[Influence of blood pressure variability during office visit on the estimation of blood pressure control in treated hypertensive patients]. / Influence de la variabilité de la pression artérielle en consultation sur le diagnostic du contrôle tensionnel chez des hypertendus traités.

OBJECTIVE: To evaluate the variability in blood pressure observed during office visit in treated hypertensive patients and its consequences on the diagnosis of controlled hypertension. METHOD: The medical records of 144 subjects seen consecutively in a hypertension excellence center were extracted from a computerized medical database including hypertension subjects treated and followed-up for at least one year. BP measured with an automatic device (four consecutives measurements at 2min intervals) where compared to BP values of home BP performed in the previous week's visit. Thresholds were 140/90mmHg for office BP and 135/85mmHg for HBP. RESULTS: The population has the following characteristics: age 62 years with 26% over 70 years, treated with a monotherapy (33%), bitherapy (35%), triple therapy (17%), quadri-therapy or more (8%). A white coat effect SBP above 20mmHg was noted in 32% of patients when BP at 2min is taken and in 2% when BP at 8min is taken (P<0.01). After 8min, a masked effect is noted in 16% for SBP above 20mmHg and in 44% for DBP above 10mmHg. White coat hypertension or masked hypertension was noted in 40% or 16% respectively (BP 2min) and in 5% or 29% (BP 8min) in treated hypertensive. CONCLUSION: In treated hypertensive, office BP measured by an automatic device shows significant variability. When the BP is taken with an automatic device, measures taken after 8minutes of rest avoid the misleading effects of white coat effect, but the masked hypertension is present in nearly one third of the subjects. The use of AMT for monitoring hypertensive patients is the best way to monitor treatment efficacy.

[Frequency of hypertension resistant to treatment and indication for renal denervation]. / Fréquence de l'hypertension résistante aux traitements et indication à la dénervation rénale.

OBJECTIVE: To evaluate in hypertensive patients followed in a specialized hypertension unit, the prevalence of subjects uncontrolled despite triple therapy including a diuretic. The aim is to estimate the percentage of hypertensive patients with an indication to renal denervation. METHOD: From a database of computerized medical records of a unit specialized in hypertension, it was extracted 144 consecutive cases of subjects treated and followed for at least 1year and having had a home pressure monitoring (HPM) on treatment, and if necessary a work-up for a secondary hypertension. The blood pressure (BP) was evaluated in office by automated method (after 2 and 8minutes) and with HPM (average of three measurements in the morning and evening for three consecutive days). RESULTS: The population has the following characteristics: age 62 with 26% over 70years, treated dyslipidemia (39%), treated diabetes (11%), adrenal hypertension treated medically (14%), severe renal failure (3%). The means of treatment are: a monotherapy (33%), bitherapy (35%), triple therapy (17%), quadritherapy (7%), pentatherapy or more (1%), spironolactone (45%), thiazide diuretics (49%). The uncontrolled hypertension was observed in 26% if the BP is evaluated with HPM, in 52% if the BP is evaluated at the office after 2minutes of rest and 7% if the BP is evaluated after 8minutes of rest (P<0.01). In patients treated with at least a tritherapy in association with a diuretic, an uncontrolled hypertension was observed in 5% if the BP is evaluated with HPM. Failure to control for the SBP is the cause of 80% of resistant hypertension. CONCLUSION: The frequency of resistant hypertension is 5% of hypertensive patients followed in a specialized hypertension unit when guidelines are applied in the case of uncontrolled hypertension. These results indicate that the indication for renal denervation affects only a small percentage of patients treated for hypertension.

Is psychosis in DSM-IV mania due to severity? The relevance of selected demographic and comorbid social-phobic features.

OBJECTIVE: We tested whether factors other than episode severity contributed to psychosis in mania. METHOD: Psychiatrists collected systematic clinical data on 1090 hospitalized DSM-IV manic patients in France, and completed the Mania Rating Scale (MRS) and the Scale for the Assessment of Positive Symptoms (SAPS). RESULTS: Using DSM-IV specifiers, 21.9% were non-severe, 28.2% severe without psychosis, and 49.9% severe with psychosis. On the MRS, patients with psychosis scored significantly higher (P < 0.0001) than non-severe, but did not differ from the severe without psychosis. We found significant correlations between both the Hallucination and the Delusion subscores of the SAPS and the MRS, as well as correlations between age, single marital status, comorbid social phobia and psychotic mania. CONCLUSION: Apart from episode severity, social isolation - associated with younger age, single marital status and social phobia - seems to make a contribution to the origin of manic psychosis largely independent from such severity.

