[Impact of music therapy on anxiety and depression for patients with Alzheimer's disease and on the burden felt by the main caregiver (feasibility study)]. / Intérêts de la musicothérapie sur l'anxiété, la dépression des patients atteints de la maladie d'Alzheimer et sur la charge ressentie par l'accompagnant principal (étude de faisabilité).

INTRODUCTION: The impact of music therapy on dementia care for patients with Alzheimer's disease (AD) is well-recognized. Music alters the different components of the disease through sensory, cognitive, emotional, behavioral and social impacts. The academic aspect of music therapy in this area was based on the fact that music can alter the various components of the overall evolution of this disease. We found around 10 case studies presenting various results from receptive music therapy sessions on patients with Alzheimer's disease. The results of these studies point out the interest of music therapy in the multidisciplinary care of Alzheimer's disease and its related syndromes. It has been deemed useful for significantly reducing the medication given to AD patients. A music therapy protocol, specifically tailored to the patient's needs has been shown to significantly reduce anxiety, depression and aggressiveness in patients suffering from Alzheimer's disease. This technique has also demonstrated its impact on helping AD patients recall their previous life experience. OBJECTIVE: To demonstrate the feasibility and to evaluate the impact of music therapy on anxiety and depression at the early to moderate stage of Alzheimer's disease and on the main caregiver burden. METHOD: Five outpatients suffering from early stage of Alzheimer's disease (MMS: 18-26) were prospectively included. They were living in Montpellier with a reliable caregiver. A weekly receptive music therapy session was delivered to patients over a 10-week period, according to the U method standardized protocol. This technique was based on the recommendations made by Gardner and Good relating to the importance given to an individualized choice of music. Instrumental tracks were selected from various music styles (classic, jazz, world music...) and were tailored to the patient's requirements. This individual session was always followed by an interview with the music therapist in order to allow the patient to express the emotions felt during the session and to stimulate the patient's cognitive functions by recalling memories and images from his past life experience. The main evaluation criterion was regular session attendance at the hospital. Secondary criteria were: anxiety score (Hamilton scale), depression score (Cornell scale) and the burden score felt by the main caregiver (Zarit scale). Evaluations took place at W1, W4 and W10. The score evolution on the Hamilton, Cornell and Zarit scales were tested using the Wilcoxon test on paired data. The significance threshold has conventionally been set at 5% for all tests used. The statistical analysis was done using the SAS software (8th version) (SAS Institute, Cary, N.C.; proc npar1way, proc univariate, proc freq). Alzheimer's disease is a recognized indication for music therapy. A simple oral consent was collected prior to the study inclusion. RESULTS: Five patients were included for a total of 44 sessions. The patients' regular attendance at the music therapy sessions showed its feasibility. Thanks to oral feedback, we were able to see that music therapy was very well-accepted both by patients and caregivers. After the sessions, all patients expressed a sensation of well-being and pleasure, such as: "Music made me feel better, I feel more relaxed", "I feel better", "I didn't know that music could have such an impact on me"... Other verbal comments were collected regarding the patients' previous life experience: "This music reminds me of my childhood", "I imagined myself dancing just like I used to in the old days", "This reminds me of my trip to Italy with my children"... The level of anxiety (Hamilton scale) dropped significantly from 9.4 (+/-2.2) to 3.4 (+/-2.6) between the first session and the fourth session (P<0.004). The differences observed between W4-W10 and W1-W10 were close to the threshold of significance due to a major drop in the anxiety level starting at W4 (P=NS). On the Cornell scale, the depression level dropped significantly from 10.8 (+/-5.3) to 2.2 (+/-1.9) between the first session and the fourth session (P<0.01). The differences observed between W4-W10 and W1-W10 were not significant (P=NS). The weight of the physical and emotional burden experienced by the main caregiver (Zarit scale) fell significantly from 30.2 (+/-11.7) to 15.6 (+/-10.4) between W1-W4 (P<0.002). The differences observed between W4-W10 and W1-W10 were not significant (P=NS). DISCUSSION/CONCLUSION: This preliminary study demonstrates the feasibility as well as the initial efficacy of music therapy in terms of its impact on the overall care for patients suffering from Alzheimer's disease. This easily applicable technique can be useful in treating anxiety and depression in a patient with Alzheimer's disease and also in relieving the emotional and physical burden experienced by the main caregiver.

