Biomedical subjects
M Lejoyeux
Publications and source records attributed to M Lejoyeux.
Absence of discontinuation symptoms with agomelatine and occurrence of discontinuation symptoms with paroxetine: a randomized, double-blind, placebo-controlled discontinuation study.
The effects of an abrupt interruption of agomelatine, a new melatonergic/serotonergic antidepressant, were explored in a double-blind, placebo-controlled study. Paroxetine was used as active control. After 12 weeks of double-blind treatment with agomelatine 25 mg/day or paroxetine 20 mg/day, sustained remitted depressed patients were randomized for 2 weeks, under double-blind conditions, to placebo or to their initial antidepressant treatment. Discontinuation symptoms were assessed at the end of the first and second week of discontinuation with the Discontinuation Emergent Signs and Symptoms (DESS) checklist. One hundred and ninety-two sustained remitted patients were randomized to the 2-week discontinuation period. Patients who discontinued agomelatine did not experience more discontinuation symptoms than those who continued on agomelatine. Patients who discontinued paroxetine for placebo experienced significantly more DESS discontinuation symptoms, during the first week, compared to those who continued with paroxetine (respective mean number of emergent symptoms: 7.3+/-7.1 and 3.5+/-4.1, P<0.001). No significant difference was shown between the continuing and interrupting groups in the second week of discontinuation. By contrast to paroxetine, abrupt cessation of agomelatine is not associated with discontinuation symptoms.
Comparison of alcohol-dependent patients with and without physiological dependence.
Sociodemographic and clinical characteristics of alcohol-dependent patients with or without physiological dependence (e.g. tolerance to alcohol or withdrawal) were compared. 186 consecutive alcohol-dependent patients hospitalized for alcohol detoxification were assessed. Diagnosis of alcohol dependence, tolerance and withdrawal was determined according to DSM-IV criteria. Assessment also included modalities of alcohol consumption and the Michigan Alcohol Screening Test (MAST). All patients presented alcohol dependence, 124 presented tolerance, 116 alcohol withdrawal and 146 (78.5%) tolerance and/or withdrawal. Patients with physiological dependence were older (51.4 vs. 46.9 years), drank more alcohol each day (20.3 vs. 11.3 drinks/day) and began alcohol consumption more often in the morning (67 vs. 37.5%). MAST scores were significantly higher in patients with physiological dependence (28.8 vs. 24.5), as was the mean corpuscular volume of erythrocytes (108 vs. 83 fl). No difference was found in terms of age, marital status, rate of unemployment, level of education and psychiatric comorbidity between the patients with and without physiological dependence.
Epidemiology of behavioral dependence: literature review and results of original studies.
The extension of the definition of dependence leads to the consideration of some impulsive disorders as a form of dependence disorder. This pathological condition is characterized by the repetitive occurrence of impulsive and uncontrolled behaviors. Other clinical characteristics are failure to resist an impulse, drive or temptation to perform some act harmful to oneself and/or others, an increasing sense of tension or excitement before acting out, and a sense of pleasure, gratification or release at the time of the behavior or shortly thereafter. Behavioral dependences most often described are pathological gambling, kleptomania, trichotillomania and compulsive buying. Studies using a specific assessment scale, the South Oaks Gambling Screen, distinguished problem gambling from pathological gambling. Social gamblers spend 5% of their money and pathological gamblers 14 to 45%. Prevalence of 'problem gambling' is 4% and pathological gambling 2%. Several studies have suggested that the incidence of pathological gambling is eight to ten times greater in alcohol-dependent patients than in the general population. No systematic study has assessed the prevalence of kleptomania. Data come from case reports. Among subjects arrested after a theft, prevalence of kleptomania varied between 0 and 24%. Trichotillomania prevalence rate is 0.6% among students. Studies using less restrictive diagnostic criteria found a prevalence rate of 3.4% in women and 1.5% in men. The disorder is often unrecognized; 40% of the cases are not diagnosed and 58% of the patients have never been treated. Prevalence studies of compulsive buying found a rate between 1 and 6% in the general population. Compulsive buying is significantly more frequent among women (90% of the cases). Study of family history of compulsive buyers showed a high frequency of alcohol-dependence disorder (20%) and depression (18%). In all cases of behavioral dependence disorders, a high level of impulsivity and sensation-seeking could determine an increased risk.
