Oral Methadone Research Articles

Sexual Dysfunction as a Side Effect of Hyperprolactinemia in Methadone Maintenance Therapy

Although endocrine abnormalities are recognized in opiate users, very little is known about the range of hormones affected, their pathophysiology and their clinical relevance. various endocrine abnormalities have been reported in these patients including, increased prolactin levels and abnormalities in sexual hormone. Path physiological mechanism postulated does explain these findings including direct action of heroin or methadone at the hypothalamic pituitary level. The aim of this study was to explore the effects of heroin and methadone maintenance treatment on the plasma prolactin levels and sexual function. We evaluated 20 male narcotic addicts maintained of methadone more than 3 years on oral high dose methadone 60-120 mgr/day. Patients taking neuroleptic therapy were excluded from the study because neuroleptic-included hyperprolactinemia. We also evaluated group of twenty male heroin addicts on the street heroin .The prolactin plasma levels were assayed using the chemiluminescent immunometric essay (CLIA)--high sensitive methods. The normal range of prolactin levels was 1,5-17 ng/ml (53-360 nmol/l) for men and 1,90-25,0 ng/ml for women. The sexual function was assessed using a Questionnaire: International Index of Erectile Function (IIEF) with 15 items in four levels of sexual function. The differences between two examination groups were determined by a students t test. The results show that street heroin addicts (55% of them have high level of prolactin) have significantly higher plasma prolactin levels (p = 0.006) then the group of methadone maintenance patients (only 15% of them have high prolactin level). In our study, when we compared sexual dysfunction in examination groups in some domains, we did not find statistical significant results (sexual desire p = 0.52 and overall satisfaction p = 0.087). But in domains of erectile function p = 0.011 and orgasm function p = 0.033 we got statistical significant results.

The necessity of checking the status and performance of methadone maintenance treatment centers in iran.

The necessity of checking the status and performance of methadone maintenance treatment centers in iran.

The treatment of alcohol and opioid dependence in pregnant women

This article addresses the question of 'best treatment options', which clinicians face when treating pregnant women with alcohol and opioid dependence. Studies show that alcohol consumption is associated with fetal abnormalities and long-term cognitive problems depending on the amount consumed, drinking pattern, and time of gestation. Screening and evaluation of specific interventions are important to reduce alcohol consumption during pregnancy and associated problems in infants. Opioid detoxification is only recommended beyond the first trimester and only in those pregnant women who refuse opioid maintenance therapy. Methadone is the most established treatment of pregnant opioid-dependent women, though recent results indicate some advantages of buprenorphine, slow-release oral methadone and diamorphine compared with methadone. Benzodiazepines seem to be the most recommendable option for managing alcohol withdrawal, and psychosocial interventions succeed in reducing alcohol consumption or in maintaining abstinence in alcohol-dependent pregnant women. Regarding opioid dependence, current results suggest that factors like the health status of the mother, the need for additional medications (e.g. treatment for HIV), comorbid drug dependence, and concurrent drug use need to be considered in order to find the 'best opioid substitute'.

Pain management

Despite published guidelines and educational programs on the assessment and treatment of cancer-related pain, in any stage of oncological disease, unrelieved pain continues to be a substantial worldwide public health concern either in patients with solid and haematological malignancies. The proper and regular self-reporting assessment of pain is the first step for an effective and individualized treatment. Opioids are the mainstay of analgesic therapy and can be associated with non-opioids drugs such as paracetamol or non-steroidal anti-inflammatory drugs and to adjuvant drugs (for neuropathic pain and symptom control). The role and the utility of weak opioids (i.e. codeine, dihydrocodeine, tramadol) are a controversy point. Morphine has been placed by World Health Organization on its Essential Drug List. In the comparative study with other strong opioids (hydromorphone, oxycodone), there is no evidence to show superiority or inferiority with morphine as the first choice opioid. Oral methadone is a useful and safe alternative to morphine. Methadone presents the potential to control pain difficult to manage with other opioids. although the oral route of opioid administration is considered the one of choice, intravenous, subcutaneous, rectal, transdermal, sublingual, intranasal, and spinal routes must be used in particular situation. Transdermal opioids such as fentanyl and buprenorphine are best reserved for patients whose opioid requirements are stable. Switching from one opioid to another can improve analgesia and tolerability.