[Methadone: from pharmacokinetic profile to clinical pharmacology]. / Méthadone: de la pharmacocinétique à la pharmacologie clinique.

In January 2002, the official French methadone legislation prescription was modified. Thus, the number of clinicians authorized to introduce methadone substitution was increased. Knowledge of the pharmacokinetic and pharmacological properties of this compound remains particularly important for its appropriate prescription. Bearing this in mind, we linked methadone pharmacokinetics to its pharmacological use in this article. METHADONE PHARMACOLOGY: Methadone is a synthetic opiate. Its mean bioavailability is around 75%. Cytochrome P450 3A4 and 2D6 are involved in its hepatic metabolism. Its volume of distribution is of around 4 L/kg. The value of half-life elimination is of around 22 hours. These pharmacokinetic properties (long half-life, steady state concentration) are in favour of substitution use of this opiate. In practice, clinicians progressively introduce this substitution therapy to reach 80 mg +/- 20 mg per day, once daily. Therapeutic clinical goals are mainly to reduce craving, withdrawal symptoms, and to manage psychosocial problems and psychiatric co-morbidity. Practitioners should bear the latter in mind once substitution therapy has been appropriately initiated and stabilized. However, wide, interpatient, interindividual variability impacts on pharmacokinetic parameters. Subjects may be either high or poor metabolizers. Thus, bioavibility ranges from 36 to 100%. Induction or inhibition of CYP450 significantly modifies methadone pharmacodynamic properties. Genetic variability and medication can induce non response to substitution, craving, or withdrawal symptoms. PHARMACOLOGICAL INTERACTIONS: We describe here a large number of medications involved in pharmacokinetic or pharmacological interactions. Classical enzymatic inductors, such as antiepileptic molecules (phenobarbital, carbamazepin), antituberculosis compounds (rifampicin), or antiretroviral therapy (efavirenz, nevirapin, ritonavir), could possibly lead to respiratory depression for example. Metabolism inhibitors such as selective serotonin reuptake inhibitors (fluvoxamine, fluoxetine, paroxetine, sertraline) or antifungals of the azol groups could enhance plasma concentration and may sometimes lead to respiratory depression or death. Nevertheless, clinicians should know methadone pharmacokinetic properties and pharmacological interactions for the optimal opiate-dependant patients' management. CLINICAL USE: Clinicians can use plasma concentrations as a useful indicator to reach substitution goals. The methadone plasmatic target value of 400 microg/ml can be recommended for therapeutic drug monitoring. This dosage not only facilitates interaction detection, but also hand encourages communication with the patient.

Patterns of prescription of four major antipsychotics: a retrospective study based on medical records of psychiatric inpatients.

PURPOSE: (1) To identify factors associated with the choice among the three atypical antipsychotics available in France (amisulpride, olanzapine, risperidone) and the typical antipsychotic of reference: (haloperidol), (2) to compare psychotropic co-prescription rates according to antipsychotic. METHODS: All antipsychotic prescriptions including at least one of the four antipsychotics (n=421) for all inpatients (n=372) hospitalized 24 hours or more in the 6 months previous to the start of the study were included (2003). Data were obtained from medical records and psychiatrist interviews. Of the prescriptions, 13.3% included amisulpride, 39.4% olanzapine, 27.3% risperidone, and 20.0% haloperidol. Mean dosages were 142 mg (amisulpride), 15 mg (olanzapine), 4.5 mg (risperidone), and 19.5 mg (haloperidol). RESULTS: Differences between antipsychotics were observed in relation to patients' age (younger patients prescribed amisulpride and olanzapine, p=0.04), diagnoses (affective disorders more frequently prescribed olanzapine and risperidone, p=0.005), and mode of hospitalization (admissions under constraint more frequently prescribed haloperidol, p<0.001). Antidepressant and anxiolytic-hypnotic co-prescription rates were lower with haloperidol than with atypicals. Mood-stabilizer co-prescription rates were higher for olanzapine and risperidone than for haloperidol and amisulpride. Anticholinergic co-prescription was higher with haloperidol than with atypicals (p<0.001). CONCLUSIONS: Haloperidol was prescribed to a minority and targeted male patients hospitalized under constraint, using high dosages. Type and rate of co-prescriptions varied considerably between haloperidol and atypicals.

