Nov 11.
A variety of studies were addressed to differentiate responders and non-responders to substitution treatment among heroin dependent patients, without conclusive findings. In particular, preliminary pharmacogenetic findings have been reported to predict treatment effectiveness in mental health and substance use disorders. Aim of the present study was to investigate the possible association of buprenorphine (BUP) treatment outcome with gene variants that may affect kappa-opioid receptors and dopamine system function. One hundred and seven heroin addicts (West European, Caucasians) who underwent buprenorphine maintenance treatment were genotyped and classified into two groups (A and B) on the basis of treatment outcome. Non-responders to buprenorphine (group B) have been identified taking into account early drop out, continuous use of heroin, severe behavioral or psychiatric problems, misbehavior and diversion during the 6 months treatment period. No difference was evidenced between responders and non-responders to BUP in the frequency of kappa opioid receptor (OPRK1) 36G>T SNP. The frequency of dopamine transporter (DAT) gene polymorphism (SLC6A3/DAT1), allele 10, was evidently much higher in "non-responder" than in "responder" individuals (64.9% vs. 55.93%) whereas the frequency of the category of other alleles (6, 7 and 11) was higher in responder than in non-responder individuals (11.02% vs. 2.13% respectively). On one hand, the hypothesis that possible gene-related changes in kappa-opioid receptor could consistently affect buprenorphine pharmacological action and clinical effectiveness was not confirmed in our study, at least in relation to the single nucleotide polymorphism 36G>T. On the other hand, the possibility that gene-related dopamine changes could have reduced BUP effectiveness and impaired maintenance treatment outcome was cautiously supported by our findings. DAT1 gene variants such as allele 10, previously reported in association with personality and behavioral problems, would have influenced the effects of BUP-induced dopamine release, modulated through mu and kappa opioid receptors, and probably the related reinforcing capacity of the drug.