Yvon D. Lapierre

Computerized EEG correlates of depression and antidepressant treatment

Quantitative EEG was used to examine: differences between non-medicated depressives and normal controls; chronic effects of antidepressant drug treatment. Spectral analysis of cortical EEG activity revealed: significant group differences in slow and fast wave activity and significant differences in hemispheric asymmetry; limited effects of antidepressants which were restricted to slow wave activity. Group differences are supportive of cortical disactivation of the right-hemisphere in depressive disorders and the limited drug-EEG effects in depressives argue for additional studies on multi-lead oriented pharmaco-EEG profiles in psychiatric populations.

Lithium as an adjunct in the treatment of major depression.

This paper reports a double-blind cross-over study (1) to investigate the efficacy of lithium carbonate to produce rapid relief of major depression in patients who were previously unresponsive to at least 4 weeks of antidepressant therapy; (2) to study the effect of acute lithium administration on antidepressant blood levels. In contrast to other studies, lithium was found to be no more effective than placebo. The effect of lithium adjunct on antidepressant levels was not significant.

Panic induced by sodium lactate: Electrophysiological correlates

Abstract 1. 1. This pilot study examined physiological concomitants of lactate-precipitated panic in six patients selected according to DSM-III criteria for panic disorder. 2. 2. Electrophysiological measures of central, autonomic and skeletal-muscular activities were monitored during a baseline period, i.v. administration of 5% D/W and of 0.5 M sodium lactate. 3. 3. Panic episodes were elicited in all patients following lactate administration. Marked increases in HR, EOG and EMG together with EEG alpha reduction, P 2 -N 2 amplitude reductions of the AEP and paradoxical increases in EEG delta activity indicate that experimentally induced panic states are characterised by physiological hyperarousal.

Comparison of chlormethiazole (Heminevrin) and chlordiazepoxide (Librium) in the treatment of acute alcohol withdrawal.

This study was carried out to compare the efficacy of chlormethiazole and chlordiazepoxide in the treatment of acute alcohol withdrawal syndrome in 40 patients. Repeated biochemical, clinical, and psychophysiological measurements were obtained in a randomized, double-blind design in which one group of patients received chlormethiazole and a second group received chlordiazepoxide over a period of 7 days. Analysis indicated both drugs to be of equivalent potency and were equally well tolerated by patients. The more severe aspects of withdrawal were brought under control within the first 4 days of treatment. However, even at 7 days, there still persisted some symptoms attributable to the withdrawal from alcohol.

Erythroccyte membrane sodium-potassium and magnesium ATPase in primary affective disorder

Erythrocyte membrane Mg2+ ATPase and Na+-K+ ATPase were measured in patients with affective disorder, their well relatives, and normal controls during euthymic moods. On the average, the Mg2+ ATPase activity was high in subjects belonging to affective disorder families. However, the difference between normal and affective disordered individuals was not statistically significant. Only the well individuals from affective disorder pedigrees as a group had significantly higher than normal Mg2+ ATPase activity (p less than 0.05). The Na+-K+ ATPase activity was similar for all the groups, including normal, bipolar manic-depressive (with or without lithium), unipolar depressive, and well individuals. Lithium treatment did not seem to have any effect on Mg2+ ATPase. Even though the values of Na+-K+ ATPase in the lithium-treated group were high, it is not certain that this was due to lithium per se.

Preparatory brain potentials in major depressive disorder

1. Psychomotor slowing in depression is frequently reflected by delayed reaction times (RT). 2. The role of central arousal mechanisms in response slowing was examined by comparing scalp-recorded slow negative potentials of depressed patients with normal controls in two separate studies. 3. Varying fore-warned RT conditions elicited contingent negative variation (CNV) waveforms and the resultant mid-point amplitudes of these waveforms together with orienting (O-wave), expectancy (E-wave) and post-imperative negative variation (PINV) component amplitudes and sensory evoked responses (N1, P2) were compared between groups. 4. RTs were significantly slowed in depressed patients and the patient group exhibited consistently larger PINV amplitudes. Depending on the RT condition, patients also exhibited larger mid-point CNV amplitudes and smaller N1 and P2 amplitudes.

Erythrocyte Lithium Transport Variables as a Marker for Manic-Depressive Disorder

This study examines whether variability in the efflux of lithium from erythrocytes may be a marker for manic-depressive disorder in related individuals. The subjects of the study were 73 individuals from 12 families in which there was more than one bipolar manic-depressive member. Using an in vitro procedure, we subjected erythrocytes to four conditions which are believed to inhibit lithium efflux. Only phloretin, an inhibitor of Na+-Li+ countertransport, produced significant inhibition. Variability in this inhibition was not related to the presence or absence of manic-depressive disorder, although it was related to family membership. The implications of these findings are discussed.

Temporal segmentation of response speed in depression: Neuro-electrophysiological approaches

1. Depressive psychomotor retardation, as observed by delayed reaction times (RT), may be related to a slowing in information processing speed. 2. Two separate studies compared indices of information processing speed in depressed patients and non-clinical controls by segmenting behavioral RT with brain event-related potentials (ERPs) and electromyographic (EMG) responses. 3. In Study I, slower behavioral RTs in depression were concomitant with slower central processing times (CPT) but not motor execution times (MET). 4. In Study II, P165, a putative early cognitive ERP related to stimulus evaluation time, was found to be slower but within normal range in depressed patients.

Cholinesterases in primary affective disorders

Cholinesterase activities were measured in plasma (ChE) and in intact erythrocytes (AChE) in patients suffering from manic-depressive illness, their first degree relatives who were well, and unrelated normal volunteers. All the subjects were in a normal mood state at the time of testing. Plasma cholinesterase activity was found to be significantly lower than normal in bipolar (BP), unipolar (UP), other affective disorder (OA) and well subjects belonging to manic-depressive families. Intact erythrocyte cholinesterase (true cholinesterase) activity was also found to be significantly lower than normal in all the above mentioned patients and their relatives. Half of the BP subjects were on lithium treatment and their cholinesterase activities were similar to those patients not on lithium treatment. The data suggest a significant role of cholinergic mechanisms in the etiology of manic-depressive illness.

Are all benzodiazepines clinically equivalent

Clinical observations are not always consistent with laboratory findings where half-life or pharmacokinetics do not always correlate with pharmacodynamics, ie. clinically effective duration of action. The parent compound, chlordiazepoxide, was observed to have anticonvulsant, anxiolytic, muscle relaxant properties to varying degrees. Subsequently, diazepam seemed to exert a greater potency in these three areas. The final metabolite, oxazepam, has been observed to have a different therapeutic profile. The advent of the triazolo compounds brought a new dimension to benzodiazepine treatment both in primary and side effects. The relationship between blood levels and clinical efficacy is considered in the light of clinical observations as well as in the perspective of clinical management. Problems of tolerance and escalation of dosage must be addressed in the administration of these drugs where the confluence of pharmacokinetic and pharmacodynamic findings may serve as a guide in the management of anxious patients.