Clonidine and opiate receptor antagonists in the treatment of heroin addiction. Rapid opiate detoxication in outpatient treatment: relationship with naltrexone compliance. Efficacy of clonidine and of methadone in the rapid detoxification of patients dependent on heroin. Efficacy of clonidine, guanfacine and methadone in the rapid detoxification of heroin addicts: a controlled clinical trial. Efficacy of methadone versus methadone and guanfacine in the detoxification of heroin-addicted patients. Double-blind study of lofexidine and clonidine in the detoxification of opiate addicts in hospital. [Methadone, clonidine and levomepromazine in the treatment of opiate abstinence syndrome: double-blind clinical trial in heroin-addicted patients admitted to a general hospital for organic pathology]. Accelerated lofexidine treatment regimen compared with conventional lofexidine and methadone treatment for in-patient opiate detoxification. [Clonidine in opiate withdrawal syndrome]. Randomised double-blind comparison of lofexidine and methadone in the in-patient treatment of opiate withdrawal. Clonidine in outpatient detoxification from methadone maintenance. [Tizanidine in the treatment of acute withdrawal symptoms in heroin dependent patients]. Prison based detoxification for opioid dependence: a randomised double blind controlled trial of lofexidine and methadone. Clonidine in heroin withdrawal syndrome: a controlled study in India. Use of qigong therapy in the detoxification of heroin addicts. Double-blind randomised controlled trial of lofexidine versus clonidine in the treatment of heroin withdrawal. The association carbamazepine-mianserin in opiate withdrawal: a double blind pilot study versus clonidine. Opioid detoxification with buprenorphine, clonidine, or methadone in hospitalized heroin-dependent patients with HIV infection. A Phase 3 placebo-controlled, double-blind, multi-site trial of the alpha-2-adrenergic agonist, lofexidine, for opioid withdrawal. Randomised double-blind comparison of lofexidine and clonidine in the out-patient treatment of opiate withdrawal.
Good results in detoxification methods have been reached using both together clonidine and opiate receptors antagonists. One hundred fifty-two heroin-abusing patients were studied evaluating withdrawal symptoms after therapy with (a) clonidine only, (b) clonidine and naltrexone, (c) clonidine and naloxone, and (d) placebos. Treatment results, emotional and behavioral changes, and involvement in psychosocial programs were evaluated after a 6-month follow-up. Although opiate antagonists were able to induce slight and transient withdrawal signs and symptoms, there was, in the group of patients treated with clonidine and naltrexone together, a low percentage of catabolites in urine and an improvement in mood and family relationships. Furthermore, the patients that underwent longer naltrexone treatment showed a stronger involvement in psychosocial programs, and even their relatives demonstrated more interest in the recovery program. A decrease in the difficulties of accepting an opiate antagonists treatment and a different evaluation of withdrawal syndrome were the results of an early use of naltrexone. A variety of detoxification methods have been utilized for the treatment of heroin withdrawal before individuals begin long-term opiate-free and naltrexone programs. While methadone in decreasing doses is still widely used for detoxication procedures, rapid and ultrarapid protocols including clonidine and opiate receptors antagonists have been proposed. This study compares the efficacy of different detoxification methods and investigates possible changes in naltrexone compliance. Ninety-eight heroin-addicted individuals were studied to evaluate withdrawal symptoms, craving, mood, urine toxicologic screens, and drop-out rate during therapy with: Group A: clonidine only (5 days); Group B: clonidine, oxazepam, baclofen, and ketoprofene with naloxone and naltrexone (2 days); and Group C: methadone in decreasing doses (10 days). Naltrexone compliance and relapse rates were evaluated during a 6-month follow-up period. Rapid detoxification with opiate antagonists (Group B) induced slight and transient withdrawal symptoms, and resulted in a significantly lower percentage of heroin catabolites in urine controls during the detoxification procedure, lower negative and positive craving, less mood problems, and higher compliance in extended naltrexone treatment. In comparison with clonidine only (Group A) and methadone (Group C), the early use of naltrexone during detoxification in combination with benzodiazepines and clonidine