Arto J. Hiltunen

Comparison of urinary 5-hydroxytryptophol, breath ethanol, and self-report for detection of recent alcohol use during outpatient treatment: a study on methadone patients

This study compared urinary 5-hydroxytryptophol (5HTOL) with breath-ethanol testing as objective ways to disclose recent drinking by outpatients attending a methadone maintenance treatment clinic. Information about quantity and frequency of alcohol use was obtained by confidential self-reports. Random screening was performed on Mondays-Fridays in connection with routine clinic visits for methadone dosing. An observed urine sample for monitoring of illicit drug use and determination of 5HTOL, expressed as a ratio to 5-hydroxyindole-3-acetic acid (5HIAA), was obtained from 202 patients (59 women and 143 men), 16 of whom refused to complete the self-report and/or do a breath-ethanol test. Patients taking disulfiram or calcium carbimide for alcohol detoxification were excluded. Among the 177 subjects remaining, 47 (26.6%) reported intake of any alcohol on the previous day (range, 10-230 g ethanol; median, 40). Only four of those could be identified by a positive breath-test, while 17 showed a urinary 5HTOL/5HIAA ratio above the cutoff limit. Their alcohol consumption (median, 60 g) was significantly higher compared with those showing ratios within the reference interval (median, 35 g). The sensitivity of 5HTOL/5HIAA testing for detecting self-reported drinking in excess of 50 g ethanol was 77%. An additional nine patients who claimed abstinence still showed abnormal 5HTOL/5HIAA ratios, and so did three of the patients who refused to do a breath-ethanol test and/or complete the self-report. Altogether, 59 of 190 methadone-maintained patients (31.1%) had been drinking any alcohol on the previous day (i.e. Sunday-Thursday) according to self-report and/or urinalysis data, 29 (49.2%) of whom were identified by the urinary 5HTOL/5HIAA ratio and only four (6.8%) by utilizing breathalyzer.

Subjective and objective symptoms in relation to plasma methadone concentration in methadone patients

Two rating scales, which were originally developed for measurements of objective and subjective signs of opiate withdrawal, were used to evaluate potential estimates (correlates) of methadone effects in relation to plasma methadone concentrations. Patients participating in our regular methdone maintenance treatment project were studied during 24 h after the intake of the daily methadone dose. Methadone concentrations in plasma were compared to the subjective (estimated by the patients) and objective (estimated by the investigator) signs of the drug effects before, and 2.5, 5, 9 and 24 h after intake of methadone. Some new items possibly related to rising methadone concentrations were added to the subjective scale. Results indicated that, for subjective ratings, the majority of the items investigated corresponded well with the plasma methadone concentrations. The most significant associations were found for the following items: low psychomotor speed, alertness, running nose, yawning and anxiety. For objective ratings, only the items rhinorrhea, piloerection and signs of anxiety were significantly associated with the methadone concentrations. These rating scales may, together with plasma methadone determinations, be of considerable value when making dose adjustments for methadone maintenance patients. Further work is, however, needed to establish concentration — effect relationships.

Rated well-being in relation to plasma concentrations of l- and d-methadone in satisfied and dissatisfied patients on methadone maintenance treatment

