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Biomedical subjects

R Dardennes

Publications and source records attributed to R Dardennes.

At least 19 recordsLinked to original sources
PubMed2005

Olanzapine for schizophrenia.

BACKGROUND: Olanzapine is an atypical antipsychotic reported to be effective without producing disabling extrapyramidal adverse effects associated with older, typical antipsychotic drugs. OBJECTIVES: To determine the clinical effects and safety of olanzapine compared with placebo, typical and other atypical antipsychotic drugs for schizophrenia and schizophreniform psychoses. SEARCH STRATEGY: We updated the first search [Biological Abstracts (1980-1999), The Cochrane Library (Issue 2, 1999), EMBASE (1980-1999), MEDLINE (1966-1999), PsycLIT (1974-1999) and The Cochrane Schizophrenia Group's Register (October 2000)] in October 2004 using the Cochrane Schizophrenia's Group's register of trials. We also searched references of all included studies for further trials, and contacted relevant pharmaceutical companies and authors. SELECTION CRITERIA: We included all randomised clinical trials comparing olanzapine with placebo or any antipsychotic treatment for people with schizophrenia or schizophreniform psychoses. DATA COLLECTION AND ANALYSIS: We independently extracted data and, for homogeneous dichotomous data, calculated the random effects relative risk (RR), the 95% confidence intervals (CI) and the number needed to treat (NNT) on an intention-to-treat basis. For continuous data we calculated weighted mean differences. MAIN RESULTS: Fifty five trials are included (total n>10000 people with schizophrenia). Attrition from olanzapine versus placebo studies was >50% by six weeks, leaving interpretation of results problematic. Olanzapine appeared superior to placebo at six weeks for the outcome of 'no important clinical response' (any dose, 2 RCTs n=418, RR 0.88 CI 0.8 to 0.1, NNT 8 CI 5 to 27). Although dizziness and dry mouth were reported more frequently in the olanzapine-treated group, this did not reach statistical significance. The olanzapine group gained more weight. When compared with typical antipsychotic drugs, data from several small trials are incomplete. With high attrition in both groups (14 RCTs, n=3344, 38% attrition by six weeks, RR 0.81 CI 0.65 to 1.02) the assumptions included in all data are considerable. For the short term outcome of 'no important clinical response', olanzapine seems as effective as typical antipsychotics (4 RCTs, n=2778, RR 0.90 CI 0.76 to 1.06). People allocated olanzapine experienced fewer extrapyramidal adverse effects than those given typical antipsychotics. Weight change data for the short term are not statistically significant but results between three to 12 months suggest a clinically important average gain of four kilograms for people given olanzapine (4 RCTs, n=186, WMD 4.62, CI 0.6 to 8.64). Twenty three percent of people in trials of olanzapine and other atypical drugs left by eight weeks; 48% by three to12 months (11 RCTs, n=1847, RR 0.91 CI 0.82 to 1.00). There is little to choose between the atypicals, although olanzapine may cause fewer extrapyramidal adverse effects than other drugs in this category. Olanzapine produces more weight gain than other atypicals with some differences reaching conventional levels of statistical significance (1 RCT, n=980, RR gain at 2 years 1.73 CI 1.49 to 2.00, NNH 5 CI 4 to 7). There are very few data for people with first episode illness (1 RCT, duration 6 weeks, n=42). For people with treatment-resistant illness there were no clear differences between olanzapine and clozapine (4 RCTs, n=457). AUTHORS' CONCLUSIONS: The large proportion of participants leaving studies early in these trials makes it difficult to draw firm conclusions on olanzapine's clinical effects. For people with schizophrenia it may offer antipsychotic efficacy with fewer extrapyramidal adverse effects than typical drugs, but more weight gain. There is a need for further large, long-term randomised trials with more comprehensive data.

Antipsychotic Agents↗
PubMed2004

[Prevalence of depression in multiple sclerosis: a review and meta-analysis].

