Christian G. Schütz

Predictors for completing an inpatient detoxification program among intravenous heroin users, methadone substituted and codeine substituted patients

Up to 1999 more opioid dependent patients in Germany were substituted with codeine or dihydrocodeine (summarised as codeine) than with methadone. The current retrospective study compares the differences in detoxification treatment outcome for codeine-substituted patients, methadone-substituted patients and patients injecting illicit heroin. The study is based on the medical records of 1070 patients admitted consecutively for opioid and polytox detoxification between 1991 and 1997. The main hypothesis was that injecting illicit-heroin users would complete detoxification treatment less often than codeine- or methadone- substituted patients, and that methadone-substituted patients who had received more structured treatment would complete more often than codeine-substituted patients who did not receive any structured treatment beyond the prescription of codeine. We analysed a number of demographic and drug related variables as possible predictors. Our bivariate analyses confirmed our main hypothesis: 50.4% (OR: 1.8) of the methadone-substituted patients, 45.5% (OR: 1.5) of the codeine-substituted patients and 35.9% (OR: 1 comparison group) of the injecting illicit-heroin users completed the detoxification program (P=0.006). This finding remained significant even after correcting for a number of confounders. Using stepwise multiple logistic regression analyses, we found age, education, history of imprisonment, regular contact with a counsellor, currently being on probation and reported plans for participating in an abstinence treatment program to be significant predictors of completing detoxification treatment. Although the current analysis did not rule out differences in pharmacological effects as a contributing factor, the results are consistent with an interpretation of a dose-response association between psychosocial/psychotherapeutic support and detoxification outcome. More psychosocial/psychotherapeutic support leads to better detoxification treatment response.

Alcohol consumption in heroin users, methadone-substituted and codeine-substituted patients--frequency and correlates of use

This retrospective study aims to determine whether there is a difference in the additional consumption of alcohol between addicts treated with methadone or dihydrocodeine (DHC) and untreated addicts injecting heroin.1,685 patients admitted for opioid withdrawal between 1991 and 1997 were reviewed. Cross-reference tables and multiple logistic regression analyses were carried out. 28% of patients take more than 40 g of alcohol daily (on average 176 g). We found that patients who are treated with methadone or DHC drink alcohol significantly more often daily than the heroin-dependent patients (p < 0.01). Using multiple regression analyses, the results were confirmed. Additionally, we found that co-abuse of alcohol was predicted by male gender, longer duration of drug use, additional daily consumption of tetrahydrocannabinol and daily consumption of benzodiazepines. Alcohol consumption by opioid-addicted patients treated with methadone or DHC presents a serious medical problem. Co-abuse of alcohol will receive more attention.

NMDA receptor challenge with dextromethorphan : subjective response, neuroendocrinological findings and possible clinical implications

Summary. Glutamatergic NMDA receptors are believed to play a major role in the pathophysiology of numerous neuropsychiatric disorders including substance use and schizophrenia. Neuropharmacological studies measuring subjective response, psychopathology and biological parameters are helpful in studying pathophysiology of these disorders. We report preliminary data of a placebo-controlled double-blind challenge study in recently detoxified alcoholics (n = 20) and healthy controls (n = 10) using the non-competitive NMDA antagonist dextromethorphan. Findings suggest that dextrometorphan can produce ethanol-like subjective effects in both alcoholics and controls and induce a mild form of craving in alcoholics only. The results of this study give further support to the hypothesis of glutamatergic NMDA receptors mediating much of ethanols psychotropic effects. Possible clinical implications of these findings are discussed.

Age-specific patterns of hallucinogen use in the US population: an analysis using generalized additive models

Although there has been growing concern in recent years about an escalation in the use of LSD and other hallucinogens, little is known about the distribution of the use of these drugs in the United States population. In order to fill this gap, we used generalized additive models to analyze data from the 1988, 1990, and 1992 National Household Survey on Drug Abuse, to compare the age-specific prevalence of hallucinogen use by level of socio-economic indicators. In addition, we used survival analysis to compare patterns in the onset of use. Use of hallucinogens in the past year was highest at the age of 19 years for each of the NHSDA surveys, but use was not linked to enrollment in school at this age. Past year prevalence was highest among whites and respondents with high family income. The onset of hallucinogen use was most likely to occur between ages 15-19 years, regardless of birth cohort. These results indicate a stable pattern since hallucinogens were made widely available in the late 1960s, in which the transition from adolescence to adulthood has been the period of highest risk for hallucinogen use.