Rationale: One of the major problems in methadone maintenance treatment is to find optimal individual doses for the patients. Objective: The present study investigated whether the use of rating scales together with enantioselective analysis of l-methadone might facilitate dose adjustments in a clinical situation. Methods: Rating scales were used to evaluate subjective and objective signs of well-being in relation to plasma methadone concentrations in two groups of patients receiving methadone maintenance treatment. The first group (n = 25) was well-adjusted according to clinical observations and were satisfied with their methadone doses (86.2 ± 4.3 mg). The second group (n = 25) was in need of the methadone dose adjustment; they complained of low dosing, despite a dose level of 69.2 ± 4.0 mg/day. Results: Results indicated a significant correlation between dose and methadone concentration among dissatisfied patients only. The trough levels of d,l-methadone and l-methadone, as well as their elimination rates, were similar in the two groups of patients. There was a variable predominance of l- over d-methadone in plasma (ratio ≈1.2; range 0.7–3.6). Illicit use of drugs by the patients was related to the methadone dose and to satisfaction with the dose received. Increased illicit drug use among dissatisfied patients was successfully eliminated by raising the methadone dose. Subjective and objective ratings of the satisfied patients were quite stable throughout the evaluation period, whereas the ratings of the dissatisfied patients were unstable. These patients seemed to be more sensitive to low trough levels of methadone than the satisfied patients. Associations between the subjective and objective ratings and plasma methadone, along with background characteristics, were characterized by multiple regression analyses. The plasma concentrations of l-methadone were one of the most important explanatory variables in these analyses. Associations between well-being and methadone concentrations in plasma were stronger for l-methadone than for d,l-methadone. Conclusions: Selective measurements of the active isomer and the use of rating scales should be of clinical value when monitoring methadone maintenance treatment patients.

Neuropsychological changes during steady-state drug use, withdrawal and abstinence in primary benzodiazepine-dependent patients

Impairment on neuropsychological tests during steady‐state drug use and withdrawal, and after discontinuation of benzodiazepines, was studied in primary benzodiazepine‐dependent patients. One group of patients was tested before and the other group after the initiation of a gradual tapering‐off of the drug, and both groups were tested approximately 1 year later. At the initial assessment, both groups of patients showed impairment on most of the tests of general intelligence and on several of the tests in the Halstead‐Reitan battery, as well as on a test of nonverbal memory, in comparison with healthy controls. At follow‐up the patient groups had reached the level of the control group. This study confirmed earlier observations of neuropsychological deficits in long‐term benzodiazepine‐using patients and demonstrated that these changes are at least partly reversible by discontinuing drug intake.

Effects of flumazenil in the treatment of benzodiazepine withdrawal : a double-blind pilot study

Abstract Flumazenil, a partial benzodiazepine agonist with low intrinsic activity, was tested for potential use in patients experiencing withdrawal symptoms after traditional treatment for benzodiazepine dependency. On two occasions, separated by 1–13 weeks, ten patients treated for benzodiazepine dependency and ten controls received cumulative doses of flumazenil (0.05, 0.10, 0.25, 0.50 and 1.00 mg at 15-min intervals) or placebo, with assessments of withdrawal symptoms and physiological variables after each dose. As expected, there was an overall difference between patients and controls, with patients scoring higher on negative and somatic items and lower on positive psychological items. Flumazenil reduced symptoms thought to be important in withdrawal in patients treated for benzodiazepine dependency. In contrast to the patient group, controls reacted in the opposite direction with increases in negative experience when given flumazenil. Further research may develop flumazenil as a therapeutic option in the treatment of benzodiazepine withdrawal.

Detoxification from Methadone Maintenance Treatment in Sweden: Long-Term Outcome and Effects on Quality of Life and Life Situation

Of 59 subjects who have undergone voluntary and serious attempts to terminate methadone maintenance treatment (MMT) within the framework of the Swedish methadone program, 50 could be reached for an interview. Of these, 25 were classified--with some reservations--as successful (Group 1), i.e., they lived opiate-free and to all appearances well-ordered lives. The other 25 had failed in their attempts (Group 2) and were all in methadone treatment, most functioning well. A comparison was made between the two groups with regard to change in perceived quality of life and actual life situation from the time before the detoxification attempts were begun (Period 1) until the time preceding the interview (Period 2). The results indicate that Group 1 has achieved a higher quality of life and a more stable actual life situation compared with Group 2.

