[Hepatitis C in a psychiatric setting: A forgotten reservoir?] / Hépatite C en milieu psychiatrique : un réservoir oublié ?

Hepatitis C is a transmissible hepatic and extra-hepatic disease caused by the hepatitis C virus (HCV). HCV develops into a chronic infection among approximately 70% of the contaminated subjects. Chronic HCV infection is estimated to affect between 0.5% and 1 % of the general population in France, which causes an important burden of disease, in particular due to the occurrence of cirrhosis and liver cancer. New antiviral drugs now allow to cure more than 95% of patients in just a few weeks of treatment with very limited safety issues. This therapeutic revolution has led the World Health Organization and many national governments to aim for an elimination of HCV, which has been defined as a 90%-reduction of the incidence rate, and a 65%-reduction in the number of HCV-related deaths on the basis of the 2015 figures. In this respect, the French Ministry of Health has recently decided to extend the ability to prescribe the new antiviral drugs to any physician. However, the elimination campaign of HCV will also need to correctly identify, screen, and treat the main target populations. If people who inject drugs (PWIDs) certainly constitute the most important population concerned by the challenge of HCV elimination, more hidden reservoirs in which HCV transmission can insidiously evolve should be identified and specifically targeted as well. Inpatient psychiatric populations might constitute one of these hidden reservoirs. International data suggest that chronic HCV infection affects approximately 5% of psychiatric inpatients in Europe. This very high prevalence estimate can in part be due to the very frequent psychiatric disorders found among the current or former PWIDs. However, a part of the seropositive patients does not report a history of drug use, and other factors could contribute to the increased risk of contamination in this population including atypical routes of transmission related to institutional promiscuity. Exploring the general profile and risk-behaviors of the psychiatric inpatients found infected by the HCV is thus warranted for future studies. Screening and treating HCV in the specific population of psychiatric patients is part of the general public health objective of eliminating HCV at a national level. Moreover, it also directly fits into the individualized psychiatric care. Many recent data suggest that HCV also has a neural tropism, in particular within glial cells, such as astrocytes or oligodendrocytes. As such, HCV foments inflammatory processes in the brain and contributes to cognitive impairments and psychiatric symptoms such as anxiety or depression. At the individual level, treating HCV infection can improve the psychiatric state and increase patients' outcomes in terms of well-being and quality of life. For all these reasons, the field of psychiatry needs local and national actions for informing and training professionals about HCV screening and treating modalities. Patient and family associations also need to be involved in this general effort of micro-elimination. A key role should be assigned to the general practitioners embedded within inpatient psychiatric units. They are the best fitted professionals to screen, treat, and empower patients, to inform and train other caregivers of the psychiatric field, and to act as a relay with hepatology teams if required. Hospital pharmacists are other important stakeholders. In a national context in which the funding of psychiatric care, including medications, is based on predefined funding envelops, innovative initiatives will have to be set up by local or national health authorities, in partnership with pharmacists, to allow for the treatment of psychiatric inpatients. In conclusion, the world of psychiatry is a possible hidden reservoir of HCV and, as such, a part of the challenge for eliminating the virus. Patients, families, and caregivers will have to be correctly sensitized and trained to play their role in the process. Specific investigations will be required to better understand why such an increased prevalence of HCV is observed in this population. Specific adaptations of the cascade of care within psychiatric settings, including access to treatment, will need to be designed, implemented, and evaluated for reaching micro-elimination of HCV in psychiatry.

RNA editing blood biomarkers for predicting mood alterations in HCV patients.