A French translation of the obsessive-compulsive drinking scale for craving in alcohol-dependent patients: a validation study in Belgium, France, and Switzerland.
The Obsessive-Compulsive Drinking Scale (OCDS) is an instrument developed to measure cognitive aspects of alcohol craving. The aim of this study was to validate the French translation of the OCDS according to the international methodology as published by Hunt and coworkers (see text), including forward-backward translations, patient interviews (9 patients), patient's perception of acceptability (15 patients), and final validation within a treatment program (50 patients). All 74 patients were native French-speaking alcohol-dependent patients from Belgium, France, and Switzerland. The derived aggregated total (TOT) score and both subscores corresponding to the obsessive (OB) and compulsive (CP) dimensions were shown to be asymptomatically normal. Good internal consistencies were found, with Cronbach alpha: TOT = 0.88; OB = 0. 82; CP = 0.79. The test-retest procedure was used to examine intrarater reliability (r = 0.81). The construct validity was examined with linear correlation of the two main components: r(OB, CP) = 0.62; r(OB, TOT) = 0.86; r(CP, TOT) = 0.92. Principal-components analysis revealed two main factors: the first factor representing the total scale score, while the obsessive and compulsive subscale scores were distributed along factor two. The translated scale seems to be psychometrically as valid as the original English scale and confirms the psychometric properties of the OCDS.
Study of impulse-control disorders among alcohol-dependent patients.
BACKGROUND: Impulse-control disorders (ICDs) include intermittent explosive disorder, kleptomania, trichotillomania, pyromania, and pathological gambling. Several studies have suggested that the incidence of pathological gambling is substantially higher in alcoholics than in the general population. The rate of co-occurrence of other ICDs and alcohol dependence has never been systematically investigated. In our study, we assessed the frequency of all ICDs in a population of alcohol-dependent patients. We also examined the possibility that the presence of an ICD can correspond to earlier onset and more severe forms of alcoholism, which have a greater association with antisocial personality. METHOD: All patients hospitalized at our psychiatric unit for detoxification between January and August 1997 met DSM-IV criteria for alcohol dependence and were included in this study. Diagnosis of alcohol dependence was confirmed with the Mini-International Neuropsychiatric Interview. ICDs were investigated using the Minnesota Impulsive Disorders Interview. All patients completed the Michigan Alcoholism Screening Test. RESULTS: Among the 79 patients included in the study, 30 (38.0%) met criteria for an ICD. Included in the study were 19 cases of intermittent explosive disorder, 7 cases of pathological gambling, 3 cases of kleptomania, and 1 case of trichotillomania. Patients with co-occurring ICDs were significantly younger than patients without an ICD (mean age = 40.7 vs. 44.5 years; p = .03). Patients with co-occurring pathological gambling were significantly younger at the onset of alcohol dependence than patients without ICDs (mean age = 19.5 vs. 25.9 years; p = .0008). Pathological gamblers had significantly longer duration of alcohol dependence compared with patients without ICDs (26.0 vs. 17.9 years; p = .02). Patients with co-occurring intermittent explosive disorder had the shortest duration of alcohol dependence of all patients (9.9 years). Prevalence of antisocial personality disorder was no different in patients with or without co-occurring ICDs. CONCLUSION: Thirty-eight percent of the alcohol-dependent patients studied presented with an ICD. Patients with ICDs were younger than those without an ICD. The presence of an ICD was not associated with a specific form of alcohol dependence or with antisocial personality. Co-occurrence of pathological gambling, however, was associated with lower age at onset of alcohol dependence, a higher number of detoxifications, and a longer duration of alcohol dependence than was absence of an ICD.
Impulse-control disorders in alcoholics are related to sensation seeking and not to impulsivity.
