Frontocortical N-acetylaspartate reduction associated with long-term i.v. heroin use.

To examine possible metabolic frontal lobe alterations in i.v. heroin-dependent patients with different histories of concomitant substance use, N-acetylaspartate (NAA), a putative marker of neuronal viability, was measured by (1)H-MRS. Compared with controls, NAA levels in patients were reduced by 7% in gray matter (p = 0.015) but not in white matter. To what extent comorbid conditions or substance use, including alcohol, contributed to these frontocortical metabolic changes remains to be elucidated.

Onset and pattern of substance use in intravenous drug users of an opiate maintenance program.

OBJECTIVES: To assess the initiation of substance use of participants in an opiate maintenance program by a cross-sectional survey. METHOD: Participants (n=184) filled out a questionnaire assessing age at initial substance use and age at onset of regular drug use. RESULTS: Of 15 substances investigated, alcohol, nicotine, analgesics and marijuana were initiated and consumed regularly before the age of 18 years. Barbiturates, benzodiazepines, cocaine, and opiates were begun later. The time gap between initial and regular use varied depending on the substance. Regular use exceeded 50% for alcohol, benzodiazepines, cocaine, heroin, marijuana and nicotine. CONCLUSIONS: Specific knowledge about the age of onset and sequence of substances used by drug addicts may help to prevent substance use more age specifically.

Double-blind randomized trial of buprenorphine and methadone in opiate dependence.

This study compared the safety and efficacy of sublingual buprenorphine tablets with oral methadone in a population of opioid-dependent individuals in a double-blind, randomized, 6-week trial using a flexible dosing procedure. Fifty-eight patients seeking treatment for opioid dependence were recruited in three outpatient facilities and randomly assigned to substitution with buprenorphine or methadone. The retention rate was significantly better in the methadone maintained group (90 vs. 56%; P<0.001). Subjects completing the study in both the treatment groups had similar proportions of opioid positive urine samples (buprenorphine 62%; methadone 59%) and positive urine specimens, as well as mean heroin craving scores decreased significantly over time (P=0.035 and P<0.001). The proportion of cocaine-positive toxicology results did not differ between groups. At week six mean stabilization doses were 10.5 mg per day for the sublingual buprenorphine tablet, and 69.8 mg per day for methadone, respectively. Patient performance during maintenance was similar in both the groups. The high attrition rate in the buprenorphine group during the induction phase might reflect inadequate induction doses. Thus, buprenorphine is a viable alternative for methadone in short-term maintenance treatment for heroin dependence if treatment induction is done with adequate dosages.

Do caffeine-containing analgesics promote dependence? A review and evaluation.

OBJECTIVE: Debates about the suspected association between kidney disease and use of analgesics have led to concern about whether caffeine could stimulate an undesirable overuse of phenacetin-free combined analgesics. A committee was asked to critically review the pertinent literature and to suggest guides for clinical practice and for consideration of international regulatory authorities. PARTICIPANTS: A group of international scientists, jointly selected by the regulatory authorities of Germany, Switzerland, and Austria and the pharmaceutical industry. EVIDENCE: All invited experts evaluated relevant literature and reports and added further information and comments. CONCLUSIONS: Caffeine has a synergistic effectiveness with analgesics. Although caffeine has a dependence potential, the potential is low. Experimental data regarding dependence potential for caffeine alone may not correspond to the conditions in patients with pain. Withdrawal is not likely to cause stimulation or sustainment of analgesic intake. For drug-induced headache, no single or combined analgesic was consistently identified as causative, and no evidence exists for a special role of caffeine. Strong dependence behavior was observed only in patients using phenacetin-containing preparations, coformulated with antipyretics/analgesics and caffeine. This finding may have led to the impression that caffeine stimulates overuse of analgesics. SUMMARY: Although more experimental and long-term data would be desirable to show possible mechanisms of dependence and to offer unequivocal proof of safety, the committee concluded that the available evidence does not support the claim that analgesics coformulated with caffeine, in the absence of phenacetin, stimulate or sustain overuse.

A comparison of heroin chasers with heroin injectors in Switzerland.

