Twenty-Year Trends in the Psychopharmacological Treatment of Outpatients with Borderline Personality Disorder: A Cross-Sectional Naturalistic Study in Spain.

OBJECTIVE: Although no psychotropic drugs have been officially approved for the treatment of borderline personality disorder (BPD), medications are routinely prescribed for these patients. The primary aim of this study was to evaluate changes in the pharmacological management of patients with BPD treated in an outpatient specific unit in Spain over the past 20 years, while a secondary aim was to identify the factors associated with the prescription. METHODS: Observational and cross-sectional study of all patients with a primary diagnosis of BPD (n = 620) consecutively admitted to a BPD outpatient program in Barcelona, Spain, from 2001 through 2020. We examined trends in the prescription of antidepressants, benzodiazepines, mood stabilizers, and antipsychotics. For the analysis, prescription data were grouped into four 5-year periods (2001-2005, 2006-2010, 2011-2015, and 2016-2020). Logistic regression models were performed to identify sociodemographic and clinical variables associated with pharmacological prescription and polypharmacy. RESULTS: The percentage of patients receiving pharmacotherapy decreased over time. Antidepressant prescription rates remained high and stable over time (74% of patients), while benzodiazepine use decreased significantly during the study period (from 77 to 36%) and second-generation antipsychotic (SGA) use increased from 15 to 32%. Psychiatric comorbidity was the main factor associated with pharmacological treatment (odds ratio 2.5, 95% confidence interval 1.5-4.2) and polypharmacy, although a high percentage of patients without comorbidity were also taking medications. CONCLUSIONS: Over the past 20 years, the pharmacological treatment of BPD outpatients has undergone important changes, most notably the decrease in benzodiazepines and increase in SGAs. The findings of this study demonstrate that pharmacotherapy is much more prevalent in patients with BPD than recommended in most clinical guidelines.

Cannabinoids: Emerging developments in neuropsychopharmacology and biological psychiatry.

Cannabinoids from the cannabis plant were one of the earliest psychoactive phytochemicals harnessed by humanity for their medicinal properties and remain one of the most frequently used and misused classes of chemicals in the world. Despite our long-standing history with cannabinoids, much more is said than is known regarding how these molecules influence the brain and behavior. We are in a rapidly evolving discovery phase regarding the neuroscience of cannabinoids. This period of insight began in the mid-1990s when it was discovered that phytocannabinoids (e.g., delta-9-tetrahydrocannabinol) act on G protein-coupled receptors (i.e., CB1/CB2) in the brain to produce their psychoactive effects. Shortly thereafter, it was discovered that endogenous ligands (i.e., endocannabinoids) exist for these receptor targets and, that they are synthetized on demand under a variety of physiological conditions. Thus, we can now study how phytochemicals, endogenous ligands, and synthetic/metabolic enzymes of the endocannabinoid system influence the brain and behavior by activating known receptor targets. Our increased ability to study cannabinoid interactions with the brain and behavior coincides with an increase in international interest in utilizing cannabinoids as a medicine. At the same time, the potency of, and administration routes by which cannabinoids are used is rapidly changing. And, these trends in cannabinoid misuse are producing lasting neural adaptations that have implications for mental health. In this special edition, we will summarize our recent period of discovery regarding how: 1) phytocannabinoids, synthetic cannabinoids and endocannabinoids act on the brain to produce behavioral effects; 2) cannabinoids can be harnessed to produce pharmacotherapeutic utility in the field of medicine; and 3) use of increasingly more cannabinoid variants through unique routes of administration alter the brain and behavior, especially when used in critical developmental periods like pregnancy and adolescence.

A banalidade do mal psicofarmacológico em tempos de performance / La banalidad del mal psicofarmacológico en tiempos de performance / La banalité du mal psychopharmacologique en temps de performance / The banality of psychopharmacological evil in times of performance

Resumo Este artigo tem por objetivo percorrer um caminho que parte da identificação do fenômeno da medicalização da vida. O estudo será organizado dentro de uma perspectiva genealógica, na medida em que é importante localizar que este objeto de estudo não se restringe apenas a uma questão médica, mas exige um esforço de articulação com outras áreas do saber. Assim, esta genealogia articula questões médicas com a crítica social acerca desse fenômeno, aliando medicina, sociologia, psicologia, economia e teoria política. O desenvolvimento será organizado tendo como pano de fundo as exigências de autonomia e performance na atualidade, no contexto do aumento da demanda psicofarmacológica. Se os benefícios da administração medicamentosa podem propiciar bem-estar subjetivo, por outro lado, os excessos ou a banalidade do mal psicofarmacológico tornam opacas as fronteiras entre o normal e o patológico.

