[The course of the drug, clinical research and commercialization. Constraints, obstacles, delays and costs].
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Biomedical subjects
Publications and source records attributed to F Rouillon.
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The association of diabetes mellitus and mental illness, in particular, schizophrenia, has been remarked upon for over a century. Recent epidemiological studies have shown the age- and sex-matched prevalence of diabetes in patients with schizophrenia to be 1.5-2 times those in the general population. This difference is particularly noticeable in younger patients. The explanation for this finding probably resides in both environmental and biological factors. Patients with schizophrenia tend to be sedentary and have a poor diet, which are both known risk factors for diabetes. However, familial studies have indicated a heritable component to the risk of diabetes in patients with schizophrenia. A number of biological mechanisms have been proposed to explain this, including neuroendocrine changes and neurodevelopmental anomalies, but none are entirely satisfactory. In addition, it has been suggested that treatment with antipsychotic medication may potentially increase the risk of diabetes and account for some of the increased prevalence seen in patients with schizophrenia. It has been suggested that different antipsychotic drugs may differ in their ability to facilitate the emergence of poor glycaemic control in patients with schizophrenia. However, the situation is far from clear and more work is required to accurately assess the potential risk associated with different antipsychotic drugs.
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BACKGROUND: Traumatic events are frequently followed by an acute stress reaction that may develop into a post-traumatic stress disorder. An intervention called psychological debriefing has been proposed to prevent these disorders. Although this method is widely used at present, its preventive effect is controversial. This article consist in a review of the studies which evaluated psychological debriefing efficiency in the prevention of post-traumatic stress disorder and associated disorders in adults. METHOD: We carried out a bibliographical search on MEDLINE (1966-2001), PASCAL (1987-2001), EMBASE (1988-2001), FRANCIS (1984-2001) and SCIENCEDIRECT (1967-2001). The key words were posttraumatic stress disorder, debriefing, treatment, psychological follow up, and prevention. We selected the studies with the following criteria: adults, one psychological debriefing session in the Month following the event, inclusion of a control group, more than 20 persons per group and evaluation of psychological disorders with standardized instruments more than one Month after the trauma. RESULTS: Twenty nine studies were identified and 8 selected. Four studies did not show any intervention effect, 3 suggested a negative intervention effect, and 1 suggested a positive effect on anxiety, depressive symptoms and alcohol dependence. CONCLUSION: Psychological debriefing implies re-exposure through memory processes to the trauma, which can interfere with the natural course of adjustment and recovery. Several Authors have suggested that psychological debriefing may delay the diagnosis and thus the early treatment of post-traumatic stress disorder. Psychological debriefing may not be appropriate to all victims of every type of incident or trauma. We discuss the intervention and its design. This review did not show evidence for psychological debriefing efficiency, as a unique session, in the prevention of posttraumatic reactions. The design and the objectives may be re-examined. Further evaluations following rigorous methods are warranted.
AIMS: To investigate psychiatric disorders, somatic health, and professional effects in French train drivers having experienced a "person under train" accident, and somatic health and professional effects. METHODS: A total of 202 train drivers were evaluated several times: immediately after the event, three months later, and one, two, and three years later. These drivers were compared with 186 train drivers not exposed to that psychotraumatic shock. The evaluations relied primarily on the GHQ-28 and MINI questionnaires. RESULTS: In the exposed group, at the first evaluation, the prevalence of post-traumatic stress was 4%; scores > or =5 on the GHQ-28 were significantly higher than in the non-exposed group (32% versus 6%), for both the overall result and three sub-scores (somatic symptoms, anxiety and sleep, and psychosocial functioning). All these differences disappeared within a year. Vulnerability factors concerned prior traumas, acute and lasting life events, and the particular occupational situation where the driver is not accompanied but drives the train away alone in the aftermath of the accident. Over 95% of subjects had no short, medium, or long term impairment of their occupational fitness. CONCLUSIONS: Most of the psycho-behavioural disorders were observed in the immediate aftermath of the accident and disappeared within a year. The driver's occupational future does not seem to be affected by the "person under train" accident. Consideration of a traumatic accident as a job related risk and close psychological support of drivers after an accident probably increase the subject's ability to recover from the event.
