Different acute tolerance development to EEG, psychomotor performance and subjective assessment effects after two intermittent oral doses of alprazolam in healthy volunteers.

BACKGROUND/AIMS: Benzodiazepines (BZDs) are the most effective of the psychotropic drugs in the treatment of anxiety disorders. Tolerance has been reported for the majority of BZDs after chronic administration. However, little attention has been paid to the possibility that tolerance might be present after the intermittent oral administration of BZDs. The objectives of the present study were to assess tolerance development after the administration of two intermittent single oral doses of alprazolam given 15 days apart in healthy volunteers, and to compare the results obtained using measures from different domains: neurophysiological, psychomotor and subjective. METHODS: Twenty-four healthy volunteers received 2 mg of alprazolam orally on two experimental days, 15 days apart. Plasma concentrations and pharmacodynamics (PD) were assessed before drug intake and at different times in the following 24 h. PD was assessed through EEG (relative alpha and relative beta-1 activities), cancellation task (total and correct number of responses) and visual analogue scales (activity and drowsiness). RESULTS: No differences were observed in the PKs of alprazolam between occasions. A proteresis was present in both administrations for impairments of psychomotor performance and relative beta-1 activity, whereas it was present only after the second administration for subjective assessments and relative alpha activity. The proteresis on the second occasion was higher than on the first one. CONCLUSIONS: The administration of two single oral doses of alprazolam, 2 weeks apart in healthy volunteers, yielded the same PKs on both occasions, but significant changes were observed in the PD profile. Acute tolerance was observed after the second administration. Two patterns of acute tolerance development were obtained: (1) impairments of psychomotor performance and relative beta-1 activity, and (2) subjective assessments and relative alpha activity.

Psychometric assessment of the Hallucinogen Rating Scale.

Reliability and convergent-discriminant validity of a Spanish version of the Hallucinogen Rating Scale (HRS) were assessed in two differentiated populations of hallucinogen users involving the retrospective assessment of drug effects. In Study 1 (immediate assessment), 75 European users of the South American hallucinogenic drink ayahuasca answered the HRS 4 h after drug intake in their habitual setting. In Study 2 (delayed assessment), 56 adult polydrug users answered the HRS and a short form of the Addiction Research Center Inventory (ARCI) recalling the effects they experienced when they last took a hallucinogen, in order to test the convergent-discriminant validity of HRS with the scales of the standard questionnaire used in most studies involving psychoactive drugs. The HRS scales showed increases after both the immediate and delayed retrospective assessment of drug effects. Reliability data indicated that four of the six scales show an acceptable level of internal consistency. Significant but limited correlations were found between the Perception and Somaesthesia scales and the ARCI LSD scale, pointing out the questionnaire's construct validity. Thus, the HRS was sensitive to hallucinogenic drug effects other than those elicited by intravenous N,N-dimethyltryptamine (DMT), for which it was originally designed, and showed reasonable reliability and convergent validity. Results suggest its usefulness in the evaluation of subjective effects elicited by psychoactive drugs with hallucinogenic properties, and constitute a preliminary approach to the effects of ayahuasca in European subjects.

Evaluation of psychotropic drug consumption related to psychological distress in the elderly: hospitalized vs. nonhospitalized.

The use of psychotropic drugs in general has become more extended in the past 20 years. The elderly, particularly geriatric inpatients, are the group with the highest consumption. The aim of the present study was to evaluate in two groups of elderly, hospitalized patients (H) vs. nonhospitalized subjects (nH), psychotropic drug consumption related to psychological distress. This was carried out in a total 238 subjects aged above 65 years (112 geriatric inpatients and 126 interviewed in social welfare centers). Sociodemographic, clinical and pharmacological data, general health and psychological distress were evaluated. The latter was assessed by means of the Symptom Distress Checklist (SCL-90) which included 9 subscales. 23% of the subjects received psychotropic drugs (P), of which 84% were benzodiazepines, 10% antidepressants and 1.5% antipsychotics. After evaluating the SCL-90 subscales, it was noted that anxiety, depression and obsessiveness/compulsiveness scored higher in P subjects than in those not receiving psychotropic drugs (nP). When treated nH and H were analyzed separately, it was observed that the former scored higher in anxiety and depression, while the latter showed higher scores in anxiety and obsessiveness/compulsiveness. Considered globally, the H group compared to nH showed higher scores in depression. Although evaluating psychotropic drug utilization in geriatric patients is complex due to the large number of influencing factors, SCL-90 has proved to be useful for assessing the qualitative aspects of this drug consumption in the elderly.