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Buprenorphine treatment of opioid dependence: clinical trial of daily versus alternate-day dosing.

Buprenorphine, a mu-opioid partial agonist, has demonstrated efficacy for the treatment of opioid dependence comparable to that of methadone. The clinical utility of buprenorphine would be enhanced if it could be dosed on a less than daily basis. The current study is a parallel-group outpatient clinical trial of daily versus alternate-day dosing with 8 mg sublingual (s.l.) buprenorphine. Participants were randomly assigned to daily (n = 51) or alternate-day (n = 48) schedules of active medication administration for an 11-week double-blind trial. Patients assigned to alternate-day buprenorphine received placebo every other day. Primary outcome measures were retention in treatment and urine specimens positive for opiates. Clinic attendance, dose adequacy ratings, withdrawal symptomatology, and urine specimens positive for cocaine were secondary outcome measures. Neither endpoint analysis with the intent-to-treat sample nor time course analysis with treatment completers revealed any statistically significant differences between the dosing schedules on any outcome measure. Examination of 95% confidence intervals suggested a non-significant trend for the daily dosing schedule to have superior clinical efficacy at the dose tested. Nevertheless, these results are generally consistent with previous studies of less than daily dosing with buprenorphine and support the conclusion that an alternate-day dosing schedule can be effective in and acceptable to a substantial portion of patients.

Adult↗

Stability of opioid craving over time as measured by visual analog scales.

Sixteen methadone maintenance patients reported their 24-h peak opioid craving on a visual analog scale and the time of day at which the peak craving occurred on weekdays over a 4-week period. Both intersubject and intrasubject craving scores were highly variable. Craving scores did not correlate highly with time since the previous dose, mean methadone dose, requests for changes in maintenance dose, or occurrence of positive urine-drug screens. These data suggest that 24-h craving recall (as measured by visual analog scales) varies over time and is not closely correlated with changes in methadone blood levels.

Adult↗

Acupuncture heroin detoxification: a single-blind clinical trial.

The increasing prevalence of HIV infection among injection drug users mandates the development of innovative treatments. While extensive clinical experience suggests that acupuncture detoxification is both safe and acceptable to those in withdrawal, little research has been conducted to assess its efficacy as a treatment modality. In this first controlled study of acupuncture heroin detoxification, 100 addicted persons were randomly assigned, in a single-blind design, to the standard auricular acupuncture treatment used for addiction or to a "sham" treatment that used points that were geographically close to the standard points. Attrition was high for both groups, but subjects assigned to the standard treatment attended the acupuncture clinic more days and stayed in treatment longer than those assigned to the sham condition. Additionally, attendance varied inversely with self-reports of frequency of drug use, suggesting that those with lighter habits found the treatment modality more helpful. Limitations of the study are discussed.

Acupuncture Points↗

Behavioral response to buspirone in cocaine and phencyclidine withdrawal.

The effects of buspirone in treating cocaine and phencyclidine (PCP) withdrawal were studied. Withdrawal symptoms of these two street-drugs are thought to be due to norepinephrine, dopamine and possibly serotonin depletion. Buspirone acts by enhancing dopaminergic and noradrenergic firing as well by suppressing serotonergic activity. Thirty-two cocaine abusers and 24 PCP abusers were withdrawn over a 30-day period. Half of each group received buspirone 10 mg t.i.d. and the other half 10 mg placebo t.i.d. In the cocaine group, buspirone was significantly more effective from the fifth day onward. In the PCP group, significant improvement was seen on the thirtieth day. Delayed effectiveness in PCP is thought due to its actions at other neurotransmitter sites.

Arousal↗

Outpatient benzodiazepine detoxification procedure for methadone patients.

Benzodiazepines are used by a substantial minority of opioid addicts on methadone maintenance. Alprazolam, now the most widely prescribed benzodiazepine in the United States, appears to have supplanted diazepam as the benzodiazepine drug of choice in this population. Its greater addiction liability, shorter half-life, and more intense withdrawal symptoms make addiction to alprazolam more likely and its management in methadone patients more complicated. This article describes a slow outpatient tapered reduction procedure that was utilized to detoxify benzodiazepine dependent methadone patients seen over a two-year period. The reduction procedure was offered to 22 opioid addicts on methadone maintenance who were regularly ingesting low to moderate amounts of benzodiazepines, primarily alprazolam. Of the 22 patients, 4 patients refused outpatient detoxification, and 18 were started on a reduction procedure. Twelve patients completed the detoxification procedure which averaged 7.8 weeks. Comparisons are made between completers and non-completers and essential design features of the procedure are discussed.