[Effect of music therapy among hospitalized patients with chronic low back pain: a controlled, randomized trial]. / Intérêt de la musicothérapie dans la prise en charge de la lombalgie chronique en milieu hospitalier (Etude contrôlée, randomisée sur 65 patients).

OBJECTIVE: To evaluate the influence of music therapy in hospitalized patients with chronic low back pain. METHODS: A controlled, randomized study (N = 65). During a stationary rehabilitation stay of 12 days, 65 patients with low back pain were randomized to receive on alternate months standardized physical therapy plus 4 music therapy sessions between day 1 and day 5 (intervention group; N = 33) or standardized physical therapy alone (control group; N =32). Scores for pain (as measured on a visual analogue scale [VAS]), disability (Oswestry index) and anxiety and depression (as measured on the hospital anxiety and depression scale [HAD]) were collected on day 1, 5 and 12. Pain intensity was also evaluated on a VAS just before and after music therapy sessions. RESULTS: Introduced music therapy sessions during a stationary rehabilitation stay in patients with chronic low back pain reduce pain (-2.0+/-2.7 vs -1.8+/-2.6) but not significantly. However, music therapy significantly (p < 0.01) reduced disability as measured on the Owestry index between day 1 and day 5 (-11.8+/-17.8 vs -2.5+/-9.4), anxiety (-3.5+/-3.7 vs -0.9+/-2.7) and depression (-2.1+/-3.0 vs 0.6+/-2.4). The immediate effect on pain intensity (VAS score) was confirmed (p < 0.001). CONCLUSION: Our results confirmed the effectiveness of music therapy for hospitalized patients with chronic low back pain. Music therapy can be a useful complementary treatment in chronic pain and associated anxiety-depression and behavioural consequences.

Involvement of K+ channel permeability changes in the L-NAME and indomethacin resistant part of adenosine-5'-O-(2-thiodiphosphate)-induced relaxation of pancreatic vascular bed.

1. We have previously demonstrated that adenosine-5'-O-(2-thiodiphosphate) (ADPbetaS), a potent P2Y-purinoceptor agonist, relaxed pancreatic vasculature not only through prostacyclin (PGI2) and nitric oxide (NO) release from the endothelium but also through other mechanism(s). In this study, we investigated the effects of an inhibitor of the Na+/K+ pump, of ATP-sensitive K+ (K(ATP)) channels and of small (SK(Ca)) or large (BK(Ca)) conductance Ca2+-activated K+ channels. Experiments were performed at basal tone and during the inhibition of NO synthase and cyclo-oxygenase. 2. In control conditions, ADPbetaS (15 microM) induced an initial transient vasoconstriction followed by a progressive and sustained vasodilatation. In the presence of N(omega)-nitro-L-arginine methyl ester (L-NAME, 200 microM) the transient vasoconstriction was reversed into a one minute vasodilator effect, which was then followed by a progressive and sustained vasodilatation similar to that observed with ADPbetaS alone. The addition of indomethacin (10 microM) did not significantly modify the profile of ADPbetaS-induced vasodilatation. 3. Ouabain (100 microM) decreased basal pancreatic flow rate and did not modify ADPbetaS-induced relaxation. This inhibitor of the Na+/K+ pump increased the pancreatic vasoconstriction induced by L-NAME or by the co-administration of L-NAME and indomethacin. Ouabain did not modify either the L-NAME or the L-NAME/indomethacin resistant part of the ADPbetaS vasodilatation. 4. The K(ATP) inhibitor tolbutamide (185 microM) did not significantly modify basal pancreatic flow rate and ADPbetaS-induced relaxation. This inhibitor which did not change L-NAME-induced vasoconstriction, significantly diminished the L-NAME resistant part of ADPbetaS-induced vasodilatation. Tolbutamide intensified the vasoconstriction induced by the co-administration of L-NAME and indomethacin. In contrast, the L-NAME/indomethacin resistant part of ADPbetaS vasodilatation was not changed by the closure of K(ATP). 5. The SK(Ca) inhibitor apamin (0.1 microM) did not significantly change pancreatic vascular resistance whatever the experimental conditions (in the absence or in presence of L-NAME or L-NAME/indomethacin). In the presence of L-NAME, the closure of SK(Ca) channels changed the one minute vasodilator effect of ADPbetaS into a potent vasoconstriction and thereafter modified only the beginning of the second part of the L-NAME-resistant part of the ADPbetaS-induced vasodilatation. In contrast, the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation remained unchanged in the presence of apamin. 6. Charybdotoxin (0.2 microM), an inhibitor of BK(Ca), increased pancreatic vascular resistance in the presence of L-NAME/indomethacin. In the presence of L-NAME, the closure of BK(Ca) channels reversed the one minute vasodilator effect of ADPbetaS into a potent vasoconstriction and drastically diminished the sustained vasodilatation. In contrast the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation was not modified by the presence of charybdotoxin. Under L-NAME/indomethacin/charybdotoxin/apamin infusions, ADPbetaS evoked a drastic and transient vasoconstriction reaching a maximum at the second minute, which was followed by a sustained increase in the flow rate throughout the ADPbetaS infusion. The maximal vasodilator effect of ADPbetaS observed was not modified by the addition of apamin. 7. The results suggest that the L-NAME-resistant relaxation induced by ADPbetaS in the pancreatic vascular bed involves activation of BK(Ca), K(ATP) and to a lesser extent of SK(Ca) channels, but the L-NAME/indomethacin resistant part of ADPbetaS-induced relaxation is insensitive to the closure of K(ATP), SK(Ca) and BK(Ca) channels.