[Assessment of metabolic impairments inducted by atypical antipsychotics among schizophrenic patients]. / Evaluation des troubles du métabolisme induits par les antipsychotiques atypiques chez les patients schizophrènes.

Conventional and atypical antipsychotics are known to induce weight gain, cause glucose and lipid impairments among schizophrenic patients. These impairments contribute to the intrinsic risk factors linked to the psychiatric pathology (sedentary state, nicotin addiction, diabetes) increasing numbers of cardiovascular complications. We propose to study ponderal modifications and presence of metabolic abnormalities in a population of schizophrenic patients treated by conventional or atypical antipsychotics, depending on the received treatment; 32 patients, whose schizophrenia diagnosis had been previously made, were consecutively included over a 4 months period. They were divided into three groups: patients treated by conventional antipsychotics (n = 6), by atypical antipsychotics (n = 16) or by a combination of both (n = 10); 6 patients (18%) display overweight problems, 4 patients (12.5%) got hypertriglyceridemia and 4 other patients (12.5%) have hypercholesterolemia. No particular drug could be directly targeted, partly because of the restricted size of our sample, but the patients presenting metabolism impairment were treated by atypical antipsychotic. The observance of these abnormalities is reflected in publications and lead to some antipsychotic treatments monitoring rules.

[Schizophrenia, diabetes mellitus and antipsychotics]. / Schizophrénie, diabète et antipsychotiques.

During the last years, a contribution of antipsychotic drugs in the increase of diabetes prevalence in schizophrenic population has been repetitively suggested. The debate focused mainly on the second-generation antipsychotics. The analysis of the scientific literature indicates however that this discussion is not recent and an increase of diabetes prevalence in schizophrenic populations was already described before the introduction of neuroleptics. Then, after the introduction of the first neuroleptics in the 1950s, an increase of diabetes prevalence was reported among treated patients and the same alarms occurred in the 1990s after the introduction of second-generation antipsychotics. These treatments were related to an increase of glucose tolerance impairment, type II diabetes and diabetic acidoketosis. Recent epidemiological studies have confirmed the increase prevalence of diabetes in schizophrenic patients, particularly in schizophrenic patients before any antipsychotic treatment. Among the suggested mechanisms, there are sedentary life (due to hospitalisation and sedative effects of neuroleptics), food imbalance, shared genetic factors for diabetes and schizophrenia. Moreover, the frequency of the metabolic syndrome is increased in schizophrenic populations. This syndrome associates blood glucose increase, lipid metabolism disorders and android obesity. This could explain--via an increase of the cortisol production--the increase of mortality due to cardiovascular diseases observed in schizoprhenic patients. Thus, it seems well established that schizophrenia is associated with an increased risk for diabetes. It is however more difficult to evaluate the role of antipsychotic treatment as a causative factor of diabetes. Indeed, there are many published case reports or diabetes or diabetic acidoketosis after an antipsychotic treatment, but the level of evidence in controlled trials is low. Many studies were performed on large databases, but were retrospective and subjected to many flaws: concomitant diseases not taken into account, diabetes status evaluated by drug consumption, unknown diabetes status before antipsychotic treatment, etc. In the few prospective studies performed, no significant differences between the atypical versus typical antipsychotics were evidenced for new cases of diabetes. Moreover, in general population, the glucose tolerance impairment is underdiagnosed and it is estimated that people with a glucose tolerance impairment have a 5-10% annual risk of type II diabetes. Thus, this concern has to be replaced among the world epidemic increase of diabetes and in a population of patients whose the disease itself and life style are risk factors for diabetes. Some studies have explored the pathophysiological mechanisms that could support a diabetogenic effect of antipsychotics. Although it does not seem to be a direct effect of antipsychotics on insulin secretion by pancreatic cells, body weight increase has been evidence for both typical and atypical antipsychotics. However, it remains unclear whether this weight increase is responsible for a visceral adiposity, which is a risk factor better fitted to the cardiovascular mortality tha the body weight itself. Other hypotheses involving an effect on the leptin, which regulates the appetite, have been proposed. In waiting of new prospective controlled studies, and without denying the impact of antipsychotics on the glucose and lipid metabolisms (on the weight increase, for example), it should be recognized that the benefit/risk ratio remains largely in favour of the treatment, particularly for the atypical antipsychotics, more effective and better tolerated at the neurological level than the conventional antipsychotics. One of the benefits of the mainly articles in professional media about this concern is to draw attention on the metabolism disorders in schizophrenic patients, which are important risk factor of their frequent cardiovascular surmortality whatever the causes. Consequently, it is advised to monitor glucose and lipid metabolisms of schizophrenic patients before and during their treatment (body weight, fast blood glucose, blood cholesterol and triglycerides). In conclusion, schizophrenic patients are a population with an increased metabolic risk, which is a cause of their increased mortality. Although these data are known since a long time ago, this population does not benefit from the same metabolic follow-up than the non-schizophrenic population. The debate on the possible relationship between diabetes and antipsychotics should be also taken as a helpful recall of the necessity to follow simple rules of prevention and monitoring in this at-risk population. This should make it possible to preserve the benefit of the antipsychotics, the contribution of which in the treatment of schizophrenia is not any more to demonstrate.

