Objective Opioid Withdrawal Scale Research Articles

Effectiveness and Safety of Haloperidol Add-on Methadone in Acute Opium Withdrawal Symptoms of Opioid-dependent Patients: A Double-blind Randomized Placebo-controlled Clinical Trial.

BackgroundThe aim of this double-blind clinical trial was to evaluate the efficacy and safety of haloperidol on acute opioid withdrawal symptoms.MethodsIn this randomized double-blind clinical trial, fifty-two eligible patients were assigned to two groups according to previous opioid consumption, low dose (LD) and high dose (HD). Then, patients in each group were randomly assigned to one of the two subgroups of haloperidol or placebo. Patients in the haloperidol subgroup in LD group received 2.5 mg and in HD group received 5 mg/day haloperidol with methadone. Methadone was discontinued ten days after the beginning of the study and haloperidol or placebo continued for up to two weeks after methadone discontinuation. The severity of opioid withdrawal symptoms was assessed with the Objective Opioid Withdrawal Scale (OOWS) every other day.FindingsAlthough both treatment protocols either in LD or HD opioid consumption groups significantly increased the score of the OOWS over the trial period (all subgroups, P < 0.001), the combination of 2.5 mg/day of haloperidol and methadone in LD opioid consumption group showed a significant superiority over methadone alone in decreasing opium withdrawal symptoms during the study (P = 0.001). The frequency of adverse effects was comparable between two treatment protocols in both groups (P > 0.050).ConclusionThe results of this study suggest that 2.5 mg/day of haloperidol may be an effective adjuvant agent in the management of opium withdrawal symptoms in patients with LD opioid consumption. Nevertheless, results of larger controlled trials are needed before recommendation for a broad clinical application can be made.

Impact of Ondansetron on Withdrawal Signs, Fentanyl Requirement and Pain Relief in Opioid-addicted Patients under General Anesthesia.

Serotonin 5-HT3 receptor antagonists such as ondansetron have been investigated to attenuate opioid withdrawal signs in studies. Therefore, we designed a randomized double-blinded placebo-controlled trial to evaluate this effect on opioid-addicted patients who were admitted to the orthopedic department for surgery due to bone fractures. Male adults who were addicted to opioids, aged 18 to 79 years were enrolled (n=96) and randomized into intravenous doses (4 & 8 mg) of ondansetron (n=32) and placebo (n=32). The vital signs, withdrawal symptoms and the frequency requirement of fentanyl were recorded during anesthesia, and opioid (pethidine) analgesic was received during the recovery period. Outcome parameters were analyzed for reduction of withdrawal symptoms in addicted adults. We indicated that ondansetron demonstrated significant differences with few vital outcomes including systolic blood pressure (SBP) 20 (SBP3) and 50 min (SBP4) after injection of ondansetron during the period of surgery. Ondansetron could also significantly reduce the frequency requirement of fentanyl at 20 min (dose 3) in general anesthesia. Furthermore, requirement for further administration of opioid analgesic drugs such as pethidine was significantly reduced in the ondansetron groups. Objective opioid withdrawal scale (OOWS) results indicated that few clinical parameters including tremor, hot and cold flushes and anxiety were significantly attenuated in addicted patients who received ondansetron. This study demonstrated supporting evidence for the beneficial treatment of ondansetron for the control of withdrawal symptoms and pain in addicted patients, and more clinical studies are suggested in this regard.

Safety of oral methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain.

PurposeOral methylnaltrexone was shown to be effective in treating opioid-induced constipation (OIC) in patients with chronic noncancer pain in a Phase III randomized controlled trial. This report provides a detailed safety analysis from that study.MethodsAdults (n=803) with chronic noncancer pain for ≥2 months and confirmed OIC while receiving opioid doses ≥50 mg morphine equivalent per day for ≥14 days were randomized 1:1:1:1 to oral methylnaltrexone (150, 300, or 450 mg) or placebo once daily for 4 weeks, followed by as-needed use for 8 weeks. Safety was evaluated by examining treatment-emergent adverse events (TEAEs), clinical laboratory parameters, vital signs, electrocardiography, rescue-laxative and opioid use, Objective Opioid Withdrawal Scale (OOWS) and Subjective Opioid Withdrawal Scale (SOWS), and pain-intensity scores.ResultsTEAEs occurred at a similar incidence in the methylnaltrexone groups (59.0%) and placebo group (63.0%). The most common TEAEs with methylnaltrexone were abdominal pain (8.0% vs 8.5% with placebo), nausea (6.8% vs 9.0%), and diarrhea (6.0% vs 3.5%). Cardiac-related TEAEs occurred in 1.8% and 1.0% of patients, respectively, and no major adverse cardiovascular events were reported. No patient had a cluster of TEAEs associated with opioid withdrawal after excluding gastrointestinal TEAEs. Changes in laboratory parameters, vital signs, and electrocardiography were generally small and similar across treatment groups. Rescue-laxative use was more common with placebo than methylnaltrexone 450 mg (6.20% vs 4.27% of study days, P=0.024). Changes in opioid dose, OOWS and SOWS scores, and pain-intensity scores during treatment were minimal.ConclusionOral methylnaltrexone had a safety profile comparable with placebo in the treatment of OIC in patients with chronic noncancer pain, with no evidence of cardiac toxicity or opioid withdrawal.