Treatment-emergent depression is a common complication in patients with chronic hepatitis C virus (HCV) infection undergoing antiviral combination therapy with IFN-α and ribavirin. It has recently been shown that changes in A-to-I RNA editing rates are associated with various pathologies such as inflammatory disorders, depression and suicide. Interestingly, IFN-α induces gene expression of the RNA editing enzyme ADAR1-1 (ADAR1a-p150) and alters overall RNA editing activity. In this study, we took advantage of the high prevalence of pharmacologically induced depression in patients treated with IFN-α and ribavirin to test the interest of RNA editing-related biomarkers in white blood cells of patients. In this 16-week longitudinal study, a small cohort of patients was clinically evaluated using standard assessment methods prior to and during antiviral therapy and blood samples were collected to analyse RNA editing modifications. A-I RNA editing activity on the phosphodiesterase 8A (PDE8A) gene, a previously identified RNA editing hotspot in the context of lupus erythematosus, was quantified by using an ultra-deep next-generation sequencing approach. We also monitored gene expression levels of the ADAR enzymes and the PDE8A gene during treatment by qPCR. As expected, psychiatric evaluation could track treatment-emergent depression, which occurred in 30% of HCV patients. We show that PDE8A RNA editing is increased in all patients following interferon treatment, but differently in 30% of patients. This effect was mimicked in a cellular model using SHSY-5Y neuroblastoma cells. By combining the data of A-I RNA editing and gene expression, we generated an algorithm that allowed discrimination between the group of patients who developed a treatment-emergent depression and those who did not. The current model of drug-induced depression identified A-I RNA editing biomarkers as useful tools for the identification of individuals at risk of developing depression in an objective, quantifiable biological blood test.

[Education care in patients with psychiatric disorders in France: Psychoeducation or therapeutic patient education?] / L'éducation thérapeutique pour les patients souffrant de troubles psychiatriques en France : psychoéducation ou éducation thérapeutique du patient ?

CONTEXT: Psychoeducation and therapeutic patient education can be effectively included in treatments for patients with psychiatric disorders. These two effective educational therapies have the common purpose of improving disorder-related morbidity, compliance with treatment and patients' quality of life. While they have different methods of application, both teach patients to play an active role in their own care. However, it is still critical to combine them for care of patients with psychiatric and addiction disorders in a manner that allows for specificity. To do this, the differences between psychoeducation and therapeutic patient education must be considered, and their potential for the management of patients with psychiatric and addiction disorders must be determined. METHODS: In our article, we review the literature concerning therapeutic education programs for patients and discuss the literature based on the experiences of psychiatrists trained in these therapies. RESULTS: Despite rather nonrestrictive guidelines, and after reviewing numerous studies, we found that psychoeducation seems to be rarely used in psychiatry. The use of therapeutic patient education programs for psychiatric patients has doubled in four years but still accounts for less than 4% of validated programs in France. Only 154 programs were developed in 1175 public psychiatric facilities in 2016. Therapeutic patient education has a legal framework and recommendations, which make it suitable for inclusion in care and in the training of care providers. The rigor in the development of therapeutic patient education programs and the requirement for training and financial support reinforce the need for their establishment in healthcare institutions. As such, they could help to modify professional practices and the culture of care in mental health fields. CONCLUSION: There is a place for therapeutic patient education in psychiatry as it provides a real benefit for patients. It could modify care practices and costs, and is suitable for patients with psychiatric or addiction disorders by helping them play an active role in their care, thereby improving treatment outcomes and quality of life.

Psychiatric and substance use disorders in HIV/hepatitis C virus (HCV)-coinfected patients: does HCV clearance matter? [Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) HEPAVIH CO13 cohort].