[Comparison of two assessment tools of antidepressant side-effects: UKU scale versus spontaneous notification]. / Comparaison de deux outils de mesure des effets indésirables d'un traitement antidépresseur: la notification spontanée et l'échelle UKU.

BACKGROUND AND AIM OF THE STUDY: Overall, the efficacy of the newer antidepressants: serotonin selective reuptake inhibitors (SSRI), selective serotonin/norepinephrine reuptake inhibitor (SNRI), noradrenergic and specific serotonergic antidepressant (NaSSA) and tianeptine is similar to that of the tricyclics, and so their acceptability/safety becomes a selection criterion for the clinician. However, side-effect assessment comes up against several difficulties: distinguishing between somatic symptoms caused by the depression and those caused by the treatment -- which assessment tool to use (spontaneous notification, standardized scales that are not specific for the side effects caused by psychotropic drugs, standardised scales specific for the side effects caused by psychotropic drugs, meta-analysis, etc.) -- which data sources to consult (anecdotal reports, reviews, prospective studies), and which data set to use, etc. As a result, the question of the exhaustiveness and reliability of the data consulted by the clinician can arise. We therefore conducted a comparative study in patients treated with these newer antidepressants, of 2 antidepressants side-effect assessment tools: spontaneous notification (SN) versus the UKU scale, a standardised scale specific for the side effects of psychotropic drugs. METHODOLOGY: The depressed outpatients were selected from a psychiatric unit in a French psychiatric hospital and from a non-hospital consulting room. The main inclusion criteria were: male or female subjects, suffering from major depression without melancholia or psychotic features or suffering from mood disorders (according to DSM IV criteria), who had been treated for at least 4 weeks with one of the newer antidepressants. The main exclusion criteria were: any other psychiatric disorder, a serious physical disorder, treatment with neuroleptics, mood-changing drugs or other antidepressants, and patients who were not able to understand the questionnaire. The investigation was carried out by a clinical pharmacist. RESULTS: Fifty patients were included in the study. There were 18 men and 32 women. The mean age was 53.5 15.9 years [22 - 77], the mean period of treatment was 24 30.5 months [1 - 127] and 52% of the patients received concomitant medication with anxiolitic or hypnotic drug(s). The percentage of patients who reported at least one side effect was significantly higher for the UKU scale than for SN (84% vs 58%, p<0.01). The ratio between SN and UKU scale scores was 2/3. A similar pattern was found for the total number of side effects (n=177 vs n=47, p<0.001). The ratio between the total number of side effects for the SN and UKU scale was 1/4. The side effects were divided into five subgroups: psychiatric, neurovegetative, sexual, neurological and others. In all these subgroups, the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. The values were as follows: psychiatric (n=44 vs n=15, p<0.001), neurovegetative (n=59 vs n=15, p<0.001), sexual (n=36 vs n=10, p<0.001), neurological (n=11 vs n=2, p<0.001) and other side effects (n=27 vs n=5, p<0.001). Nineteen side effects were only reported when SN was used (for example: dry eyes, incompatibility with alcohol, euphoria...). Twenty-four side effects were only reported when the UKU scale was used (for example: increased libido, loss of bodyweight...). The side effects had no impact on daily life in most of 80% of the patients; there was no significant difference between the patient's assessment of the discomfort caused by side effects and the clinician's assessment. In 90% of cases, the side effects did not lead to any change in the treatment. DISCUSSION: The findings of this study show that the collection of data regarding side effects depends on the assessment tool used: the number of side effects reported was significantly higher when the UKU scale was used than when SN was used. However, this finding must viewed with caution, because it has been showed that checklists can induce symptoms in suggestible patients. Neurovegetative troubles are the most commonly reported side effects, and neurological troubles the least often reported. This matches the tolerability profile of these antidepressants. The disorders that were least frequently spontaneously reported were the neurological, sexual and "other" side effects. These emerged only when the clinician asked the patient about them. The 19 side effects that were only reported when SN was used were side effects that were not included in the UKU scale or that had not been present during the three days before we started the investigation. The 34 side effects that were only reported when the UKU scale was used were either side effects with no apparent link with the treatment (for example: micturition troubles) or embarrassing effects (such as increased libido). CONCLUSION: Our findings show that the collection of data on side effects depends on the assessment tool used. These findings need to be confirmed by large-scale comparative studies, and the standardization of the assessment of side effects is a question that needs to be raised.

