Double-blind randomized controlled trial of baclofen vs. clonidine in the treatment of opiates withdrawal

BACKGROUND: A variety of detoxification methods have been utilized for the treatment of opiate withdrawal syndrome, of which alpha-adrenergic agonists have attracted considerable attention over the last two decades. However, accumulating evidence in rats shows the efficacy of the GABAB receptor agonist, baclofen, in reducing alcohol intake and self-administration of cocaine. OBJECTIVE: To examine the ability of baclofen, in the management of opiate withdrawal. METHOD: A total of 62 opiate addicts randomly assigned to treatment with baclofen or clonidine during a 14-day, double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. Maximum daily doses were 40 mg for baclofen and 0.8 mg for clonidine given three times a day in divided doses. The severity of the opiate withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale (SOWS). RESULTS: Baclofen and clonidine were equally effective in treating the physical symptoms of withdrawal syndromes. However, baclofen showed a significant superiority over clonidine in the management of mental symptoms. CONCLUSION: These results suggest that baclofen might be a novel therapeutic agent for opiate withdrawal syndrome. However, a larger study to confirm our results is warranted.     

Characteristics of postictal headache in patients with partial epilepsy

Migraine-like features sometimes characterize the headache that follows epileptic seizure (postictal headache, PIH). We compared patients with different types of epilepsy to investigate the association between migraine-like PIH and seizure type. Subjects comprised 364 patients with partial epilepsy. Epilepsy types were temporal lobe epilepsy (TLE, n = 177), frontal lobe epilepsy (FLE, n = 116), and occipital lobe epilepsy (OLE, n = 71). Patients participated in a structured interview pertaining to PIH as well as interictal headache and family history of migraine. Headaches were classified according to the International Headache Society criteria, which was modified for this study. Forty percent had PIH and 26% of these patients had migraine-like PIH. Migraine-like PIH occurred significantly more often in cases of TLE and OLE than in cases of FLE. In addition, the incidence of interictal migraine headache was significantly higher in patients with migraine-like PIH. These results suggest that migraine-like PIH is related to particular regions of epileptogenic focus and that susceptibility to migraine headache predisposes to migraine-like PIH.     

New insights and treatments: opiate withdrawal and cocaine addiction

Basic research in the neurosciences has led to a theory of opiate withdrawal involving endogenous opioid peptides and hyperactive norepinephrine neurons. This theory predicts the efficacy of clonidine, a nonopiate agent, in the management of opiate withdrawal. Clonidine, which offers numerous advantages over methadone as a means of opiate detoxification, may be appropriate for use by general practitioners. Clonidine-aided detoxification can be followed immediately by naltrexone maintenance, which facilitates rehabilitation. Cocaine users' reports and clinical and basic studies, when pieced together, provide an outline of the natural history of chronic cocaine abuse. How certain users become addicts is not clear, however. Additional neurochemical research and neurophysiological studies are needed for the development of nonaddictive methods of detoxification (à la clonidine) and prophylaxis (à la naltrexone). In the absence of such studies, cocaine treatment programs use the methods of Alcoholics Anonymous, contingency contracting, and inpatient therapies for addiction.     

"Induced detoxification treatment" of opiate dependent patients--a new therapy concept

Induced detoxification treatment of opiate addicts by means of naloxone was developed at the intensive care unit of the Department of Psychiatry at the University of Vienna. Two methods were tested 1. Rapid opiate withdrawal by means of a staggered naloxone regimen. 2. Ultrashort opiate detoxification during general anaesthesia using high doses of naloxone. In an open trial 15 patients were treated with staggered doses of naloxone while under tiapride. The various discomforts were satisfactorily reduced, and the detoxification syndrome was limited to 50 hours. In a second open trial 6 patients were administered 10 mg naloxone under general anaesthesia. All naloxone induced withdrawal syndromes can be suppressed by barbiturate anaesthesia. They do not appear even after the effect of the anaesthesia wears off if the patient is kept on a naloxone regimen as long as opiates remain present in the circulatory system. Both methods shorten detoxification treatment and provide smooth transition to a naltrexone maintenance programme.     

Opiate Detoxification Under General Anesthesia by Large Doses of Naloxone

Abstract

For opiate detoxification 6 volunteer opiate addicts were intravenously administered 10?mg naloxone within one hour while under barbiturate anesthesia.

During administration of naloxone none of the patients demonstrated significant changes in the hemodynamic parameters of heart rate, mean arterial pressure, cardiac index, peripheral resistance or in the oxygen saturation.

