[A guide to psychiatric prescribing in pregnancy, postpartum and breastfeeding]. / Guide de prescription psychiatrique pendant la grossesse, le postpartum et l'allaitement.

Perinatal psychopharmacology is an emerging specialty that is gradually developing alongside perinatal psychiatry. The management of psychiatric disorders during the perinatal period is a challenge for perinatal practitioners due to the multiple changes occurring during this crucial period. This little-known specialty still suffers from inappropriate considerations on the impact of psychotropic treatments on the mother and the infant during pregnancy and postpartum, which can promote a deficiency in perinatal psychic care. However, the risks associated with insufficient management of mental health are major, impacting both the mental and physical health of the mother and the infant. In this paper, we propose a perinatal psychopharmacology prescription guide based on available scientific evidence and international and national recommendations. We thus propose a decision-making process formalized on simple heuristics in order to help the clinician to prescribe psychotropic drugs during the perinatal period.

[Anticholinergic scales: Use in psychiatry and update of the anticholinergic impregnation scale]. / Les échelles anticholinergiques : usage en psychiatrie et mise à jour de l'échelle d'imprégnation anticholinergique.

Anticholinergic properties are well known to prescribers, notably in mental health, as a therapeutic strategy for i.e. extrapyramidal syndrome but also as a source of numerous adverse side effects. Herein, we propose a narrative literature review describing: (i) cholinergic pharmacology and anticholinergic properties; (ii) the importance of anticholinergic therapeutic properties in psychiatry; (iii) the existing anticholinergic drug scales and their usage limitations in Psychiatry and; last (iv) an update to the anticholinergic drug impregnation scale, designed for the French psychiatry practice. The anticholinergic side effects can appear both in the peripheral level (dry mouth, constipation, etc.) and in the central level (especially as cognitive deficits). Many of the so called « anticholinergic ¼ drugs are in fact entirely or mostly antimuscarinic and act essentially as parasympathetic system antagonists. Overall, anticholinergic/antimuscarinic side effects are usually attributed to psychotropic medications: to certain antipsychotics, notably classical neuroleptics such as phenothiazine and also to tricyclic antidepressants. In practice, the impact of anticholinergic toxicity treatments is often highlighted due to their excessively prolonged use in patients on antipsychotics. Interestingly, these antipsychotic treatments are better known for their anticholinergic side effects, especially cognitive ones, with an early onset specially in elder patients and/or in the case of polymedication. In order to evaluate anticholinergic side effects, metrics known as anticholinergic burden scales were created in the last few decades. Nowadays, 13 different scales are documented and accepted by the international academic community, but only three of them are commonly used: the Anticholinergic Drug Scale (ADS), the Anticholinergic Risk Scale (ARS) and the Anticholinergic Burden Scale (ACB). All of them are based on a similar principle, consisting of grading treatments individually, and they are normally scored from 0 - no presence of side effects - to 3 - anticholinergic effects considered to be strong or very strong. Using these scales enables the calculation of the so-called "anticholinergic burden", which corresponds to the cumulative effect of using multiple medications with anticholinergic properties simultaneously. The application of anticholinergic scales to patients with psychiatric disorders has revealed that schizophrenic patients seem to be especially sensitive to anticholinergic cognitive side effects, while elder and depressed patients were more likely to show symptoms of dementia when exposed to higher anticholinergic burden. Unfortunately, these tools appear to have a low parallel reliability, and so they might induce large differences when assessing side effects predictability. In addition, the capacity of these scales to predict central adverse effects is limited due to the fact they poorly or do not differentiate, the ability of treatments to cross the blood-brain barrier. Finally, one last limitation on the validity of these scales is prescription posology is not accounted for side effects considered to be dose dependent. Recently, the MARANTE (Muscarinic Acetylcholine Receptor ANTagonist Exposure) scale has incorporated an anticholinergic burden weighting by posology. Nevertheless, this new model can be criticized, due to the limited number of medications included and due to testing a limited number of potency ranges and dosages for each treatment. Herein, we propose an update to the Anticholinergic Impregnation Scale, developed specifically for the French Psychiatry practice. The scale validation was based on an evaluation of the prescriptions correcting anticholinergic peripheral side effects (constipation, xerostomia and xeropthalmia). This indirect evaluation allowed us to show patients with an anticholinergic impregnation score higher than 5 received significantly more treatments for constipation and xerostomia. This strategy bypasses the bias of a cognitive evaluation in patients with severe mental health disorders. Moreover, the relevance of a tool developed specifically for French psychiatry is justified by the fact that some highly prescribed treatments for mental illness in France (cyamemazine and tropatemine) are strong anticholinergics, and also by the fact they are rarely included in the existing anticholinergic scales. This update of the original scale, published in 2017, includes information whether prescribed drugs cross the blood-brain barrier and thus makes possible a more accurate assessment when evaluating anticholinergic central side effects. Finally, the anticholinergic impregnation scale will soon be integrated into a prescription help software, which is currently being developed to take into consideration dose dependent adverse effects.