Feasibility of Double-Blind Clinical Trials with Oral Diacetylmorphine: A Randomized Controlled Phase II Study in an Inpatient Setting

The aim of this study was to evaluate the feasibility of conducting double-blind controlled randomized clinical trials using twice-a-day immediate-release oral diacetylmorphine (DAM) in heroin-dependent patients, by means of measuring the capacity of oral DAM to block opiate withdrawal and clinicians’ ability to distinguish it from morphine and methadone. This was a randomized, phase II, double-blind, multicenter pilot study comparing immediate-release oral DAM, slow-release oral morphine and oral methadone administered twice a day during 10 days. Forty-five heroin-dependent patients were randomly assigned to these three treatment groups in an inpatient regime. Patients were stabilized with a mean of 350 mg (SD = 193) of immediate-release oral DAM, 108 mg (SD = 46.2) of slow-release oral morphine and 40 mg (SD = 17.9) of methadone. No statistically significant differences were found between any studied medication in clinical outcome. Neither patients nor clinicians were able to identify the administered medication. This study shows the feasibility of double-blind clinical trials using b.i.d. immediate-release oral DAM allowing further phase III clinical trials in the process of introducing oral DAM as a medication for heroin-dependent patients not responding to standard maintenance treatments.

The relationship between sugar-containing methadone and dental caries: A systematic review

Objectives: To review the evidence of a relationship between sugar-containing methadone and dental caries. Data sources: A systematic search of Cochrane Library, PubMed, PsychINFO, EMBASE, MEDLINE, Current Controlled Trials, WHO, OHRN, SIGLE and ERIC databases was conducted from January 1978 up to June 2010. Study selection: Articles were assessed and data abstracted independently by two reviewers. Papers that provided information about methadone and dental caries and were written in English were included, regardless of type of publication, authors, source of financial support and outcomes. Nineteen articles were identified; of these only three contained quantitative evidence, one of which was a survey. Conclusions: Many people on oral methadone maintenance programmes have been reported to have high levels of dental caries. However, there is no strong evidence to support a direct link between sugar-containing methadone and an increase in dental caries. High quality studies are required to assess the potential adverse effects of methadone on oral health.

Fentanyl transmucosal tablets: current status in the management of cancer-related breakthrough pain

Breakthrough pain is a newly recognized pain category that was first described by Portenoy and Hagen in 1990. The term describes pain that increases in intensity to “break through” chronic pain that is being controlled by a scheduled opioid regimen. The development of fluctuations in pain intensity is challenging due to their unpredictable nature, rapid onset, and need for rapid treatment intervention. Breakthrough pain has been treated by using an extra opioid dose in addition to the scheduled opioid being used for pain. Recommendations for dose and frequency are based on expert opinion only, and have included dosing based on a percentage of the total opioid dose. Other recommendations include increasing the regularly scheduled opioid dose. Clinical trials have now focused on delivery of opioids that have both potency and a rapid onset of action. Lipophilic opioids have received a substantial amount of study due to their quick absorption and rapid onset of analgesia. Lipophilic opioids that have been studied to date include transmucosal fentanyl, sublingual fentanyl, intranasal sufentanil, and oral and sublingual methadone. Initial clinical trials have established the superiority of transmucosal fentanyl as a breakthrough analgesic when compared with immediate-release oral opioid formulations. Problems with bioavailability have led to a search for newer formulations of transmucosal delivery. Newer formulations, such as fentanyl transmucosal tablets, have been developed to ensure superior delivery for the patient suffering from breakthrough pain. The purpose of this paper is to discuss the current status of transmucosal tablet formulations for cancer breakthrough pain.