After patients awoke from anesthesia, they experienced no or only minimal withdrawal symptoms. Possible explanations for the suppression of withdrawal symptoms are discussed.     

Headaches in Hospitalized Cocaine Users

We reviewed the medical records of 283 cocaine users consecutively admitted to a municipal hospital and identified 37 patients (13.1%) complaining of headaches. These patients were divided into three groups. Three patients had migraine-like headaches and transient hemiparesis associated with cocaine use. Five patients had headaches associated with cocaine withdrawal. In 29 patients headaches were not clearly associated with cocaine. Twenty-two of the 29 had chronic daily headaches; nine of these patients were depressed. Three had focal brain lesions with chronic daily headache or acute onset global headache. The four remaining patients had other headaches. Based on these findings, we conclude that: (1) Headache is a common complaint in hospitalized cocaine users; (2) Cocaine may occasionally trigger a syndrome which resembles hemiplegic migraine. The potential mechanisms of this syndrome will be discussed; (3) Hospitalized cocaine users who present with headaches most frequently have depression with suicidal ideation, often associated with cocaine withdrawal; and (4) Structural brain disease in these patients may result from a variety of causes.     

Passionflower in the treatment of opiates withdrawal: a double-blind randomized controlled trial

OBJECTIVE: Clonidine-based therapies have been utilized as the main protocol for opiate detoxification for several years. However, detoxification with clonidine has its limitations, including lack of efficacy for mental symptoms. Accumulating evidence shows the efficacy of Passiflora incarnata extract in the management of anxiety. In our continuing study of traditional medicines, which have neurotropic effects, this plant had an anxiolytic effect, which may be used as an adjuvant agent in the detoxification of opiates by clonidine. We present the results of a double-blind randomized controlled trial of clonidine plus passiflora extract vs. clonidine plus placebo in the outpatient detoxification of 65 opiates addicts. METHODS: A total of 65 opiates addicts were assigned randomly to treatment with passiflora extract plus clonidine tablet or clonidine tablet plus placebo drop during a 14-day double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. The fixed daily dose was 60 drops of passiflora extract and a maximum daily dose of 0.8 mg of clonidine administered in three divided doses. The severity of the opiate withdrawal syndrome was measured on days 0, 1, 2, 3, 4, 7 and 14 using the Short Opiate Withdrawal Scale (SOWS). CONCLUSION: Both protocols were equally effective in treating the physical symptoms of withdrawal syndromes. However, the passiflora plus clonidine group showed a significant superiority over clonidine alone in the management of mental symptoms. These results suggested that passiflora extract may be an effective adjuvant agent in the management of opiate withdrawal. However, a larger study to confirm our results is warranted.     

Opiate use to control bowel motility may induce chronic daily headache in patients with migraine

OBJECTIVES: To investigate whether opiate overuse might cause chronic daily headache in those with migraine, we studied patients who were taking codeine (or other opiates) for control of bowel motility after colectomy for ulcerative colitis. BACKGROUND: Analgesic overuse is considered by many to be one factor which can result in the transformation of migraine into a chronic daily headache pattern. Most of the evidence for this comes from patients with migraine who are taking increasing amounts of analgesia for headache. Many of these patients revert to an intermittent migraine pattern once the analgesics are stopped. METHODS: Women who were 1 year postcolectomy for ulcerative colitis were identified in several colorectal surgery practices in Calgary. They were sent a questionnaire designed to determine if they had a history of migraine prior to surgery, if they currently had chronic daily headache, what medications they were taking to control bowel motility, and what medications they were taking for headache. RESULTS: Twenty-eight patients who met our inclusion criteria returned completed questionnaires. Eight of these exceeded the recommended limits for opiate use in patients with headache. Eight patients met diagnostic criteria for migraine. Two patients had chronic daily headache starting after surgery. Both used daily opiates beginning after their surgery, and both had a history of migraine. The other six patients who used opiates daily did not have a history of migraine and did not have chronic daily headache. All patients with migraine who used daily opiates to control bowel motility following surgery developed chronic daily headache after surgery. CONCLUSIONS: Patients with migraine who use daily opiates for any reason are at high risk of developing transformed migraine with chronic daily headache. This risk appears much lower in patients without a history of migraine who use opiates for nonpain indications.     