Effects of homocysteine on acetylcholine- and adenosine-induced vasodilatation of pancreatic vascular bed in rats.

1. Epidemiological and experimental data have shown that homocysteine may provoke vascular lesions and that moderate homocysteinaemia may constitute an independent risk factor for vascular disease. It is now documented that homocysteine damages human endothelial cells in culture, possibly by producing hydrogen peroxide in an oxygen-dependent reaction. 2. In this study, we have examined the direct effect of this sulphur amino acid on pancreatic vascular resistance. Experiments were performed on the vascular bed of the rat isolated pancreas perfused at constant pressure; thus, any change in pancreatic vascular resistance resulted in a change in the flow rate. D,L-Homocysteine perfused for one hour at three different concentrations (200 microM, 2 mM, 20 mM) did not induce any significant change in the flow rate per se. Homocysteine infusion for 30 min at a concentration of 200 microM or 2 mM abolished the endothelium-dependent vasodilatation induced by acetylcholine (0.05 microM), but did not modify adenosine (1.5 microM)-induced vasodilatation. 3. The effect of D,L-homocysteine (200 microM or 2 mM) cannot be ascribed to a direct antimuscarinic effect since 30 min pretreatment of rat ileum with these concentrations did not significantly change the contractile effect of increasing concentrations of acetylcholine (0.015-15 microM). 4. Preincubation of human umbilical vein endothelial cells with D,L-homocysteine (0.2-5.0 mM) had no significant effect on overall cell number or viability during 18 h of incubation; the endothelial cells exposed to concentrations up to 5 mM exhibited a spindle-shaped, whirled pattern. This pattern was reversed 48 h after the removal of homocysteine. A cytotoxic effect was seen after 18 h incubation in 10 mM D,L-homocysteine. 5. In conclusion, an acute infusion of homocysteine altered acetylcholine endothelium-induced vasodilation, whereas the adenosine vasodilatator effect was insensitive to the deleterious action of homocysteine in vitro.

Comparative effects of LN 5330 and diazoxide on insulin release and 86Rb+ permeability in perifused rat islets of Langerhans.