Psychotropics and COVID-19: An analysis of safety and prophylaxis.

The use of psychotropics during the COVID-19 pandemic has raised two questions, in order of importance: first, what changes should be made to pharmacological treatments prescribed to mental health patients? Secondly, are there any positive side effects of these substances against SARS-CoV-2? Our aim was to analyze usage safety of psychotropics during COVID-19; therefore, herein, we have studied: (i) the risk of symptomatic complications of COVID-19 associated with the use of these drugs, notably central nervous system activity depression, QTc interval enlargement and infectious and thromboembolic complications; (ii) the risk of mistaking the iatrogenic impact of psychotropics with COVID-19 symptoms, causing diagnostic error. Moreover, we provided a summary of the different information available today for these risks, categorized by mental health disorder, for the following: schizophrenia, bipolar disorder, anxiety disorder, ADHD, sleep disorders and suicidal risk. The matter of psychoactive substance use during the pandemic is also analyzed in this paper, and guideline websites and publications for psychotropic treatments in the context of COVID-19 are referenced during the text, so that changes on those guidelines and eventual interaction between psychotropics and COVID-19 treatment medication can be reported and studied. Finally, we also provide a literature review of the latest known antiviral properties of psychotropics against SARS-CoV-2 as complementary information.

Panic and pandemic: Narrative review of the literature on the links and risks of panic disorder as a consequence of the SARS-CoV-2 pandemic.

Although the "panic" word has been abundantly linked to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific literature very few studies have considered whether the current epidemic could predispose to the onset or the aggravation of panic attacks or panic disorder. Indeed, most studies thus far have focused on the risk of increase and aggravation of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic disorder, especially the subtype with prominent respiratory symptoms, which is characterized by a fear response conditioning to interoceptive sensations (e.g., respiratory), and hypervigilance to these interoceptive signals, could be expected in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea, are among the most commonly associated with the SARS-CoV-2 (59-82% and 31-55%, respectively), and respiratory symptoms are associated with a poor illness prognosis. Hence, given that some etiological and maintenance factors associated with panic disorder - i.e., fear conditioning to abnormal breathing patterns attributable or not to the COVID-19 (coronavirus disease 2019), as well as hypervigilance towards breathing abnormalities - are supposedly more prevalent, one could expect an increased risk of panic disorder onset or aggravation following the COVID-19 pandemic in people who were affected by the virus, but also those who were not. In people with the comorbidity (i.e., panic disorder or panic attacks and the COVID-19), it is particularly important to be aware of the risk of hypokalemia in specific at-risk situations or prescriptions. For instance, in the case of salbutamol prescription, which might be overly used in patients with anxiety disorders and COVID-19, or in patients presenting with diarrhea and vomiting. Hypokalemia is associated with an increased risk of torsade de pointe; thus, caution is required when prescribing specific psychotropic drugs, such as the antidepressants citalopram and escitalopram, which are first-line treatments for panic disorder, but also hydroxyzine, aiming at anxiety relief. The results reviewed here highlight the importance of considering and further investigating the impact of the current pandemic on the diagnosis and treatment of panic disorder (alone or comorbid with the COVID-19).