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OBJECTIVE: Several, but not all epidemiological studies, have demonstrated a positive correlation between exposure to the virus during the second trimester of pregnancy and an increased risk to the infants for subsequently developing schizophrenia. The present study is the first be designed in France to examine the risk of gestational exposure to the influenza virus and subsequent development of schizophrenia. METHOD: A total of 974 adults with schizophrenia born between 1949 and 1981 were compared for risk of exposure to influenza with their non-schizophrenic siblings and with matched control patients. RESULTS: Significantly more schizophrenic subjects than controls (both groups) had been exposed to the influenza virus during the fifth month of pregnancy (OR=2.24, CI: 1.49-3.35, and OR=1.61, CI: 1.04-2.49). CONCLUSION: These results suggest that influenza infection during pregnancy is a neurodevelopmental risk factor for schizophrenia in adult life.
OBJECTIVES: Reinforcement and reward processes have been proposed as being an intermediate link between the risk for alcohol dependence and the gene coding for the dopamine receptor D2 (DRD2). This hypothesis remains open to speculation, and personality traits such as impulsiveness, a core dimension in addictive disorders, should also be taken into account. For instance, recent evidence in rats showed that DRD2 antagonists might increase impulsivity in decreasing the value of delayed rewards. METHODS: Considering the pro-impulsiveness role of ethanol observed in clinical practice and epidemiological studies, we analysed the Barratt impulsiveness scores in a sample of 92 alcohol-dependent French patients (57 men and 35 women), according to the TaqI A polymorphism of the DRD2 gene. RESULTS: A2/A2 and A1/A2 genotypes were significantly associated with a higher global impulsiveness than A1/A1 genotype (P=0.02 and P=0.03, respectively). CONCLUSIONS: We propose that reward-related impulsiveness may constitute a risk factor for alcohol dependence, and that this core temperament could be partly mediated by the DRD2 gene.
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BACKGROUND: Major depression is highly recurrent. Antidepressant maintenance treatment has proven efficacy against recurrent depression. AIMS: Comparison of prophylactic efficacy of citalopram versus placebo in unipolar, recurrent depression. METHODS: Patients 18-65 years of age with recurrent unipolar major depression (DSM-IV), a Montgomery-Asberg Depression Rating Scale score of > or =22 and two or more previous depressive episodes, one within the past 5 years, were treated openly with citalopram (20-60 mg) for 6-9 weeks and, if responding, continued for 16 weeks before being randomised to double-blind maintenance treatment with citalopram or placebo for 48-77 weeks. RESULTS: A total of 427 patients entered acute treatment and 269 were randomised to double-blind treatment. Time to recurrence was longer in patients taking citalopram than in patients taking placebo (P:<0.001). Prophylactic treatment was well tolerated. CONCLUSIONS: Citalopram (20, 40 and 60 mg) is effective in the prevention of depressive recurrences. Patients at risk should continue maintenance treatment at the dose necessary to resolve symptoms in the acute treatment phase.
BACKGROUND: Genes involved in the serotonin system are major candidates in association studies of suicidal behavior. In this case-control study we investigated whether the serotonin transporter (5-HTT) gene encoding the protein responsible for the reuptake of serotonin from the synapse after its release from serotonergic neurons is a susceptibility factor for suicidal behavior. METHODS: A functional polymorphism of the 5-HTT gene (a 44-base pair insertion/deletion in the 5-HTT-linked polymorphic region [5-HTTLPR]) was studied in a population of 237 consecutive patients with affective disorder (unipolar or bipolar) and 187 control subjects. Ninety-nine patients had attempted suicide at least once, of whom 26 made a violent attempt. RESULTS: No association was found between the "s" allele of the 5-HTTLPR and suicide attempt; however, there was a significant difference in allele distributions between patients who had made violent suicide attempts and control subjects. CONCLUSIONS: A genetic variant of the 5-HTT gene may predispose individuals to violent suicidal behavior. The precise phenotype associated with the 5-HTT gene is unclear, and therefore further studies are required to replicate these findings.