OBJECTIVES: The objective of this nested study was to assess the prevalence of psychiatric disorders in a sample of HIV/hepatitis C virus (HCV)-coinfected patients according to their HCV status. METHODS: The nested cross-sectional study, untitled HEPAVIH-Psy survey, was performed in a subset of HIV/HCV-coinfected patients enrolled in the French Agence Nationale de Recherche sur le SIDA et les Hépatites Virales (ANRS) CO13 HEPAVIH cohort. Psychiatric disorders were screened for using the Mini International Neuropsychiatric Interview (MINI 5.0.0). RESULTS: Among the 286 patients enrolled in the study, 68 (24%) had never received HCV treatment, 87 (30%) were treatment nonresponders, 44 (15%) were currently being treated and 87 (30%) had a sustained virological response (SVR). Of the 286 patients enrolled, 121 patients (42%) screened positive for a psychiatric disorder other than suicidality and alcohol/drug abuse/dependence, 40 (14%) screened positive for alcohol abuse/dependence, 50 (18%) screened positive for drug abuse/dependence, 50 (17.5%) were receiving an antidepressant treatment and 69 (24%) were receiving an anxiolytic. Patients with an SVR did not significantly differ from the other groups in terms of psychiatric disorders. Patients receiving HCV treatment screened positive less often for an anxiety disorder. The highest rate of drug dependence/abuse was among HCV treatment-naïve patients. CONCLUSIONS: Psychiatric disorders were frequent in HIV/HCV-coinfected patients and their rates were comparable between groups, even for patients achieving an SVR. Our results emphasize the need for continuous assessment and care of coinfected patients, even after HCV clearance. Drug addiction remains an obstacle to access to HCV treatment. Despite the recent advent and continued development of directly acting antiviral agents (DAAs), it is still crucial to offer screening and comprehensive care for psychiatric and addictive disorders.

[Alcohol consumption in patients with psychiatric disorders: assessment and treatment]. / Usage d'alcool chez les patients souffrant de troubles psychiatriques : quelles évaluations ? Quelle prise en soin ?

Alcohol consumption in France exceeds the European average (12.7L of pure alcohol/habitant/year in 2009 for an average of 12.5 L). This consumption has a major professional, social and health impact on the individuals and their families. The cost of such, estimated in Europe to be of 155.8 billion Euros in 2010, is the highest among the central nervous system diseases in Europe, far higher than that of depression or dementia. Patients suffering from psychiatric disorders are more frequently affected by problems related to alcohol use than the general population. They are also more vulnerable to the immediate and subsequent consequences of their consumption. The alcohol related disorders that are often accompanied by risk taking and other addictive behaviour require a global assessment of the addiction, with and without substance, and of the complications. These have a strong impact on risk taking, compliance with care, and the morbidity of somatic and psychiatric disorders, as well as access to optimal care and the life span of patients suffering from psychiatric disorders. The development of addictology care, with integrative treatment programs, is recommended in response to these public health issues. Nevertheless, specific addictology practices and partners with addictology care structures are still scarcely developed in psychiatry. Firstly, it would be necessary to set up such integrated treatments through the systematisation of an "addictology" checkup on admission, a global assessment of addictive behaviour and cognitive disorders, using pragmatic tools that are user-friendly for the care teams, maintain the reduction in risk taking, and apply prescriptions for addiction to psychotropic treatments, in liaison with the referring general practitioner. As early as possible, accompanied by specific training in addictology for the psychiatrists and the mental health nursing teams, such care could be enhanced by the development of liaison and advanced psychiatric consultation teams, specialised in addictology, together with the installation of a addictology care network in supplementary psychiatry of levels 1, 2 and 3 in addictology. This network of specific care would notably permit the integrated management of patients suffering from acute psychiatric disorders or requiring care under constraint. More specific care networks for particular problems (maternity issues, adolescence, HIV and hepatitis, cognitive disorders…) and programs of therapeutic education could reinforce this proposal within a protocol of care that should be legible, coherent and coordinated. The psychiatrist and the addictologist must therefore learn to work together over and above the dogmatic boundaries and positioning in a constructive and efficient partnership, beneficial for the patient.

[Atypical depression: Clinical perspectives]. / La dépression atypique : perspectives cliniques.