[Psychopharmacotherapeutic guidelines : a challenge during health crisis]. / Recommandations psychopharmacothérapeutiques : un défi en temps de crise sanitaire.

The construction of pharmacological guidelines is a complex endeavor, and this is all the truer amidst a health crisis such as the current SARS-CoV-2 pandemic. In psychiatric settings, guidelines have to consider the handling of other drugs (i.e., psychotropic medications), that have been suggested as potentially prophylactic for COVID-19. These dialectics are discussed here, and the methodological foundations used for the elaboration of guidelines are put forward.

Réaliser des recommandations pharmacothérapeutiques est une démarche complexe, plus encore dans une période de crise sanitaire, comme celle que nous traversons avec la pandémie liée au SARS-CoV-2. En psychiatrie, les préconisations formulées se doivent de rappeler la légitime prudence à adopter dans le maniement des psychotropes, dans un contexte qui, par ailleurs, présente certaines de ces médications comme potentiellement prophylactiques de la COVID-19. Ces enjeux contradictoires sont débattus, les concepts méthodologiques de l'élaboration des recommandations sont rappelés.

[Panic and pandemic: Review of the literature on the links between panic disorder and the SARS-CoV-2 epidemic]. / Panique et pandémie : revue de la littérature sur les liens entre le trouble panique et l'épidémie à SARS-CoV-2.

Although the "panic" word has been abundantly linked to the SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) pandemic in the press, in the scientific literature very few studies have considered whether the current epidemic could predispose to the onset or the aggravation of panic attacks or panic disorder. Indeed, most studies thus far have focused on the risk of increase and aggravation of other psychiatric disorders as a consequence of the SARS-CoV-2 epidemic, such as obsessive-compulsive disorder (OCD), post-traumatic stress disorder (PTSD), and generalized anxiety disorder (GAD). Yet, risk of onset or aggravation of panic disorder, especially the subtype with prominent respiratory symptoms, which is characterized by a fear response conditioning to interoceptive sensations (e.g., respiratory), and hypervigilance to these interoceptive signals, could be expected in the current situation. Indeed, respiratory symptoms, such as coughs and dyspnea, are among the most commonly associated with the SARS-CoV-2 (59-82% and 31-55%, respectively), and respiratory symptoms are associated with a poor illness prognosis. Hence given that some etiological and maintenance factors associated with panic disorder - i.e., fear conditioning to abnormal breathing patterns attributable or not to the COVID-19 (coronavirus disease 2019), as well as hypervigilance towards breathing abnormalities - are supposedly more prevalent, one could expect an increased risk of panic disorder onset or aggravation following the COVID-19 epidemic in people who were affected by the virus, but also those who were not. In people with the comorbidity (i.e., panic disorder or panic attacks and the COVID-19), it is particularly important to be aware of the risk of hypokalemia in specific at-risk situations or prescriptions. For instance, in the case of salbutamol prescription, which might be overly used in patients with anxiety disorders and COVID-19, or in patients presenting with diarrhea and vomiting. Hypokalemia is associated with an increased risk of torsade de pointe, thus caution is required when prescribing specific psychotropic drugs, such as the antidepressants citalopram and escitalopram, which are first-line treatments for panic disorder, but also hydroxyzine, aiming at anxiety reduction. The results reviewed here highlight the importance of considering and further investigating the impact of the current pandemic on the diagnosis and treatment of panic disorder (alone or comorbid with the COVID-19).

[Informations on psychotropics and their adaptations for patients suffering from mental disorders in France during the SARS-CoV-2 epidemic]. / Informations relatives aux psychotropes et à leurs adaptations éventuelles pour les patients souffrant de troubles psychiques en France pendant l'épidémie à SARS-CoV-2.

