H. Mantanus

Action of Lysine-Vasopressin on Human Electroencephalographic Activity

This study is an investigation of the central effects of vasopressin in man, as this hormone proved able to modify learning processes in animals and was applied successfully to post-traumatic, amnesic patients. Electrophysiological techniques were used to assess the effects of lysine-vasopressin (LVP) given by nasal spray (7 and 14 IU) on night sleep pattern (12 subjects), auditory evoked potentials (AEP; 26 subjects), and contingent negative variation (CNV; 26 subjects). Night sleep EEG was not modified to a great extent: in particular REM sleep did not undergo any change after LVP. Nor were AEPs modified, either in the 6-hour period following drug administration or 1 week after; CNV, however, reacted in a significant manner 6 h after drug intake, and the modifications were still present after 1 week. LVP did not affect CNV amplitude itself but its evolution through time, as CNV habituation was prevented. Such effects are discussed with regard to the neurochemical mechanisms of vasopressin action and CNV genesis.

Inhibitory influence of oxytocin infusion on contingent negative variation and some memory tasks in normal men

A double-blind study combining electrophysiological and psychometrical approaches was carried out to investigate the central effects of an intravenous oxytocin (OT) infusion in normal men. Contingent negative variation (CNV) was selected as the measure of central cognitive evoked potential, and the psychometric tests measured mood, vigilance and memory. OT infusion induced a significant decrease of CNV amplitude and an increase of post-imperative positive potentials in vertex derivations. A similar effect was still evidenced one week after treatment in frontal derivations, suggesting a long time effect of OT on human brain. No significant influence of OT on mood or vigilance tests was apparent; only one item of a memory test revealed a significant impairment of some mnesic performances. These observations provide new electrophysiological arguments supporting a central action of peripheral OT administration in man.

Comparison of adinazolam, amitriptyline, and diazepam in endogenous depressive inpatients exhibiting DST nonsuppression or abnormal contingent negative variation

Adinazolam, a triazolobenzodiazepine that has an action similar to antidepressants in several pharmacological tests, was compared with amitriptyline and diazepam in endogenous depressive inpatients exhibiting dexamethasone suppression test non-suppression and/or abnormal contingent negative variation. Three parallel groups of 22 patients received in double-blind conditions either adinazolam (60-90 mg/day), amitriptyline (150-225 mg/day), or diazepam (30-45 mg/day) over a 4-week period, with weekly assessments by the Hamilton Rating Scale for Depression. Results showed significant superiority of amitriptyline over diazepam on total Hamilton depression scores. On the endogenomorphy subscale, amitriptyline induced significantly better improvement than both diazepam and adinazolam, whereas both amitriptyline and adinazolam exhibited significantly better antidepressant efficacy on the core symptoms of depression. Moreover, the dropout rate for inefficacy after 2 weeks of treatment was higher in the diazepam group. Taken together, these findings suggest that adinazolam has an antidepressant efficacy intermediate between amitriptyline and diazepam. Adinazolam was, however, much better tolerated than amitriptyline, and produced significantly fewer anticholinergic side effects.

Self-Reports of Anxiety Level and EEG Changes after a Single Dose of Benzodiazepines

A new formulation of oxazepam especially designed to increase the speed of absorption and eliminate the need to use water (freeze-dried dosage formulation; FDDF) was compared in double-blind and crossover conditions with the standard tablets of the same compound. 5 inpatients with generalized anxiety disorder received at 1-week intervals a single 30 mg dose of one of the compounds. Every 8 min for 96 min after drug intake, they completed a battery of visual analogue scales and had an EEG recording with computerized spectral analysis. Results showed a significantly more rapid onset of activity of FDDF oxazepam for both the self-reports of anxiety level (p less than 0.005) and the specific beta 2 EEG changes (p less than 0.0001), which were significantly correlated (r = -0.73; p less than 0.01). Moreover, all patients rated FDDF oxazepam as having faster onset of action in clinical change than regular tablets (p less than 0.05). This study shows the value of visual analogue scales, pharmaco-EEG, and crossover design in well-selected anxious inpatients in substantiating clinical differences between anxiolytic pharmacotherapies.

A Study of Psychological and Endocrine Variables on 14 Patients Treated by Chronical Haemodialysis

In 13 patients suffering from renal dysfunction and treated by chronic haemodialysis, the mnemic functions appeared within the limits of normality and there was no positive correlation between blood levels of neurophysines and free cortisol. On the other hand, a negative correlation was found between levels of neurophysine I and items 3 and 5 of the memory test PRM. This negative result indicates that in haemodialyzed patients a discrepancy may exist between blood levels of neurophysines and vasopressin release, or that there is no direct relationship between plasma and CSF concentrations of such hormones.