Adult↗

A preliminary investigation of ibogaine: case reports and recommendations for further study.

A naturally occurring substance, ibogaine, was taken by seven individuals who were addicted to opiates. Ibogaine, an alkaloid with psychotropic effects at doses of 200-300 mg and above, was taken in single doses of 700-1800 mg by the subjects in the study. At the end of the 24-38-hr psychoactive period induced by the drug at these doses, none of the subjects displayed significant opiate withdrawal symptoms. At the lowest dose of 700 mg, one subject recontinued his drug abuse after 2 days; of the remaining six individuals who took 1,000 mg or above, two relapsed after a number of weeks, one reverted to intermittent heroin use, and three appear to have remained drug-free 14 weeks or more after undergoing this experimental treatment. Ibogaine may be of value in the present and could serve as a model for the development of improved agents for the treatment of substance abuse in the future.

Adult↗

A randomized double-blind study of neuroelectric therapy in opiate and cocaine detoxification.

Prior research on the use of transcranial neuroelectric stimulation suggested that the application of low-amperage, low-frequency alternating current via surface electrodes placed in the mastoid region could relieve the physiological signs and subjective symptoms of withdrawal and craving during opiate detoxification. These effects were reported without gradual tapering of the opiate or the addition of other medications. To test the efficacy of one particular form of neuroelectric therapy (NET), a double-blind, randomized, placebo-controlled study was conducted comparing active NET and placebo NET in the treatment of withdrawal and stabilization of 18 opiate-dependent and 25 cocaine-dependent subjects. Scores on scales for measuring substance withdrawal and craving for each abused substance, as well as the multiple dimensions of mood, were compared for degree of difference across the 10 days of treatment. There was an overall completion rate of 88%, with both cocaine and opiate groups reporting a comfortable detoxification and substantial improvement over the course of a 12-day hospitalization. There was no significant difference between the active or placebo groups, suggesting that placebo was as effective as active NET in reducing drug withdrawal or craving during cocaine and opiate detoxification. However, all placebo patients received 0.2 mA of current, which may have provided a degree of active current. Suggestions are offered for future research.

Adult↗

A double-blind, placebo-controlled trial of amantadine, propranolol, and their combination for the treatment of cocaine dependence in patients with severe cocaine withdrawal symptoms.

BACKGROUND: This trial evaluated the efficacy of amantadine, propranolol and their combination in cocaine dependent patients with severe cocaine withdrawal symptoms. METHODS: Cocaine withdrawal symptom severity was measured by the cocaine selective severity assessment (CSSA). One hundred and ninety-nine patients with high scores on the CSSA participated in a 10-week double-blind trial. Patients were randomly assigned to receive amantadine (300 mg/day), propranolol (100mg/day), a combination of amantadine (300 mg/day) and propranolol (100mg/day) or matching placebo capsules. The primary outcome measure was cocaine abstinence. RESULTS: In the intent-to-treat sample, there were no significant differences between the four medication groups in treatment retention. The odds of cocaine abstinence showed a marginally significant increase over time in the propranolol group (p=0.06) but not in the other three groups. In highly medication-adherent patients, treatment retention was significantly better in the propranolol group compared to the placebo group (p=0.01) and the odds of cocaine abstinence increased significantly over time in the propranolol group but not in the other three groups. CONCLUSION: In the intent-to-treat sample, none of the three active treatments (propranolol, amantadine or their combination) was significantly more effective than placebo in promoting abstinence from cocaine among patients who entered treatment with more severe cocaine withdrawal symptoms. Among patients highly adherent to study medication, propranolol treatment was associated with better treatment retention and higher rates of cocaine abstinence compared to placebo.

Adrenergic beta-Antagonists↗

Hospitalized patients and alcohol: who is being missed?