Prevalence of HIV antibodies in intravenous drug-dependent patients 1986 and 1987 in Vienna

As one of the most important risk groups for HIV infection 82 intravenous drug addicts were tested in December 85/January 86 and 159 in December 86/January 87 for HIV antibody when entering a detoxification programme of our drug addition outpatient clinic. All these drug addicts had used intravenous drugs, mostly opiates. Serum antibodies to HIV were found in 7 (8.5%) of the first sample and in 23 (14.4%) of the second sample. Among seronegative drug addicts a significantly higher use of sterile needles was found than among HIV seropositive drug addicts. Among the seropositive drug abusers a history of intravenous drug abuse outside Austria was found more often than in seronegative drug addicts. The incidence of HIV antibodies in i.v. drug addicts in Vienna appears low in comparison with figures in the Austrian Tyrol (44%), Scotland (33%), Italy (53%) and Switzerland (53%), but similar to England (10%). The low frequency in Vienna could be explained by a significantly higher use of sterile equipment. Furthermore, at the first test period a change in abuse behaviour was found; an increasing number of patients was taking oral opiates exclusively, or reduced intravenous drug intake.     

Detoxification of nonopiate drugs in the chronic pain setting and clonidine opiate detoxification.

Although the pain physician is most familiar with the treatment of the opiate withdrawal syndrome, other drugs are abused by the chronic pain patient. The pain physician should then be familiar with the withdrawal syndromes associated with other drug groups. The withdrawal syndromes associated with hypnosedatives, psychotomimetics, nicotine, stimulants, ergot alkaloids, beta adrenergic blocking agents, antidepressants, muscle relaxants, and alpha-adrenergic agonists are described. Drug detoxification protocols for these drugs are reviewed. Additionally, the rationale for clonidine opiate detoxification is discussed, and current clonidine detoxification protocols are reviewed.     

Influence of caffeine and caffeine withdrawal on headache and cerebral blood flow velocities

Caffeine consumption may cause headache, particularly migraine. Its withdrawal also produces headaches and may be related to weekend migraine attacks. Transcranial Doppler sonography (TCD) has shown changes in cerebral blood flow velocities, (BFV) during and between attacks of migraine. In order to examine whether headache and changes in BFV could develop from controlled caffeine alterations, 20 healthy volunteers, without a headache history, underwent clinical evaluation, TCD and serum caffeine measurements on four occasions, comparing conditions of regular caffeine intake, caffeine withdrawal and "re-caffeination". After 24 h of complete caffeine abstinence, 10 suffered from moderate to severe headaches with complete recovery within 1 h after caffeine intake. The BFVs in both middle cerebral, both posterior cerebral and basilar arteries were higher following the withdrawal period, reaching statistical significance in the left middle cerebral, basilar and both posterior cerebral arteries. BFVs decreased significantly within half an hour after caffeine intake in all subjects, and were similar to baseline values after 2 h. Our results emphasize the relationship between caffeine withdrawal, the development of headache and alterations in cerebral blood flow velocities. Also, these findings indicate that accurate interpretation of TCD measurements should account for the influence of caffeine on BFVs.     

Behavioral activation induced by D(2)-like receptor stimulation during opiate withdrawal

Withdrawal is a potent motivator of drug-seeking behavior in human opiate addicts. Paradoxically, opiate withdrawal reduces dopamine release and suppresses behavioral responding in several animal models of addiction. These findings pose critical questions about how a withdrawal state that depresses dopaminergic and behavioral functioning contributes to drug seeking. This study addressed this issue by investigating factors that increase behavioral activity during opiate withdrawal. Initial experiments revealed that the D(2)-like agonists propylnorapomorphine HCl (NPA; 0.05-0.4 mg/kg, i. p.) and quinpirole (0.2-0.4 mg/kg, s.c.) each produced strong locomotor activating effects during opiate withdrawal that were not apparent in the absence of withdrawal. Concurrent stereotypy ratings indicated that these effects of NPA and quinpirole during withdrawal were not an indirect consequence of changes in the stereotypy-inducing effects of these drugs. Subsequent experiments showed that locomotion was not increased when opiate withdrawal was induced in the presence of the D(1)-like agonist SKF 38393 (1.0-8.0 mg/kg, i.p.), that the locomotor activation produced by NPA during withdrawal could be attenuated by the D(2)-like antagonist eticlopride (0.1-0.2 mg/kg, i.p.), and that locomotor activating effects of NPA could be observed when withdrawal was induced by extracting the implanted morphine pellets, but not when the NPA was given after naltrexone antagonism of acute morphine treatment in nondependent rats. These findings indicate that opiate withdrawal regulates the behavioral impact of D(2)-like receptor stimulation so that locomotion is markedly increased when these receptors are stimulated during periods of withdrawal. This potentiation may be important for facilitating behavioral responses during periods of opiate detoxification.     