INTRODUCTION: The aim of this paper was to review and summarize the data about the frequency of depression during multiple sclerosis (MS). MATERIAL AND METHODS: We performed a metaanalysis to combine the results of the studies which compared the frequency of depression in MS patients with the prevalence in patients with other chronic diseases. Eight controlled studies were identified via manual and computerized search of the Medline and PsychInfo databases. Given the various ways these studies reported their results, we used statistical procedures based on the combination of significance levels (the method of adding Zs and the method of adding ts). An additional statistical procedure, Cohen's d, was performed to estimate the effect of size. RESULTS: The two statistical methods yielded highly significant summary statistics: z=4.15 and z=3.98, respectively (p<0.0001). The effect of size (Cohen's d), which ranged from 0.02 to 0.70 with an average of 0.29 (95 percent confidence interval: 0.09-0.49), can be considered as medium and hence clinically meaningful. CONCLUSION: These results suggest that the association between MS and depression is specific, that is not just casual nor due to the nonspecific factors inherent in every chronic disease.

Clinical Trials as Topic↗
PubMed2003

Alexithymia in insulin-dependent diabetes mellitus is related to depression and not to somatic variables or compliance.

OBJECTIVES: To assess the prevalence of alexithymia in insulin-dependent diabetic mellitus (IDDM) outpatients. To examine whether alexithymia is associated with diabetic somatic variables, depression, and compliance. METHOD: Our sample comprised 69 diabetic outpatients followed in a university hospital. We assessed the prevalence of alexithymia (26-item Toronto Alexithymia Scale, TAS-26) and the relationships among alexithymia, depression (13-item Beck Depression Inventory, BDI-13), somatic diabetic variables (glycosylated hemoglobin, number of mild or severe hypoglycemia, somatic complications), and compliance (observer-rater scale completed by diabetologist). RESULTS: The prevalence of alexithymia in IDDM patients was low (14.4%). Alexithymia and depression, as measured by TAS-26 and BDI-13 scores, respectively, correlated with each other. Alexithymia was not correlated with glycemic control, somatic complications, or compliance. CONCLUSION: In our sample, alexithymia was related to depression and not to somatic factors or compliance.

Adult↗
PubMed1999

Comparison of the cost-effectiveness of milnacipran (a SNRI) with TCAs and SSRIs: a modeling approach.

A simulation model based on the theory of clinical decision analysis was used to compare outcomes and costs when treating patients with major depressive episodes using either a selective serotonin re-uptake inhibitor (SSRI) or a tricyclic antidepressant (TCA), in comparison with milnacipran (a serotonin), and a norepinephrine re-uptake inhibitor (SNRI). The clinical data used were taken from published meta-analyses. This analysis supports: (1) a comparable efficacy of milnacipran and TCA with a better tolerance; and, (2) an advantage of milnacipran over SSRI for efficacy with a comparable tolerance. Based on these findings, a decision tree was constructed with the assistance of a panel of psychiatrists in order to provide a model of usual clinical practice. Estimates not available from clinical studies were obtained either from literature analysis or from the panel. Economic appraisal was performed according to the viewpoint of the French national sickness fund (sécurité sociale), and expenditure assessment was limited to direct costs (hospitalizations, antidepressant medications, visits, and laboratory tests). The results suggest that milnacipran is a cost-effective alternative: the expected cost of treatment per depressive episode is lower than either a French representative panel of TCAs (a saving of 288 FF), or SSRIs (a savings of 961 FF). The expected length of clinical remission is slightly higher than comparators. The robustness of these findings was supported by sensitivity analyses.

Adrenergic Antagonists↗
PubMed1998

[Current trends in the therapeutic use of thymic regulators].

LITHIUM: Current research in the field of dysthymia therapy is dominated by the discovery of alternatives to lithium. Lithium remains however the gold standard, whether used alone or combination with anti-seizure drugs such as carbamazepine, valpromide or valproate. The most recent data on lithium therapy emphasize the need for precaution in case of pregnancy. New interactions, particularly with converting enzyme inhibitors, have also been evidenced. Finally, like beta blockers, lithium should be tapered off progressively over a two-month period to avoid early relapse. OTHER TREATMENTS: New candidate drugs such as lamotrigine offer some promising perspectives. For severe states, long-term electroconvulsivotherapy can be proposed. Finally, drug therapy should be integrated into a structured psychotherapy program in order to favor the prevention of relapse and reduce the negative psychosocial consequences of mood disorders. Both the patient and close family and friends should participate in the psychotherapy; several methods have been developed with promising efficacy to be confirmed by controlled studies.