facilitated extended naltrexone acceptance and improved the recovery outcome in outpatients. The efficacy of a rapid detoxification schedule (8 to 10 days) with clonidine or methadone was evaluated in 30 patients addicted to heroin. The dose of study drug was preestablished according to the subject's weight and the amount of opioid consumption, and the total daily dose was reduced by approximately 15% during the study. All subjects completed the detoxification program and stayed in the hospital for at least 12 days. Clonidine and methadone therapies proved to be highly effective. There was a marked reduction in anxiety during opioid detoxification, although subjects' experiences differed according to the drug used. On the day of discharge, subjects who had received methadone still had attenuated withdrawal symptoms, whereas there were no such symptoms in the clonidine group. Muscular aching, flatulence, and daily drowsiness were more common among subjects in the methadone group, while subjects in the clonidine group had more sleep disturbances and weeping. Syncopal episodes and bradycardia occurred more frequently in the clonidine group. The efficacy of clonidine, methadone, and guanfacine in rapid detoxification of heroin inpatients was assessed in a randomized controlled clinical trial. Signs and symptoms of abstinence and of side effects were analysed in 90 heroin addicts successfully completing a 12-day inpatient trial. All patients fit DSM-III criteria for opioid dependence, the age range being 18 to 36 years. All three drugs were effective in controlling abstinence; however, the course of abstinence was different in the methadone group as compared to the adrenergic agonists, the latter showing limitations in their ability to suppress withdrawal manifestations. While mean number of withdrawal signs and symptoms was significantly lower during days 2 to 5 in the methadone group (p less than 0.01), adrenergic agonists were slightly more effective at the end of the trial. Incidence of side effects was closely related to the dose administered. Hypotensive action of adrenergic agonists was more marked in orthostatic position. The present results suggest that methadone is superior to adrenergic agonists. Between these drugs clonidine appears to be less effective than guanfacine in controlling some withdrawal manifestations, and causes more side effects, mainly of cardiovascular nature. In a randomized double-blind study, the clinical efficacy of methadone vs. methadone and guanfacine was assessed in terms of evolution of opioid withdrawal symptoms during inpatient detoxification. A total of 144 patients were included and randomly allocated to three different treatment groups: methadone alone, and two combined treatment schedules (methadone plus 3 or 4 mg of guanfacine). No differences were observed among the three groups with regard to retention rate throughout the study period. Both therapies, methadone and methadone plus guanfacine, determined a slight increase in withdrawal scores when methadone was discontinued. However, guanfacine was unable to effectively control methadone-associated withdrawal symptoms. These results indicate that guanfacine does not effectively reduce the opioid withdrawal symptoms. Twenty eight opiate addicted inpatients who had been stabilised on methadone took part in a double-blind randomised trial of clonidine and lofexidine (14 on each treatment) for opiate detoxification: clonidine or lofexidine dosage was titrated according to symptoms. The course of withdrawal symptoms was very similar with both treatments, representing an appreciable suppression of symptoms when compared with experiences of sudden methadone withdrawal, but lofexidine resulted in significantly less hypotension and adverse events. These results suggest that lofexidine is a valuable drug for opiate detoxification and may be more acceptable to patients wishing to withdraw from opiates. nan This open study compares an accelerated 5-day lofexidine regimen with orthodox 10-day lofexidine and methadone regimens in the treatment of opiate withdrawal in 61 polysubstance abusing opiate addicts. Significant differences in levels of withdrawal symptoms were found on days 11, 13-15 and 17-20, symptoms resolving most rapidly in the 5-day lofexidine treatment group, whilst withdrawal responses in the 10-day lofexidine treatment group were intermediate between the 5-day lofexidine and standard methadone treatment conditions. When the two lofexidine regimens were separately compared with methadone the 5-day lofexidine treatment was significantly more effective on day 10, 11 and 13-20, whilst the 