The benzothiadiazine derivative LN 5330 (chloro-7 trifluoromethyl-6 benzothiadiazine-1,2,4-dioxide-1,1) has been shown to inhibit insulin secretion and calcium uptake. The present study was carried out to investigate the effects of LN 5330 on insulin release and 86Rb- efflux from perifused rat pancreatic islets; a comparison was made with the structural analogue diazoxide. In the presence of 8.3 mM glucose, LN 5330 (100 microM) accelerated 86Rb+ efflux while reducing insulin output from the islets. LN 5330 induced a dose-dependent acceleration of 86Rb+ efflux and appeared to be a more potent activator of 86Rb+ efflux than diazoxide. The stimulatory effect of LN 5330 on 86Rb+ efflux persisted in the absence of extracellular calcium. In the absence of glucose, 86Rb+ permeability also increased, LN 5330 being again significantly more efficient than diazoxide at an equimolar concentration. These data indicate that the benzothiadiazine derivative LN 5330 inhibits insulin secretion by increasing the potassium permeability of the plasma membrane. It is suggested that, like diazoxide, this drug could activate the ATP-sensitive K+ channel.

Effects of alpha-adrenoceptor agonists and antagonists on insulin secreting cells and pancreatic blood vessels: comparative study.

The effects of alpha-adrenergic drugs were studied on glucose-induced insulin secretion and effluent flow rate on the same preparation: the isolated perfused rat pancreas. An alpha 1-adrenoceptor agonist, phenylephrine 0.05 microM slightly decreased insulin secretion (-25%); this inhibition was counteracted by an alpha 2-adrenoceptor antagonist, yohimbine 0.6 microM. Phenylephrine evoked a fall in liquid flow rate (-13%) which was reversed by an alpha 1-adrenoceptor antagonist, prazosin 6 microM, but not by yohimbine. An alpha 2-adrenoceptor agonist, clonidine 0.01 and 0.05 microM decreased insulin secretion (-80%). This inhibition was reversed by yohimbine 0.6 and 6 microM respectively. Only the concentration of 0.05 microM clonidine evoked a fall (-25%) in liquid flow rate; this fall was counteracted by yohimbine 0.6 microM. In conclusion our results show that adrenergic inhibition of insulin secretion is mediated only by alpha 2-receptors whereas both types of adrenoceptors are implicated in the vasoconstrictor effect. The insulin inhibitory effect of adrenoceptor agonists is not related to vasoconstriction.

Involvement of a central nervous pathway in yohimbine-induced insulin secretion.

Yohimbine hydrochloride, an alpha 2-adrenoceptor antagonist, was administered (3.3 mg/kg i.v.) to anesthetized normal dogs provided with a T-shaped catheter inserted in the pancreaticoduodenal vein. The effects on blood glucose levels and pancreatic hormones were investigated. We show that yohimbine induced an immediate and pronounced stimulatory effect on insulin secretion accompanied by a clear decrease in blood glucose levels. Yohimbine also stimulated the pancreatic secretion of somatostatin and glucagon. However, the secretion kinetics were not the same for the three hormones: the stimulation was rapid and immediate for insulin and somatostatin, whereas it was progressive for glucagon. All these stimulatory effects were suppressed by propranolol, thus implicating beta-adrenergic mechanisms. Bilateral cervical vagotomy markedly reduced the immediate effect of yohimbine on insulin secretion, suggesting that a central neural pathway was implicated. In contrast, the progressive elevation in glucagon secretion was not decreased by vagotomy. Our results suggest that yohimbine stimulates, at least in part, insulin secretion by blocking central alpha 2-adrenoceptors.

Carboxypeptidase G2 rescue in delayed methotrexate elimination in renal failure.

We report here the case of a 68-year-old woman who presented severe renal failure following the first cycle of high dose methotrexate (HDMTX) for the treatment of a cerebral malignant lymphoma. Before HDMTX administration, serum creatinine value was normal and three days after HDMTX, it reached 457 micromol/L. Leucovorin rescue, hemodialysis and cholestyramine did not increase MTX clearance. Because of the persistence of renal failure, and the high risk of important hematological side-effects associated with high MTX plasma levels, the patient received carboxypeptidase G2 (CPDG2). This allowed MTX plasma levels to decrease by 80% in 15 minutes. No side effects were observed and renal function normalized rapidly. In some patients, when high-dose leucovorin associated with hemodialysis and cholestyramine are unable to restore normal MTX clearance, CPDG2 should be considered because it may represent a safe and efficient alternative for the management of MTX intoxication.