Impulse-control disorders (ICD) include intermittent explosive disorder, kleptomania, trichotillomania, pyromania and pathological gambling. Several studies have suggested that the incidence of pathological gambling and impulsive violent behavior is substantially higher in alcohol-dependent patients than in the general population. The association between ICD and alcoholism, as well as personality characteristics such as sensation seeking and impulsivity, has never been systematically studied. The present study compared the levels of impulsivity and sensation seeking in age- and sex-matched groups of alcohol-dependent patients with concomitant ICD (ICD+, n = 30), alcohol-dependent patients without ICD (ICD-; n = 30) and control subjects (n = 30). All the alcohol-dependent patients (ICD+ and ICD-) were hospitalized for alcohol detoxification. Diagnoses of ICD were based on DSM-IV criteria and the Minnesota Impulsive Disorders Interview. All patients completed the Zuckerman Sensation-Seeking Scale (SSS) and the Barratt Impulsiveness Rating Scale (BIS). Mean scores on the SSS general factor, the SSS disinhibition subscale, and the SSS experience-seeking scale were significantly higher in ICD+ patients than in either ICD- patients or control subjects. By contrast, total scores and subscale scores on the BIS showed no significant differences among the three groups. Thus, it appears that measures of sensation seeking, rather than impulsivity, are relevant in distinguishing between alcohol-dependent patients with and without concomitant impulse control disorders.
Antidepressant discontinuation reactions.
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[Intermittent alcoholic behavior].
Intermittent alcohol disorders are defined by the paroxystic aspect of alcohol consumption followed by periods of time without alcohol ingestion. The most typical form of intermittent alcoholism is dispomania. During the acute episode of dipsomania, the patient presents an extreme craving for alcohol and a complete loss of control. The alcohol consumption usually leads to severe overdoses and coma. The cases of pure dipsomania are relatively rare in daily practice. Most often, intermittent forms of alcohol abuse or dependence are observed in patients who present, between the acute ingestions of alcohol, a chronic consumption. Intermittent ingestions of alcohol can also be present among subjects presenting a pathological personality (antisocial personality) and a past or present dependence syndrome to heroine. These patients use alcohol like a drug in order to get a modification of the conscience, a high, a sedation or a trip.
Study of compulsive buying in depressed patients.
BACKGROUND: Compulsive buying is defined by the presence of repetitive impulsive and excessive buying leading to personal and familial distress. Patients with this disorder also suffer from mood disorder in 50% to 100% of the cases studied, and antidepressants help to decrease the frequency and the severity of uncontrolled buying. To define the correlation between compulsive buying and depression, we assessed this behavior among 119 inpatients answering to DSM-III-R criteria for major depressive episode. Additionally, we evaluated for comorbidity in the patients suffering from compulsive buying and in those free from this disorder. Impulsivity and sensation seeking were also compared in the two groups. METHOD: Diagnosis of compulsive buying was made using standardized criteria and a specific rating scale. Diagnosis of depression and assessment of comorbidity were investigated using the Mini International Neuropsychiatric Interview and a modified version of the Minnesota Impulsive Disorders Interview. All patients answered the Zuckerman Sensation-Seeking Scale and the Barrat Impulsivity Rating Scale. RESULTS: The prevalence of the disorder was 31.9%; 38 of the 119 depressed patients were diagnosed as compulsive buyers. Patients from the compulsive buying group were younger in age, more often women than men, and more frequently unmarried. They presented more often than others with recurrent depression (relative risk = 1.4), disorders associated with deficits in impulse control such as kleptomania (relative risk = 8.5) or bulimia (relative risk = 2.8), benzodiazepine abuse or dependence disorder (relative risk = 4.7), and two or more dependence disorders (relative risk = 1.99). Subscores for experience seeking using the Zuckerman Sensation-Seeking Scale were significantly higher (p = .04) and scores of impulsivity were much higher (p < .0001) than corresponding scores in the group without compulsive buying behavior. CONCLUSION: Compulsive buying is frequent among depressed patients. In most cases, the behavior is associated with other impulse control disorders or dependence disorders and a high level of impulsivity.
Serotonin reuptake inhibitor discontinuation syndrome: a hypothetical definition. Discontinuation Consensus panel.