10-day lofexidine treatment was not significantly different from methadone. There were no significant differences in rates of completion of detoxification between the three treatments. Both the lofexidine treatment regimens had a similar effect on blood pressure. Five patients experienced side effects which resolved with dose reduction, all remaining in the study. An accelerated 5-day lofexidine regimen may attenuate opiate withdrawal symptoms more rapidly than conventional 10-day lofexidine or methadone treatment schedules without exacerbating hypotensive side effects. nan 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. Inpatient narcotic detoxification with clonidine hydrochloride has been used since 1978. Outpatient withdrawal, potentially more useful, has not been adequately studied. This report describes a double-blind random assignment of 49 methadone hydrochloride-maintained patients whose dose had been lowered to 20 mg. Twenty-five were detoxified using methadone at 1-mg decrements, 24 by abrupt substitution with clonidine. Approximately 40% of both groups achieved successful detoxification, with one third maintaining abstinence over the subsequent six months. The groups were also largely equivalent on withdrawal symptoms, but the clonidine group experienced symptoms in the first half of the study and the methadone group in the second half. Clonidine appears to be a safe and efficacious outpatient treatment for opiate withdrawal, although the results were less favorable than those obtained in open or inpatient studies. One of the treatment alternative of withdrawal symptoms of patients suffering from opiate dependence is to apply the clonidine in combination or itself. This remedy is not in commercial trade in our country. It is expectable according to the recent data analysing the effects of the alfa2 adreneregic agonist tizanidine that tizanidine has the similar protective effect as clonidine with the resembling target point. Based on this theory a research was done, in the course of which the i.v. heroin users who presented themselves at the Drug Outpatient Department of Buda between 1.10.1998-8.01.1999. were divided into two groups. The groups had got the usual detoxification treatment, but in the experimental group tizanidine were given in 3 x 8 mg/day dose too. Sixteen patients were in the tizanidine group, 10 patients were in the control group. The patients estimated the intensity of 7 symptoms of withdrawal (sweating, nervousness, insomnia, tremor, diarrhoea, muscle pain, drug craving) on a subjective scale day by day. The analysis showed that the tizanidine treatment decreased the intensity of the withdrawal symptoms in every symptom type examined. The ten days long acute withdrawal period were accomplished by all of the patients, but in the short course of the following (mean 9 and 11 weeks in the treated and the control groups respectively) there were three relapses in each group (3/16 in the treated and 3/10 in the control). This paper reports results from the first controlled trial of opioid withdrawal treatment in the UK using lofexidine in a prison setting. Seventy-four opioid dependent male inmates at a Southern England prison were randomised to receive either methadone (the standard prison treatment) or lofexidine using a randomised double-blind design. No significant statistical difference between the treatment groups was found in relation to the primary variable of severity of withdrawal symptoms (effect size=0.12). No discernible difference was found in the sitting blood pressure or heart rate of the two groups during the trial. These results provide support for the use of lofexidine for the management of opioid detoxification in the prison setting. nan Qigong is a traditional Chinese health practice believed to have special healing and recovery power. Little scientific documentation was found on qigong and its effectiveness, and no literature was found on qigong as a treatment of substance addiction.
                To explore the effectiveness of qigong therapy on detoxification of heroin addicts compared to medical and nonmedical treatment.
                Participants were randomly assigned to 1 of 3 groups: qigong treatment group (n = 34), medication group (n = 26), and no-treatment control group (n = 26).
                Eighty-six male heroin addicts, aged 18 to 52 years, who met the substance-dependence criteria of the Diagnostic and Statistical Manual of Mental Disorders, Third Edition Revised, with a history of heroin use from .5 to 11 years. All were residents at a mandatory drug-treatment center in the People's Republic of China.