Perinatal Effects of Combined Use of Heroin, Methadone, and Amphetamine during Pregnancy and Quantitative Measurement of Metabolites in Hair

There has been very limited research on the clinical features of newborns exposed to combined use of heroin, methadone, and amphetamine in the uterus. We describe a technique for the quantification of drug metabolites in neonatal hair samples. In a tertiary neonatal care center in Taiwan, three neonates whose mothers self-reported heroin abuse with methadone treatment during pregnancy were studied. Involuntary exposure to amphetamine was not suspected before the births. To assess long-term illicit drug exposure during pregnancy, a quantifying technique of gas chromatography/mass spectrometry (GC/MS) for hair samples from neonates was developed to replace current methods for urine and blood specimens. All three mothers were addicted to heroin and prescribed oral methadone treatment during pregnancy. Two males and one female were born and then admitted to the neonatal intensive care unit because of apparent neonatal abstinence syndrome (NAS) after birth. Additional hypertonicity and cerebral dysfunction were also diagnosed by electroencephalography in one case. Supportive care was given to the neonates, unless special treatments were needed in responding to tachypnea, fetal distress, or withdrawal symptoms. During follow-up periods from 10 months to 15 months, the signs of NAS remained and delays in milestones of development were observed. Further follow-up on the infants' neurobehavioral development is necessary. Measurement results of neonates' hair samples revealed high levels of metabolites of heroin, methadone, and amphetamine, reflecting the amount of illicit drug exposure 2-3 months before delivery. The current study suggested the possibility of polydrug exposure, which was previously unknown in pregnant women in Taiwan. Measurement of neonatal hair samples could provide a basis for clinical evaluation and potential corresponding treatment.

Use of methadone for prevention of opioid withdrawal in critically ill children.

Opioids are commonly administered to critically ill children for analgesia and sedation, but many patients experience opioid withdrawal upon discontinuation. The authors' institution developed a protocol for using methadone to prevent opioid withdrawal in children who have received morphine by continuous IV infusion for 5 days or longer in the pediatric intensive care unit (PICU). The primary objectives were to determine if opioids were tapered according to the protocol and to determine the conversion ratio for IV morphine to oral methadone that was used. Secondary objectives were to describe the methadone dosage used and the clinical outcomes, to evaluate adjustments to methadone dosing, and to report the incidence of adverse effects. A retrospective analysis of charts was conducted for pediatric patients who had received morphine by continuous IV infusion for 5 days or longer followed by methadone in the PICU between May 2008 and August 2009. Validated scoring systems (the Withdrawal Assessment Tool and the State Behavioral Scale) were used to assess symptoms of withdrawal and degree of sedation, respectively. Forty-three patients were included in the study, with median age of 8 months (range 0.25-201 months). For 31 patients (72%), the protocol was not used, and there were no patients for whom the protocol was followed to completion. The median duration of weaning was 10 days (range 0-91 days). The conversion ratio for IV morphine to oral methadone was 1:0.78 for anticipated 5-day weaning and 1:0.98 for anticipated 10-day weaning. During the first 10 days of weaning, 18 patients (42%) experienced withdrawal symptoms. The methadone dose was increased for 11 (26%) of the 43 patients. Patients were sedated for a median of 1 day (range 0-9 days), were comfortable for a median of 6.5 days (range 1-64 days), and were agitated for a median of 2.5 days (range 0-23 days). Naloxone was required for 2 patients. The institution's methadone protocol was not followed consistently during the study period, and practices for transitioning from morphine by continuous IV infusion to methadone with tapering were also inconsistent. Further studies are needed to determine the optimal conversion ratio for morphine to methadone and the optimal tapering regimen to minimize withdrawal symptoms and adverse events.

Sex work involvement among women with long-term opioid injection drug dependence who enter opioid agonist treatment

BackgroundSubstitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Survival sex work, very common among injection drug users, has been associated with poor Opioid Agonist Treatment (OAT) engagement, retention and response. Therefore, this study was undertaken to determine factors associated with engaging in sex work among long-term opioid dependent women receiving OAT.MethodsData from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone to injectable diacetylmorphine or injectable hydromorphone, the last two on a double blind basis, over 12 months. A research team, independent of the clinic services, obtained outcome evaluations at baseline and follow-up (3, 6, 9, 12, 18 and 24 months).ResultsA total 53.6% of women reported engaging in sex work in at least one of the research visits. At treatment initiation, women who were younger and had fewer years of education were more likely to be engaged in sex work. The multivariate logistic generalized estimating equation regression analysis determined that psychological symptoms, and high illicit heroin and cocaine use correlated with women's involvement in sex work during the study period.ConclusionsAfter entering OAT, women using injection drugs and engaging in sex work represent a particularly vulnerable group showing poorer psychological health and a higher use of heroin and cocaine compared to women not engaging in sex work. These factors must be taken into consideration in the planning and provision of OAT in order to improve treatment outcomes.Trial RegistrationNCT00175357.

Heroin maintenance for chronic heroin-dependent individuals

Several types of medications have been used for stabilizing heroin users: Methadone, Buprenorphine and levo-alpha-acetyl-methadol (LAAM.) The present review focuses on the prescription of heroin to heroin-dependent individuals. To compare heroin maintenance to methadone or other substitution treatments for opioid dependence regarding: efficacy and acceptability, retaining patients in treatment, reducing the use of illicit substances, and improving health and social functioning. A review of the Cochrane Central Register of Trials (The Cochrane Library Issue 1, 2005), MEDLINE (1966 to november 2009), EMBASE (1980 to 2005) and CINAHL until 2005 (on OVID) was conducted. Personal communications with researchers in the field of heroin prescription identified ongoing trials. Randomised controlled trials of heroin maintenance treatment (alone or combined with methadone) compared with any other pharmacological treatment for heroin-dependent individuals. Two reviewers independently assessed trial quality and extracted data. Eight studies involving 2007 patients met the inclusion criteria. Five studies compared supervised injected heroin plus flexible dosages of methadone treatment to oral methadone only and showed that heroin helps patients to remain in treatment (valid data from 4 studies, N=1388 Risk Ratio 1.44 (95%CI 1.19-1.75) heterogeneity P=0.03), and to reduce use of illicit drugs. Maintenance with supervised injected heroin has a not statistically significant protective effect on mortality (4 studies, N=1477 Risk Ratio 0.65 (95% CI 0.25-1.69) heterogeneity P=0.89), but it exposes at a greater risk of adverse events related to study medication (3 studies N=373 Risk Ratio 13.50 (95% CI 2.55-71.53) heterogeneity P=0.52). Results on criminal activity and incarceration were not possible to be pooled but where the outcome were measured results of single studies do provide evidence that heroin provision can reduce criminal activity and incarceration/imprisonment. Social functioning improved in all the intervention groups with heroin groups having slightly better results. If all the studies comparing heroin provision in any conditions vs any other treatment are pooled the direction of effect remain in favour of heroin. The available evidence suggests an added value of heroin prescribed alongside flexible doses of methadone for long-term, treatment refractory, opioid users, to reach a decrease in the use of illicit substances, involvement in criminal activity and incarceration, a possible reduction in mortaliity; and an increase in retention in treatment. Due to the higher rate of serious adverse events, heroin prescription should remain a treatment for people who are currently or have in the past failed maintenance treatment, and it should be provided in clinical settings where proper follow-up is ensured.

Staff concerns in heroin‐assisted treatment centres

Heroin-assisted treatment (HAT) is a solution for improving the condition of treatment-resistant heroin addicts. Since 1994, six randomized controlled trials have concluded that HAT is more efficacious than oral methadone for severe heroin addicts. We visited seven HAT treatment centres in four countries in order to observe diacetylmorphine (DAM) administration and to study the main concerns of the staff. Nurses were concerned by the risk taken if a previously intoxicated patient received his dose of DAM. Another concern was the smuggling of DAM doses. The HAT centres face a dilemma: treating patients while at the same time allowing their risky street habits in the centre.