OBJECTIVE: This paper examines whether atypical depression is still a valid entity as a diagnosis subtype in the light of publications with most recent antidepressants. METHOD: First, we present the origins of the diagnosis sub-specification of atypical depression, which is based on a different drug response to tricyclic antidepressants and mono amino oxydase inhibitors. Secondly, we discuss the different definitions that can be found for the terms of atypical depression. We present more specifically the definition of atypical depression as it is described in the DSM-IV, with its most important criterion: mood reactivity. Then we present a review of scientific publications questioning atypical depression validity as a clinical syndrome (based on medline researches). We will see whether this diagnosis is still relevant with the latest drugs used to treat mood disorders. A special focus is made on the link between atypical depression and bipolar disorder, based on Benazzi's work. RESULTS: Most of publications confirm that atypical depression is a valid syndrome regarding first antidepressants clinical trials. Nevertheless, more studies with the latest antidepressants and atypical antipsychotics are needed to confirm this hypothesis. The link between atypical depression and bipolar disorders seems to be quite strong although it requires further investigations. DISCUSSION: There are very few double-blind drug trials focusing on atypical depressions and results need to be confirmed by trials with new drugs. Moreover, we regret that there are no studies including cerebral imagery. More studies are also needed on neurobiology and psychotherapy specificity. CONCLUSION: Atypical depression is still a useful concept, because of its specific clinical presentation, evolution and treatments, even if more studies should be done. Atypical depression could also be useful to diagnose more easily some bipolar disorders and should help clinicians to focus more on suicidal risks and addiction evaluation for these patients, considering the mood reactivity and the link with bipolar disorder. To conclude, we propose that atypical depression should still figure in the future DSM-V for these different reasons.

[Management of patients with hepatitis C by French psychologists and psychiatrists: a practical investigation]. / Prise en charge des patients atteints d'hépatites C par les psychiatres et les psychologues: une enquête de pratique.

INTRODUCTION: A first part of this survey showed that up to 19% of patients with hepatitis C virus did not receive optimal treatment because of a psychiatric problem (psychiatric disorders or addictive behaviours) and that less than 50% of the managing clinicians worked with a psychiatrist or a psychologist in these cases. The aim of the second part of the survey was to describe the current practices provided by the psychiatrists and the psychologists to HCV infected patients as well as the knowledge and expectations of professionals in this area. PATIENTS AND METHODS: Forty-seven psychiatrists and 43 psychologists who were or were not working with French reference poles for hepatitis C virus responded to a questionnaire of their practices. RESULTS: Analysis of the 90 questionnaires showed that psychiatric and/or psychological care was not systematic. Psychiatrists and psychologists should be given more information and specific training about this topic. CONCLUSION: Psychiatric and psychological care of chronic hepatitis C virus infected patients should be improved. French reference poles should also become "references" for psychiatric care.

Management of psychiatric disorders and addictive behaviors in patients with viral hepatitis C in France.

INTRODUCTION: Guidelines concerning the management of psychiatric disorders and addictive behaviors in patients with chronic hepatitis C and the conditions of collaboration between hepatogastroenterologists, infectiologists, psychiatrists and psychologists have not been published. This has a negative influence on optimal therapeutic management of chronic hepatitis C virus (HCV) infection. The aim of this study was to describe the current clinical practices for ambulatory management of psychiatric disorders and addictions, and the influence of a possible psychiatric and/or psychological collaboration. PATIENTS AND METHODS: A retrospective survey was conducted among 101 clinicians treating patients with chronic hepatitis C. Data were collected from personal interviews with the managing clinicians and from the files of patients with chronic hepatitis C patients who presented psychiatric disorders. RESULTS: Analysis of the 101 interviews and 598 patient files showed that 19% of patients had not received an optimal treatment for their HCV infection because of a psychiatric problem, and that less than 50% of the managing clinicians were working in collaboration with a psychiatrist or a psychologist. In conclusion, lack of collaboration between hepatogastroenterologists and psychiatrists could be deleterious for the optimal treatment of HCV infected patients. Improvement is required.

[Adherence to pegylated combination therapy in patients with chronic hepatitis C. Importance of the hepatologist, general practitioner, and nurse]. / Adhésion à la bithérapie pégylée au cours de l'hépatite chronique C. Importance du trio hépatologue, médecin généraliste, infirmière.