                The qigong group practiced Pan Gu qigong and received qi adjustments from a qigong master daily. The medication group received the detoxification drug lofexidine-HCl by a 10-day gradual reduction method. The control group received only basic care and medications to treat severe withdrawal symptoms.
                Urine morphine test, electrocardiogram, Hamilton Anxiety Scale, and a withdrawal-symptom evaluation scale were applied before and during the 10-day intervention.
                Reduction of withdrawal symptoms in the qigong group occurred more rapidly than in the other groups. From day 1, the qigong group had significantly lower mean symptom scores than did the other groups (P <.01). Both the qigong and medication groups had much lower anxiety scores than did the control group (P<.01), and the qigong group had significantly lower anxiety scores than did the medication group (P<.01). All subjects had a positive response to the urine morphine test before treatment. Fifty percent of the qigong group had negative urine tests on day 3, compared to 23% in the control group and 8% in the medication group (P <.01). By day 5 of treatment, all subjects in the qigong group had negative urine tests, compared to day 9 for the medication group and day 11 for the control group.
                Results suggest that qigong may be an effective alternative for heroin detoxification without side effects, though we cannot completely eliminate the possibility of the placebo effect from the current study. Lofexidine is an analogue of clonidine, an agonist at the alpha 2 noradrenergic receptor. Reports from preliminary open studies have suggested that it may be at least as effective as clonidine in the management of opiate withdrawal, and without the same limitation of postural hypotension. We report on a randomised double-blind comparison of lofexidine versus clonidine in the treatment of heroin withdrawal. A total of 80 hospitalized heroin addicts were randomly assigned to treatment with lofexidine or clonidine during in-patient opiate withdrawal. Maximum daily doses were 1.6 mg for lofexidine and 0.6 mg for clonidine. There was marked diurnal variation of withdrawal symptoms with severity being greatest at the daytime reading at 16.00 h and being markedly less at the night-time reading (recorded at 08.00 h). Lofexidine and clonidine were equally effective in treating the withdrawal syndrome. However, significantly more problems relating to hypotension were encountered with subjects on clonidine, with twice as many instances of withholding medication due to hypotension in the clonidine group. Better treatment retention rates were seen in the lofexidine group, although no difference was found in the proportion who had reached minimal symptom severity by the time of their discharge. We conclude that lofexidine and clonidine are equally effective, but with significantly fewer hypotensive problems with lofexidine. Further benefit from lofexidine may be possible with revised dosing regimens. Outpatient studies of lofexidine are now indicated. Our clinic has fortuitously developed the therapeutic use of the association of mianserin (maximum daily dose 90 mg) and carbamazepine (maximum daily dose 400 mg) in opiate withdrawal management. If animal studies have suggested efficacy of mianserin in such indication, no human studies have been performed. To test the efficacy of such an association, a comparison was made to clonidine (maximum daily dose 0.600 mg) in a one week treatment period according to a double blind pilot study design. Thirty-two patients were included (16 in each treatment group). The two treatments did not differ in the intensity of the withdrawal, according to the rate of retention in treatment and symptoms, and the psychic distress which were auto-evaluated every other day with the Opiate Withdrawal Questionnaire and several Visual Analog Scales (VAS). The clonidine group, however, scored significantly higher (P < 0.05) on the VAS rating of the global feeling of satisfaction on the last day. The patients in the mianserin group fortuitously had a moderately lower number of daily heroin intakes but there was no significant correlation between this variable and the global OWQ scores on Days 1, 3, 5 and 7. Given the size of the groups, we cannot conclude that the association carbamazepine-mianserin is as effective as clonidine, but a real effectiveness is probable. A study versus placebo would be necessary to draw more definitive conclusions. With the growing role of intravenous drug use in the transmission of HIV infection, HIV-infected patients frequently present with comorbid