After the randomised injectable opiate treatment trial: Post-trial investigation of slow-release oral morphine as an alternative opiate maintenance medication

To establish if slow-release oral morphine (SROM) is an acceptable maintenance medication in heroin users currently being prescribed injectable diamorphine, who are intolerant to supplementary methadone. Case note review of interviews and medication details before and after change in medication in 12 treatment-resistant chronic heroin users attending a supervised injecting clinic twice a day for prescribed injectable diamorphine plus supplementary oral methadone to ensure 24 h stability. SROM was substituted for oral methadone by cross-titration. The patients' experiences of methadone treatment and expectations of SROM were recorded before the switch. Their responses to SROM and changes in injectable diamorphine requirements were recorded after a mean of 10 weeks' SROM treatment. The patients described a dislike and intolerance of methadone but had positive expectations of SROM which they believed would allow them to reduce their diamorphine dose. The mean stable methadone : SROM maintenance dose ratio was 1:7.5. After 10 weeks' SROM treatment, the average daily diamorphine dose reduced from 382 mg to 315 mg and patients reported fewer cravings and improved sleep and well-being. Alternative forms of maintenance medication are required for patients who are intolerant to methadone. SROM is a valuable alternative which enabled some patients to reduce both their dose and number of injections of diamorphine. SROM treatment may therefore represent a route to stop injecting.

Client satisfaction among participants in a randomized trial comparing oral methadone and injectable diacetylmorphine for long-term opioid-dependency.

BackgroundSubstitution with opioid-agonists (e.g., methadone) has shown to be an effective treatment for chronic long-term opioid dependency. Patient satisfaction with treatment has been associated with improved addiction treatment outcomes. However, there is a paucity of studies evaluating patients' satisfaction with Opioid Substitution Treatment (OST). In the present study, participants' satisfaction with OST was evaluated at 3 and 12 months. We sought to test the relationship between satisfaction and patients' characteristics, the treatment modality received and treatment outcomes.MethodsData from a randomized controlled trial, the North American Opiate Medication Initiative (NAOMI), conducted in Vancouver and Montreal (Canada) between 2005-2008, was analyzed. The NAOMI study compared the effectiveness of oral methadone vs. injectable diacetylmorphine over 12 months. A small sub-group of patients received injectable hydromorphone on a double blind basis with diacetylmorphine. The Client Satisfaction Questionnaire (CSQ-8) was used to measure satisfaction with treatment. CSQ-8 scores, as well as retention and response to treatment, did not differ between those receiving hydromorphone and diacetylmorphine at 3 or 12 months assessments; therefore, these two groups were analyzed together as the 'injectable' treatment group.ResultsA total of 232 (92%) and 237 (94%) participants completed the CSQ-8 at 3 and 12 months, respectively. Participants in both groups were highly satisfied with treatment. Independent of treatment group, participants satisfied with treatment at 3 months were more likely to be retained at 12 months. Multivariate analysis indicated that satisfaction was greater among those randomized to the injection group after controlling for treatment effectiveness. Participants who were retained, responded to treatment, and had fewer psychological symptoms were more satisfied with treatment. Finally, open-ended comments were made by 149 (60.3%) participants; concerns about the randomization process and the study ending were most commonly reported by participants receiving the oral and injectable medications, respectively.ConclusionsThe higher satisfaction among those receiving medically prescribed injectable diacetylmorphine (or hydromorphone) supports current evidence regarding the attractiveness of this treatment for long-term, opioid-dependent individuals not benefiting sufficiently from other treatments. In addition, the measurement of treatment satisfaction provides valuable information about participants at risk of relapse and in need of additional services.Trial RegistrationClinicalTrials.gov Identifier: NCT00175357

Is oral methadone better than placebo or other oral/transdermal opioids in the management of pain?