Initiation of carbamazepine therapy in partial epilepsy: a regional cerebral blood flow study.

The effect of the initiation of carbamazepine (CBZ) treatment on regional cerebral blood flow (rCBF) was studied using the intravenous Xenon technique in a group of epileptic patients suffering from complex partial seizures. A slight increase in mean rCBF (10.8 +/- 8.8%, P less than 0.01) was observed in 12 patients after the first month of CBZ treatment, while no rCBF change was found after 6 months of CBZ treatment. Regional analysis showed that the rCBF increase following 1 month of CBZ treatment involved all cortical regions with the exception of the right occipital region, irrespective of the initial value. Repeated rCBF measurements performed in normal volunteers (N = 6) and in epileptic patients (N = 10), chronically treated and not subjected to therapeutic modification, showed no significant change. The initial effect of CBZ on CBF found at the onset of the treatment but not after 4-6 months may be related to the improvement in epilepsy and in cerebral function (as suggested by cognitive findings).

An imidazopyridine anxiolytic alters glucose tolerance in patients: a pilot investigation.

We have recently shown that compounds with high affinity for peripheral-type benzodiazepine receptors inhibited glucose-induced insulin secretion in vitro. We therefore performed an oral glucose tolerance test in anxious inpatients treated with the imidazopyridine derivative alpidem, which has been shown to display high affinity for these binding sites. The test was performed before and after 1 week of daily administration of the drug. As compared with pretreatment values, a significant alteration of the insulin response to glucose was observed. It is suggested that daily administration of alpidem, at therapeutically effective doses for the treatment of anxiety, may alter glucose tolerance.

A double-blind comparison of clonazepam and placebo in the treatment of neuroleptic-induced akathisia.

The present study was designed to investigate the efficacy of clonazepam in neuroleptic-induced akathisia. Twelve patients were treated during 2 weeks with clonazepam or placebo in a double-blind randomized design. Akathisia was scored by an independent rater before and after treatment, as well as 1 week after medication withdrawal. Clonazepam (0.5-2.5 mg/day) induced a significantly higher reduction in the akathisia scores than placebo (p < 0.05). One week after stopping the drug, there was a partial but significant relapse in the treated group as compared with controls, in whom the symptoms remained stable. In addition, the clinical improvement was significantly correlated with the daily dose of clonazepam (rs = 0.827; p < 0.002). These results support the potential usefulness of clonazepam in the treatment of neuroleptic-induced akathisia and suggest an optimal daily dose in the range of 10-40 micrograms/kg.

Statistical analysis of performance of a liquid chromatographic assay of anticonvulsants involving solvent-demixing extraction and reciprocal internal standardization.

Analysis of variance both factorial and nested was used to validate a HPLC method intended for routine clinical assay of ethosuximide, phenobarbital, phenytoin and carbamazepine. Drugs were salted out, together with the solvent, from 0.5 ml acetonitrile-deproteinized plasma samples with 80-90% recovery. The acetonitrile extraction solution contained a known amount of all four drugs. This added amount of any drug was used when absent from plasma as an internal standard for those present and when present as a calibrator. Results showed that assay precision was acceptable (CV 6%) over and above the therapeutic range when additions did not exceed the lower therapeutic plasma level and if as many replications were made as there were drugs to assay. In return for some loss of sensitivity, reciprocal internal standardization provides increased assay reliability owing to the usual availability of more than one internal standard and to easier identification of interfering chromatographic peaks.

[Pharmacovigilance of new antidepressants: evaluation of neuro-psychobehavioral disorders]. / La pharmacovigilance des nouveaux antidépresseurs: évaluation des troubles neuro-psychocomportementaux.