A Prospective Study of Chronic or Recurrent Headache in Systemic Lupus Erythematosus

This study was conducted to analyze the prevalence and features of chronic or recurrent headache in Systemic Lupus Erythematosus (SLE), and also the relationship of such headache with other manifestations of the disease. A total of 76 patients (69 women and 7 men) with a mean age of 40 years (r: 24-74 years) were included. An overall severity index for SLE was applied. Fifty-two patients (68%) presented headache, 27 (52%) being vascular and 25 (48%) muscle contraction type. Headache in general was more frequent after the onset of SLE (p less than .001). Prevalence of muscle contraction headache in particular was greater following manifestations of SLE. Family history of migraine was recorded in 54% of the patients with vascular headache. This antecedent was more common in patients in whom migraine started before the onset of SLE (p = .05). A greater number of neuropsychiatric symptoms was observed in the patients with vascular headache and family history (p less than .02). Patients with thrombocytopenia presented headache less frequently (p less than .05). Our results showed headache, of both vascular and muscle contraction types, to be frequent in SLE. We note that there is an increased frequency of muscle contraction headache after the onset of SLE, and that there is a migraine-like headache directly related to SLE. Migrainous patients with familial history have a greater probability to suffer neuropsychiatric manifestations. Finally, it is suggested that severity of SLE is not related to presence of headache.     

Baclofen versus clonidine in the treatment of opiates withdrawal, side-effects aspect: a double-blind randomized controlled trial

OBJECTIVE: Baclofen is known for the alleviation of signs and symptoms of spasticity. Reports from our previous study have suggested that it may be at least as effective as clonidine in the management of physical symptoms of opiate withdrawal syndromes and superior to clonidine in the management of mental symptoms. We now report on a randomized double-blind comparison of baclofen vs. clonidine in view of side-effects profile. METHODS: A total of 62 opiates addicts were randomly assigned to treatment with baclofen or clonidine during a 14-day, double-blind clinical trial. All patients met the DSM IV criteria for opioid dependence. Maximum daily doses were 40 mg for baclofen and 0.8 mg for clonidine. This trial medication was given three times per day in divided doses. The severity of side-effects was measured in days 0, 1, 2, 3, 4, 7 and 14. RESULTS: There was no significant difference between two treat7ments in terms of retention in treatment (dropout) and overall side-effect. Nevertheless, significantly more problems relating to hypotension were encountered with subjects on clonidine. CONCLUSION: We conclude that, the low incidence of hypotension with baclofen suggests that the drug may be suitable for outpatient ambulatory treatment of withdrawal from opiates.     

Medication overuse headache and applicability of the ICHD-II diagnostic criteria: 1-year follow-up study (CARE I protocol)

Medication overuse headache (MOH) is a growing problem worldwide and a challenge for clinicians and investigators. This study aims to contribute to the ongoing debate surrounding the classification of MOH. Applying the revised diagnostic criteria for MOH contained in the updated International Classification of Headache Disorders (ICHD-II), we enrolled 140 probable MOH (p-MOH) patients. They were submitted to an in-patient detoxification protocol and re-examined 2, 6 and 12 months later to confirm, or otherwise, the diagnosis of MOH and to observe the evolution of their headache. MOH diagnosis was confirmed 2 months after detoxification in 71% of patients, who reverted to an episodic headache pattern and stopped their drug overuse The overall clinical situation at 2 months closely reflected the 1-year trend. The 2-month period after drug withdrawal should be retained as a diagnostic criterion in the ICHD-II because it is useful not only as a diagnostic parameter, but also as predictor of a good outcome of 1-year drug withdrawal. In addition, the present findings point to the need for a more objective criterion to quantify headache frequency after drug withdrawal.     