Resumen Este artículo pretende seguir un camino que parte de la identificación del fenómeno de la medicalización de la vida. El estudio se organizará dentro de una perspectiva genealógica, debido a la importancia de conocer que este objeto de estudio no se limita a un tema médico, sino que requiere un esfuerzo para articularse con otras áreas del conocimiento. Así, esta genealogía articula la problemática médica con la crítica social sobre este fenómeno, combinando la medicina, la sociología, la psicología, la economía y la teoría política. Esta trama se organizará en el contexto de las demandas de autonomía y desempeño de la actualidad, en el contexto de una mayor demanda psicofarmacológica. Si, por un lado, los beneficios de la administración de medicamentos pueden proporcionar un bienestar subjetivo, por otro, los excesos o la banalidad del mal psicofarmacológico hacen que los límites entre lo normal y lo patológico sean opacos.

Résumé Cet article retrace un chemin qui commence par l'identification du phénomène connu sous le nom de médicalisation de la vie. Puisque cet objet d'étude n'est pas seulement une question médicale, nécessitant une articulation avec d'autres domaines de connaissance, l'étude propose une généalogie qui articule la critique médicale et sociale sur ce phénomène, en combinant la médecine, la sociologie, la psychologie, l'économie et la théorie politique. Cette tapisserie est tissé sur fond d'exigences actuelles d'autonomie et de performance, dans un contexte de demandes psychopharmacologique croissantes. Si les bénéfices de l'administration de médicaments peuvent procurer un bien-être subjectif, les excès ou la banalité du mal psychopharmacologique, en revanche, brouille les frontières entre normal et pathologique.

Abstract This paper traces a path that begins by identifying the phenomenon known as medicalization of life. Since this object of study is not only a medical issue, requiring an articulation with other areas of knowledge, the study proposes a genealogy that articulates medical and social criticism on this phenomenon, combining medicine, sociology, psychology, economics, and political theory. Such tapestry is weaved against the backdrop of current demands for autonomy and performance, in the context of increasing psychopharmacological urges. If the benefits of drug administration can provide subjective well-being, the excesses or the banality of psychopharmacological evil, on the other hand, blur the boundaries between normal and pathological.

Consumo de fármacos opiáceos en la ciudad de Madrid: Factores sanitarios y sociodemográficos asociados / Opiate drug use in the city of Madrid: Associated health and sociodemographic factors

El consumo de analgésicos opiáceos ha provocado una situación deemergencia sanitaria y social en Estados Unidos. En España, segúndatos oficiales, la prescripción de estos fármacos ha experimentadoun espectacular ascenso en la última década. Este estudio explora laprevalencia del uso de estos fármacos y las características sanitarias ysociodemográficas de sus consumidores en la ciudad de Madrid. Serealizó una encuesta telefónica aplicando un muestreo estratificadoy aleatorizado, en la que se preguntó por el uso de estos fármacos ysi fueron médicamente prescritos o no. La muestra estuvo compuestapor n= 8.845 sujetos de edades entre 15 y 98 años. Un 16,0% declara haber usado estos fármacos en el último año y un 9,1 los tomaen las dos últimas semanas. El consumo es más frecuente en mujeres, clase social baja y menor nivel de estudios. El grupo más joven(15-29 años) ya lo usa en el 12,5%. Quienes usan opioides refierenpeor salud percibida, menor calidad de vida, más problemas de saludmental, más soledad no deseada, más uso de otros psicofármacos, másfrecuente uso diario de tabaco y menos consumo problemático dealcohol. Un 10% de quienes los usan lo hacen sin prescripción médica. Combinando estos datos con los de prescripción ofrecidos por elMinisterio de Sanidad, resulta necesario prestar atención a un problema que puede hacerse patente en los próximos años, aconsejando laadopción de medidas urgentes para atajarlo antes de que aproxime lasituación española a la ya bien conocida en otros países. (AU)