Drug surveillance data can be obtained from different sources: spontaneous French and European reporting, data from WHO, bibliographic analysis. We are more interested, in this paper, in the type of data obtained than in the surveillance of each antidepressant. Our study is focused on psychiatric and neurobehavioural effects of antidepressants. The French drug surveillance database was examined for reactions associated with fluoxetine. Psychiatric side effects are not the most frequent. The psychiatric safety profiles of the three SSRIs (fluoxetine, fluvoxamine and paroxetine) are similar. However withdrawal reactions with fluvoxamine and paroxetine occur in a greater proportion of reports (13 and 14 per cent) than with fluoxetine (1.5 per cent). In contrast, pharmacodependance was observed in 79 per cent of reports with amineptine. Tricyclic antidepressants do not seem to confer increased risk of teratogenesis. Preliminary data regarding risk of prenatal exposure to fluoxetine suggest that its use during pregnancy is relatively safe. Data regarding neurobehavioural effects of prenatal exposure are lacking for all antidepressants. Cognitive disorders induced by antidepressants are complex, due to the involvement of several factors that can intervene in the pathogenesis and evaluation of these disorders : most studies evaluate the modifications of neurobehavioural effects in healthy subjects, few studies concern chronic patients. Proposals are made to improve the evaluation of these side effects.

[Iatrogenic medication: estimation of its prevalence in French public hospitals. Regional Centers of Pharmacovigilance]. / Iatrogénie médicamenteuse: estimation de sa prévalence dans les hôpitaux publics français. Centres régonaux de pharmacovigilance.

The French network of Regional Centres of Pharmacovigilance has made an estimation of the occurrence of adverse drug reactions in a representative sample of patients in French public hospitals (departments of medicine, of surgery and of geriatrics). The study looked at one specific day in the spring of 1997. Each observed case of adverse drug reaction was validated. The total sample comprised 2132 patients of whom 969 were in a university hospital and 1163 in a general hospital. The hospitals and units concerned are representative of the country as a whole. One adverse drug reaction at least was present for 221 patients on the day of the investigation. This means a prevalence rate of 10.3 per cent (95 per cent CI: 8.7 to 11.9 per cent). In 33 per cent of cases (95 per cent CI: 26 to 42 per cent), the observed effects were rated as serious. From an incidence rate of 1.8 per cent (95 per cent CI: 1.0 to 25 per cent) on one specified day it can be estimated that in France an adverse drug reaction will occur in about 1,300,000 patients per year during a stay in hospital.

[Immunoallergic reactions of drug origin: epidemiologic and clinical data]. / Les réactions immuno-allergiques d'origine médicamenteuse: données épidémiologiques et cliniques.

Allergic and pseudoallergic reactions frequently occur in hospitalized patients and represent up to one-third of adverse drug reactions. Allergic reactions are unpredictable reactions, related to immunologic mechanisms. Pseudoallergic reactions mimic allergic reactions but no drug-specific antibody or T-cell proliferation can be demonstrated. Clinical presentations are numerous and heterogeneous, from a mild urticaria to a dramatic anaphylactic shock and an extensive bullous skin disease. A true diagnosis is rarely set up and the tools for it are lacking. In this review, we will focus on some epidemiological data concerning these reactions, including data on incidence, mortality and cost.

[Inter-regional differences in dysthyroidism due to amiodarone: comparison of spontaneous notifications in Aquitaine, Midi-Pyrenees and Languedoc-Roussillon]. / Différences inter-régionales des dysthyroïdies à l'amiodarone: comparaison des notifications spontanées en Aquitaine, Midi-Pyrénées et Languedoc-Roussillon.

Amiodarone hydrochloride is used in the treatment of ventricular and supraventricular arrhythmias. Because of its iodinated structure, thyroid dysfunction can occur during amiodarone therapy. The reported overall incidence is variable (2-24 per cent) and depends on several factors (past thyroid history, daily iodine intake,...). The present retrospective (1990-97) study was performed using the French pharmacovigilance database in order to compare the frequency of hypo- and hyperthyroidism in three areas in the South of France: Midi-Pyrénées, Aquitaine and Languedoc-Roussillon. For each case, the following data were recorded: age, sex, dysthyroidism history, dosage, duration and indication of amiodarone and delay to onset of dysthyroidism. We collected respectively 37, 50 and 9 cases of hypothyroidism in Midi-Pyrénées, Aquitaine and Languedoc-Roussillon and 20, 69 and 11 cases of hyperthyroidism respectively in the same areas. These data show the predominance of reported amiodarone-induced hyperthyroidism in Aquitaine and Languedoc-Roussillon. Hypothyroidism seems more frequent in Midi-Pyrénées, a non-maritime area. The sex ratio (male/female) was significantly different for the occurrence of hypothyroidism in Midi-Pyrénées (1.8 versus 0.5 in Aquitaine and 0.8 in Languedoc-Roussillon). The delay to onset of hypothyroidism was significantly shorter in Midi-Pyrénées (17.1 months +/- 24.5) when compared with Aquitaine (28.7 +/- 28.1) or Languedoc-Roussillon (43.4 +/- 45). Our results show an interregional difference in the occurrence of hypo/hyperthyroidism due to amiodarone.