Adverse events following discontinuation from serotonin reuptake inhibitors (SRIs) are being reported in the literature with increasing frequency; the frequency and severity of these symptoms appear to vary according to the half-life of the SRI, e.g., the incidence appears higher with the shorter half-life agents than with fluoxetine, which has an extended half-life. Yet, there have been no systematic studies of the phenomenon to date. Therefore, a group of experts convened in Phoenix, Arizona, to develop a clear description or definition of the phenomenon based on these reports. The SRI discontinuation syndrome, referred to as "withdrawal symptoms" in many anecdotal case reports, is distinctly different from the classic withdrawal syndrome associated with alcohol and barbiturates. Anti-depressants are not associated with dependence or drug-seeking behavior. SRI discontinuation symptoms tend to be short-lived and self-limiting, but can be troublesome. They may emerge when an SRI is abruptly discontinued, when doses are missed, and less frequently, during dosage reduction. In addition, the symptoms are not attributable to any other cause and can be reversed when the original agent is reinstituted, or one that is pharmacologically similar is substituted. SRI discontinuation symptoms, in most cases, may be minimized by slowly tapering antidepressant therapy, but there have been several case reports where symptoms occurred consistently even through repeated attempts to taper therapy. Physical symptoms include problems with balance, gastrointestinal and flu-like symptoms, and sensory and sleep disturbances. Psychological symptoms include anxiety and/or agitation, crying spells, and irritability. Further analyses of data bases and clinical studies are needed to define this proposed syndrome more clearly.
Antidepressant discontinuation: a review of the literature.
Sudden or tapered withdrawal from treatment with antidepressants, including monoamine oxidase inhibitors (MAOIs), tricyclic antidepressants (TCAs), and serotonin selective reuptake inhibitors (SSRIs), can produce phenomena consisting of somatic and psychological symptoms. The literature about these discontinuation phenomena consists mainly of case reports and a limited number of controlled prospective studies. The symptoms are generally mild and transient for the TCAs and the SSRIs but may be serious for the MAOIs. They are much more common with a shorter acting SSRI, such as paroxetine, than with the longer acting agent fluoxetine. Because the symptoms of antidepressant discontinuation include changes in mood, affect, appetite, and sleep, they are sometimes mistaken for signs of a relapse into depression. Thus, it is important to directly question patients about new symptoms that occur during antidepressant discontinuation to optimally manage treatment discontinuation.
Possible biological mechanisms of the serotonin reuptake inhibitor discontinuation syndrome. Discontinuation Consensus Panel.
Although the number of documented serotonin reuptake inhibitor (SRI) discontinuation reactions is increasing, to date no systematic studies have been completed; therefore the mechanism of action for these reactions is not clearly understood. However, several hypotheses have been proposed. Researchers have postulated that discontinuation events result from a sudden decrease in the availability of synaptic serotonin in the face of down-regulated serotonin receptors. In addition, other neurotransmitters, such as dopamine, norepinephrine, or gamma-aminobutyric acid (GABA), may also be involved, although little research in this area has been published. Individual patient sensitivity, i.e., genetics or cognitive mindset, may also be a factor in SRI discontinuation phenomena. Finally, experts have hypothesized that since some symptoms associated with paroxetine withdrawal are similar to those of tricyclic antidepressant discontinuation, they may be caused by cholinergic rebound.
Modifications of erythrocyte membrane fluidity from patients with anorexia nervosa before and after refeeding.
Erythrocyte membrane characteristics were compared in 15 normal women and 15 women with anorexia nervosa; the patients were studied at hospital admission and again after 1 month of refeeding. At admission, physical properties of erythrocyte membranes, studied with electron spin resonance spectrometry, significantly differed between the anorexic patients and the normal volunteers. Fluidity from the hydrophobic part of the erythrocyte membrane, estimated by the correlation frequency, was decreased in the patients. After 1 month of refeeding, fluidity increased. One of the possible mechanisms of the variation of membrane fluidity could be the effect of cholesterol on membrane structure. Increased cholesterol levels in anorexic subjects could reduce fluidity. These alterations in membrane fluidity could explain some of the neurobiological abnormalities observed in anorexia nervosa.
Phenomenology and psychopathology of uncontrolled buying.