The 2019-20 coronavirus pandemic (SARS-CoV-2; severe acute respiratory syndrome coronavirus 2) has dramatic consequences on populations in terms of morbidity and mortality and in social terms, the general confinement of almost half of the world's population being a situation unprecedented in history, which is difficult today to measure the impact at the individual and collective levels. More specifically, it affects people with various risk factors, which are more frequent in patients suffering from psychiatric disorders. Psychiatrists need to know: (i) how to identify, the risks associated with the prescription of psychotropic drugs and which can prove to be counterproductive in their association with COVID-19 (coronavirus disease 2019), (ii) how to assess in terms of benefit/risk ratio, the implication of any hasty and brutal modification on psychotropic drugs that can induce confusion for a differential diagnosis with the evolution of COVID-19. We carried out a review of the literature aimed at assessing the specific benefit/risk ratio of psychotropic treatments in patients suffering from COVID-19. Clinically, symptoms suggestive of COVID-19 (fever, cough, dyspnea, digestive signs) can be caused by various psychotropic drugs and require vigilance to avoid false negatives and false positives. In infected patients, psychotropic drugs should be used with caution, especially in the elderly, considering the pulmonary risk. Lithium and Clozapine, which are the reference drugs in bipolar disorder and resistant schizophrenia, warrant specific attention. For these two treatments the possibility of a reduction in the dosage - in case of minimal infectious signs and in a situation, which does not allow rapid control - should ideally be considered taking into account the clinical response (even biological; plasma concentrations) observed in the face of previous dose reductions. Tobacco is well identified for its effects as an inducer of CYP1A2 enzyme. In a COVID+ patient, the consequences of an abrupt cessation of smoking, particularly related with the appearance of respiratory symptoms (cough, dyspnea), must therefore be anticipated for patients receiving psychotropics metabolized by CYP1A2. Plasma concentrations of these drugs are expected to decrease and can be related to an increase risk of relapse. The symptomatic treatments used in COVID-19 have frequent interactions with the most used psychotropics. If there is no curative treatment for infection to SARS-CoV-2, the interactions of the various molecules currently tested with several classes of psychotropic drugs (antidepressants, antipsychotics) are important to consider because of the risk of changes in cardiac conduction. Specific knowledge on COVID-19 remains poor today, but we must recommend rigor in this context in the use of psychotropic drugs, to avoid adding, in patients suffering from psychiatric disorders, potentially vulnerable in the epidemic context, an iatrogenic risk or loss of efficiency.

[Challenges for psychotropics in the context of the SARS-Cov-2 pandemic]. / Enjeux de l'utilisation des psychotropes dans le cadre de la pandémie au SARS-Cov-2.

French recommendations have been proposed for psychotropics use and possible adaptations during the SARS-CoV-2 epidemic. Between uncertainties linked to the lack of data and speculations about possible benefits of psychotropics against the coronavirus, we propose here elements allowing to base the pharmacotherapeutic decisions potentially useful in Covid+ patients with psychiatric disorders.

[IDEM-depression: Characteristics and evaluation of an open group that combines psychoeducation and cognitive-behavior therapy]. / IDEM-dépression : caractéristiques et évaluation d'un groupe ouvert combinant psycho-éducation et thérapie cognitivo-comportementale.