Lofexidine versus diazepam for the treatment of opioid withdrawal syndrome: A double-blind randomized clinical trial in Singapore

BackgroundMany individuals leave costly inpatient detoxification programs prematurely because of the severity of withdrawal symptoms experienced. In the absence of opioid-assisted detoxification in Singapore, diazepam is used to manage withdrawal. However since diazepam is addictive, there is a need to explore the effectiveness of alternative medications. Design and proceduresThe study aimed to examine the safety and efficacy of lofexidine, a non-opiate, non-addictive, alpha 2-adrenergic agonist in assisting opioid detoxification in Singapore, using a randomized, double-blind, investigator-initiated placebo-controlled trial comparing lofexidine against diazepam. Opioid dependent patients (n = 111) were randomized to receive a 10-day course of lofexidine (n = 56) or diazepam (n = 55). The primary endpoint was the Objective Opioid Withdrawal Scale (OOWS) score on days 3 and 4 and secondary outcomes were the Short Opioid Withdrawal Scale (SOWS) score, program retention rate, and ratings of opiate craving. Main findingsThe OOWS, SOWS and opiate craving scores were consistently lower in the lofexidine group relative to the diazepam group over the 14-day study period; however no statistically significant differences were found on days 3 and 4 (peak withdrawal). Changes in mean pupil size during peak withdrawal were significantly smaller in the lofexidine group and more participants in the lofexidine group remained in treatment and completed detoxification. ConclusionsLofexidine was at least as effective as diazepam in reducing the opioid withdrawal syndrome and increased treatment retention. In addition to its non-addictive and non-abuse properties, lofexidine has several clinical advantages over diazepam. The use of lofexidine is recommended when opioid-assisted medications are not available.

Abuse deterrence testing: A dose ratio escalation study examining naloxone coadministered with intravenous hydromorphone in non-treatment-seeking, opioid-dependent drug users.

To assess the reduction in intravenous (IV) abuse potential of hydromorphone from different dose ratio combinations with naloxone in opioid-dependent drug users. Randomized, blinded, dose ratio escalation study. Single center. Following conversion to a stable IV dose of hydromorphone, 12 non-treatment-seeking, opioid-dependent subjects were randomly assigned and received at least one dose of study drug; seven subjects received all five study treatments. Five subjects withdrew early from the treatment phase: adverse events (2) and participant decision (3). Participants underwent a dose-selection phase to stabilize on an individualized hydromorphone dose. Stable subjects were dosed intravenously on 5 consecutive days. The dose received was one of five hydromorphone/naloxone dose ratios that included the combination of hydromorphone and placebo naloxone. Hydromorphone/naloxone treatment always involved increasing dose ratios of naloxone (8:1, 6:1, 4:1, and 2:1) with the hydromorphone-placebo naloxone treatment randomly assigned within the sequence of dose ratios. Drug Liking visual analog scale (VAS), Objective Opioid Withdrawal Scale (OOWS) and Subjective Opioid Withdrawal Scale (SOWS). Hydromorphone/naloxone placebo produced subjective effects typical of opioid administration, while hydromorphone/naloxone dose ratios were associated with significant increases in SOWS and OOWS scores (p < 0.05). Compared with hydromoprophone/naloxone placebo, naloxone reduced the effects of hydromorphone on most measures, including Drug Liking VAS, the antagonism was greatest for the 4:1 and 2:1 ratios. This study was an ethical investigation of the abuse deterrence potential of four hydromorphone/naloxone dose ratios. The IV coadministration of commercially available IV solutions of hydromorphone and naloxone in 4:1 and 2:1 ratios had statistically greater reductions of abuse-related opioid effects and triggers of withdrawal symptoms and there was a convergence of subjective and objective pharmacodynamic results and safety findings. An oral modified-release product, developed with a 2:1 hydromorphone/naloxone ratio, may have important public health benefits by reducing high-risk, IV abuse of prescription opioids, while providing pain relief when ingested orally and used in accordance with the Product Monograph.