Anticonvulsants↗
PubMed1995

Comparison of carbamazepine and lithium in the prophylaxis of bipolar disorders. A meta-analysis.

BACKGROUND: This meta-analysis assessed the equipotency of carbamazepine and lithium prophylaxis in bipolar disorder. METHOD: We selected only randomised, double-blind, controlled studies comparing carbamazepine with lithium from a manual and computerised search, and subjected them to a quality inventory. Their statistical results were weighted by their quality score and combined. RESULTS: Four studies met our criteria, yielding, overall, P = 0.15. This result is not straightforward because the studies showed significant heterogeneity (P < 0.01). CONCLUSION: Differences in statistical power and sensitivity of outcome measure explain this heterogeneity and the conflicting results of the studies. Therefore, the prophylactic efficacy of carbamazepine remains questionable.

Bipolar Disorder↗
PubMed1990

Self-inhibiting action of nortriptyline's anti-immobility effect at high plasma and brain levels in mice.

Animals were treated acutely with 0, 2.5, 5, 10, 20 and 40 mg/kg nortriptyline (NT) 30 min before the tail suspension test (TST). They were sacrificed after test for evaluation of plasma and brain levels of NT. The anti-immobility effect increased with increasing doses and concentrations of the drug, reaching statistical significance (P less than 0.01, Dunnett test) at a dose of 20 mg/kg, 865 ng/ml in plasma and 11 micrograms/g in brain tissue. The anti-immobility effect was, however, blocked with the highest, non-toxic, concentrations. Results seem to indicate a biphasic curvilinear relationship between plasma and brain levels of NT and behaviour in mice.

Animals↗
PubMed1984

A quantitative Golgi analysis of the postnatal maturation of dendrites in the central nucleus of the inferior colliculus of the rat.

In this work, we used Golgi impregnation and computer assistance to analyze the quantitative development of the dendrites of neurons in the central nucleus of the inferior colliculus in the rat from 8 (P8) to 20 (P20) days of age, i.e., during the period of functional maturation of the auditory system. The number and length of the dendritic segments and the number of spines of a total of 516 impregnated cells were studied. The variations of both the mean number of peripheral dendritic segments and the mean dendritic domain area suggest that the dendritic tree of these cells is orientated preferentially in the sagittal plane before the onset of functional maturation, but undergoes a reorientation in the frontal plane during this critical period. The length of dendritic segments varies as a function of both the stage of the period of functional maturation and the order of magnitude of these segments. During the first stage, from P8 to P16, only proximal and intermediate segments lengthen, the distal segments increasing their length later from P16 to P20. The lengthening of the dendritic segments is associated with dramatic reabsorption of the dendritic spines on all dendritic segments and seems closely related to the functional maturation of the auditory pathways.

Animals↗
PubMedDate not supplied

[The costs of bipolar disorder].

INTRODUCTION: According to the estimates of the World Bank and the World Health Organization bipolar disorder is the sixth leading cause of handicap throughout the world. The burden of this disease is similar to the one of schizophrenia. But cost-of-illness studies are too seldom. Although preventive treatments of bipolar disorder are available for more than fifty years, their economic impact has rarely been studied. LITERATURE FINDINGS: This review shows that the yearly cost of bipolar disorder is between 10,000 and 16,000 euro (12,000 and 18,000 US dollars). Eighty percent are indirect costs, 15% are linked to hospitalization and 5% to drugs. Hospitalization costs are lower in Health Maintenance Organization or general population studies than in studies performed on populations receiving care from psychiatric institutions or with a low socio-economic status. DISCUSSION: The use of mood stabilizers has a substantial impact on direct costs which are halved and consequently on indirect costs. But different surveys all agree on the dramatic under-use of mood stabilizers which may be adequately prescribed to only a quarter of bipolar patients. CONCLUSION: Therefore, the optimization of mental health system resources should prompt incentives to better screen, diagnose, and treat patients with a bipolar disorder.

Anticonvulsants↗
PubMedDate not supplied

[determining factors of depression in multiple sclerosis: review of the literature].