[Venlafaxine withdrawal syndrome: report of six cases and review of the literature]. / Syndrome de sevrage à l'arrêt de la venlafaxine: à propos de six cas et revue de la littérature.

INTRODUCTION: Venlafaxine is an antidepressant that selectively inhibits serotonin reuptake and is a norepinephrine inhibitor. Withdrawal syndromes can occur after abrupt drug discontinuation of long-term regimens. EXEGESIS: We report six cases of withdrawal symptoms after venlafaxine discontinuation. CONCLUSION: Physicians must be aware of the frequency, rapidity and potent severity of these withdrawal syndromes.

[Neurologic toxicity caused by zelitrex (valaciclovir) in 3 patients with renal failure. Is overdose associated with improvement of product bioavailability improvement?]. / Toxicité neurologique induite par le Zelitrex (valaciclovir) chez trois patients insuffisants rénaux. Surdosage lié à l'amélioration de la biodisponibilité du produit?

INTRODUCTION: We report three cases of neurotoxicity in patients with renal failure, treated with Zelitrex (valacyclovir). EXEGESIS: The patients are two women and a man, aged 76 +/- 4.6 years, who presented acute mental confusion during a treatment with valacyclovir. In two cases, the patients previously had altered renal function and were under peritoneal dialysis. In the last case, the patient had simultaneous neurotoxicity and acute renal failure. After the discontinuation of the drug, the outcome was favourable in all cases. CONCLUSION: Our cases focus attention on the possible neurotoxicity of valacyclovir, which is an amino acid ester prodrug of acyclovir, rapidly and almost completely hydrolysed to acyclovir prior to systemic exposure. The bioavailability of valacyclovir is 54% compared to approximately 20% for oral acyclovir and may account for unexpected overdoses, which may lead to serious neurological toxicity.

[Use of very high doses of haloperidol in the treatment of acute psychotic episodes. Clinical and pharmacokinetic analysis apropos of 15 cases]. / Utilisation de très fortes posologies d'halopéridol dans le traitement des épisodes psychotiques aigus. Analyse clinique et pharmacocinétique à propos de quinze cas.

High-dosage haloperidol treatment was administered during three weeks in a rapid neuroleptization technique to fifteen patients suffering from acute psychotic episodes. Haloperidol plasma levels were determined by radioimmunoassay. The efficacy of such a therapeutic design seemed fairly good, particularly the rapid improvement during the first week. Yet, tolerance appeared to be low, with a high incidence of adverse effects, some of them unexpected. A very good correlation was observed between haloperidol plasma levels and haloperidol oral doses. By contrast, there was no correlation between plasma levels and clinical improvement. In the same way, the occurrence of adverse effects did not seem to be related to haloperidol plasma levels.

[Drug information and prescription guidance: role of regional centers of pharmacovigilance]. / Information du prescripteur et aide à la prescription: rôle des centres régionaux de pharmacovigilance.

MISSIONS: Drug information is one of the missions of the French Regional Pharmaco-Vigilance Centers together with the evaluation of adverse drug reaction (ADR) reports, expertise, teaching and research. SERVICES: Physicians and other health professionals call their regional center (the address and phone numbers are on the first pages of the Vidal, the French national drug compendium) for any kind of information pertaining to adverse drug reactions or proper use of drugs such as drug use in pregnancy or lactation. RELIABILITY: This information activity is successful because of the competence and impartiality of the regional centers which are based in university hospitals under an agreement signed with the French Medicines Agency.