INTRODUCTION: Depression is a highly prevalent mental illness that is associated with high rates of morbidity and functional impairment. At the psychiatric unit of the University Hospital of Strasbourg, France, we have developed an open group that combines psychoeducation and cognitive-behavior therapy (CBT), the information, discovery, exchange and mobilization for depression group (IDEM-depression). IDEM-depression is composed of 17 thematic, structured, and independent sessions, which address different aspects of depression (i.e., rumination, pharmacological treatments). Because of its flexible format, patients with varying degrees of depression severity (from remission up to severe depressive symptoms) and whose depression might be bipolar or unipolar, are able to participate in the group. Thus, the group is well suited to a large number of patients with major depression. In the present study we aimed at describing the IDEM-depression group and presenting results regarding patients' overall satisfaction, assessed via two self-report questionnaires (the Client Satisfaction Questionnaire, the CSQ-8, and the IDEM ad hoc questionnaire), as well as its effect on mood following each session assessed via a visual analog scale (VAS) ranging from 0 up to 100. METHOD: Sixty-five patients participated in 50 sessions of the IDEM-depression group in two hospitals in Alsace. 61% of the patients had bipolar disorder, and 41% of them were inpatients. Sessions took place on a weekly basis, lasted 2hours and were proposed by a CBT-trained clinical psychologist. Patients were asked to fill-out the VAS at the beginning and at the end of each session. Moreover, they were asked to fill-out the CSQ-8 and the IDEM ad hoc questionnaire when they left the group. Other than one session ("yoga and mindfulness"), all the sessions (16 out of 17) were structured on a Powerpoint© presentation. During the first hour information was given regarding the topic (i.e., rumination), and a shared CBT conceptualization of the topic was formulated by the participants and the psychologist. For most sessions, the first hour was therefore communication and information-based, whereas during the second hour participants were asked to participate in in-session behavioral experiments and/or to evaluate specific aspects of their behavior (thoughts, emotions, activity, mindful behavior) during the last few days. The therapist manual and the slides for each session are available via e-mail to the first author. RESULTS: Regarding the results, self-reported mood on the VAS was compared between the onset (225 VAS) and the end (225 VAS) of each session. Overall, results suggest that self-reported mood is significantly improved following the participation in sessions (t=-5. 87, P<0.001). Moreover, mean results on the CSQ-8 suggest that patients are highly satisfied with the group (M=24.46, SD=6.42). Among them, 82% reported a moderate-high satisfaction with the group. On the IDEM ad hoc questionnaire, patients reported an overall high satisfaction level regarding (i) the content of sessions, (ii) the duration of sessions, (iii) the frequency of sessions, (iv) how much they felt they could express themselves during sessions. In the qualitative comments of this questionnaire, patients reported that the group helped them to gain an understanding of the mechanisms involved in depression; to feel less isolated and guilty; and to learn about specific psychotherapeutic tools (i.e., mindfulness) and to try to implement them. CONCLUSION: Our results suggest that an IDEM-depression group is well suited to a wide-array of clinical pictures associated with depression (varying severity, bipolar or unipolar, inpatients and outpatients). This is probably due to its open-group format which is particularly well-adapted to the dynamic symptomatology associated with major depression, and may stimulate decentering in patients who have different levels of severity of symptoms but participate in the same session. Moreover, its impact on mood improvement, and the high satisfaction level reported by patients, seem to be related to its CBT and psychoeducation-based content on the one hand, which has shown its efficacy in depression. On the other hand, IDEM's structured open-group format might have also contributed to the improvement in mood and the overall good satisfaction reported by patients, through the social support provided by the group, improved feeling of self-efficiency, and its effect on stigmatization. Thus, IDEM-depression group is an efficacious, flexible, low-cost, and easy to implement (in different clinical settings) psychotherapeutic option for major depression.

[Psychopharmacology of anxiety and depression: Historical aspects, current treatments and perspectives]. / Psychopharmacologie de l'anxiété et de la dépression : aspects historiques, traitements actuels et perspectives.

Pharmacological treatment of acute anxiety still relies on benzodiazepines, while chronic anxiety disorders and depression are treated with different antidepressants, according to specific indications. The monoaminergic axis is represented by two families which are being developed: (i) serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRI), also called triple reuptake inhibitors (TRI), for the treatment of depression (amitifadine), (ii) multimodal antidepressants for depression and anxiety disorders (generalized anxiety disorder mainly) (tedatioxetine, vortioxetine and vilazodone). Third-generation antipsychotics (aripiprazole, lurasidone, brexpiprazole, cariprazine) appear relevant in the treatment of resistant depression and some anxiety disorders. Among the modulators of the glutamatergic axis, promising compounds include: (i) ionotropic regulators of NMDA receptors: esketamine, AVP-923 and AVP-786, CERC-301, rapastinel (Glyx-13), NRX-1074 developed for depression, rapastinel and bitopertine developed for obsessive compulsive disorder, (ii) metabotropic glutamate receptors modulators: decoglurant and basimglurant developed for depression and mavoglurant developed for obsessive compulsive disorder.

Zolpidem test and catatonia.

