Christian Even

Treatment response in major depression: Effects of personality dysfunction and prior depression

BACKGROUND The impact of personality dysfunction on the outcome of treatment for depression remains debated. AIMS To examine the relationship between the number of prior depressive episodes, personality dysfunction and treatment response for depression. METHOD In a large sample (n = 8229) of adult out-patients with a major depressive episode (DSM-IV), personality dysfunction was assessed using the Standardised Assessment of Personality - Abbreviated Scale (SAPAS). Potential predictors of treatment response at 6 weeks were examined via structural equation modelling. RESULTS The amount of personality dysfunction and number of prior episodes of depression were both associated with poor response to treatment. Once personality dysfunction was controlled for, the number of prior episodes of depression was not associated with treatment response. CONCLUSIONS Personality dysfunction is associated with impaired short-term response to antidepressant treatment in major depression. The apparent detrimental effect of prior depression on treatment response may be accounted for by pre-existing personality dysfunction.

Frequency of Hospitalisations and Inpatient Care Costs of Manic Episodes: In Patients with Bipolar I Disorder in France

AbstractBackground: Bipolar disorder is a chronic illness that may involve multiple relapses and result in substantial psychosocial impairment. However, very few recent studies have investigated the economic burden of the disease. Objective: To assess the frequency of hospitalisation and the inpatient care costs associated with manic episodes in patients with bipolar I disorder in France. Method: A cost-of-illness study was conducted based on available data using a hospital payer perspective. The lifetime prevalence of manic episodes was estimated from published epidemiological data using a random-effects meta-analysis. Data were obtained by a computerised literature search using the main scientific and medical databases. Additional epidemiological references were identified from published studies and textbooks. Data on frequency of hospitalisation and length of stay were collected from a large psychiatric university hospital. Data on unit costs for inpatient care were obtained from the accounting system of the largest hospital group in Paris, France for the year 1999. Results: Extrapolating from international data on the average prevalence of bipolar I disorder, the proportion of rapid cycling patients and the average cycle duration, we estimated the annual number of manic episodes in patients with bipolar I disorder to be around 265 000 in France. Based on hospital data in Paris, the proportion of manic episodes that require hospitalisation was estimated to be around 63%. The average length of stay was 32.4 days and the hospitalisation-related costs were estimated to be around 8.8 billion French francs (€1.3 billion) [1999 values]. Conclusion: Our study highlights the lack of medical and economic data on the frequency and hospitalisation-related costs of manic episodes in patients with bipolar I disorder in France. As the lifetime prevalence of bipolar I disorder may be as high as 3% among adults, further studies are required in order to provide representative national data and to allow economic evaluations of costs related to bipolar I disorder in France.

Characteristics of voluntary participants versus nonparticipants in a psychoeducation program for euthymic patients with bipolar disorder.

We aimed to assess the participation rate and predictive factors of participation in psychoeducation programs for euthymic outpatients with bipolar disorder. Ninety-five consecutive euthymic outpatients with bipolar disorder treated with lithium were recruited in a university department of psychiatry. The participants and nonparticipants in a program of psychoeducation were compared for sociodemographic, clinical, and psychological characteristics. According to univariate statistics, a younger age, a higher education level, a shorter duration of illness, a better initial knowledge about lithium, and a less external locus of control were predictive of participation in the program. A binary logistic regression model showed that an external locus of control was an independent predictor of participation. Among bipolar patients, the older, the less educated, those who have less knowledge about their treatment, and those with a more external locus of control were less likely to participate in hospital-based psychoeducation programs.