Aim: To address the question: is oral methadone better than placebo, or other oral/transdermal opioids in the management of cancer pain? Method: A literature search was performed to identify relevant studies. Search strategies included: (1) methadone (title) AND placebo (title or abstract) AND pain (title or abstract); (2) methadone (title) AND randomized (title or abstract) AND pain (title or abstract) AND cancer (title or abstract). Papers were reviewed for relevance to first-line opioid therapy. Results: No studies were identified comparing methadone to placebo for cancer pain. A single study compared methadone to placebo for neuropathic pain and demonstrated evidence of analgesic effect at a dose of 20 mg/day but not at a dose of 10 mg/day. Four studies compared oral methadone to either oral morphine, or oral morphine and transdermal fentanyl in a first-line setting: Gourlay 1986 (N = 18), Ventafridda 1986 (N = 54), Bruera 2004 (N = 106) and Mercadante 2008 (N = 108). All studies demonstrated comparable, but not superior, analgesia with, overall, a comparable adverse effect profile. The duration of the study period for the three largest studies was 28 days. Two of these studies, Ventafridda 1986 and Mercadante 2008, indicated that, over time, the opioid escalation index was lower for methadone than for morphine. One study that used a 2:1 dose ratio between morphine and methadone was associated with a high attrition rate in the first week because of excessive sedation. This effect was not seen in the study that used a 4:1 morphine to methadone dose ratio with dose titration. Conclusion: This limited data suggests that (1) methadone may be an equally effective candidate for first-line opioid therapy, (2) that it is possibly less expensive, (3) that there may be a propensity to sedation and dose accumulation unless there is close monitoring and conservative dose selection and (4) that it should be initiated with a calculated dose based on a morphine to methadone dose ratio of not less than 4:1.

The effects of concurrent administration of cytochrome P-450 inhibitors on the pharmacokinetics of oral methadone in healthy dogs

ObjectiveThe objective was to examine the effects of inhibiting cytochrome P450 (CYP) on the pharmacokinetics of oral methadone in dogs. Study designProspective non-randomized experimental trial. AnimalsSix healthy Greyhounds (three male and three female). MethodsThe study was divided into two phases. Oral methadone (mean = 2.1 mg kg−1 PO) was administered as whole tablets in Phase 1. In Phase 2 oral methadone (2.1 mg kg−1 PO) was administered concurrently with ketoconazole (13.0 mg kg−1 PO q 24 hours), chloramphenicol (48.7 mg kg−1 PO q 12 hours), fluoxetine (1.3 mg kg−1 PO q 24 hours), and trimethoprim (6.5 mg kg−1 PO q 24 hours). Blood was obtained for analysis of methadone plasma concentrations by liquid chromatography with mass spectrometry. The maximum plasma concentration (Cmax), time to Cmax (Tmax), and the area under the curve from time 0 to the last measurable time point above the limit of quantification of the analytical assay (AUC0–LAST) were compared statistically. ResultsThe Cmax of methadone was significantly different (p = 0.016) for Phase 1 (5.5 ng mL−1) and Phase 2 (171.9 ng mL−1). The AUC0–LAST was also significantly different (p = 0.004) for Phase 1 (13.1 hour ng mL−1) and Phase 2 (3075.2 hour ng mL−1). Conclusion and clinical relevanceConcurrent administration of CYP inhibitors with methadone significantly increased the area under the curve and plasma concentrations of methadone after oral administration to dogs. Further studies are needed assessing more clinically relevant combinations of methadone and CYP inhibitors.

Effect of oral methadone on the QTc interval in patients with increased risk for QTc prolongation

Methadone induced QTc-interval prolongation (QTcP) or torsades de pointes, and when and who should have EKG testing is controversial.1 We are performing EKG and 24 h Holter monitoring on >50 years old (increased risk for QTcP) participants on methadone for chronic pain to assess this issue. Objective is to compare EKG to 24 h Holter on QTcP in patients at higher risk for QTcP on methadone for chronic pain. >50 years old chronic pain patients on methadone: EKG, 24 h Holter and electrolytes (K, Ca, Mg) (visit#1), repeated 8 weeks later (visit#2) (completers=20/36).