Opium tincture versus methadone syrup in management of acute raw opium withdrawal: A randomized, double-blind, controlled trial

ABSTRACTThe aim of this study was to evaluate the effectiveness of opium tincture versus methadone syrup in the management of acute withdrawal syndrome in opium dependent patients during the detoxification period. In this double-blind randomized controlled study, a total of 74 adult male raw opium dependent patients were treated with opium tincture or methadone syrup 2 times daily for 5 consecutive days. Detoxification was initiated by tapered dose reductions to reach abstinence. At the end of the 10th day, the medications were discontinued. The Objective Opioid Withdrawal Scale was used to assess withdrawal symptoms every day. Significant decreases on the Objective Opioid Withdrawal Scale were found for both treatment methods during the study period (p < .0001). However, there was no significant difference between groups on the total Objective Opioid Withdrawal Scale, and adverse effects existed. Opium tincture can be considered as a potential substitute for methadone syrup for suppression of raw opium withdrawal symptoms, with minimal adverse effects.

Analysis of opioid-mediated analgesia in Phase III studies of methylnaltrexone for opioid-induced constipation in patients with chronic noncancer pain.

BackgroundSubcutaneous methylnaltrexone is efficacious and well tolerated for opioid-induced constipation (OIC) but may theoretically disrupt opioid-mediated analgesia.MethodsOpioid use, pain intensity, and opioid withdrawal (Objective Opioid Withdrawal Scale [OOWS] and Subjective Opiate Withdrawal Scale [SOWS] scores) were reported in a randomized, double-blind trial with an open-label extension (RCT) and an open-label trial (OLT) evaluating safety in adults with chronic noncancer pain. In the RCT, patients taking ≥50 mg of oral morphine equivalents daily with <3 rescue-free bowel movements weekly received methyl naltrexone 12 mg once daily (n=150), every other day (n=148), or placebo (n=162) for 4 weeks, followed by open-label methylnaltrexone 12 mg (as needed [prn]; n=364) for 8 weeks. In the OLT, patients (n=1,034) on stable opioid doses with OIC received methylnaltrexone 12 mg prn for up to 48 weeks.ResultsMinimal fluctuations of median morphine equivalent dose from baseline (BL) were observed in the RCT double-blind period (BL, 154.8–161.0 mg/d; range, 137.1–168.0 mg/d), RCT open-label period (BL, 156.3–174.6; range, 144.0–180.0) and OLT (BL, 120 mg/d; range, 117.3–121.1 mg/d). No significant change from BL in pain intensity score occurred in any group at weeks 2 or 4 (both P≥0.1) of the RCT double-blind period, and scores remained stable during the open-label period and in the OLT (mean change, −0.2 to 0.1). Changes from BL in OOWS and SOWS scores during the double-blind period were not significantly impacted by methylnaltrexone exposure at weeks 2 or 4 (P>0.05 for all).ConclusionMethylnaltrexone did not affect opioid-mediated analgesia in patients with chronic noncancer pain and OIC.

Sleep profile in opioid dependence: a polysomnographic case-control study.

Many opioid receptors are located in the same nuclei that are active in sleep regulation. It has been suggested that opioid peptides are involved in the induction of the sleep state. Prolonged opioid use has been hypothesized to cause disturbed sleep. It also causes excessive daytime sleepiness and fatigue. This study was conducted to compare the polysomnographic sleep profile of patients with opioid dependence with normal matched controls and to see the correlation between various clinical profiles of patients with opioid dependence with their polysomnographic sleep profile. Fifteen opioid-dependent male patients were selected, and after the detoxification procedure, the patients were assessed using Objective Opioid Withdrawal Scale, Obsessive Compulsive Drug Use Scale, Hamilton Rating Scale for Depression, Hamilton Anxiety Rating Scale, and Global Assessment of Functioning. Fifteen healthy volunteers matched for age, education, and handedness were taken as controls and were assessed using Epworth sleepiness scale and General Health Questionnaire-12. All night polysomnography recording was done on patient and control group, and staging of sleep was done. Patients had significantly decreased total sleep time, sleep efficiency and stage N1 sleep, prolonged sleep latency, and increased limb movement index. No significant correlation was found between sleep profile and various clinical variables. Use of opioids cause sleep disturbance, and these changes occurring in sleep can persist even after substance use has been stopped. Opioids seem to affect non-rapid eye movement stages of sleep.