BACKGROUND: Depression is now seen as a chronic disabling condition that spans the patient's lifetime and creates significant medical, economic and quality of life consequences. METHODS: 500 depressed patients were treated with milnacipran for 6 months. A total of 214 recovered patients were randomised to receive either milnacipran (50 mg bid) or a matching placebo for a 1-year recurrence prevention phase. Recurrence rate was the primary criteria; quality of life (QoL) consequences were evaluated through a shortened version of the French Sickness Impact Profile (SIP), the Depression Impact Profile (DIP). RESULTS: Milnacipran demonstrated its ability to reduce recurrences (Odds-Ratio=1.5; P<0.05), with a more marked effect in recovered patients with few residual symptoms (Odds-Ratio=3.0). Responders who continued treatment with milnacipran had a dramatic improvement in their quality of life, although patients with residual symptoms still experienced some deterioration in their QoL (recreation, emotional, social, alertness and home assistance scores). Even recovered patients having zero scores on the Hamilton Depression Rating Scale-21 items (HDRS) had some QoL deterioration. The DIP emotional score was found to be more predictive of recurrence than the HDRS. Overall, the QoL was improved for those in the milnacipran group in comparison to placebo on the mobility, communication, psycho-social and total scores. LIMITATIONS: The QoL evaluation was a secondary criteria; no a priori sample size estimate was performed. The choice of a generic QoL instrument might have reduced the sensitivity to clinical changes in depression. CONCLUSIONS: Prevention of recurrence in MDD with milnacipran contributes to an improvement in the QoL.
To compare the efficacy and assess the tolerability of milnacipran 50mg p.o. b.i.d. to placebo in the prevention of recurrence in depressed patients who had responded an acute treatment and had remained in remission during a 4-month continuation phase. Remission criteria were: a Hamilton Depression Rating Scale (HDRS) (21-item) < or = 8, improvement or disappearance of the initial symptoms, and an assessment of 'very much improved' or 'much improved' on the Clinical Global Impression (CGI) Subscale: Global Improvement. Recurrence was defined by a major depressive episode according to DSM-III-R criteria and a minimum score of 18 on the HDRS, with the need to treat the recurrence. The primary analysis was the rate of recurrence as a function of time in the intent-to-treat population. Groups were compared using the Cox model. Absolute recurrence rates were 16.3% (17/104) in milnacipran-treated patients and 23.6% (26/110) in placebo-treated patients, with a significant difference in the reduction of recurrence as a function of time (Kaplan Meier Survival Analysis analysis, P < 0.05). There was no difference in tolerability between groups. This study demonstrates that milnacipran is effective with good tolerability in preventing recurrence in major depressive disorder over 1 year in patients with recurrent depression who responded to acute treatment with milnacipran and continued their response for 18 weeks.
