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Resume Objectifs Les Inhibiteurs Selectifs de la Recapture de la Serotonine (ISRS) et les Inhibiteurs de la Recapture de la Serotonine et de la Noradrenaline (IRSNA) peuvent induire des hyponatremies par le syndrome SIADH. Les objectifs de cette etude etaient de comparer le taux d’incidence des notifications d’hyponatremie en fonction des differents ISRS/IRSNA de maniere a identifier l'existence de molecules plus a risque, et de caracteriser un profil de patient a risque. Methode Les cas d’hyponatremie ont ete extraits de la Base Nationale de Pharmacovigilance (BNPV) et rapportes a l’exposition aux differents ISRS/IRSNA dans la population francaise. L’estimation de l’exposition a ete calculee a partir des donnees de delivrance extraites de l’Echantillon Generaliste des Beneficiaires (EGB), rassemblant les donnees du Systeme National d’Information Inter-regimes de l’Assurance Maladie (SNIIRAM). L’etude a porte sur la periode du 01/01/2011 au 31/12/2013. Resultats Le nombre de cas d’hyponatremie inclus dans l’etude etait de 169 pour 3 749 800 sujets majeurs ayant initie un traitement (taux d'incidence de cas notifies de 1,64/100 000 patients annee). La comparaison des taux d’incidence standardises ne montre pas de difference entre les molecules sauf pour la duloxetine qui preente un taux d'incidence significativement plus eleve (2,79/100 000 PA p > 0,03). Les facteurs de risque identifies sont l'âge avec un taux 12,5 fois plus important apres 75 ans, et le sexe feminin avec un taux d'incidence 2,4 fois plus eleve. Conclusions La comparaison des taux d’incidence a partir de la notification spontanee indique un risque d’hyponatremie plus important pour la duloxetine pour la periode 2011-2013. Ce resultat necessite d'etre confirme par d’autres etudes. L’âge eleve et le sexe feminin sont des facteurs de risque quelle que soit la molecule.

Selective Serotonin Reuptake Inhibitors (SSRIs) and Serotonin-Norepinephrine Reuptake Inhibitors (SNRIs) are frequently prescribed. These antidepressants can potentially induce serious hyponatremia through the SIADH syndrome. That seems to concern all molecules of these classes but the individual risk of each molecule is not well known. The aims of the study were to compare the incidence rate of each molecule in order to identify the existence of molecules more at risk of inducing hyponatremia and to characterize a profile of patients at risk for hyponatremia during a treatment with a SSRI or a SNRI.The cases of hyponatremia under SSRI/SNRI were extracted from the French pharmacovigilance database (BPNV). The exposition to the different SSRIs/SNRIs in the French population was estimated from the French National Health Insurance database (SNIIRAM) using a sampled database (Echantillon Généralistes des Bénéficiaires). The study ran from 01/01/2011 to 31/12/2013. The primary study endpoint was the incidence rate of notifications of the hyponatremia cases in patients treated by SSRI/SNRI and recorded into the BNPV database, related to the average annual number of corresponding treatments initiated during the same period.The number of cases of hyponatremia included in the study was 169 for 3 749 800 adult patients initiating treatment. The incidence rate of cases was 1.64 for 100 000 persons per year (PY). The standardized incidence rates between the different molecules showed no difference except for duloxetine (2.79/100 000 PY p 0.03). Identified risk factors were age, with a large increase of incidence rate from 75 years old (incidence 12.5 higher) and female gender.Comparison of the incidence rates from spontaneous reports indicates a greater risk of hyponatremia for duloxetine for 2011-2013. This result needs to be confirmed by other studies. The advanced age and female sex are risk factors, irrespective of the molecule.

In humans, some psychotropic agents (alcohol, drugs, illicit substances) have been suggested to play a role in the occurrence of major behavioural disorders, mainly due to the suppression of psychomotor inhibition. Behavioural disinhibition is a physiological mechanism which allows humans to behave appropriately according to a given environmental situation. The behavioural disinhibition induced by either therapeutic dosage or misuse involves the loss of restraint over certain types of social behaviour and may increase the risk of auto or hetero-aggression and acting out. The increased use of psychotropic agents in recent years and the occurrence of unwanted effects are worrying and must be detected and evaluated. The objective of the present study was to establish a causal relationship between psychoactive substance use and occurrence of major behavioural disorders, such as paradoxical rage reactions and suicidal behaviour, based on a literature analysis. It consisted of reviewing reports of drug-induced violent reactions in healthy volunteers and demonstrating, where possible, a cause-effect relationship. Patients with schizophrenia and psychopathic personalities were not included in our study since psychiatric comorbidity could influence behavioural responses. Psychotropic agents included drugs, licit and illicit substances already associated with violence in the past. Many reports used the "Go/No Go test" to evaluate the disinhibiting effect of psychotropic substances; this allows the "cognitive mapping" of drugs. The results suggest that only alcohol, antidepressants, benzodiazepines and cocaïne are related to aggressive behaviour. The best known precipitant of behavioural disinhibition is alcohol, which induces aggressive behaviour. However, there are large differences between individuals, and attentional mechanisms are now recognised as being important in mediating the effects of alcohol. Suicidal tendency as an adverse antidepressant reaction is rare, especially with atypical antidepressants. However, the risk of acting out exists and the responsibility of antidepressant agents in the genesis of suicidal tendencies is now established. The disinhibiting effects of benzodiazepines are well-known and proven by clinical trials. It's a "model" of acting out, and the causal relationship is undeniable. That cocaïne is related to violent behaviour is demonstrated by its pharmacological actions on CNS. The chronic use of cocaïne induces "a limbic dyscontrol syndrome" based on the altered activity of limbic structures. On the contrary, we could not demonstrate a causal relationship between aggression and either cannabis, ecstasy or phencyclidine. Cannabis abusers look particularly for euphoria and relaxing effects. Aggression as an adverse cannabis reaction is very rare and occurs in most cases in association with other drugs and in predisposed individuals. Ecstasy use may lead to long-term alterations of neuronal function in the human CNS and cause psychiatric disorders. However, there is insufficient information about long-term use of ecstasy to estimate its role in the occurrence of behavioural disorders. Clinical and forensic assumptions about phencyclidine and violence were not warranted. However, the substance-effect relationships can be criticized in the case of alcohol, antidepressants, benzodiazepines and cocaïne. In fact, individual, social and psychiatric factors exert an influence on behaviour that is superior to the pharmacological effect of psychotropic agents. The most important parameter in drug-induced behavioural disinhibition is dosage, but mode of administration is also important. In addition, polysubstance abuse is very common. Substances may be taken simultaneously and alcohol is frequently combined with drugs. The combinations of substances result in multiple interactions, and very little is known about the effects of these interactions on violence in humans. Co-occurrence of substance abuse and other mental disorders is also very frequent. Multiple substance abuse should be avoided, because potential interactions between two or more drugs are more likely to cause violent behaviour. In the future, a specific treatment of these deleterious phenomena will have to be considered in order to reduce drug-induced iatrogenic behavioural disorders.