The use of opiate analgesics has led to a health and social emergencyin the United States. In Spain, according to official data, the prescription of these drugs has risen dramatically in the last decade. This studyexplores the prevalence of the use of these drugs and the health andsocio-demographic characteristics of their consumers in the city ofMadrid. A telephone survey was carried on a stratified, randomisedsample, asking about the use of these drugs and whether or not theywere medically prescribed. The sample consisted of n=8,845 subjectsaged between 15 and 98 years. Sixteen percent stated that they hadused these drugs in the last year and 9.1% had taken them in the lasttwo weeks. Consumption was more frequent among women, lower social class and lower level of education. Among the youngest group (15-29 years old) 12.5% had already used it. Those who use opioids reportworse perceived health, lower quality of life, more mental health problems, more loneliness, more use of other psychoactive drugs, morefrequent daily use of tobacco and less problematic consumption ofalcohol. Ten percent of those who use them do so without a doctor’sprescription. Combining these data with the prescription data offeredby the Ministry of Health, it is necessary to pay attention to a problem that may become apparent in the coming years, and the adoptionof urgent measures to tackle it before it brings the Spanish situationcloser to that already well known in countries of our socio-politicalenvironment is advised (AU)

Farmacogenética y trastornos mentales / Pharmacogenetics and mental disorders

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Solving the crisis in psychopharmacological research: Cellular-membrane(s) pharmacology to the rescue?

There is an urgent need for the introduction of novel and better (i.e., improved risk-benefit profile) compounds for the treatment of major psychiatric disorders, in particular mood and psychotic disorders. However, despite increased societal awareness and a rising public and professional demand for such agents from patients and physicians, the pharmaceutical industry continues to close down its psychopharmacology research facilities in reaction to the lack of success with the search for new psychotropics. It is high time to stop this untoward trend and explore "new" lines of investigation to solve the current crisis in psychopharmacological research. In line with the prevailing molecular view in drug research in general, also in psychopharmacology mechanistic explanations for drug effects are "traditionally" looked for at the level of molecular targets, like receptors and transporters. Also, more recent approaches, although using so-called systems- and function-based approaches to model the multidimensional characteristics of psychiatric disorders and psychotropic drug action, still emphasize this search strategy for new therapeutic leads by identification of single molecules or molecular pathways. This "psychomolecular gaze" overlooks and disregards the fact that psychotropic agents usually are highly hydrophobic and amphipathic/amphiphilic agents that, in addition to their interaction with membrane-bound proteins in the form of e.g. receptors or transporters, also interact strongly with the lipid component of cellular membranes. Here we suggest to develop a program of systematic, whole-cell level based, investigation into the role of these physical-chemical cellular membrane interactions in the therapeutic action of known psychotherapeutics. This complementary yet conceptually different approach, in our opinion, will complement drug development in psychopharmacology and thereby assist in overcoming the current crisis. In this way the "old" physical theory of drug action, which antedates the current, primary molecular, paradigm may offer "new" options for lead discovery in psychopharmacological research.

Future paths in psychopharmacology
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Drug development in psychiatry is gradually moving from serendipity to personalized medicine. Some promising paths will be reviewed in this issue.
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Genomics and the future of psychopharmacology: MicroRNAs offer novel therapeutics
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MicroRNAs (miRNAs) are short, noncoding RNAs functioning as regulators of the transcription of protein-coding genes in eukaryotes. During the last two decades, studies on miRNAs indicate that they have potential as diagnostic and prognostic biomarkers for a wide range of cancers. Research interest in miRNAs has moved to embrace further medical disciplines, including neuropsychiatric disorders, comparing miRNA expression and mRNA targets between patient and control blood samples and postmortem brain tissues, as well as in animal models of neuropsychiatric disorders. This manuscript reviews recent findings on miRNAs implicated in the pathology of mood disorders, schizophrenia, and autism, as well as their diagnostic potential, and their potential as tentative targets for future therapeutics. The plausible contribution of X chromosome miRNAs to the larger prevalence of major depression among women is also evaluated.
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Los microARN (miARNs) son ARN cortos y no codificantes que funcionan como reguladores de la transcripción de genes que codifican proteínas en los eucariotes. Durante las últimas dos décadas, los estudios sobre miARNs señalan que tienen un potencial como biomarcadores diagnósticos y pronósticos para una amplia gama de cánceres. El interés de la investigación en los miARNs se ha extendido a otras disciplinas médicas, como los trastornos neuropsiquiátricos, donde se compara la expresión de los miARNs y los blancos de ARNm entre las muestras de sangre de pacientes y controles y los tejidos cerebrales postmortem, como también en modelos animales de trastornos neuropsiquiátricos. Este artículo revisa los hallazgos más recientes sobre los miARNs implicados en los trastornos del ánimo, la esquizofrenia y el autismo, así como su potencial en el diagnóstico y como blancos experimentales para futuras terapias. También se evalúa la eventual contribución de los miARNs del cromosoma X a la mayor prevalencia de depresión mayor entre las mujeres.