Prévalence de la dépression dans la sclérose en plaques. Revue et méta-analyse

Resume Introduction L’objectif de cette revue est d’evaluer la frequence de la depression au cours de la sclerose en plaques (SEP). Materiel et methode Nous avons realise une meta-analyse en utilisant deux methodes de combinaison basees sur les niveaux de signification (p). Resultats La frequence de la depression dans la SEP est significativement plus elevee que dans d’autres pathologies chroniques. Cette meta-analyse fournit un p combine significatif, indicateur d’un effet de la SEP par rapport a d’autres maladies chroniques sur la frequence de la depression. L’importance de cet effet peut etre qualifiee de moyen (effet standardise d de Cohen a 0,29, intervalle de confiance a 95 p. 100 : 0,09-0,49) et est donc probablement cliniquement pertinente. Conclusion Ce resultat plaide en faveur du caractere specifique de l’association SEP et depression qui ne serait donc ni fortuite ni seulement liee aux facteurs non specifiques de toute maladie chronique.

Validité du concept de dépression vasculaire : une revue de la littérature

Resume L’hypothese selon laquelle une pathologie cerebrovasculaire peut predisposer, precipiter ou entretenir certaines depressions du sujet âge par l’intermediaire de perturbations du reseau neuronal striato-pallido-thalamo-cortical a ete developpee par Alexopoulos et al. qui ont propose le concept de « depression vasculaire ». Dans le but d’examiner la validite de cette categorie diagnostique, nous avons realise une revue de la litterature explorant quatre niveaux de validation : validite de surface, validite descriptive, validite de construction et validite predictive. Les validites de surface et predictive apparaissent bonnes. Les validites descriptive et de construction semblent moyennes au regard des donnees actuelles. Cette methodologie nous a permis de conclure en faveur du concept de depression vasculaire et donne un eclairage sur les liens complexes qui unissent depression et pathologies vasculaires. D’autres etudes utilisant des criteres diagnostiques plus restrictifs doivent etre menees pour confirmer la validite de ce diagnostic et mieux en cerner les specificites.

Coût du trouble bipolaire : revue de la littérature

Resume Le trouble bipolaire est la sixieme cause mondiale de handicap chez l’adulte jeune, selon la Banque Mondiale et l’Organisation Mondiale de la Sante. Ce handicap est du meme ordre que celui de la schizophrenie. Cependant, l’evaluation des consequences economiques du trouble bipolaire n’a fait l’objet que de rares etudes. De plus, alors qu’un traitement preventif, le lithium, est utilise depuis bientot 50 ans, l’impact economique de l’utilisation des thymoregulateurs sur le long terme est un domaine neglige. Deux etudes anglosaxonnes estiment le cout annuel du trouble bipolaire a 10 000 et 16 000 € dont 80 % sont lies aux couts indirects, 15 % au cout de l’hospitalisation et 5 % au traitement medicamenteux. Les couts d’hospitalisation les plus eleves sont retrouves dans les etudes sur des populations suivies en milieu specialise ou des populations defavorisees et handicapees, tandis qu’ils sont moins eleves dans les systemes d’assurances privees (Health Maintenance Organizations ou HMO) et dans les estimations sur l’ensemble de la population. L’utilisation des thymoregulateurs a un impact tres important sur les couts directs qu’elle divise par 2 ainsi que sur les couts indirects. Cependant, toutes les enquetes montrent que les thymoregulateurs sont sous-utilises et qu’au total, seul 1 patient souffrant de trouble bipolaire sur 4 recevrait un traitement adequat. L’optimisation des ressources du systeme de sante necessite sans nul doute d’importants efforts pour ameliorer le depistage, l’identification et le traitement du trouble bipolaire.

Grossesse, allaitement et thymorégulateurs : éléments de décisions et règles pour la pratique