[Minimizing the risks associated with QTc prolongation in people with schizophrenia. A consensus statement by the Cardiac Safety in Schizophrenia Group]. / Comment minimiser les risques associés à un allongement significatif de l'intervalle QTc chez les personnes souffrant de schizophrénie. Recommandations consensuelles du Cardiac Safety in Schizophrenia Group.

Schizophrenia is one of the most debilitating mental illnesses, complicated by an increased incidence of suicide amongst patients compared with the general population. A recent report has also demonstrated a 33% increase in -relative risk of death associated with circulatory disease, indicating that the latter may be a more critical factor than either suicide or accidental death in this population. Indeed, the average life expectancy of a person with schizophrenia is currently approximately a decade less than that of the general population. Additionally, it has been shown that in over 50% of people with schizophrenia, there is a reduction in their chance of reaching psychosocial goals. Since the arrival of the first antipsychotic drugs in the middle of the last century, the outlook for patients with schizophrenia has improved markedly. In particular, the introduction of the new generation (atypical) class of antipsychotic agents in the 1980s and 90s has resulted in a significant reduction in the incidence of violent and aggressive episodes in treated patients. A better side-effect profile of these drugs, especially reduced extra pyramidal symptoms (EPS), has resulted in improved patient outcomes and the possibility of good long-term control of the disorder. However, while the introduction of antipsychotic agents has undoubtedly revolutionised the prognosis for patients with schizophrenia, these medications are not without their own problems. One of the concerns to emerge over the last fifteen years is unpredictable, sudden and unexplained death in patients taking antipsychotic drugs. The cause of sudden death in this population is controversial and the role of drugs is not clear. People with schizophrenia also appear to be at higher risk of cardiovascular disease compared with the general population. Many factors may play a role in this including a higher prevalence of smoking, poorer diet, more sedentary lifestyle and a greater likelihood of alcoholism and substance abuse. However, it is possible that the impact of adverse effects on the cardiovascular system related to certain antipsychotic drug use may well increase the prevalence of mortality and morbidity due to cardiovascular events and may also play a significant role in the reduced life expectancy of the patient with schizophrenia. The range of mechanisms whereby antipsychotic drugs can influence cardiovascular function is very broad and includes: receptor blockade; conduction disturbance (eg bundle branch block); delayed ventricular repolarisation (prolonged QTc interval); left ventricular dysfunction; sinus node abnormalities; myocarditis; postural hypotension; polydipsia-hyponatremia syndrome; weight gain; glucose intolerance. Of these, QTc interval prolongation, with the risk of progression to the potentially fatal ventricular tachyarrhythmia Torsades de Pointes (TdP), is of particular concern as this arrhythmia is unpredictable and difficult to manage. Coupled with these clinical concerns are regulatory issues regarding several compounds that have received warnings or been withdrawn from the market. Recently, there has been no clear guidance for psychiatrists regarding QTc interval prolongation and TdP. This document seeks: 1) to explore drug-induced ventricular arrhythmias with particular emphasis on QTc interval prolongation as a warning of increased vulnerability, 2) to provide guidelines on the therapeutic management of the patient with schizophrenia to minimize the risk of iatrogenic cardiotoxicity. Several guidance documents have previously been published in this area including the report published by the UK Working Group of the Royal College of Psychiatrists' Psychopharmacology Sub-Group in 1997, and the policy document on the potential for QTc prolongation and proarrhythmia by non-antiarrhythmic drugs published in June 1999 under the auspices of the European Society of Cardiology. This document seeks to supplement currently published guidelines.

