Lars Saxon

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.

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.

Knowledge of status and assessment of personal health consequences with hepatitis C are not enough to change risk behaviour among injecting drug users in Stockholm County, Sweden.

This was a multicentre study with risk perception as the theoretical framework, investigating if risk behaviours change when injecting drug users (IDUs) are aware of their hepatitis C virus (HCV) status and had assessed the health consequences with HCV infection. Two hundred and thirteen participants aged 15–40 y were analysed. Sharing of needles and of other injecting equipment were common both among participants who reported HCV-positive status (74%, 95% confidence interval (CI) 65.3–80.1%) and among those who reported HCV status unknown (68%, 95% CI 56.0–78.4%). Participants associating very severe health consequences with HCV infection and those who did not know of any health consequences with HCV infection shared needles at almost the same rate (78%, 95% CI 62.5–87.7 vs 69%, 95% CI 8.0–78.9, respectively). Sharing of other injecting equipment was most common among participants with verified HCV-positive status (adjusted risk ratio 5.64, 95% CI 2.64–12.07). Knowledge of HCV status and assessment of health consequences with HCV infection were not enough to change injecting risk behaviours. Sharing of other injecting equipment was a more important risk factor than sharing needles for participants with verified HCV-positive status. It is suggested that professionals engage IDUs in risk analysis and open a dialogue about assessment in order to identify, quantify and characterize risks.

Reliability of the Karolinska Psychodynamic Profile (KAPP) among Patients with and without Psychoactive Substance Abuse Disorders

Background: The Karolinska Psychodynamic Profile (KAPP) is a rating instrument, based on psychoanalytic theory, that assesses different aspects of character from clinical interviews. The aim of the present study was to examine interrater reliability of the KAPP in a sample of patients with and without psychoactive substance abuse disorders, using interviewers and a reliability judge who had not been trained by the developers of the instrument. Methods: The sample comprised 47 consecutive patients with and without psychoactive substance abuse disorders, who were referred to an outpatient psychotherapy unit specializing in the treatment of substance abuse and dependence. The two interviewers and the reliability judge had not been trained by the developers of the KAPP, and they worked outside the setting where it was constructed. Results: The intraclass correlations were satisfactory for the total sample (mean 0.84, median 0.89, range 0.62–0.95), as well as for various subsamples, such as males and females, and patients with and without substance abuse disorders. Conclusions: The results show that interviewers and a reliability judge who had not been trained by the developers of the KAPP can attain high interrater reliability in a sample of patients with substance abuse disorders. Some recommendations for conducting KAPP interviews are given.

Reduction of aggression during benzodiazepine withdrawal: effects of flumazenil.

Benzodiazepine withdrawal has been associated with hostile and aggressive behavior. The benzodiazepine antagonist flumazenil has reduced, increased or not affected hostility and aggression in animal and human studies. In the present study we analyzed data collected in a placebo-controlled study of the effects of the benzodiazepine antagonist flumazenil in patients previously treated for benzodiazepine dependency, and healthy controls. The aim was to analyze the effects of flumazenil on hostility and aggression. Ten patients and 10 controls received, on two separate occasions, cumulative doses of flumazenil (0.05, 0.1, 0.25, 0.5 and 1mg at 15min intervals) or placebo. Withdrawal symptoms were rated after each injection. Patients had been free from benzodiazepines for 47 (4-266) weeks on the first occasion. A three-way interaction (groupxtreatmentxdose) was found, and was explained by: 1) patients rating aggression and hostility higher than controls at all times during placebo, while 2) during the flumazenil provocation i) the initial significant difference between patients and controls was no longer significant above the 0.5mg dose, and ii) patients rated aggression and hostility significantly lower above the 0.5mg dose compared to base-line. The results suggest that self-rated aggression and hostility in patients treated for benzodiazepine dependency was reduced by the partial benzodiazepine agonist flumazenil.

Personality, Levels of Psychological Distress and Premature Termination of Psychodynamic Group Therapy: Results from a Prospective Longitudinal Study

This study investigated personality factors and type of psychological distress associated with an increased risk of premature termination of psychodynamic group therapy. Data was part of a larger ongoing longitudinal project. Subjects who had completed the group therapy (n = 53) were compared to subjects who had terminated the therapy prematurely (n = 41) with respect to their pre-therapy personality profiles (as measured with KAPP) and self-reported symptoms (as measured with the SCL–90). Overall, differences between the groups were modest but subjects that dropped out of therapy showed more difficulties with handling frustration, had a more distorted body image, felt more needed and reported higher levels of phobic anxiety.

The development of depression during psychodynamic group psychotherapy among subjects in substance abuse remission.

The aim of the present study was to examine the development of self-reported depression during psychodynamic group therapy among patients manifesting a history of substance use related problems between 1993–2,2000. Subjects (n=100) were prospectively followed with respects to depression levels at intake and after 6, 12, and 18 month in therapy. Depression was measured with the Beck Depression Inventory. Overall, there was a significant decrease in depression after 18 months in therapy. The development of depression in different subgroups was also analyzed.

Affective changes during cognitive behavioural therapy – as measured by PANAS

Background: Previous researches have indicated that self-reported positive affect and negative affect is changing in a healthy direction during Cognitive Behavioural Therapy (CBT). Objective: The aim of the present study was to examine how affective personality is related to psychopathology before and after CBT. Method: A group of clients (n = 73) was measured before and after CBT, differentiated by their problem areas at pre-therapy (i.e., depressive, anxious and mixed). Results: After therapy, clients experienced higher positive affect (p < .02, d=0.66), lower negative affect (p < .001, d=0.98) and there was a significant change in the distribution of affective personality regardless of problem area, χ2 = 8.41, df = 3, two-tailed p = .04, 99% CI [0.03, 0.04]. The change in the distribution was largest for the two most relevant personality types, self-actualization and self-destructive affective personality. Conclusion: Results indicate that CBT can achieve changes in affect and affective personality.

Should mood during intravenous alcohol administration be studied as a bi- or unipolar phenomenon? a pilot study

In this study, alcohol was administered intravenously to study whether its effects on mood should preferably be studied as a bi- or unipolar phenomenon. This was studied in a double-blind, placebo-balanced, design on six healthy male volunteers. Of the three bipolar aspects of mood (calmness, activity, and pleasantness), only calmness was significantly affected by intravenous alcohol. In contrast, there were significant differences between alcohol and placebo for five of the six unipolar indexes. This support the hypothesis that subjective effects of alcohol on mood are preferably studied with self-ratings that allows positive and negative aspects to be analyzed separately. Further, our data suggest that the effects of alcohol are primarily on negative aspects of mood rather than on positive.

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