Depression is considered to occur more frequently in multiple sclerosis than in other chronic organic disorders. The determining factors of this specific association have been appraised by most authors in a dichotomic manner, confronting organic to psychogenic hypotheses. To assess these hypotheses two investigational methods have been used in the literature: either the search for correlations between depression and other parameters linked to the neurologic process, or the comparison of the course of neurologic and thymic symptoms. Systematically scrutinizing this literature enabled us to discuss its findings as well as its methodologic and conceptual limitations.

Cognition Disorders↗
PubMedDate not supplied

[Prophylactic treatment of mood disorders: cost effectiveness analysis comparing lithium and carbamazepine].

Economic impact of lithium therapy has seldom been assessed, economic comparisons with alternative mood stabilizers are almost non existent. This economic evaluation of preventive treatment of mood disorders recurrences (whether unipolar or bipolar) compared lithium with carbamazepine, through data from a randomized controlled clinical trial. A retrospective analysis of medical files of index patients is included in this trial, with experts' global ratings. A brief survey checked for representativity of in-patients length of stay. The model compared two cohorts of patients followed-up for two years after prophylactic treatment had begun. Rates of recurrence and direct medical costs related to mood disorders (prophylactic treatment, treatment of recurrences and serious adverse effects) were assessed. Data extrapolation was necessary because of variable lengths of follow-up during the trial and was based on medical review of index patients. Assessment of consumed health care resources were derived from the available database of the clinical trial, when necessary practice guidelines and experts' opinions were added to the model. Costs were valued according to available french unit costs (Vidal, NGAP, and Comptes de la santé). Analysis only included direct costs. An estimate of mean cost of care of 15,404 French francs per year per patient was calculated. The components of health costs show that in-patient costs are the most important part of annual medical costs for mood disorders (70% of the total costs). Prophylactic medication costs accounted for only 6.9% of total costs. Comparison of prophylactic alternatives gave lithium a clinical benefit with 27% fewer recurrences than carbamazepine. Lithium led to an economic benefit of 4,280 French francs per year of treatment for a single patient. Robustness of this finding was assessed through a sensitivity analysis on estimate of length of stay. Total costs of treatment would be equal between lithium and carbamazepine if length of stay in hospital for lithium patients was increased by 51%. According to the cost-effectiveness analysis developed in this study, lithium should stay the "gold standard" of prophylactic treatment of recurrent mood disorders, and has both clinical and economic advantages compared to carbamazepine.

Adult↗
PubMedDate not supplied

[Clinico-economic assessment of milnacipran in the prevention of depressive episodes].

The objective of this study was to evaluate, for patients at risk of a new depressive episode, the net cost of maintenance therapy with milnacipran compared with a symptomatic treatment of further episodes. Using clinical decision analysis techniques, a Markov-state transition was constructed to estimate the 12 months direct costs of the two therapeutic strategies. Model construction and probabilities for performing the analysis were primarily based on a controlled phase III clinical trial demonstrating the prophylactic efficacy of milnacipran compared to placebo. Others parameters and unit costs were obtained from published sources. For each group (maintenance and episodic treatment groups), the model simulated the clinical evolution of patients on 6 successive 2-months cycles. Costs were affected for each health state period (remission, depression, abandonment of health care, suicide). The baseline analysis showed the mean costs per patient and year were 627 FF (105 US$) higher for maintenance treatment. Sensitivity analysis suggested that costs were equal under a 25% rate of hospitalization hypothesis for a depressive episode. Maintenance costs were 1,587 FF (265 US$) lower than episodic treatment costs for depressed subjects with a good initial response to milnacipran (HDRS-21 score at remission < 5); this economic benefit remained under a lower rate of hospitalization hypothesis (12%). Based on the study assumptions, maintenance treatment with milnacipran appears to be clinically and economically justified for patients at high risk of hospitalization when having a recurrence, and even more for patients with an excellent initial acute response.

Acute Disease↗
PubMedDate not supplied

[Tricyclic antidepressants dosage and depressed elderly inpatients: a retrospective pharmaco-epidemiologic study].