Resume De nombreuses femmes en âge de procreer posent le probleme de la thymoregulation lors de la grossesse et plus particulierement lors du premier trimestre. Nous proposons une revue des risques et options therapeutiques afferents aux questions que posent la grossesse chez les patientes bipolaires. Deux idees recues sont particulierement a denoncer : celle selon laquelle la grossesse protegerait des rechutes et celle qui edicte l’arret du lithium dans tous les cas. Le lithium est le seul thymoregulateur dont la prescription est parfois possible au premier trimestre. Nous avons formalise les conditions minimales pour en envisager la possibilite. Lorsqu’elles sont reunies, une reflexion de la patiente et du couple doit etre proposee et assortie d’une information tres complete, au mieux orale et ecrite, concernant les risques et benefices de l’interruption comme de la poursuite du lithium. Les autres thymoregulateurs, soit du fait de leur teratogenicite, soit du fait du manque de recul pour les plus recents, ne paraissent pas pouvoir etre prescrits lors du premier trimestre. L’allaitement est deconseille sous lithium mais possible sous carbamazepine et sous valproate/divalproate/valpromide. Dans tous les cas la prescription d’un thymoregulateur des le debut du post-partum est un imperatif.

Long-term outcome of anxiety disorders: a review of double-blind studies.

Purpose of review Although anxiety disorders are acknowledged as chronic, the issue of the pharmacological treatment duration remains unsettled. This review focuses on the long-term outcome of patients with anxiety disorders as demonstrated by randomized controlled trials. Recent findings Results from long-term randomized controlled trials of antidepressants in anxiety disorders indicate that maintenance treatment significantly reduces the odds of relapse, whatever the anxiety disorder is. This result appears to be similar to what is reported in long-term studies in depressive disorders. In addition, regarding the natural course of depressive disorders, acknowledged as mostly recurrent, some patients may require very long-term treatment, that is, more than 2 years. Moreover, naturalistic studies in anxiety disorders indicate that the relapse risk after discontinuation is not associated with the treatment duration. Finally, there is no predictor to identify those patients who require long-term pharmacotherapy for anxiety disorders. Summary In light of this review, other long-term studies in anxiety disorders have to be undertaken to identify predictors of relapse after treatment discontinuation. As it is now acknowledged for depressive disorders, some patients may require very long-term pharmacological treatment for anxiety disorders.

La démence frontotemporale : revue de la littérature

CLINICAL CHARACTERISTICS Frontotemporal dementia (FTD) is a neurological disorder characterised by the progressive degeneration of the frontal and anterior temporal cortex. FTD, as well as nonfluent progressive aphasia and semantic dementia, belongs to the more generic entity of frontotemporal lobe degeneration. Considering the involvement of the frontal lobe, the initial clinical presentation of FTD may be psychiatric, such as changes in personality or behavioural disorders. Psychiatrists, therefore, have to establish the differential diagnosis with late-onset schizophrenia or affective disorders. An accurate history of the onset of symptoms, thanks to the patient and especially to his/her family, is essential to recognize this dementia. In addition to behavioural changes, memory impairment, and speech disturbances are often present from the beginning. Consensus criteria have been proposed in 1998 that help to bring this diagnosis to mind in clinical practice. The progressive occurrence of personality changes or inappropriate social conducts in the fifth or sixth decade must prompt cognitive evaluation. NEUROCOGNITIVE AND BRAIN IMAGING DATA: A brief cognitive evaluation, such as the frontal assessment battery (FAB) may help to identify a dysexecutive syndrome and to prompt a thorough neuropsychological evaluation. The pattern of neuropsychological impairment reflects the involvement of the frontal lobe and appears different from that of other degenerative diseases, such as Alzheimers dementia, which involves hippocampal damage. Additional investigations should however be made to detect a potentially curable dementia. Cerebral imaging is essential to the differential diagnosis and also shows evidence for the positive diagnosis of FTD. Structural MRI may initially not show the bilateral atrophy of the frontal lobe, but functional imaging may be helpful in the early stages of the illness by showing evidence of abnormalities in the anterior cerebral hemisphere. PATHOPHYSIOLOGICAL FINDINGS: In recent years, significant advances in the understanding of the pathological characteristics of FTD were made with genetic contribution, especially the discovery of the tau protein involvement. In fact, neuropathological examination with immunohistochemical analysis defines Picks disease with Pick bodies that belong to tauopathies. Ubiquitinated intraneuronal inclusions may also be found, and some types of FTD have no distinctive pathological feature. However, although a definite diagnosis would only be established after postmortem pathological examination, the clinical, neuropsychological and imaging data enable the early identification of patients with FTD and, subsequently, the appropriate management. THERAPEUTICS Although the prevalence of FTD reaches 1 Alzheimers disease (AD) to 1.6 FTD in the general population between 45- and 64-year old, only few studies have focused on the treatment of FTD. Some evidence supports the positive effect of serotonergic agents, especially with regard to behavioural symptoms. Selective serotonin reuptake inhibitors or trazodone should therefore be prescribed in preference to acetylcholinesterase medications as in AD. However, no drug yet has the ability to stop or slow down the degenerative process. The management of daily life also bears specificities related to the younger age of these patients and to their behavioural disorders. Caregivers should receive some education about the characteristics of this dementia and should be helped in social management. As concerns aggressive behaviour, neuroleptics should generally be avoided because of poor tolerance. Finally, the outcome is characterized by a rapid loss of autonomy and sometimes by a premature institutionalisation.