In a cross-sectional multicentre study, we compared the characteristics of heroin chasers and heroin injectors. Subjects were 162 primarily opioid-dependent volunteers for whom either chasing (n = 85) or injecting (n = 77) was the principal route of heroin administration. Each subject was rated by means of the Swiss version of the European Addiction Severity Index. Additionally, subjects completed a questionnaire battery including the Severity of Dependence Scale, the Symptom Checklist SCL-90-R, a self-constructed peergroup questionnaire and a semantic differential list to assess the connotative meaning of heroin chasers and injectors. The heroin injectors were older and more likely to use one or more other drugs besides heroin than the chasers. They had longer heroin-using careers, a longer duration of detention and a higher prevalence of some type of hepatitis. In conclusion, the differences between chasers and injectors were rather related to a longer history of heroin use than to the route of heroin administration.

Rapid cortical hemoglobin deoxygenation after heroin and methadone injection in humans: a preliminary report.

The short-term effects of intravenous opioids (heroin 20-300 mg, methadone 30-180 mg) on cortical hemoglobin oxygenation were examined by near infrared spectroscopy in ten opioid-dependent subjects and were compared with the effects of saline in ten age-matched normal controls. Heroin and methadone produced a rapid and dramatic decrease in cortical hemoglobin oxygenation. Saline had no effects. Opioid-induced acute deoxygenation of cortical hemoglobin is most likely associated with respiratory depression. Thorough medical monitoring is strongly recommended in intravenous opioid maintenance treatments.

Comparison of buprenorphine and methadone in the treatment of opioid dependence. Swiss multicentre study.

A three-centre, randomised, double-blind study was designed to compare the efficacy and safety of buprenorphine and methadone. This was the first European study to compare these agents and was based on a previous trial performed in the US. Opioid-dependent subjects were randomised to receive either sublingual buprenorphine or oral methadone daily. Both objective and subjective measures of efficacy were monitored weekly, and safety parameters were regularly monitored over the entire six-week study. Urinalysis showed that the two treatments were similar with a slight increase in opioid-negative urines noted in both groups. The retention rate in the buprenorphine group was lower than in the methadone group, although it has been suggested that the buprenorphine dose may have been too low for some patients. None of the side effects noted were considered serious and all were attributable to chronic opioid dependence. Experience of two years substitution treatment in Fribourg suggests that initial induction onto buprenorphine allows for patients to be subgrouped before being given the most appropriate maintenance agent. Further investigation is required into the different dose-related effects of buprenorphine seen in particular subsets of addicts.

[Drug dependence--diagnostic and therapeutic aspects]. / Medikamentenabhängigkeiten--diagnostische und therapeutische Aspekte.

In Switzerland, dependence on these drugs reflects primarily the relationship between patient and doctor, due to the strict regulations. Drugs involved are in most cases benzodiazepines and other sedatives, less frequently stimulants including weight-control products and drugs containing opioids. Patients' characteristics and motivations include 1.) attempt for specific psychotropic effects, 2.) habituation developed during long-term treatment, 3.) overconsumption of drugs without seeking specific psychotropic effects. Clinical syndromes and therapeutic and preventive strategies are described.

High prevalence and coinfection rate of hepatitis G and C infections in intravenous drug addicts.

BACKGROUND/AIMS: The hepatitis G virus is a newly discovered RNA virus which is possibly transmitted parenterally. Hepatitis G virus is associated with acute or chronic hepatitis and may lead to cirrhosis and liver cancer, characteristics shared by the hepatitis C virus. Hepatitis C virus is prevalent in drug users, but the frequency and role of hepatitis G virus is not yet well established. METHODS: One hundred and seventeen heavy i.v. drug users were enrolled in a prospective, controlled, randomized study for i.v. administration of heroin and/or methadone. Hepatitis G virus was detected using a hot start polymerase chain reaction followed by an ELISA polymerase chain reaction assay. Hepatitis C virus genotyping was done using the Inno-Lipa strip assay. RESULTS: Hepatitis G virus infection was detected in 35% (41/117) of the study population and hepatitis C virus infection in 95.7% (112/117). Ninety-seven percent of hepatitis G virus positive patients were coinfected with hepatitis C virus, of whom 75% were infected with hepatitis C virus genotype 3a. This genotype was prevalent in 48.3% of patients infected with hepatitis C virus alone. The presence or absence of hepatitis G virus infection had no influence on chronic hepatitis. Twenty-two percent of patients who started injecting heroin before 1980 and 40% of those who started after 1980 were hepatitis G virus positive. Overall, 16 patients were infected with human immunodeficiency virus, six were coinfected with hepatitis G virus and hepatitis C virus, and 10 only with hepatitis C virus. CONCLUSIONS: Hepatitis G virus infection is highly prevalent in i.v. drug users, but less frequent than hepatitis C virus infection. The fact that all but two patients were coinfected with hepatitis C virus, 75% with one genotype, supports a common route of transmission for both viruses. The course of hepatitis C virus infection is not altered by hepatitis G virus infection.