Respective potencies of Botox and Dysport: a double blind, randomised, crossover study in cervical dystonia.

OBJECTIVES: Botulinum toxin type A is a potent neuromuscular paralyzing agent used in various disorders including cervical dystonia. Two preparations of botulinum toxin are now commercially available ( Dysport and Botox), but much controversy remains about their respective potencies. The aim of the study was to compare the efficacy of Botox with two different ratios of Dysport. METHODS: A double blind, randomised, three period cross over study involving 54 patients with cervical dystonia was performed. The patients received the following treatments in a randomised order: Botox at the usually effective dose, Dysport at a dose of 1:3 (conversion factor of 3 between Botox and Dysport units-that is, one Botox unit=three Dysport units) and at a dose of 1:4 (conversion factor of four). The improvement of the Tsui (primary outcome criteria) and of the TWSTRS pain scales between baseline and a control visit 1 month after each of the three injections, as well as the incidence of adverse events, were assessed. RESULTS: Comparison of the Tsui scores and of the TWSTRS pain scores showed a better effect on impairment and pain with Dysport 1:3 (p=0.02 and 0.04, respectively) and 1:4 (p=0.01 and 0.02, respectively) than with Botox. The number of adverse events was higher with both Dysport treatments. The most frequent adverse event was dysphagia, found in 3%, 15.6%, and 17.3% (Botox, Dysport 1:3 and 1:4, respectively) of the patients. No adverse event required withdrawal of therapy or specific management. CONCLUSIONS: Dysport 1:3 (and Dysport 1:4 to a greater extent) is more efficient than Botox for both impairment and pain in cervical dystonia although with a somewhat higher incidence of minor adverse effects. This strongly suggests that the most appropriate conversion factor between Botox and Dysport units is less than 3 in cervical dystonia.

[Antipsychotic drugs and cardiovascular safety: current studies of prolonged QT interval and risk of ventricular arrhythmia]. / Antipsychotiques et sécurité cardio-vasculaire: données actuelles sur les allongements de l'intervalle QT et le risque d'arythmies ventriculaires.

Cardiovascular mortality is higher among schizophrenic patients than in the general population, and it is possible that most unexplained sudden deaths among these patients are due to ventricular arrhythmias for which antipsychotic drugs are either the cause or a predisposing factor. Most antipsychotic agents show electrophysiological effects resembling those of class 1a antiarrhythmic agents, and may be responsible for prolonging the QT interval, potentially going on to cause torsades de pointes. Some of the antipsychotic agents carry a high risk of arrhythmias, related to their effects on the QT interval. These include thioridazine, pimozide, sultopride, droperidol, and to a lesser extent haloperidol and chlorpromazine. In the case of the new atypical antipsychotic agents, it is possible to rank the risks of different drugs, with sertindole (now withdrawn from sale) having the highest risk, and ziprasidone somewhat lower, followed by risperidone and finally by quetiapine, clozapine and olanzapine which have negligible effects on the QT interval. A number of risk factors have been demonstrated, particularly: hypokalaemia and hypomagnesaemia, bradycardia, congenital long QT syndrome, and any underlying cardiac pathology. Lastly, the risk associated with any given antipsychotic agent is increased if it is combined either with any other drug known to prolong the QT interval and provoke torsades de pointes, or with any drug capable of inhibiting the hepatic metabolism of the antipsychotic agent. A list of such drugs is provided, together with advice on the action to be taken when prescribing an antipsychotic agent to a patient with a long QT interval.