Adhesion to pegylated combination therapy is a key factor for therapeutic success in patients HCV infected. To optimize it, goals to reach are to limit dose reduction and premature discontinuation of treatment due to adverse events ; to improve the patient compliance to treatment, particularly during the first three months, particularly to ribavirin. Therapeutic education, management of psychiatric adverse events, epoetin alfa, have demonstrated their benefit in terms of sustained virologic response or quality of life. Preparing the treatment with the patient and a multi-disciplinary team, setting successive therapeutic goals with the predictive value of the early virologic response will promote adhesion to treatment. A hepatitis C training program for general practitioners (GP) allows an efficient follow-up of treated patients by a trio hepatologist - GP - nurse and a concrete implication of GP in the field of hepatitis C. Further developments are needed for : taking in account the patient quality of life during treatment to anticipate premature discontinuation, promotion of therapeutic education by specialized nurses, standardization of the diagnosis of depression during treatment, and regular updating of general practitioners on antiviral C treatment.

Comparison of the effects of iodine and iodide on thyroid function in humans.

Concerns have been raised over the use of iodine for disinfecting drinking water on extended space flights. Most fears revolve around effects of iodide on thyroid function. iodine (I2) is the form used in drinking-water disinfection. Risk assessments have treated the various forms of iodine as if they were toxicologically equivalent. Recent experiments conducted in rats found that administration of iodine as I- (iodide) versus I2 had opposite effects on plasma thyroid hormone levels. I2-treated animals displayed elevated thyroxine (T4) and thyroxine/triiodothyronine (T/T3) ratios, whereas those treated with I- displayed no change or reduced plasma concentrations of T4 at concentrations in drinking water of 30 or 100 mg/L. The study herein was designed to assess whether similar effects would be seen in humans as were observed in rats. A 14-d repeated-dose study utilizing total doses of iodine in the two forms at either 0.3 or 1 mg/kg body weight was conducted with 33 male volunteers. Thyroid hormones evaluated included T4, T3, and thyroid-stimulating hormone (TSH). TSH was significantly increased by the high dose of both I2 and I-, as compared to the control. Decreases in T4 were observed with dose schedules with I- and I2, but none were statistically significant compared to each other, or compared to the control. This human experiment failed to confirm the differential effect of I2 on maintenance of serum T4 concentrations relative to the effect of I- that was observed in prior experiments in rats. However, based on the elevations in TSH, there should be some concern over the potential impacts of chronic consumption of iodine in drinking water.

[Benzodiazepines and forensic aspects]. / Benzodiazépines et passage à l'acte criminel.

Adverse effects of benzodiazepines are well known since the first one was used in 1958 (chlordiazepoxide). The literature collects study-cases or rarely controlled studies concerning side effects or paradoxical reactions to benzodiazepines. They mostly described drowsiness and behavioral disinhibition, including increased well-being feeling but also hostility, rage access with feeling of invulnerability, serious crimes and sometimes homicides. Delusional, manic, confusional or depressive states are also pointed out. Rate for aggressive behaviour is 0.3 to 0.7% but distinction should be done between accidental or "idiosyncratic" reaction and voluntary sought disinhibition, clearly more frequent. No benzodiazepine has any specificity for these adverse effects but pharmacology, doses, associated drugs (or alcohol) and psychopathology interact to produce hazardous psychic states. Pharmacology: GABA induces a decrease in serotonin compound and vigilance. Pharmacokinetic: first dose effect or over-dose effect, short half-life, lipophily, affinity, digestive absorption, active metabolites interact. Psychopathology: age, alcohol association, psychological status (high initial level of hostility, impulsivity, frustration, personality disorder and depressive status). External conditions: chronic illness, affective and professional frustrations, physical or psychic exhaustion contribute also. Some benzodiazepines (flunitrazepam, diazepam, clorazepate, triazolam, alprazolam, lorazepam, for example) are more often concerned for pharmacokinetics characteristics but also prescription habits. Forensic aspects should be considered in case of homicide. Especially, reality of benzodiazepines consumption and awareness of the potential paradoxical reaction should be precisely evaluated. Special focus on voluntary induced disinhibition has to be done for forensic considerations. Relationship but also crime facilitations are sometimes consciously sought. Some benzodiazepines have already been identified for this use: flunitrazepam, clorazepate but also triazolam and temazepam in UK, alprazolam in USA. Flunitrazepam is prohibited in USA and considered as narcotics in France. A Swedish study showed that violent acts were more frequent and serious in juvenile offenders taking flunitrazepam/alcohol than other young offenders staying in the same correctional institution. They recommended classification of flunitrazepam as narcotic. A study from Belgium with drug addicts concluded in the same way and asked for an increased information of professionals and a more efficient control of the delivery. Before concluding to idiosyncratic effect, and then possibly to penal irresponsibility, the forensic approach should consider: firstly the reality of the benzodiazepines absorption and implication in committing violence (urine test, chronology, amnesia); secondly, the association of unusual behaviour and converging circumstances (pharmacological, pharmacokinetic, psychopathology, external conditions); thirdly the consumer's knowledge of the disinhibition effect. In our prison practice, we have to be particularly cautious as population frequently associates personality disorder, drug addiction and high level of frustration related to penitential context. Special information should be given to inmates when benzodiazepines are prescribed, but more extensively, a preventive strategy should be adopted in general population.