A Double-Blind, Placebo-Controlled Trial of Dextromethorphan Combined With Clonidine in the Treatment of Heroin Withdrawal

Dextromethorphan has been reported to ameliorate opioid withdrawal symptoms in both animal and human subjects. In the present study, we investigated the efficacy of dextromethorphan as an add-on medication in heroin detoxification treatment in a double-blind, placebo-controlled design. Sixty-five heroin-dependent patients (male, 63; female, 2) participated in this inpatient detoxification trial after giving informed consent. Clonidine 0.075 mg 4 times a day was given as an antiwithdrawal medication at baseline. Each patient was then randomly assigned to treatment with either dextromethorphan 60 mg or placebo 4 times a day as additional medication. Flurazepam 30 mg was given before bedtime for insomnia. Other medications that were allowed included loperamide for diarrhea and lorazepam for agitation. Participants were monitored using the Objective Opioid Withdrawal Scale 3 times a day as the primary outcome to compare drug efficacy between groups. Generalized estimating equation model analysis revealed that the Objective Opioid Withdrawal Scale had no group difference between dextromethorphan and placebo group overall (P = 0.29), whereas a significant difference between groups was found during day 3 to day 6 (P = 0.04) by post hoc analysis. There was no difference in the Clinical Global Impression Scale, patient's impression of treatment, and use of ancillary medications between groups. No severe adverse effects were noticed. We suggest that dextromethorphan has some beneficial effect in attenuating the severity of opioid withdrawal symptoms and can be used as an adjunction medication in the treatment of opioid withdrawal, whereas the exact efficacy needs further investigation.

Pharmacokinetic-Pharmacodynamic Modeling of Mood and Withdrawal Symptoms in Relation to Plasma Concentrations of Methadone in Patients Undergoing Methadone Maintenance Treatment

The aims of the present study were to characterize the relationship between plasma racemic methadone and its enantiomers' concentrations with respect to their pharmacodynamic effects and to investigate the influence of potential covariates on the pharmacodynamic parameters in patients on methadone maintenance treatment (MMT). Eighty-eight regular subjects at the Sheffield Care Trust Substance Misuse Services were studied. Samples of blood and urine were collected before the daily dose of methadone. Blood samples were taken up to 5 hours after dose. Total plasma concentrations of (RS)-methadone and total and unbound plasma concentrations of both enantiomers were measured by liquid chromatography-mass spectrometry. The Total Mood Disturbance Score (TMDS), the Objective Opioid Withdrawal Scale (OOWS), and the Subjective Opioid Withdrawal Scale (SOWS) were used as measures of mood and withdrawal. Population pharmacokinetic/pharmacodynamic analysis and subsequent multiple regression analysis were used to determine the factors influencing the pharmacodynamic effects of methadone. Significant decreases (P ≤ 0.04) were observed in the scores for the TMDS, SOWS, and OOWS for 5 hours after methadone dosage. The TMDS had returned to baseline by 10 hours after dose (P = 0.98), at which time the SOWS remained significantly below baseline (P = 0.001). Multiple regression analysis revealed that 33% of the overall variation in unbound (R)-methadone EC50 was explained by 3 variables, namely CYP3A activity (9%), age (16%), and sex (8%). Age also accounted for 8% and 9% of the variation in total (rac)- and (R)-methadone EC50. The present study has confirmed that the duration of mood change in the present study was shorter than the effect of methadone in stabilizing withdrawal symptoms. Thus, it is likely that a once-daily dose of methadone, albeit effective for preventing withdrawal, may not be sufficient to improve mood in some patients. Finally, it was established that CYP3A activity, years of dependent use, sex, and age are major determinants of methadone EC50 with respect to TMDS.

Tramadol versus Methadone for Treatment of Opiate Withdrawal: A Double-Blind, Randomized, Clinical Trial

The aim of this study was to compare the efficacy and safety of tramadol versus methadone for treatment of opiate withdrawal. Seventy patients randomly were assigned in two groups to receive either prescribed methadone (60 mg/day) or tramadol (600 mg/day). The withdrawal syndrome of patients was evaluated before and after rapid opiate detoxification using the Objective Opioid Withdrawal Scale (OOWS). No significant differences existed in overall OOWS scores between two groups (P = 0.11). Dropout rates were similar in both groups. Side effects in the tramadol group were as or less common than in the methadone group, with the exception of perspiration. Tramadol may be as effective as methadone in the control of withdrawal and could be considered as a potential substitute for methadone to manage opioids withdrawal.