Improved compliance with antipsychotic medication is a major issue in schizophrenic management. For this purpose educational programs have been used, but up to now, little or no information has been gathered or published in France concerning schizophrenic patients' opinion on information they have about their disease and their treatment. Thus we conducted a survey in concert with 78 psychiatrists from the French psychiatric health service. From this cross sectional survey we assessed 336 outpatients (male: 72%; mean age: 36 +/- 10.4 years) with schizophrenia according to the DSM IV (paranoid sub type: 57%, disorganized: 12%, catatonic: 1%, undifferentiated: 12%, residual: 18%). The mean duration of the illness was 11.6 years (sd: 8.5) and the mean duration of the follow up with the same psychiatrist was 5.4 years (sd: 5.1). Patients completed a questionnaire which assessed their level of information on mental illness and treatment. The diagnosis of schizophrenia has been told to their patients by 39% of the psychiatrists, and treatment has been explained to the patients by 96% of the practitioners. Results indicate less than half of the patients (45%) felt ill, only 46% thought they knew their illness well or very well (nevertheless only 31% of them named spontaneously the diagnosis of schizophrenia or psychosis), and 61% considered that they had been given sufficient information. Most of the patients (79%) were persuaded that their treatment was useful, and 75% of patients were completely satisfied with their treatment. Surprisingly 92% reported taking their medication regularly. Most patients think that a high level of information about their illness (74%) and treatment (79%) help them to cope better with their schizophrenia. Analysis performed according to patients characteristics indicated that paranoid patients felt more ill (p = 0.035) than others, thought to know less about their illness (p = 0.0065), and were less satisfied with their treatment (p = 0.04) and their level of information (p = 0.03). Patients with a duration of their illness longer than 10 years were more convinced of the utility of their treatment (p = 0.02) and had debated more on the choice of their treatment with their psychiatrist (p = 0.047). Patients older than 35 years were more satisfied with their information (p = 0.002). More patients with atypical antipsychotics accepted to take their treatment on a regular basis (p = 0.035) compared to patients under classical neuroleptics. This survey underlines that mental health consumers' opinions can be obtained even in the field of schizophrenia, and argues in favour of further such investigations. It also highlights the need for educational programs on schizophrenia and antipsychotic medications.
In the community, depression and anxiety are highly prevalent. The relationship between these two conditions is often unclear and has been the subject of much discussion. The classical viewpoint considered depression and anxiety to be two disorders with separate treatment options: anxiolytic agents for anxiety and antidepressant agents for depression. Depression and anxiety may occur together representing comorbid 'pure' conditions, or anxiety may predispose depression (or vice versa), or symptoms of anxiety and depression may be external manifestations of one underlying cause, or there may be an overlap of classifications. It is also possible that a mixed anxiety and depressive disorder exists: the association of subthreshold depressive symptoms and subthreshold depressive anxiety. This review examines the relationship of co-occurring depression and anxiety. The socioeconomic burden and the need for effective treatment of comorbid anxiety and depression are highlighted. The SSRIs, e.g. paroxetine, are discussed in particular as appropriate pharmacological therapy for anxiety with depression.
This study was designed to explore the dose-response relationship for clomipramine in patients with panic disorder, with or without agoraphobia. After 1 week of single-blind placebo pretreatment, 180 such patients were assigned to a multicentre placebo-controlled comparison of the effects of high and low doses of clomipramine, and were followed up for 8 weeks. In alleviating anxiety and panic disorder, both clomipramine doses were more efficacious than placebo for panic disorder and, to a lesser degree, for phobia. The lower dose was better tolerated and at least as effective as the higher dose, sometimes more so. These results indicate the clinically important possibility that low-dose clomipramine is effective and well tolerated.
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INTRODUCTION: The use of antidepressants has been questioned with respect to both undertreatment and inadequate prescription. The present investigation was therefore launched to assess the psychopathology profiles of antidepressant users. METHODS: A representative sample was constituted on the basis of usual antidepressant consumption, and ICD 10 compatible diagnoses were obtained after telephone administration of a structured psychiatric interview. RESULTS: The most often used drugs were fluoxetine, followed by tricyclic antidepressants. Coprescription existed in slightly less than two thirds of antidepressant users. ICD 10 diagnoses were compared to currently available prescription guidelines. Fluoxetine prescription, as compared to other drugs, was found to be significantly more compliant with these guidelines; conversely, in 22% of antidepressant users, no complete ICD 10 diagnosis could be documented. These results are discussed in the light of report accuracy and anecdotal or 'heterodox' indications of antidepressants. CONCLUSION: Altogether, the present study confirms previous doubts regarding appropriate use of antidepressants and stresses the need for more explicit and comprehensive clinical guidelines. It does not substantiate, however, any evidence for a 'recreational' use of these products.