Research and clinical experience have shown that alcohol use disorders are neither sufficiently identified nor addressed in hospitalized patients. This study sought to quantify and localize these missed opportunities. The setting was an urban medical center with a Level 1 trauma designation. The only eligibility requirement was a Blood Alcohol Level (BAL) greater than 300 ng/dl upon hospital admission, a "nonsubtle" value more than three times the legal intoxication limit. Charts [58] were retrospectively reviewed for treating service (medical, trauma services, or psychiatric) and evidence of psychological signs or behavioral symptoms of withdrawal. Also assessed were the presence or absence of withdrawal monitoring, withdrawal prophylaxis orders, inpatient addictions consultation, and referral for addictions aftercare. Numerous patients with admission BALs >300 failed to be identified as needing assessment for alcohol-related disorders. Patients admitted to medical or psychiatric services were significantly more likely to be diagnosed than those on trauma services (P =.02). Patients on medical or psychiatric services were also more likely to be assessed for withdrawal and referred for after-care (P <.0001) than those cared for on trauma services. The delivery of care for alcohol-related disorders was deficient, particularly for patients with traumatic injuries, even among patients severely intoxicated at admission. Failure to identify such patients represented a missed opportunity to address this vital contributor to trauma. It is suggested that both the origins of this shortfall and its resolution depend not just upon trauma providers but upon the entire medical system.

Alcoholism↗

Depression in methadone maintenance treatment patients: rate and risk factors.

BACKGROUND: Depression is widely prevalent among former heroin addicts in methadone maintenance treatment (MMT). The risk factors for depression among MMT patients that have not been well characterized, was studied. METHODS: In a cross-sectional study (January, 2004-August, 2005), 90 MMT patients were evaluated for depression by the 21-item Hamilton Rating Scale for Depression (21-HAM-D) and the Brief Psychiatric Rating scale (BPRS). To study possible induction of depression by drug abuse, urine samples tested for opiates, cocaine metabolite (benzoylecgonine), benzodiazepines (BDZ), cannabis (THC), amphetamines and methadone metabolite during 1 month preceding study entry: a drug was defined as being positive if at least one sample was positive. RESULTS: The 21-HAM-D and BPRS scores were significantly correlated (Pearson R=0.76, p<0.0005). Fifty percent were found to be suffering from depression (21-HAM-D, scored > or = 18). Fifteen new patients in MMT had better scores (5.1+/-5.7) than continuous patients (17.7+/-6.2, p<0.0005), independent of treatment duration. Higher scores were in 51 patients with any Axis I psychiatric diagnosis (18.9+/-5.7 vs. 11.4+/-7.9, p<0.0005), 74 abusing and or using prescribed BDZ (16.3+/-7.4 vs. 11.7+/-8, p=0.03), and 36 prescribed more than one type of medication (17.5+/-7.3 vs. 14.2+/-7.7, p=0.05). Females (N=40) had poorer scores than males (17.6+/-7 vs. 14.1+/-7.9, p=0.03), especially 12 admitted into treatment while pregnant (20.2+/-4.1). LIMITATION: Patient drug abuse and withdrawal could distort evaluation and lead to misclassification of depression. CONCLUSION: The major risk factors for depression were already being in MMT, female gender, any DSM-IV Axis I psychiatric diagnosis, taking any psychotropic medication, abuse or using prescribed BDZ, and methadone dose > 120 mg/day.

Adult↗

Heroin and cocaine craving and use during treatment: measurement validation and potential relationships.

Although commonly assessed with unidimensional scales, craving has been suggested to be multifaceted and to have a complex relationship with drug use and relapse. This study assessed the consistency and predictive validity of unidimensional and multidimensional craving scales. At the beginning of a 12-week outpatient treatment trial, opiate users (n = 101) and cocaine users (n = 72) completed unidimensional visual analog scales (VASs) assessing "want," "need," and "craving" and multidimensional 14- and 45-item versions of the Cocaine Craving Questionnaire (CCQ) or Heroin Craving Questionnaire (HCQ). Spearman correlations between the VASs and the first-order factors from the 45-item CCQ/HCQ were .20-.40, suggesting that the two types of assessment were not redundant. Treatment dropout and in-treatment drug use were more frequently predicted by scores on the 14- or 45-item CCQ than by VAS ratings. Results suggest that the CCQ/HCQ and the 14-item CCQ provide information that unidimensional VASs do not.

Adult↗

Cerebral phosphorus metabolite and transverse relaxation time abnormalities in heroin-dependent subjects at onset of methadone maintenance treatment.