Lithium‐induced menometrorrhagia

Lithium has been used for the treatment of bipolar disorders for over 50 years. Yet it produces a wide range of endocrine and/or metabolic adverse effects. The authors report a case of menometrorrhagia induced by lithium. Mrs X is a 24-year-old woman with a history of bipolar disorder for 7 years, and bulimia nervosa during adolescence now in remission. She had received mood stabilizing agents including carbamazepine, divalproex and lamotrigine which had been discontinued for disturbance in hepatic function, alopecia and inefficacy, respectively. She was admitted to our mood disorders unit (Centre Hospitalier Sainte-Anne, Paris, France) for a severe depressive episode (International Classification of Diseases – version 10 criteria). Her body mass index was 18.5 and she had regular menstruation for years under combined oral contraceptive containing 15 mg ethinyl estradiol and 60 mg gestodene. The clinical examination and ancillary blood tests were normal. The serum beta-hCG was negative. Lithium (sustained-release preparation) was started in combination with an antidepressant (venlafaxine 200 mg per day). The serum lithium level was 0.87 mEq/L under 600 mg per day. A few days later, Mrs X displayed menometrorrhagia that persisted during the 2 months of her hospitalization. Considering the absence of reports of menometrorrhagia under lithium in the medical literature, the same treatment was maintained. At 2 months after discharge, although the pelvic examination as well as the abdomino-pelvic ultrasound examination were normal, the menometrorrhagia had persisted. Lithium was then discontinued and the menometrorrhagia stopped within a few days. At 2 weeks later, she displayed a hypomanic episode. Venlafaxine was discontinued and, in agreement with the patient, lithium was resumed. A week later, menometrorrhagia reoccurred within a few days, ceased again within a few days when lithium was stopped again, and did not reoccur again. During this whole 6-month period, no modification of the body mass index was monitored, the eating disorder remained in remission and Mrs X did not change her combined oral contraceptive. The authors did not monitor hormonal serum levels but a placebo controlled study has shown that lithium does not influence the serum levels of prolactin, luteinizing hormone, follicle-stimulating hormone, 17-1 estradiol or progesterone. The effect of lithium might well have occurred at the cellular level. Indeed, lithium admittedly induces inositol depletion while some of the effects of luteinizing hormone are mediated via the phosphatidylinositol transduction pathway. Lithium may, therefore, have counteracted these effects and have thereby disrupted the patient’s hormonal cycle. Besides, it has been shown in mice that the chronic administration of lithium results in a complete disruption in the regularity of the estrous cycle. In France, a standardized assessment of adverse drug reactions has been used since 1977. This method, based on the combination of chronological and symptomatological criteria, leads to a 5-level ‘imputation’ score. In this case of menometrorrhagia, lithium had a very evocative challenge-dechallenge-rechallenge profile and reached the ‘likely’ level (level 4). Although lithium had not previously been reported as accountable for menometrorrhagia, practitioners should be aware of this potential adverse effect and should ask women of childbearing age about menometrorrhagia after the introduction of lithium.