[Initial results with withdrawal treatments of male and female participants in the diversified Janus opiate prescription project in Basel]. / Erste Erfahrungen mit Entzugsbehandlungen von Teilnehmern und Teilnehmerinnen des diversifizierten Opiatverschreibungsprojekts Janus in Basel.

Since the beginning of the 'Janus' opiate project in Basel in which severely opiate-dependent persons are treated intravenously with heroin, morphine or methadone 11 from 160 participants (to november 1995) were treated in the withdrawal and intervention unit at the psychiatry clinic of the university of Basel. 7 patients sought a total, 4 a partial withdrawal. Whereas the 4 patients wanting withdrawal from consumption of drugs in addition to study drugs all reached their goal 4 of the 7 persons aiming at total withdrawal interrupted treatment prematurely. The 3 patients who were successful are-as far as the authors know-still off opiates. Substitution of intravenous opiates provided by 'Janus' with oral methadone and slow tapering off of the latter over days to weeks occurred mostly without problems. Participants of the 'Janus' project thus desired a withdrawal oriented treatment with equal frequency and had not less success than persons substituted with oral methadone in achieving this goal.

[Sleep disorders in chronic pain and generalized tendomyopathy]. / Schlafstörungen bei chronischen Schmerzen und generalisierter Tendomyopathie.

Patients with a chronic pain syndrome often suffer from sleep disturbance. As both symptoms are frequent in the fibromyalgia syndrome, these patients in particular have been examined in this regard. No clear polysomnographic evaluation of the subjectively experienced sleep disturbance in these patients has been done so far. Therefore, we recorded the sleep EEG of 13 patients with a fibromyalgia syndrome in order to objectively characterize their sleep. Furthermore, we were interested in the relationship between the sleep alterations and pain intensity. In a subsequent placebo-controlled study based on pathophysiological considerations, we attempted to beneficially influence the sleep disturbance and the pain syndrome with the 5-HT2-receptor antagonist ketanserine, as this system has been proved to play a major role in the regulation of both sleep and pain. The results of our studies in patients with fibromyalgia show that the alteration of sleep is mainly characterized by a disturbance of sleep continuity associated with the experience of pain intensity. The application of 5-HT-receptor-antagonists may be a new strategy for the common treatment of sleep disturbance and the pain syndrome which needs to be evaluated in further studies. Duration of the patients' illness seems to be a predictive value in relation to intensity of the symptoms and the therapeutic outcome.

[Sleep and addiction]. / Schlaf und Sucht.

Sleep disorders and depressive symptoms are concomitant features in patients with addictive disorders. In this study, patients with addiction (alcohol and opioid, resp.) and with major depression (DSM-III-R) were examined with a sleep EEG and compared to age-matched controls. An age-dependent decrease of total sleep time and slow-wave sleep (SWS) was demonstrated. Sober patients with alcohol dependency showed a decrease of SWS, whereas patients with opioid dependency substituted with methadone showed a disorder of REM sleep (REM suppression). Depressive patients revealed a disturbance of sleep continuity and REM sleep (increased REM sleep). The neurobiological differentiation by sleep EEG is of interest for research and clinical practice.

The role of beta-carbolines (harman/norharman) in heroin addicts.

Endogenous substances resulting from interactions between alcohol and possibly opioid metabolites and neurotransmitters (dopamine, indolamines) could be mediators of the pathochemical process towards dependence. Beta-carbolines (harman/norharman) are increased in alcoholics and - according to the presented results - in heroin addicts. Psychopathological disorders such as anxiety or depression do not seem to influence the level of beta-carbolines.