Cerebral bioenergetic and phospholipid abnormalities have been reported in heroin-dependent subjects. The goal of the present study was to characterize the neurochemical profile of subjects voluntarily enrolled in a methadone maintenance (MM) treatment program to overcome their heroin addiction. Participants included 43 heroin-dependent subjects during their first month of MM and 15 age-matched healthy individuals. Phosphorus magnetic resonance spectroscopy ((31)P MRS) and transverse relaxation times (T2-RT), which can reflect steady state cerebral perfusion and metabolism, were acquired at 1.5 T from an axial slice prescribed through the orbitofrontal and occipital cortices, including basal ganglia and frontal cortex. MM subjects exhibited reduced phosphocreatine (PCr) levels (-15.3%), elevated phosphodiesters (+ 12.9%, PDE) and significantly longer T2-RT ((+) 2.1%) compared with healthy comparison subjects. When MM subjects were stratified into subgroups based on treatment duration, we found a treatment duration effect on metabolite values but not T2-RT; reduced PCr was observed only after 8+ days of MM, and phosphomonoesters (PME) were elevated in the 15-28 day MM group. Taken together, these cross-sectional data suggest that the first month of MM treatment may be associated with altered cerebral bioenergetics and phospholipid metabolite levels.

Adenosine Triphosphate↗

DHEAS and POMS measures identify cocaine dependence treatment outcome.

UNLABELLED: Early attrition is a significant problem in the treatment of cocaine dependence, but it is unclear why some patients succeed in treatment while others relapse or drop out of treatment without a demonstrated relapse. The goal of this study was to determine whether baseline levels of select hormones, including the adrenal hormone and excitatory neurosteroid dehydroepiandrosterone sulfate (DHEAS), would distinguish between treatment outcome groups. Based on the literature, completion of 90 days of treatment was established as a key outcome variable. METHODS: Quantitative urine levels of the cocaine metabolite benzoylecgonine (BE) and other substance of abuse analytes, plasma levels of DHEAS, DHEA, cortisol, and prolactin, and the profile of mood states (POMS) were serially measured in 38 male cocaine-dependent (DSM-IV) patients and in 28 controls of similar gender and age over a six month study. Exclusion criteria for the patients and controls included Axis I mood, anxiety or psychotic disorders. The patients could not manifest substance dependence except to cocaine. The patients and controls received remuneration for urine and blood collection. Blood samples for hormone levels were obtained between 8 and 10 a.m. on days 1, 14 and 21 of a 21-day inpatient treatment program and throughout 6 months of outpatient study visits at 45-day intervals. RESULTS: Attrition from treatment and study appointments occurred predominately at the junction between inpatient and outpatient programs. Forty percent of patients made the transition to outpatient treatment and remained abstinent and in treatment for a median of 103 days (ABST). Forty-two percent of patients dropped out of treatment during the inpatient stay or never returned after completing the inpatient program (DO) and 18% had a documented relapse either during, or within the first week after, the inpatient stay (REL). POMS total scores were elevated at treatment entry for both the ABST and DO groups. Plasma DHEAS levels in the DO patients were decreased compared to controls and increased in the ABST patients. POMS total scores for the REL patients at baseline were at control levels. Baseline cortisol levels were not statistically different between the outcome groups, though they were elevated for all cocaine patient groups. When treatment outcome was collapsed into whether patients completed (ABST) or did not complete 90 days of treatment (90N), ABST plasma DHEAS and cortisol were significantly elevated compared to the 90N patients and controls across the first 3 weeks of cocaine withdrawal. CONCLUSIONS: At treatment entry, each of the three patient outcome groups was identified by levels of circulating DHEAS and distressed mood. In the ABST patients, distressed mood during withdrawal may have been mitigated through antidepressant-like actions of enhanced endogenous DHEAS activity, thus contributing to improved abstinence and treatment retention. Patients, such as the DO group, with high levels of distressed mood at treatment entry and low DHEAS levels may benefit from adjunctive pharmacotherapy that targets DHEAS and POMS measures. Patients, such as the REL group, who lack distressed mood at treatment entry, may require intense application of motivational approaches plus residential treatment.

Adult↗

Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal.