[Pharmacokinetics of SSRI antidepressants: half-life and clinical applicability]. / Pharmacocinétique des ISRS: notion de demi-vie d'élimination et implications cliniques.

The selective serotonin reuptake inhibitors (SSRIs) antidepressants are at present time the most useful for the treatment of depression. SSRIs exhibit differences in potency of inhibiting serotonin reuptake, although the differences do not correlate with clinical efficacy. There are substantial pharmacokinetic differences among the five SSRIs, fluvoxamine, fluoxetine, paroxetine, sertraline and citalopram. Optimum use of these drugs requires a working knowledge of these differences. Among these pharmacokinetic parameters, half-life and metabolism pathways are the most relevant. There are substantial differences in term of their half-life between fluoxetine and others SSRIs. The half-life of fluoxetine and its active metabolite norfluoxetine is respectively 2 to 4 days and 7 to 15 days, more extended than other SSRIs (approximately 1 day). The extended half-life of fluoxetine and its active metabolite may be an advantage in the poorly compliant patient and may offer a potential safety advantage over shorter-acting SSRIs, with respect to abrupt discontinuation of therapy. Conversely, this long half-life needs a long period of wash-out (5 weeks) before introducing other drugs (MAOIs, sumatriptan) which can interact with serotonin function and can lead to the serotoninergic syndrome. SSRIs are potent inhibitors of the hepatic isoenzyme P450-2D6 and would be expected to have effects on the clearance of drugs metabolized by this enzyme. Paroxetine is the most potent inhibitor, followed by fluoxetine, sertraline, citalopram and fluvoxamine. The metabolite elimination of citalopram, paroxetine and fluvoxamine is delayed by renal disease and dosages should be lowered in elderly patients. Conversely the pharmacokinetic of fluoxetine and sertraline are not affected by either age or renal impairment and, for fluoxetine, by obesity.

[Leponex: experience of the hospital pharmacist]. / Leponex: l'expérience du pharmacien hospitalier.

Clozapine's monitoring, with a co-responsibility between psychiatrists and pharmacists, is very efficient for the prevention of neutropenia's side effects. This intensive drug safety has lowered the cases of agranulocytosis in France to a 0.5% prevalence. However the cost of clozapine led to a strict estimation for health expenditures. Our study, performed in a university department of psychiatry in Sainte-Anne Hospital (Paris), has included 14 patients treated with clozapine for at least 12 months and has displayed a decrease of 10% in their annual global cost, comparing with the same group of patients treated by classical neuroleptics during the preceding year. This global cost includes the treatment, the blood monitoring and the cost of different hospital or community cares. Quality of life, in the clozapine group, was much improved, as illustrated by the shortened full time hospitalization which was followed at an earlier stage by community care and earlier social readaptation.

[Leponex: experience of the hospital pharmacist]. / Leponex: l'expérience du pharmacien hospitalier.

Clozapine's monitoring, with a co-responsibility between psychiatrists and pharmacists, was very efficient for the prevention of neutropenia's side effects. This intensive drug safety has lowered the agranulocytosis' cases in France to a 0.5% prevalence. However the cost of clozapine led to a strict estimation for Health expenditures. Our study, trained in an university department of psychiatry in Sainte-Anne Hospital (Paris), has included 14 patients treated with clozapine during at least 12 months and has displayed a decrease of 10% in their annual global cost, comparing to the same group of patients treated by classical neuroleptics during the preceding year. This global cost includes the treatment, the blood monitoring and the cost of different hospital or community cares. Quality of life, in clozapine group, was much improved as illustrated by lowing full time hospitalization relayed earlier by community care and precocious social readaptation.