Biomedical subjects
Publications and source records attributed to H Lôo.
The antidepressant effect of citalopram, a specific inhibitor of the reuptake of serotonin, was explored in an open phase II study involving twenty-one patients hospitalized for depression. Fourteen patients responded, six did not and one was excluded from the study. These preliminary results suggest that citalopram is an effective, well tolerated antidepressant.
Cimoxatone is a new monoamine oxidase inhibitor (MAOI) in comparison to the existing non-selective and irreversible MAOIs used in the therapy of depression. A clinical study has been carried out in 10 depressed patients. Cimoxatone was given from 0.32 to 0.78 mg/kg/day for 28 days. The drug was shown to be effective against depression and well tolerated at the given doses. The inhibition of monoamine oxidase and its reversibility were assessed by urinary excretion of 3-methoxy-4-hydroxy- phenylethyleneglycol sulphate. The treatment had no effect on the plasma prolactin levels. The plasma concentrations of cimoxatone reached a plateau after 3 to 4 days of therapy. The study confirmed earlier findings in healthy volunteers that the principal metabolite is also active as a type A MAOI. The plasma elimination of cimoxatone and its metabolite is almost complete 4 days after the last dosing.
MAO inhibitors are now only exceptionnally used in France. These medications are efficient to improve depressive states resistent to tricyclic antidepressants. Some authors suggest that we have to control the efficacy of the MAOI by evaluation of the part of inhibition of the activity of the enzyme MAO. This possibility of biological control, the apparition of specific medications inhibiting MAO A or MAO B, the efficacy of some associations (MAOI + tricyclic antidepressants or MAOI + tryptophane precursors) should lead us to reconsider our opinion about these medications.
One night sleep deprivation in 10 healthy volunteers was performed: none of them presented an abnormal dexamethasone suppression test (DST) during the following afternoon. In this experimentation, a short deprivation of sleep does not alter DST. Etiopathogenic hypothesis of DST abnormalities (and other factors) have been discussed.
The plasmatic levels of free, sulfoconjugated and total dihydroxyphenylethyleneglycol (DOPEG), the main deaminated metabolite of noradrenaline, have been measured in thirty DSM3 major depressive inpatients and in thirty healthy controls matched for sex and age. DOPEG levels have been measured by a radioenzymatic assay. Almost fifty per cent of depressed inpatients were D.S.T. non suppressors, thirteen patients were unipolar and thirteen bipolar. Plasmatic DOPEG levels were significantly lower in depressed patients as compared to healthy controls despite a wide interindividual range of DOPEG values. However, the ratio of free over conjugated DOPEG was not statistically different in the two groups. DOPEG levels were slightly higher in the female population of healthy volunteers but not in the depressed patients. In the healthy volunteers, but not in depressed patients, there was a trend for free DOPEG to increase and for conjugated DOPEG to decrease with age. There was no statistical correlation between the DOPEG levels and Hamilton Depression Scores. Also plasmatic DOPEG values were not different in uni or bipolar patients and in DST suppressor or DST non suppressor inpatients. The significance of the decrease of plasmatic DOPEG levels in depressed patients is discussed: this diminution may reflect a deficiency in noradrenaline metabolism in CNS or else may be attributed to other factors e.g. alteration in circadian rhythms, differences in motor activity, in level of anxiety, in sleep and feeding behaviors; cotreatment with benzodiazepine and opiate compounds; monoamine oxidase activity.
From the plasma and red cell kinetics of lithium in 43 patients having received lithium therapy for at least 15 days, the authors try to establish a correlation between intolerance and a variety of parameters examined. Statistical analysis reveals that: intra-erythrocytic concentration is a more reliable biological index than the lithium level; it can be modified by associated drug therapy; measuring the erythroplasmic ratio at different times of the day shows important variation within individuals. This type of kinetic study can identify biologically the 2 sub-groups distinguished by clinical examination: tolerant subjects (those on lithium therapy without any neurological signs) and poorly tolerant subjects.
The use of lithium salts in the treatment of schizophrenia remains as contested as the concept of schizo-affective disorders. Many studies have attempted to define the interest and the risks of lithiotherapy beside the major effective disorders. Only a few of them can be credited with a strict methodology. The authors have only taken into account the comparative double-blind studies, namely between lithium and neuroleptics. Some predictive criteria of the therapeutic effect seem to emerge: the notion of a sudden outbreak, a good premorbid adjustment, appear more significant than the presence or absence of effective symptoms during the psychotic episode.
