Norbert Loimer

The use of plasma levels to optimize methadone maintenance treatment

The question of the optimal methadone dose during maintenance therapy is controversial. For both philosophical and practical reasons, therapeutic drug monitoring has not been generally used. Some therapists prescribe low doses of methadone more for psychological than pharmacological reasons. This study examines, in 104 methadone patients, the relation between self-rating, observer-rating, urine tests, HIV-1 sero-status, daily methadone doses and plasma levels of methadone. No differences were found between HIV-1 infected and seronegative patients in these respects. The optimal methadone plasma level as judged by self- and observer-rating was more than 150 ng/ml. For oral methadone, the best results are obtained in patients receiving more than 90 mg daily. We found a significant relationship between methadone dose and plasma levels, also in patients who also used illicit drugs. We conclude that therapeutic drug monitoring should become routine in methadone treatment to achieve optimum results, especially in patients who complain of withdrawal symptoms and continue high-risk behaviour.

Opiate detoxification under general anesthesia by large doses of naloxone.

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.

Neuropsychological findings and psychiatric symptoms in HIV-1 infected and noninfected drug users

Reports available on the extent and incidence of cognitive deficits in human immunodeficiency virus (HIV-1) patients are variable. To assess the influence of drug abuse and psychiatric symptoms on the extent of the cognitive deficit, we examined 42 drug-addicted HIV-1 patients and compared them with a group of seronegative drug addicts (n = 31) as well as with a group of healthy controls (n = 50), using a psychometric test battery and standardized psychiatric scales. We found no significant difference in the extent and incidence of cognitive deficits in the group of HIV-1 patients as compared with the seronegative drug addicts. Both groups, however, differed from the normal population group. Remarkable depressive symptoms were found in the HIV-1 infected patient group. We assume that long-term drug abuse contributes markedly to the cognitive deficit of HIV-1 patients, which is further influenced by depressive symptoms.

Combined naloxone/methadone preparations for opiate substitution therapy

Every opportunity should be used to reduce the risk of HIV-1 infection and transmission among intravenous drug users (IVDUs). Methadone maintenance is widely accepted to keep the drug user away from risk-laden practices and to stop intravenous drug use. In order to minimize the diversion and intravenous abuse of methadone in maintenance programs, the effects of a combined naloxone/methadone preparation through oral intake and the effects of an intravenous administration were tested. In opiate addicts, the intravenous administration of this mixture caused a severe withdrawal syndrome lasting for 15 to 30 minutes. The oral administration of this combination was indistinguishable from methadone alone. It is argued that this combination therapy prevents the intravenous abuse of methadone in maintenance programs.

Psychophysiological reactions in methadone maintenance patients do not correlate with methadone plasma levels

In methadone maintenance therapy methadone plasma concentrations of 400 ng/ml are necessary to suppress any further opiate action and to provide stabilized maintenance. In a controlled study we have searched for a differentiation in autonomous activation between patients having low and high methadone plasma levels, using static and dynamic pupillometry and habituation of skin conductance response. Results show that there is no difference in psychophysiological response between patients with high (>400 ng/ml) or low (<400 ng/ml) plasma levels of methadone. This indicates that there is no reduction in behavioral arousal in patients with high plasma methadone levels. On the basis of these findings, there is no rationale to maintain patients on plasma levels below 400 ng/ml.