Effects of long-term abstinence on psychological functioning: A prospective longitudinal analysis comparing alcohol-dependent patients and healthy volunteers

Using a prospective longitudinal design, differences between abstinent alcohol-dependent patients (n = 15) and abstinent healthy volunteers (n = 11) were determined with respect to their psychological functioning and alcohol consumption patterns following abstinence. Results showed no differences in alcohol consumption. In 20% of the patients and 9% of the controls more than 10% of protocols indicated alcohol intake, and in 27% of the patients and 27% of the controls less than 10% of protocols indicated alcohol intake. Total abstinence was reported by 53% of the patients and by 64% of the controls. For patients, validation of self-reported alcohol consumption was carried out via biological markers. Patients and controls differed in terms of increased sleep, euphoria, concentration, initiative, anxiety, negative and positive craving, pessimistic thoughts, autonomic disturbances, and humour. A gradual normalization back to baseline levels was observed for some symptoms. These results suggest that affective/mood states may be unstable for alcoholics, and further, that these symptoms may be related to the protracted withdrawal syndrome or may represent residual symptomatology.

Benzodiazepine tapering: : a prospective study

Background: Benzodiazepines (BZD) are the most widely used sedative-hypnotics, and evidence is rapidly accumulating suggesting potential BZD dependence, association of chronic use with adverse effects and a definite abstinence syndrome produced by withdrawal. Aims: The present investigation followed prospectively long-term BZD users over 1 year following graded BZD withdrawal in terms of clinical and withdrawal symptoms. Methods: Clinical symptoms were measured by the Comprehensive Psychopathological Rating Scale (CPRS) and by the Newcastle Anxiety and Depression Diagnostic Index (NADDI) in a sample of BZD users over a 50-week period following graded BZD withdrawal. Results: The results showed that the frequency and severity of clinical symptomatology measured by both scales significantly decreased over time. A detailed analysis of possible patterns of symptoms on both scales revealed four patterns: 1) a gradual decrease over the 50-week time period; 2) an increase in the severity of symptoms at the onset of tapering and a decrease in severity post-tapering; 3) an increase in the severity of symptoms 4 weeks after the cessation of BZD tapering; and 4) no change over the 50-week time period. Rate of BZD withdrawal was associated with CPRS ratings of global illness at admission and at end of treatment, but was not associated with duration or dosage of BZDs, type of BZD, prescriptive and/or non-prescriptive drug use prior to admission, marital status, sex or age. Conclusions: The results of the present study provide a detailed picture of the pattern of symptoms, their time course and multidimensional determinants of the BZD withdrawal symptoms.

Acute tolerance during intravenous infusion of alcohol: Comparison of performance during ascending and steady state concentrations — a pilot study

Although acute tolerance (AT) to alcohol has been demonstrated in many single-dose studies, the existence of AT at steady state concentrations of alcohol has been questioned. In the present study, six subjects were examined as (1) 7.5% alcohol or (2) placebo was administered intravenously (IV). The order of the infusions was randomized. The alcohol infusions were designed to result in similar blood alcohol concentrations at 20, 60, and 140 min (approximately 0. 7 per thousand). At 20 min, the concentrations were rising; the steady state (+/-0.10 per thousand) was reached after 60 min and continued until 140 min. Three reaction time (RT) tests from the automated psychological test system were used (simple RT, two-choice RT, and two-choice RT with auditory inhibition). When the performance of the subjects was compared at rising and steady-state concentrations of alcohol, AT was shown for the most complex task requiring parallel processing, i.e., RT with failed inhibition, test. However, at steady state (i.e., 60 vs. 140 min), AT was not found for any of the tests. Further, the analysis showed that the test results of different individuals were related to their estimated normal alcohol consumption and that these differences presumably influenced the test results in accordance with our earlier findings.

Abstinence fear in methadone maintenance withdrawal : A possible obstacle for getting off methadone

The present study attempts to shed light on methadone maintenance patients expectations regarding withdrawal symptoms during voluntary methadone detoxification. The study includes two groups of subjects; one group who have tried on their own initiative to terminate their methadone maintenance treatment (Group 1) and one group that contains rehabilitated patients who have not tried to quit using methadone (Group 2). Two main results have emerged. Group 1 has negative expectations beforehand about the intensity of withdrawal which significantly exceed the later, actual experience. Group 2 has negative expectations about the intensity of withdrawal that significantly exceed the negative expectations of Group 1. The clinical implications of these results are discussed.