Effect of Ultra-Rapid Opiate Detoxification on Withdrawal Syndrome

ABSTRACT The aim of study was determine the effect of ultra-rapid opiate detoxification (UROD) on the presence or absence of withdrawal syndrome in a group of patients with opiate dependency. In this study, withdrawal syndrome of 173 patients with opiate addiction was evaluated before and after UROD using the Objective Opioid Withdrawal Scale. Hence, each patient was observed for 5 minutes before UROD and at different hours afterward to observe any withdrawal sign. The most prevalent withdrawal sign before UROD was anxiety. Restlessness was the most prevalent finding at 1, 3, and 6 hours. After 12 hours, yawning was reported as the most prevalent finding in 39 participants. Anxiety was reported as the most prevalent finding in 61 participants after 24 hours. Patients with opioid dependency who underwent UROD showed the highest rate of withdrawal symptoms at one hour after anesthesia. Most of these symptoms subsided after 24 hours. UROD can be applied for detoxification of patients with opioid dependency with safety.

Venlafaxine for Acute Heroin Detoxification

Dissatisfaction with current available heroin detoxification regimens has led to the search for alternatives. Evidences have shown that several neurotransmission systems, including serotonin, are involved in opioid withdrawal. This study investigated the efficacy and tolerability of venlafaxine, a serotonin-norepinephrine reuptake inhibitor, in managing heroin withdrawal symptoms. This was a randomized, double-blind, and placebo-controlled 7-day trial. Thirty-four heroin-dependent inpatients seeking detoxification were enrolled and assigned to either the venlafaxine (n = 15) or the placebo group (n = 19). The subjects received either venlafaxine 300 mg/d or placebo as their treatment regimen. Outcome measures were Objective Opioid Withdrawal Scale, total sleeping time, visual analog scale for subjective withdrawal severity, Clinical Global Impression scores on discharge, patient's impression of treatment, and amount of ancillary medications used. Data of outcome measures were analyzed by generalized estimating equation model. We analyzed the data from 20 subjects (8 in venlafaxine group and 12 in placebo group) who remained in the study after the fifth day of the trial. Objective Opioid Withdrawal Scale, visual analog scale, and total sleeping time demonstrated a significant efficacy of venlafaxine compared with the placebo group (P < 0.0001, P = 0.0195, and P < 0.0001, respectively). There was no difference in Clinical Global Impression and patient's impression of treatment between the 2 groups, although the placebo group needed more ancillary medications. Despite the small sample size, this study showed that venlafaxine is effective in alleviating withdrawal symptoms of heroin with good tolerability and safety.

Drug Interactions between Opioids and Antiretroviral Medications: Interaction between Methadone, LAAM, and Delavirdine

Understanding the drug interactions between antiretrovirals and opioid therapies may decrease toxicities and enhance adherence with improved HIV outcomes in opioid-dependent individuals. The authors report the results of a clinical pharmacology study designed to determine whether significant pharmacokinetic and/or pharmacodynamic interactions occur between the non-nucleoside reverse transcriptase inhibitor, delavirdine (DLV), and either methadone or levo-alpha acetyl methadol (LAAM) (n = 40). DLV significantly decreased methadone clearance (p = .018) and increased the methadone elimination half-life (p < .001) with a resultant increase in AUC of 19% and C(min)of 29%. The combined effect of DLV on the total concentration of LAAM and its active metabolites, norLAAM and dinorLAAM, was to significantly increase AUC by 43% (p < .001), C(max) by 30% (p = .013), and C(min) by 59% (p = .004) while decreasing T(max) (p = .05). Cognitive deficits over the seven-day study period as measured by the Mini-Mental State Examination, opioid withdrawal symptoms as measured by the Objective Opioid Withdrawal Scale, or complaints of adverse symptoms were not observed. Methadone and LAAM did not affect DLV concentrations. The findings from this study show that DLV treatment in methadone- or LAAM-maintained individuals results in altered opioid pharmacokinetics with an increased exposure and potential risk for opioid toxicity with methadone or LAAM treatment and an increased risk of cardiac toxicity with concomitant LAAM and DLV administration.