Low-dose tizanidine with nonsteroidal anti-inflammatory drugs for detoxification from analgesic rebound headache

OBJECTIVE: To describe an outpatient regimen for analgesic detoxification and resolution of analgesic rebound headache. BACKGROUND: Frequent analgesic use is believed to promote the transformation of episodic migraine into a chronic, pervasive headache syndrome. Management of pain precipitated by analgesic withdrawal is crucial to treatment success. Outpatient treatment protocols designed to achieve successful withdrawal will reduce costs and potentially lead to more widespread implementation of therapy. METHODS: Patients with appropriate histories were managed on an outpatient basis for detoxification by discontinuation of the offending analgesic and initiation of treatment with tizanidine and a long-acting nonsteroidal anti-inflammatory drug. Patients kept diaries of pain and medication use. Results were evaluated at 6 and 12 weeks. Patients able to tolerate no or trivial analgesic use (ie, 4 or fewer doses in each 2-week period) were considered responders. RESULTS: At 6 weeks, 36 patients (65%) were responders. At 12 weeks, 38 patients (69%) were responders. The chronic daily headache pattern had resolved at 12 weeks in 34 patients (62%). CONCLUSIONS: This treatment protocol was well tolerated and yielded a high degree of efficacy, demonstrating that outpatient management can be effective for achieving analgesic withdrawal and resolution of analgesic rebound headache.     

Management of medication overuse headache: 1-year randomized multicentre open-label trial

It is a general belief that patients with medication overuse headache (MOH) need withdrawal of acute headache medication before they respond to prophylactic medication. In this 1-year open-labelled, multicentre study intention-to-treat analyses were performed on 56 patients with MOH. These were randomly assigned to receive prophylactic treatment from the start without detoxification, undergo a standard out-patient detoxification programme without prophylactic treatment from the start, or no specific treatment (5-month follow-up). The primary outcome measure, change in headache days per month, did not differ significantly between groups. However, the prophylaxis group had the greatest decrease in headache days compared with baseline, and also a significantly more pronounced reduction in total headache index (headache days/month × headache intensity × headache hours) at months 3 ( P  = 0.003) and 12 ( P  = 0.017) compared with the withdrawal group. At month 12, 53% of patients in the prophylaxis group had ≥ 50% reduction in monthly headache days compared with 25% in the withdrawal group ( P  = 0.081). Early introduction of preventive treatment without a previous detoxification programme reduced total headache suffering more effectively compared with abrupt withdrawal. (ClinicalTrials.gov number, NCT00159588).     

Opiate and cocaine dependencies. Techniques to help counter the rising tide

Clonidine (Catapres) is a safe and effective agent for detoxification of selected opiate addicts. It seems best suited for transitional treatment between opiate dependency and aftercare with naltrexone (Trexan). The current epidemic of cocaine abuse in the United States is associated with intensified usage patterns and an increased prevalence of adverse medical consequences. Successful treatment of the cocaine abuser may require either hospitalization or structured outpatient treatment in a specialized program.     

Diazepam tapering in detoxification for high-dose benzodiazepine abuse

The clinical characteristics and management of patients who abuse high doses of benzodiazepines are not well described. In a prospective open study, 23 subjects who abused high doses of benzodiazepines were admitted for detoxification. Urine or blood test results confirmed benzodiazepine use in all but one subject and multiple drug use in eight (35%). Median benzodiazepine dose was 150 mg (range 40 to 500 mg) of diazepam equivalent. Initial plasma concentrations (diazepam: median = 1245 ng/ml; desmethyldiazepam: median = 2961 ng/ml) were 400% to 800% higher than usual therapeutic concentrations. For detoxification, subjects were given a loading dose of diazepam equal to approximately 40% their reported daily consumption. This was followed with daily tapering of diazepam by 10%. This regimen resulted in a slow and gradual decline in drug concentrations. Withdrawal symptoms were assessed daily. Sixteen subjects completed detoxification in the hospital without complications. One subject became paranoid and confused on day 7 of withdrawal. This was attributed to a too-low initial loading dose and too-rapid tapering, which resulted in rapid drug elimination. Gradual reduction of diazepam dose appears to be an effective and safe approach for detoxifying abusers of high doses of benzodiazepines.     

清风胶囊治疗海洛因依赖脱毒后稽延性戒断症状的临床研究

目的考察中药制剂清风胶囊治疗稽延性戒断症状的临床疗效。方法将320例脱毒10d以上的海洛因依赖者随机分成安慰剂组及清风胶囊组进行比较,共用药30d。结果用药后,清风胶囊组(n=208)患者的稽延性戒断症状评分值及焦虑症状评分值明显低于给药前,也明显低于安慰剂组(n=112)。清风胶囊能明显改善睡眠,缓解焦虑症状,消除躯体的疼痛,并能降低患者对毒品的渴求。结论清风胶囊对海洛因依赖者脱毒后的稽延性戒断症状及焦虑症状具有显著治疗作用。