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The biochemical features of depressions able to guide the prescription of antidepressants are seen through a review of the literature. The papers were mainly focused on the peripheral catabolites of brain monoamines. Depressions characterized by low levels of 5 HIAA in the C.S.F. would predict a better efficacy of the antidepressants acting on the re-uptake of serotonin. The dosage of urinary MHPG seems to be a valuable index for the choice of the drug. Subjects with low levels response better to IMI, DE-IMI and NT, and those with normal levels to AMI. COMT activity and platelet MAO activity are may be a valuable index for the predictivity of the therapeutic results. Finally, the dexamethasone suppression test can be useful in order to guide the length of the treatment.
Intellectual, affective and motor inhibition is part of the syndrome encountered in: drug withdrawal in addicts especially with opiates; hebephrenia. Amineptine a new antidepressant agent with psychoanaleptic properties has been studied in these patients. Considering this psychotonic activity was logical to test both the tolerance of this compound in drug addicts and the risk of delirious reactivation in schizophrenic patients. The open study in 19 patients shows an effect of amineptine: -on inhibition and loss of activity, apragmatism and deterioration of social behaviour; -a subjective improvement of intellectual performance. And moreover: without reactivation of preexisting delirious ideas in schizophrenic patients; without drug addiction in treated toxicomaniacs.
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The authors report a trial on the antidepressive activity of L.5-H.T.P. The clinical population is relatively homogeneous; it consists of melancholic patients, aged over 50. The results are inferior to those obtained with other antidepressant therapies. They do not verify that L.5-H.T.P. has an antidepressive action in elderlies. However, the authors do not put aside that L.5-H.T.P. can be interesting in some varieties of depression.
Biochemistry of the brain has to avoid the dead-end where psychopharmacology is trapped at the present time. First of all it is needed to draw of the lack of efficacy of the antidepressants of today. Brain biochemical research must go beyond the moamine models and take into considerations the afferent and efferent influences. The sutdy of ECT and ions like lithium, rubidium, and cesium may open up new perspectives to the knowledge of new psychotropic drugs and to their mecanisms of action. Starting from clinical observations new indications for already known non psychotropic drugs could appear.
Commercialized in the U.S.A. a few years ago, the loxapine succinate appears to be interesting among neuroleptic compounds. Used in 28 chronic schizophrenics, 19 of which were neuroleptic resistent patients, the parenteral route proved to be anti-psychotic and sedative in 26 patients. The usual daily dosages were between 100 and 200 mg. The local and general tolerances were good. The side effects were mild and essentially vegetative. The therapeutic efficiency seems to be better at the same dosages with the oral form than with the parenteral form.
The antidepressants can be classified chemically. The standard division is between the tricyclic antidepressants and the chemically heterogeneous MAOIs. Many other compounds can be included among the antidepressants, e.g. the bicyclics and possibly also the beta-stimulants, the alpha-blockers and ions such as rubidium. As regards the mechanisms of action, we have the antidepressants which act selectively upon serotonin and those which act more particularly upon noradrenaline. This notion must be extended. Dopamine may be involved in certain depressive syndromes and also other systems may have a role, such as electrolyte systems, cell permeability and the multiple influences which have a bearing upon the monoamines. Finally, the effect upon receptors and their nature are discussed. A third type of classification refers to the therapeutic spectrum of the drug. We have the sedative antidepressants, active in agitated depression and the stimulant antidepressants which are active in retarded depression. However, the two categories of antidepressants have the same global antidepressant action.
Pharmacokinetic data of psychotropic drugs should allow a better understanding of therapeutic results and side effects. The different factors influencing liberation, absorption, protein binding, distribution, metabolism and excretion are reviewed. Then, the principal pharmacokinetic data of haloperidol are exposed with a special emphasis on the lack of information about the correlations between plasma levels and clinical effects. The role of pharmacokinetic informations in the interpretation of responses to treatment is detailed, wishing that the monitoring of haloperidol plasma levels will be more developped in a next future.
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