This study compares the clinical responses to methadone and lofexidine in the treatment of opiate withdrawal in 86 polydrug-abusing opiate addicts, using a randomised double-blind study design. The lofexidine treatment more severe symptoms from day 3 to 7 and again on day 10 (the last day of treatment), but thereafter both groups showed a similar progressive symptom decline. There was no significant difference in rates of treatment completion. Both treatments had similar effects on blood pressure. Lofexidine is broadly clinically equivalent to methadone, and appears to be a non-opiate treatment of opiate withdrawal without serious limiting hypotensive side effects.

Adolescent↗

Plasma methadone concentrations as an indicator of opioid withdrawal symptoms and heroin use in a methadone maintenance program.

Plasma methadone concentrations and its main metabolite D,L-2-ethylidiene-1,5-dimethyl-3,5-diphenylpyrrolidine (EDDP) were determined in 93 patients under methadone maintenance treatment to assess their relationship with heroin use and opioid withdrawal symptoms. Neither plasma concentrations of methadone nor EDDP were significantly different when patients that used heroin in last 3 months were compared with those testing negative for this drug (methadone, 355 +/- 217 versus 369 +/- 216 ng/ml, t = 0.29, P = NS; EDDP, 49 +/- 28 versus 54 +/- 40 ng/ml, t = 0.51, P = NS). No correlation between opioid withdrawal scale scores and plasma concentrations of methadone (r = 0.02, P = NS) and EDDP (r = -0.14, P = NS) was found. Therapeutic drug monitoring during methadone maintenance seems to be useful for assessing compliance with treatment but not for predicting heroin use and subjective withdrawal symptoms.

Adult↗

Long-term methadone maintenance effectiveness: psychosocial and pharmacological variables.

Data were collected from 265 heroin-dependent patients in long-term methadone maintenance treatment for methadone dosage, administration method, illicit drug and problematic alcohol use, psychiatric diagnoses, quality of interpersonal relationships, employment, legal problems, health, and cravings. Patients receiving higher methadone doses (more than 80 mg) were more likely to respond to methadone treatment than patients receiving lower doses. Superior outcome was also related to good quality of interpersonal relationships, stable employment, and lower craving scores. Comorbid psychiatric disorders did not appear to influence methadone effectiveness, but psychopharmacological treatment associated with methadone was associated with a lower rate of urine samples positive for drug use. Administration of methadone weekly or twice weekly ("home methadone") was less effective than daily administration. Although our results were obtained through a descriptive study, which does not permit a prospective evaluation, they suggest the need for higher methadone doses. Job and family relationships appear to be associated, together with psychopharmacological treatment, with a more effective outcome.

Adult↗

Follow-up of inpatient cocaine withdrawal for cocaine-using methadone patients.

Significant proportions of opiate-dependent persons entering methadone treatment are also addicted to cocaine and continue to use cocaine during treatment. One standard response to cocaine use has been inpatient detoxification. This study examined the effectiveness of this procedure by comparing pre- and posttreatment urine toxicologies for methadone patients who had been hospitalized for cocaine withdrawal. The results showed a negligible effect on cocaine abstinence (less than 1 out of 10 patients abstinent 12 weeks after detox) and a modest reduction in the frequency of cocaine use (one-quarter decline in urine tests positive after 12 weeks). These findings raise serious doubts about the cost-effectiveness of inpatient cocaine detoxification. Better strategies need to be implemented to enhance the chances of remaining abstinent once detoxified.

Adult↗

Cocaine abstinence symptomatology and treatment attrition.

Premature termination from outpatient cocaine treatment predicts a number of poor outcomes, including higher rates of relapse and unemployment. This study attempted to predict dropouts from outpatient cocaine treatment, as well as those unable to achieve initial abstinence from cocaine, using two baseline variables that had previously been shown to predict treatment dropout: a measure of the severity of cocaine abstinence symptomatology using the Cocaine Selective Severity Assessment (CSSA) and the initial urine toxicology. Results of logistic regression analyses indicated that those with more intense abstinence symptoms, as measured by the CSSA, were five times more likely to terminate treatment prematurely. When combined with the CSSA, the initial urine did not significantly predict dropouts. The CSSA and the baseline urine were equal in their ability to predict those who would fail in their initial attempts to achieve abstinence. Implications for treatment are discussed.

Ambulatory Care↗