WHAT IS KNOWN AND OBJECTIVE: There is no consensus regarding treatment of catatonia and the main recent therapeutic progress has been the development of the zolpidem diagnostic and therapeutic test. We report on the use of this test in one of our patients. CASES SUMMARY: Mr. S. suffered from a paranoid schizophrenia. Three episodes of catatonia are described to illustrate the effect of zolpidem in a patient for whom lorazepam was ineffective or inadequate. WHAT IS NEW AND CONCLUSION: Zolpidem with appropriate testing appears to be a credible alternative to electroconvulsive therapy or increased lorazepam dosing and allows continuation of antipsychotic administration.

Methylphenidate-risperidone combination in child psychiatry: A retrospective analysis of 44 cases.

INTRODUCTION: Psychotimulant-antipyschotic combinations are frequently used in child psychiatry, but have been rarely described in the literature. METHOD AND PATIENTS: We propose here a retrospective study of 44 children who received the combination methylphenidate (MPH)-risperidone (RIS). The sample is composed of children who received either MPH (n=28) or RIS (n=16) as primary treatment. A vast majority of the children had a comorbid attention deficit hyperactivity disorder (ADHD) diagnosis. RESULTS: For over 60% of patients, regardless of their initial monotherapy, bitherapy decreased the symptoms of ADHD and conduct disorder, sleep disorders and anxiety. Concerning the safety of the bitherapy, a compensation effect on weight gain and appetite was respectively observed in 70% and 50% of patients. Even though iatrogenic tachycardia can be encountered with both drugs, it has never been reported when they are associated and we have reported a total of 3 cases in our study. We have also observed a case of dyskinesia resolved with the discontinuation of the treatment. DISCUSSION/CONCLUSION: MPH-RIS bitherapy appears to be particularly effective in ADHD with conduct disorder symptoms. Although tolerance may limit its use, the benefit/risk ratio seems favourable for a number of children.

Behavioral and neurochemical effects of dietary methyl donor deficiency combined with unpredictable chronic mild stress in rats.

Methyl donor deficiencies and chronic stress cause depression independently, but their interaction has never been thoroughly evaluated. In our study, methyl donor deficient diet and chronic stress condition consisted respectively of a B2, B9, B12, and choline-free diet and a chronic mild stress procedure. Rats were randomly assigned to six groups with three "diet" conditions (free-feeding, pair-fed and methyl donor deficient diet) and two "stress" conditions (no-stress and stress) and were evaluated in the open-field, the elevated plus-maze and the forced swimming test. After the behavioral evaluation, corticosterone and homocysteine plasma levels were measured and dopamine, DOPAC, serotonin, 5HIAA concentrations were evaluated in several brain areas. Rats given a methyl donor deficient diet for 11 weeks causing elevated plasma homocysteine levels were compared to pair-fed and free-feeding rats with or without unpredictable chronic mild stress. Regardless of stress environmental conditions, the methyl donor deficient diet decreased plasma corticosterone levels and caused disinhibition in the elevated plus-maze condition relative to both control groups. However, stress potentiated the effects of the deficient regimen on rearing in the open-field and climbing in the forced swim test. The dietary changes involved in behavior and plasma corticosterone could be caused by homocysteine-induced decreases in dopamine and 5-hydroxytryptamine metabolites in selective brain regions and it can be noted that regardless of stress-conditions, methyl donor deficient diet decreases DOPAC/dopamine and 5HIAA/serotonin ratios in striatum and hypothalamus and selectively 5HIAA/serotonin ratio in the sensorimotor cortex. Our experimental data is particularly relevant in the context of neuropsychiatric disorders frequently associated with folate deficiency and hyperhomocysteinemia.

[Acute psychotic disorders related to bupropion: review of the literature]. / Troubles psychotiques aigus liés au bupropion: revue de la littérature.