Memantine Treatment in Alcohol Dementia: Rapid PET Changes and Clinical Course

Alcohol dementia (ALD) usually follows long-term alcohol dependence. The major psychiatric features of ALD are general loss of short-and long-term memory combined with disturbances in concentration and a decrease in intellectual capacity, all of which persist during abstinence. Despite its clinical importance, few studies have been published up to now on medical treatment of ALD and other alcohol-induced mental disorders [1]. The central nervous gluta-matergic system, with its N-methyl-D-aspartate (NMDA) receptors, is suggested to be involved in toxic neuronal loss [2] due to an increased glutamatergic neurotransmission during repeated alcohol withdrawal and may subsequently contribute to the development of ALD. The low-affinity NMDA receptor antagonist memantine (ada-mantine, 1-amino-3,5-dimethyladamantine hydrochloride, CAS 41100-52-1) modulates the glutamatergic system most likely through Ca 2+ influx blockage of NMDA receptors [3] and shows positive effects on memory in the treatment of other psychogeriatric disorders with memory loss such as Alzheimers dementia (AD) or Parkinsons disease [4]. We would like to report the case of a 71-year-old female patient with chronic alcoholism for at least 30 years. She was found neglected in her home and was admitted to our ward from an emergency unit with symptoms of disorientation, apraxia, ataxia, severe short-and long-term memory disturbances, deficits in intellectual capacity and concentration. There were no signs of electrolyte imbalance on admission. A further thorough neurological investigation and NMR showed a general atrophy without severe basal brain damage of Wer-nicke encephalopathy. No other signs of Wernicke encephalopathy, i.e. ophthalmoplegia or evidence of hepatic encephalopathy such as flapping tremor, were found. Ultrasound of brain arteries showed some plaques without hemodynamic compromise. After excluding Alzheimers disease or vascular dementia, the diagnosis of ALD according to ICD10 criteria was made.

Chemistry and Structures of Hexakis(halogenomethyl)‐, Hexakis(azidomethyl)‐, and Hexakis(nitratomethyl)disiloxanes

An investigation of the structures and chemistry of substituted hexamethyl disiloxanes ((XCH2)3Si)2O; X=F, Cl, Br, I, N3 , and ONO2) is reported. New synthetic routes to the precursor hexakis(chloromethyl)disiloxane are presented. The products with X=Cl, Br, I, and N3 were characterized by NMR, IR, and Raman spectroscopy. In addition, the single-crystal structures of the products with X=Cl, Br, and I are discussed in detail. The compounds with X=F and ONO2 were not obtained in their pure form; instead investigations of the decomposition products revealed their conversion into intermediates. Theoretical calculations of the gas-phase structures at the B3LYP/cc-pVDZ, B3LYP/3-21G, MP2/6-31G*, and MP2/3-21G levels of theory are used to explain the chemical and physical behavior of the compounds with X=Cl, Br, I, N3, and ONO2. A new decomposition pathway of hexakis(nitratomethyl)disiloxane is presented and is used to explain their remarkable instability. The energetic properties and values of the nitrate and azide derivatives were calculated at the CBS-4M level of theory by using the improved EXPLO5 computer code version 6.01.

Phytohemagglutinin-stimulated calcium signal in lymphocytes of alcoholics before, during and after detoxification.

Acute and chronic exposure to ethanol influences intracellular calcium homeostasis via NMDA receptors, direct regulation of calcium channels or the phosphoinositide pathway. To explore the influence of alcohol withdrawal on calcium metabolism, we have investigated the resting and phytohemagglutinin (PHA) stimulated [Ca2+]i in lymphocytes of 10 alcoholics before, during and after withdrawal. Our findings suggest that both compartments of the PHA-stimulated signal are affected in alcoholics, with flattening of the initial peak and sustained calcium influx, as long as severe vegetative signs are present. MANOVA results showed significant interaction effects for both measurement points, for the initial peak, 40 s after stimulation (P = 0.05), and especially for the sustained influx at the end of the observation period (P = 0.001). The detailed mechanisms of this disturbed calcium homeostasis need further investigation.