opioid dependence. Yet, few empirical evaluations of the efficacy and consequences of opioid detoxification medications in medically ill HIV-infected patients have been reported. In a randomized, double-blind clinical trial, we evaluated the impact of three medications on the signs and symptoms of withdrawal and on the pain severity in heroin-dependent HIV-infected patients (N=55) hospitalized for medical reasons on an inpatient AIDS service. Patients received a 3-day pharmacologic taper with intramuscular buprenorphine (n=21), oral clonidine (n=16), or oral methadone (n=18), followed by a clonidine transdermal patch on the fourth day. Observed and self-reported measures of opioid withdrawal and pain were taken 1-3 times daily for up to 4 days. Opiate administration used as medically indicated for pain was also recorded. Observer- and subject-rated opiate withdrawal scores decreased significantly following the first dose of medication and overall during treatment. Among all 55 subjects, self-reported and observer-reported pain decreased after treatment (on average observer-rated opioid withdrawal scale (OOWS) scores declined 5.6 units and short opioid withdrawal scale (SOWS) declined 4.8 units, P<0.001, for both) with no indication of increased pain during medication taper. There were no significant differences of pain decline and other measures of withdrawal between the three treatment groups. During the intervention period, supplemental opiates were administered as medically indicated for pain to 45% of the patients; only 34% of men versus 62% of women received morphine (P<0.05). These findings suggest buprenorphine, clonidine, and methadone regimens each decrease opioid withdrawal in medically ill HIV-infected patients. Lofexidine is an alpha-2-adrenergic receptor agonist that is approved in the United Kingdom for the treatment of opioid withdrawal symptoms. Lofexidine has been reported to have more significant effects on decreasing opioid withdrawal symptoms with less hypotension than clonidine.
                To demonstrate that lofexidine is well tolerated and effective in the alleviation of observationally defined opioid withdrawal symptoms in opioid dependent individuals undergoing medically supervised opioid detoxification as compared to placebo.
                An inpatient, Phase 3, placebo-controlled, double-blind, randomized multi-site trial with three phases: (1) opioid agonist stabilization phase (days 1-3), (2) detoxification/medication or placebo phase (days 4-8), and (3) post detoxification/medication phase (days 9-11).
                Sixty-eight opioid dependent subjects were enrolled at three sites with 35 randomized to lofexidine and 33 to placebo.
                Modified Himmelsbach Opiate Withdrawal Scale (MHOWS) on study day 5 (second opioid detoxification treatment day).
                Due to significant findings, the study was terminated early. On the study day 5 MHOWS, subjects treated with lofexidine had significantly lower scores (equating to fewer/less severe withdrawal symptoms) than placebo subjects (least squares means 19.5+/-2.1 versus 30.9+/-2.7; p=0.0019). Lofexidine subjects had significantly better retention in treatment than placebo subjects (38.2% versus 15.2%; Log rank test p=0.01).
                Lofexidine is well tolerated and more efficacious than placebo for reducing opioid withdrawal symptoms in inpatients undergoing medically supervised opioid detoxification. This study compares the clinical response to lofexidine and clonidine in the out-patient treatment of opiate withdrawal in 50 opiate addicts, using a randomised double-blind study design. Patients were taking 40 mg or less methadone daily, or equivalent amounts of other opiates. Fifty-eight percent of those starting treatment completed detoxification, and were opiate free at 4 weeks: more patients completed withdrawal in the lofexidine group, but the difference was not significant. Clonidine produced more hypotensive effects: more home visits were also required by medical staff. There was no other significant difference in side effects. Both drugs can be used successfully in out-patient detoxification, but lofexidine is more economical in regard to staff time.
Clonidine and lofexidine are more effective than placebo for the management of withdrawal from heroin or methadone. No significant difference in efficacy was detected for treatment regimes based on clonidine or lofexidine, and those based on reducing doses of methadone over a period of around 10 days but methadone is associated with fewer adverse effects than clonidine, and lofexidine has a better safety profile than clonidine.