Advanced Pain Therapies: Using Methadone, Ketamine, and Lidocaine for Refractory Pain (P14) (Advanced)

1.Describe methadone's unique pharmacokinetic and pharmacodynamic properties and drug-interaction profile.2.Discuss how to convert and manage appropriate patients on both oral and intravenous methadone, using a variety of accepted strategies.3.Describe protocols for the use of lidocaine and ketamine in pain management. Refractory pain management is one of the greatest clinical challenges for clinicians in hospice and palliative care settings. Helping patients who have moved beyond the World Health Organization analgesic ladder requires familiarity with methadone and less commonly used adjuvants such as lidocaine and ketamine. An understanding of methadone's unique pharmacokinetic and pharmacodynamic properties and drug interaction profile is paramount to safely prescribing methadone. Methadone prescribers must also have knowledge of various dosing ratios and methods for converting between methadone and other opioids in order to customize methadone therapy for their patients. Furthermore, prescribers of intravenous methadone must be familiar with recently published consensus guidelines for optimizing analgesia with parenteral methadone. Following didactic presentations, attendees working in small groups will apply the basic principles of methadone prescribing to patient cases that enable them to develop comfort with using methadone for pain management. Finally, the use of lidocaine and ketamine for the treatment of refractory pain will be discussed, with a focus on determining the best route of administration and dosages. Suggestions for developing protocols for their use will be offered. Physical Aspects of Care

Segmental Spinal Myoclonus Following High-Dose Intrathecal Hydromorphone Infusion (310-B)

1.Recognize the clinical picture of segmental spinal myoclonus, a possible rare complication of spinal opioid infusion.2.Discuss the treatment of this rare but serious condition. Background. Myoclonus is a well-described side effect of opioid therapy. Segmental spinal myoclonus is generated at a particular segment of the spinal cord and can be observed with certain spinal cord disorders or injuries. Segmental spinal myoclonus is a very rare complication of epidural or intrathecal opioid infusion. Case description. We will report the case of 47-year-old gentleman who developed segmental spinal myoclonus following administration of high-dose intrathecal hydromorphone. The patient has end-stage metastatic chordoma that was diagnosed 14 years ago. He was treated in Europe and at our institution with multiple surgeries, radiation, and chemotherapies. He has been followed at our pain and palliative care clinic over the last several years. After exhausting all therapeutic options for his cancer and continuous escalation of large doses of oral methadone in February and March of 2010 he was hospitalized for improvement of pain control. Initially the patient was treated with intravenous methadone, only then intrathecal infusion with hydromorphone and bupivacaine was added. On Day 2 after an intrathecal pump placement while receiving 18 mg hydromorphone intrathecally per day, the patient developed extremely painful involuntary muscle jerks of his lower body with frequency approximately every 5–10 seconds. The patient received intravenous doses of lorazepam, which provided minimal relief. Severe muscle spasms resolved with significant dose reduction of intrathecal hydromorphone. Ultimately hydromorphone was replaced with sufentanil. Conclusion. Clinicians should be aware of the clinical presentation of segmental spinal myoclonus, which can develop as a complication of intrathecal opioid infusion. Anticonvulsants, especially benzodiazepines, can be used for symptomatic relief. For definitive treatment of this rare condition, dose reduction of the intrathecal opioid or rotation to another opioid should be considered. Physical Aspects of Care

Effect of Raltegravir on the Pharmacokinetics of Methadone

A randomized, placebo-controlled, 2-period crossover study in subjects on methadone maintenance therapy was conducted to assess the effect of the HIV-1 integrase inhibitor, raltegravir, on the pharmacokinetics of methadone. Twelve HIV-negative male and female subjects stabilized on an oral methadone program were enrolled. Subjects maintained their prescribed oral doses of methadone throughout the study and, in each of 2 periods, received either 400 mg of raltegravir or matching placebo every 12 hours on days 1 through 10 of each treatment period with a washout of 7 days between periods. Plasma samples for analysis of methadone pharmacokinetics were collected over 24 hours postdose on day 10 of each treatment period. Safety and tolerability were assessed throughout the study. The geometric mean ratio (90% confidence interval) for methadone when administered with raltegravir relative to methadone alone was 1.00 (0.93-1.09) for area under the methadone concentration time curve from time 0 to 24 hours and 1.00 (0.94-1.07) for maximal concentration. There were no serious clinical or laboratory adverse experiences. There were no discontinuations due to an adverse experience. Coadministration of raltegravir and methadone is generally well tolerated. Raltegravir has no clinically meaningful effect on methadone pharmacokinetics. No dose adjustment is required for methadone when coadministered with raltegravir.