UNLABELLED: It is recommended to reduce by one half the dosages of tricyclic antidepressants for patients over 65 years of age, in order to avert the occurrence of side-effects. The question we studied was: is it rightful to prescribe tricyclic antidepressants at half-dose to hospitalized elderly people? It is important, for the following reasons, to specify the rules of prescription of tricyclics in elderly patients: 1) The elderly population is on the increase; 2) There is a high prevalence of depression in elderly patients; 3) Depression exposes the elderly person to an increased risk of suicide; 4) Depression influences the prognosis of associated organic disorders 5) Recourse to tricyclic antidepressants is often necessary within this population group because of treatment resistant forms of depression which impose the use of different families of antidepressants and thus resort to tricyclics despite their lower tolerance. OBJECTIVES AND METHODS: The aim of our study is to evaluate whether the half doses of tricyclics recommended for an elderly person are sufficient in the case of an hospitalized patient. In order to provide some answer to this question, we have carried out a retrospective study. We have studied a sample of patients over-65, hospitalized at the Clinique des Maladies Mentales et de l'Encéphale, over a period of two years, with a ICD 10 diagnosis of moderate or severe intensity major depressive episode, and treated effectively with return to the euthymia. Creatinemia was prescribed systematically to each patient on entry. Only patients with normal renal function were retained. Laboratory norms are between 45 and 120 micromol/liter. The routine practice of imipraminic blood dosages allowed the comparison of blood levels obtained among patients treated with posologies inferior or equal to 75 mg/day imipraminic, to those treated with more than 75 mg/day imipraminic for a least a week. The percentage observed were compared using the Khi2 test with Yates correction. We retained the blood concentrations of the mother molecule for tertiary amines (imipramine, clomipramine and amitriptyline). The samples were taken after at least seven days of treatment at the same dose, and twelve to thirteen hours after the last taking. The maxima of blood levels were respectively: desipramine 200 ng/ml, clomipramine 258 ng/ml, imipramine 163 ng/ml, amitriptyline 129 ng/ml. Research for evidence in favor of toxicity (fall, delirium, convulsion, reduction of dosage before discharge), was done through revision of patients' clinical files. RESULTS: The test group consisted of 87 individuals. The average age was 71.3 years (SD: 5.09). Mean creatinemia was 83.73 mmol/l (SD: 26.89). The population thus selected divided into 4 groups: 61 (70.1%) were given imipraminics, 10 (11.5%) serotonin recapture inhibitors, 11 (12.7%) other antidepressants essentially of mianserine and 5 (5.7%) treatment by electroconvulsivotherapy. The imipraminics prescribed were desipramine, imipramine, clomipramine and amitriptyline. Among the 61 patients treated with imipramine, blood level dosage was practised on 48 patients (79%). Two subgroup were distinguished: 13 (21%) received dosages inferior ou equal to 75 mg/day and 48 (79%) superior to 75 mg/day. The mean dosage found in the sub-group of patients treated with dosages superior to 75 mg/day was 140 mg/day (SD: 30). The subgroup treated with dosages superior to 75 mg/day was more frequently monitored than the subgroup receiving dosages inferior or equal to 75 mg/day, respectively 40/48 (83%), and 8/13 (62%). This difference is statistically nonsignificant (p > 0.10). The analysis of dosages used showed that:--among the dosages effected upon patients receiving doses inferior or equal to 75 mg/day, 1 (12.5%) exceeded the maximal value of therapeutic range.--Among the dosages effected upon patients receiving dosages superior to 75 mg/day, 9 (22%) exceeded the maximal value of the therapeutic range. The difference is statistically significant (p < 0.001). On revision of clinical files, no patient presented any element that might lead one to suspect toxicity such as defined in "Objectives and Methods". CONCLUSION: In our study, patients were hospitalized and so benefited from closer observation than one can expect in outpatients. In this particular context, the dosages used are close to those advocated for the general population. With the elderly subject, the systematic prescription of half-dose tricyclics runs the risk of infratherapeutic dosage. It is thus preferable to resort to blood level dosage and to look for a maximum dose tolerance before concluding ineffectuality. This allows one to monitor whether the blood levels obtained are included in the therapeutic range; to avoid toxic doses and to check weak compliance in the elderly patient. Our findings do not oppose the use, for the elderly hospitalized depressive, of doses of imipraminics close to those of a young subject. To confirm these results it would be desirable to carry out o prospective study, including a systematised evaluation of adverse effects and a comparison of clinical effectiveness for parallel groups of elderly patients receiving different doses of imipraminic antidepressants.

Aged↗