OBJECTIVE: Uncontrolled buying, defined by the presence of repetitive impulsive and excessive buying that leads to personal and familial distress, is a psychiatric disorder that has only recently been recognized. This review focuses on the prevalence, clinical features, and etiology of this disorder. METHOD: All published articles on the topic were collected and reviewed. The literature concerning the typology of normal consumerism was also reviewed. RESULTS: The prevalence of the disorder in the general population is reported to be 1.1%. The main clinical features of uncontrolled buying are impulsivity and repetition of buying, the invasive need to buy, unsuccessful attempts to control spending, and the existence of tangible negative consequences of buying (marked distress, interference with social or occupational functioning, or financial problems). Uncontrolled buying may be related to obsessive-compulsive disorder, depression, addiction, or impulsivity. CONCLUSIONS: In most cases, uncontrolled buying can be understood as "compensatory buying" that temporarily alleviates depressive symptoms and can thus be associated with the results of antidepressant treatment in cases in which uncontrolled buying is symptomatically associated with depression.
Use of serotonin (5-hydroxytryptamine) reuptake inhibitors in the treatment of alcoholism.
Animal studies have shown that alcohol consumption is reduced when serotonin (5-hydroxytryptamine, 5-HT) levels are increased in the central nervous system. Similarly, studies of alcohol-dependent human subjects have shown that treatment with 5-HT reuptake inhibitors (i.e. zimeldine, citalopram, fluoxetine, and fluvoxamine) decreases the desire to drink alcohol and improves symptoms of alcohol-related anxiety and depression in patients who have undergone detoxification. However, not all studies have shown them to be an effective treatment to help maintain recovery in alcohol dependence. The exact mechanisms of action of the 5-HT reuptake inhibitors are not yet fully understood and additional studies are needed. However, at this time, the 5-HT reuptake inhibitors may be effective pharmacotherapies for alcohol-related depression.
[Suicide and psychotropic drugs].
Suicide provocates 0.5 to 1% of the deaths in France. Suicide appears to be closely related to psychiatric morbidity. History of depression is associated with a 30-fold increase in suicide risk. Globally, the annual incidence of suicide among depressives is 1% and 15% of the depressives die by suicide. When depressive symptoms are retrospectively assessed, it appears that 45 to 70% of patients who committed suicide presented depression. Suicide is the main complication of untreated depression. Patients who commit suicide take the more easily available medications. The decrease in the prescription of barbiturates has been associated with a decrease of the frequency of self-poisoning with barbiturates. In the same time, neuroleptics, antidepressants and benzodiazpines, more often prescribed, induced more lethality by suicide. The number of deaths by millions of prescriptions variates, with the antidepressants, between 13 and 166. They correspond to 0.005% of death each year among patients taking antidepressants. In daily practice, the prescription of antidepressants, which alleviates depressive symptoms, usually prevents suicidal risk among depressives. In some rare cases, antidepressants and other psychoactive agents are used by the patients, in overdosage, to commit suicide. According to the results of all controlled studies of antidepressants, suicide attempts are more frequent among patients taking antidepressants (1.7% of the cases) than among patients receiving placebo (0.8%). These data may be related to methodological bias which are discussed here. They do not initiate to restrain the prescription of antidepressants to depressed patients but to provide more frequent consultations and even to hospitalize depressives at high risk for suicide.
Use of serotonin (5-hydroxytryptamine) reuptake inhibitors in the treatment of alcoholism.
Animal studies have shown that alcohol consumption is reduced when serotonin (5-hydroxytryptamine, 5-HT) levels are increased in the central nervous system. Similarly, studies of alcohol-dependent human subjects have shown that treatment with 5-HT reuptake inhibitors (i.e. zimeldine, citalopram, fluoxetine, and fluvoxamine) decreases the desire to drink alcohol and improves symptoms of alcohol-related anxiety and depression in patients who have undergone detoxification. However, not all studies have shown them to be an effective treatment to help maintain recovery in alcohol dependence. The exact mechanisms of action of the 5-HT reuptake inhibitors are not yet fully understood and additional studies are needed. However, at this time, the 5-HT reuptake inhibitors may be effective pharmacotherapies for alcohol-related depression.