RATIONALE AND OBJECTIVES: Bupropion, or amfebutamone, is an atypical antidepressant also used during tobacco cessation. From a structural standpoint, it resembles amphetamine drugs with psychostimulant effects, and endogenous monoamines. From a pharmacological standpoint, bupropion, and two of its most important active metabolites, inhibit dopamine and norepinephrine reuptake. It has recently been discovered that bupropion may act as a non-competitive cholinergic nicotinic receptor antagonist, and that it may inhibit the activation of reward systems triggered by nicotine. Buproprion's efficacy as a smoking cessation aid has been demonstrated by numerous clinical trials that have compared its effects with those of placebo and other nicotinic substitutes. In 2001, buproprion SR received marketing authorization in France as a smoking cessation aid, under the name ZYBAN®. Tobacco addiction indeed remains a major public health issue. Among patients with psychiatric conditions, chronic tobacco consumption is frequent. The development of non-nicotinic drugs may therefore enhance therapeutic possibilities. However, the psychotropic effects of these molecules should be taken into account. We have recently reported the case of a patient with schizoaffective disorder, who presented two acute bupropion-induced psychotic episodes. We have also undertaken an exhaustive bibliographical research on this subject. The aim of the present study is to present the information available to us, in order to suggest aetiopathogenic hypotheses and therapeutic proposals. DATA SOURCES: The following databases were consulted on a regular basis, with no date restriction: Medline, Cochrane and Elsevier. The present study identified 22 cases of psychotic conditions associated with buproprion, as well as randomized and pharmacovigilance studies published in English, from December 1985 to November 2008. Since 2002, there have been three published case-reports on patients who underwent a tobacco cessation program. DATA SYNTHESIS: Psychotic disorders associated with buproprion appear after an average of 10 days of 300 mg/d bupropion intake. In about two third of cases, the patients have no history of psychiatric conditions. In one third of cases, they have a history of thymic disorders. In our review, auditory, visual or cenaesthetic hallucinations frequently occur (85% of the reported cases), and are sometimes characterized by single episodes and/or are rationalized. Some of them occur along with delusional episodes (mystical, paranoid, etc.). The patients are restless, confused, but seldom exhibit dissociative and thymic symptoms. DISCUSSION AND CONCLUSIONS: From an aetiopathogenic, clinical and evolutive standpoint, buproprion-induced psychotic episodes share many similarities with acute organic or toxic psychosis (notably induced by amphetamines). The hypothesis of a dopaminergic hyper-reactivity should be analyzed. Moreover, most of these patients were taking other medication, and the possibility of a dopaminergic potentialization prior to buproprion intake could be suggested. In such cases, bupropion should be discontinued and complete remission is expected within an average of 10 days. Even though neuroleptic drugs are still frequently used in these cases, benzodiazepines could become a valid alternative, according to the model of amphetamine-induced acute psychosis.

Human opiorphin is a naturally occurring antidepressant acting selectively on enkephalin-dependent delta-opioid pathways.

Human opiorphin protects enkephalins from degradation by human neutral endopeptidase and aminopeptidase-N and inhibits pain perception in various behavioral rodent models of pain via endogenous enkephalin-related activation of opioidergic pathways. In addition to pain control, endogenous opioid pathways are also implicated in the modulation of emotion-related behaviors. Thus, we explored the dose-dependent motivational responses induced by opiorphin using the forced swim test, the standard rat model of depression. In addition, to further understand the endogenous events triggered by opiorphin, we investigated the specific involvement of mu- or delta-opioid receptor-dependent pathways. In parallel, the locomotor activity test was used to detect possible sedation or hyperactivity. Here, we report for the first time that at 1-2 mg/kg i.v. doses, opiorphin elicited antidepressant-like effects by activating endogenous delta-opioidergic pathways, since that activation was reversed by the selective delta-opioid antagonist naldrindole (10 mg/kg i.p.). The antidepressive behavioral responses exerted by opiorphin are specific at systemically active doses. Treated-rats did not develop either hypo- or hyper-active responses in a locomotor test or amnesic behavioral response in the passive avoidance rat model. In addition, opiorphin did not induce either anxiolytic-, or anxiogenic-like responses in the conditioned defensive burying test. Taking the data together, we conclude that opiorphin is able to elicit antidepressant-like effects, mediated via delta-opioid receptor-dependent pathways, by modulating the concentrations of endogenous enkephalin released in response to specific physical and/or psychological stimuli. Thus, opiorphin or optimized derivatives is a promising single candidate to treat disorders that include both pain and mood disorders, particularly depression.