A randomised, double-blind comparison of milnacipran and imipramine in the treatment of depression.

This multicentre, double-blind, randomised trial in 109 patients compared the efficacy and tolerance of the novel selective serotonin and noradrenaline reuptake inhibitor (SNRI) antidepressant milnacipran (50 mg twice daily, n=53) with the established tricyclic agent imipramine (75 mg twice daily, n=56) over a period of 6 weeks, in patients with major depression (Montgomery-Asberg depression rating score (MADRS) > or =25). Initiation of antidepressant medication was conducted during a 2-week period of hospitalisation, after a 3- to 7-day washout period. Concomitant psychiatric medication was limited to lorazepam, cyamemazine, chloral hydrate and long-term uncomplicated lithium therapy. Assessment for efficacy using the MADRS and Hamilton rating scales of depression, a visual analogue scale and global evaluation revealed both agents to be highly effective (P=0.0001) in this group of patients. Milnacipran was found to be of similar efficacy to imipramine. Tolerance, assessed by physiological and biochemical examinations with routine inventory and spontaneous report of adverse events, revealed a clear advantage for milnacipran. The incidence of anticholinergic events with milnacipran was about half that with imipramine and the overall incidence of adverse events by either reporting method was markedly lower with milnacipran than with imipramine. Furthermore, the patient drop-out rate with imipramine was double that experienced with milnacipran. Milnacipran appears to possess equal antidepressant efficacy to imipramine but with markedly superior tolerance. Therefore, milnacipran constitutes an important new treatment option in major depression.

Antigen specificity and cross-reactivity of fifteen monoclonal antibodies against porcine pancreatic alpha-amylase II and its AB and C domains.

Highly productive hybridoma secreting mabs specific for porcine alpha-pancreatic amylase II were established. Fifteen clones were selected. The mabs produced (KD = 1.68-11.2 nM) were checked for cross-reactivity with six heterologous antigens, namely porcine pancreatic alpha-amylase I, barley amylase, human pancreatic alpha-amylase, Taka amylase and triose phosphate isomerase, using direct ELISA assay; mabs were classified within seven groups: in a few groups mabs cross-reacted with a single heterologous antigen either porcine pancreatic amylase I (6 mabs) or barley amylase (2 mabs) or human pancreatic amylase (3 mabs). Two other groups cross-reacted with two heterologous antigen either porcine I and human or porcine I and barley. Only one mab out of fifteen cross-reacted in direct ELISA binding to all amylases and triose phosphate isomerase. Using sandwich ELISA test only three mabs were found to bind porcine amylase II present at high concentration. Results consistent with direct porcine amylase binding were obtained from binding inhibition assays. Analysis by the additivity test allowed to find that 3 mabs, B10.10, B1.11, C6.4 recognize distinct epitopes while the epitopes for the other pairs tested are either overlapping or at least close to each other. Finally mabs binding specifically either to the AB or to the C domain fragment or to both fragments have been obtained.

[Clinical and physiopathologic study of the hepatotoxicity of psychotropic drugs including the antiepileptics]. / Etude clinique et physiopathologique de l'hépatotoxicité des psychotropes y compris les anti-épileptiques.

The goal of this article is to inform psychiatrists of the hepatotoxicity of certain drugs used for the treatment of psychiatric disorders. A review of biochemical pathways lends support to the argument that toxicity is due to certain toxic metabolites. The physiopathology of these disorders, which are rare, requires an appreciation of an individual's biochemical make up which can explain the quantity of active metabolites produced, the occurrence of immunological reactions and the contributing factor of enzymatic induction resulting from the simultaneous prescription of several medications. The most serious disorder is cytotoxic hepatitis which has a 10 to 20 per cent mortality. The molecules which may cause this affection in less than one out of a thousand cases are the hydrazide M.A.O. inhibitors and valproic acid. These medications should not be prescribed without being aware of their drawbacks and after a failure to achieve improvement with other drugs having a similar action. Obviously it is important to prescribe no more than moderate doses, and to avoid prescribing medications which, together can occasion enzymatic induction. The most common complication is obstructive jaundice for which the clinical and biological diagnosis should be made early in the course of the disorder. The medication should be stopped immediately and further prescription, in patients who have already presented this disorder, when a molecule is known to have certain toxic side effects (phenothiazines and tricyclics), suspended this surveillance should be carried out over a three months period. The occurrence of jaundice during a period of treatment is not always iatrogenic. It is always necessary to ascertain the etiology by asking a specialist to do a complete workup.