Drug Addiction and AIDS

Epidemiology.- Observations on the Stabilization of HIV Seroprevalence Among Injecting Drug Users.- HIV-Antibody Testing and Risk-Prone Behaviour Amongst i.v.-DUs in Oslo, Norway.- HIV-Prevalence and Mortality in Relation to Type of Drug Abuse Among Drug Addicts in Stockholm 1981-1988.- HIV-Related Drug Addict Deaths Outside Medical Institutions in Stockholm.- HIV Infection in 403 Female Prostitutes in Italy.- How to Explain the Low Figures of AIDS Cases Among Intravenous Drug Addicts in Belgium?.- Drug Addiction and AIDS in Republic of Croatia and Yugoslavia.- Drug Abuse in Spain: Epidemiology, Policy and Health Structure.- Drug Abuse and HIV-Infection in Poland.- HIV-1-Prevalence Among Drug Deaths in Germany.- Hepatitis B, Hepatitis C and AIDS in Drug Deaths.- Monitoring of HIV-Spread in Regional Populations of Injecting Drug Users - The Berlin Experience.- 5 Years Follow-up on Viennese Heroin Addicts.- Antibody Prevalence of Parenterally Transmitted Viruses (HIV-1, HTLV-I, HBV, HCV) in Austrian Intravenous Drug Users.- Statistical Investigation on the Relation of Intravenous Drug Addiction and HIV-Infection. A Survey of the Years 1985 to 1989 by the Institute of Forensic Medicine in Vienna.- HIV-1 Infection Among Intravenous Drug Users in Vienna 1986-1991.- Methadone Treatment.- Opioid Receptors.- Addiction Potential of Opiates in Medical Use.- Methadone Maintenance Treatment for Harm Reduction Approach to Heroin Addiction.- Methadone Maintenance: A Medical Approach to Heroin Addiction.- Intravenous Methadone Maintenance: A British Response to Persistent Opiate Injectors.- The Impact of Methadone Maintenance Treatment on the Spread of HIV Among i.v. Heroin Addicts in Sweden.- Methadone Maintenance Treatment (MMT) in Stockholm, Sweden.- Methadone Treatment for Opiate-Addicted Patients First Experiences of a Prospective Trial.- HIV and Methadone Treatment: The German Experience.- Drug Addiction Treatment in Italy in the 80s: Fear of Treatment.- Psycho-Social and Psychopathological Features as Predictors of Response to Long Term and High Dosages Methadone Treatment.- Methadone Maintenance and Delinquency Rates of Opioid Drug Users.- Course and Outcome of HIV-Positive Drug Addicts in a Methadone Treatment Program.- Management and Treatment.- Managing AIDS: The European Centre/WHO Collaborative Study and Database Project.- AIDS Fear and Risk Behavior in Intravenous Drug Users.- HIV-Risk and Social Integration in Groups of Drug-Addicts.- Assessment of the Work with Pregnant i.v. Drug Users in Oslo.- Treatment of Heroin Abuse and AIDS in Italy.- Neuropsychiatric Problems and Psychotropic Medication in Patients with AIDS. Data from Warsaw.- Neopterin to Predict Disease Progression in Intravenous Drug Users Infected with HIV-1.- Spect and Transcranial Doppler Sonography for the Assessment of Cerebral Perfusion in Intravenous Drug Users with AIDS Encephalopathy.- The Treatment with Dextromethorphan of Heroin Addicts.- Buprenorphine: An Opioid Mixed Agonist-Antagonist as Possible Antidote for Acute Cocaine Toxicity.- Criminal Law and AIDS.- The Crisis and Opportunity of AIDS and Drug Misuse.- Prevention.- Observed Patterns of HIV Related Risk Behaviour Amongst Intravenous Drug Users Attending a Dublin Needle Exchange in Its First Year.- Outreach Work as a Strategy for Risk Reduction in Hard-to-Reach Populations. For Example: Injecting Drug Users.- AIDS Risk Behavior Among Intravenous Drug Users Hospitalized in a Public Psychiatric Hospital.- Campaigns of Fear and Behaviour Change in UK Drug Users.- Resocialization and AIDS-Prevention by Remedacen Substitution.- A Treatment Model to Heroin Addicts in Italy.- The Importance of i.v. Drug Users Personality Traits in AIDS Prevention.

Monitoring HIV-1 infection prevalence among intravenous drug users in Vienna 1986–1990

A standardised method to monitor HIV-1 infection levels and trends among injecting drug users (IDUs) was periodically administered at the drug addiction outpatient ward of the Psychiatric University Clinic of Vienna. A total of 715 injecting drug users were examined. HIV-1 antibodies were found in 8.5% of the IDUs in 1985/86, 14.5% in 1986/87, 27.7% in 1988, 29.7% in 1989 and 26.9% in 1990. Sharing was extensive in infected IDUs. After introduction of methadone maintenance in Austria more than 50% of the IDUs were receiving methadone and, in 1990, 88% of the infected IDUs were treated with methadone.

Rapid transition from methadone maintenance to naltrexone

SIR,-Dr Brewer and Dr Mathew (Sept 16, p 683) combine clonidine and naltrexone for rapid induction to naltrexone maintenance, but report severe side-effects and do not discuss clean urine samples as a criterion for successful detoxification treatment. We have described a humane and effective method of detoxification, with the drawback that trained staff and complex technical equipment are needed.l,2 To produce a safe, rapid, successful, painless, and economic alternative treatment we used

5-Hydroxy-indolacetic-acid (5-HIAA) serum levels in depressive patients and ECT

In 31 drug and ECT naive melancholic patients, serum levels of the major metabolite of serotonin 5-hydroxy-indolacetic-acid (5-HIAA) were estimated in the first and third ECT of a course. Plasma samples were taken before ECT and 1, 60 and 120 min thereafter. The estimations were done by a new high performance liquid chromatography method (HPLC). After the seizure, a statistically significant decrease of 5-HIAA serum levels was observed over both ECTs. There was a significant increase in 5-HIAA serum levels from the first to the third ECT. ECT was found to influence serotonin turnover. It might be interpreted that ECT improves serotonergic responsiveness and neurotransmission. There was no significant correlation between 5-HIAA levels and gender, or age of the patients, or seizure duration. Furthermore, the severity of depression and treatment response did not correlate with certain 5-HIAA serum level patterns.

Naloxone induces miosis in normal subjects

In a placebo-controlled trial, pupillary constriction was measured in healthy non-addicted subjects and in opiate addicts by using static computer-assisted pupillometry. In contrast to earlier reports, a clear-cut pupillary constriction was observed in healthy persons after a single intravenous injection of 0.4 mg naloxone. No significant changes of pupillary size were recorded in the same subjects after the administration of a placebo. In methadone-maintained subjects, the IV administration of 0.4 mg naloxone caused a significant pupillary dilatation. From these data it can be concluded that naloxone seems to have a central pharmacological action not only in opiate addicts, but also in healthy persons. This is demonstrable by studying the miotic response.