[Apropos of atypical melancholia with Sustiva (efavirenz)]. / A propos d'un état mélancolique atypique sous Sustiva (Efavirenz).

The treatment of HIV infection has changed dramatically in recent years as a result of the development of new drugs which allows a variety of multitherapy combinations more adapted to patients' needs and thereby improving compliance. Efavirenz is a non-nucleoside reverse transcriptase inhibitor. In addition to a potent antiretroviral activity, efavirenz is an easy-to-take drug with once-daily dosing and is usually well tolerated. Efavirenz, however, may induce psychic alterations which are variable and atypical in both their clinical presentation and severity. As early as the first days of treatment, efavirenz may provoke surprising phenomena such as nightmares, vivid dreams, hallucinations or illusions, and twilight states. Depersonalization and derealization episodes, personality alterations, stream of thought troubles and unusual thought contents, atypical depression and cognitive disorders have also been observed. These phenomena may occur either early or later on treatment. The prevalence of severe psychic disorders is less than 5%, but they are often responsible for harmful treatment discontinuations. Psychiatric side effects are heterogeneous and probably not related to pre-existing psychologic weakness. We do not have enough data to evaluate these side effects and their etiopathogeny. The drug could act directly on the central nervous system since it crosses the blood-brain barrier, on the serotoninergic and dopaminergic systems. Some authors have compared efavirenz-induced psychic effects to those associated with LSD and found structural similarities between the two molecules. However, the heterogeneity and low prevalence of the psychiatric side effects of efavirenz suggest and individual sensitivity. In order to improve patient care, a better clinical approach, neuropsychological evaluation, and functional brain imagery should be used to progress in the analysis and comprehension of these disorders. We discuss in this paper the case of Mister H. This HIV-infected person presented with two severe melancholic episodes associated with marked cognitive disorders which resisted two successive antidepressant treatments (viloxazine and citalopram, respectively) prescribed at effective doses and for sufficient time duration. Mister H. had no personal or family psychiatric antecedent. His psychic condition improved only when efavirenz was discontinued. However, drug discontinuation may not be an obligatory step to improve the patient's condition since antidepressant treatment has been found effective in some similar situations. Actually, each case should be discussed with the clinicians taking care of the patient.

[Assisted reproductive technique for an opiates dependant couple]. / Assistance médicale à la procréation chez un couple dépendant aux opiacés.

The aim of our network "Motherhood and Addiction Alsace" is to take care of opiates addicted pregnant women in order to permit the birth of a healthy child, raised by stabilized parents both on drug use and psychosocial status. A couple, both on methadone treatment, with chronic hepatitis for the husband had access to an in vitro fertilization program thanks to the network care. The difficulties on the path to parenthood, the adequate use of painkillers, neonatal care and the use of a coordinated action of all health professionals are discussed.