[Antidepressant treatment by I.V. route compared to oral route of administration (author's transl)]. / Le traitement antidépresseur par voie intraveineuse comparé au traitement par voie orale. Un essai en double aveugle de la quinupramine.

The therapeutic effects of oral and intravenous administration of a tricyclic antidepressant, Quinupramine, in depressive states, were compared in a double blind double placebo clinical study for an initial period of ten days. Treatment was continued by the oral route in an open study lasting one month. Thirty two patients were randomly distributed into two equal groups, and results were assessed and evaluated by Hamilton's depression rating scale. Parenteral administration was clearly superior in endogenous depressions, improvement being noted earlier and lasting longer. Maintenance therapy using the oral route produced better results when it was preceded by perfusions. This difference of activity following oral or parenteral administration was not observed in cases of neurotic or reactive depressions, where there was a good initial improvement, but this is not maintained clinically for long periods after perfusion therapy. Quinupramine injectable should be prescribed for the more severe cases of endogenous depressions as urgent therapy. The beneficial effects of the perfusions can be observed after the initial period by the quality and the continuing stability of the improvement produced.

[The development and prognosis of acute psychotic disorders (polymorphic delirium flushes)]. / Evolution et pronostic des troubles psychotiques aigus (bouffée délirante polymorphe).

The DSM IV classification of brief psychotic disorders and schizophreniform disorders is unsatisfactory because of its purely temporal criteria for diagnosing acute psychotic disorders, which are seen as a preliminary diagnosis to schizophrenia. We thus decided to use a more inclusive concept, with greater diagnostic possibilities, that of the bouffee delirante polymorphe (BDP) or non-specific delusional episode of Magnan, and then analyze its clinical use. This study examines the use of this diagnosis in a walk-in clinic for patients referred to the ER of a general hospital for acute psychiatric pathology. Over an 18-month period, out of 331 hospitalizations, 91 admissions corresponded to the diagnosis of BDP, with median age of 29 years and a median length of stay of 10 days. The initial diagnosis was of needs only approximate and became more specific with longer length of stay, results of response to therapeutic management, more exact phenomenology of the BDP, more information about the days preceding the episode, and a better knowledge of previous psychiatric episodes. Also useful were the immediate triggering circumstances: intellectual deficit, possible absorption of toxic substances, psychologically traumatic events. The subsequent time course showed the following pathologies in order of decreasing frequency: acute psychotic episodes of schizophrenia, delusional manic episodes, acute paranoid episodes, delusional depressive episodes. Finally, there were bona fide acute psychotic episodes meeting the criteria of BDP, which remained isolated or possibly repetitive and of short duration, partly because of pharmacotherapeutic treatment, but also because of an intrinsically favorable prognosis. Such cases are habitually labeled in the literature reactional psychosis, and should be in our opinion considered separate from schizophrenia.

[Anxiety-trait, anxiety-state, real change, apparent change]. / Anxiété-trait, anxiété-état changement réel, changement apparent

After reviewing the different techniques assessing state-axniety, the authors emphasize the difficulties to distinguish state from trait on the sole basis of factorial content. Results obtained on different samples (mental patients, surgical patients and normal subjects)through two new anxiety self-rating scales (trait and state) are presented. On the basis of these results, the authors show the usefulness of the score indicating the discrepancy between trait and state levels. It appear that the direction (positive or negative) of the difference between trait and state levels gives a better evaluation of the actual state than the state score alone. The results imply the utilization of both self-rating scales (trait and state) in order to obtain the optimal assessment of the state.