Les micro-ARN (miARN) sont de courts ARN non codants, fonctionnant comme des régulateurs de la transcription des gènes codant la protéine dans les cellules eucaryotes. D'après des études menées au cours des dix dernières années, les micro-ARN ont un potentiel en tant que biomarqueurs diagnostiques et pronostiques dans une large gamme de cancers. Les centres d'intérêt de la recherche sur les miARN se sont élargis à d'autres disciplines médicales, dont l'étude des maladies neuropsychiatriques, en comparant l'expression des miARN et des ARNm cibles dans des échantillons de sang de patients avec des échantillons de contrôle, dans des tissus cérébraux post-mortem, ainsi que dans des modèles animaux de maladies neuropsychiatriques. Cet article passe en revue les découvertes les plus récentes sur les miARN impliqués dans les pathologies des troubles de l'humeur, la schizophrénie et l'autisme ainsi que leur potentiel diagnostique et thérapeutique en tant que cibles expérimentales pour de futures thérapies. Il y sera également étudié la possible implication des miARN du chromosome X dans la prévalence plus grande de la dépression majeure chez les femmes.

European college of neuropsychopharmacology network on the prevention of mental disorders and mental health promotion (ECNP PMD-MHP).

Prevention is the most promising way to reduce the high personal, familial, societal, clinical and economic costs of mental disorders in Europe and worldwide. A complementary approach is to go beyond the prevention of mental ill health, to promote good mental health. This manuscript highlights the first European consortium fostering cutting-edge multidisciplinary research in these two areas. The ECNP-funded Network on the Prevention of Mental Disorders and Mental Health Promotion (ECNP PMD-MHP) brings together European sites of excellence with different expertise for translational research collaboration, including partnerships with the industry. The ECNP PMD-MHP Network adopts a transdiagnostic, lifespan, clinical staging model which cuts across different mental disorders and different methodologies. The main aims of the ECNP PMD-MHP Network are to facilitate multidisciplinary collaboration, enhance knowledge and data sharing, standardise core assessment and outcome measures, promote clinical research, apply for grant funding, and generate research reports. By supporting collaborative research, the ECNP PMD-MHP Network will be vital for fostering European psychiatry in the field of prevention of mental disorders and promotion of good mental health.

Computational psychopharmacology: a translational and pragmatic approach.

RATIONALE: Psychopharmacology needs novel quantitative measures and theoretical approaches based on computational modelling that can be used to help translate behavioural findings from experimental animals to humans, including patients with neuropsychiatric disorders. OBJECTIVES: This brief review exemplifies this approach when applied to recent published studies of the effects of manipulating central dopaminergic and serotoninergic systems in rodents and marmoset monkeys, and possible comparisons with healthy human volunteers receiving systemic agents or patients with depression and schizophrenia. METHODS: Behavioural effects of central depletions of dopamine or serotonin in monkeys in probabilistic learning paradigms are characterised further by computational modelling methods and related to rodent and human data. RESULTS: Several examples are provided of the power of computational modelling to derive new measures and reappraise conventional explanations of regional neurotransmitter depletion and other drug effects, whilst enhancing construct validation in patient groups. Specifically, effects are shown on such parameters as 'stimulus stickiness' and 'side stickiness', which occur over and above effects on standard parameters of reinforcement learning, reminiscent of some early innovations in data analysis in psychopharmacology. CONCLUSIONS: Computational modelling provides a useful methodology for further detailed analysis of behavioural mechanisms that are affected by pharmacological manipulations across species and will aid the translation of experimental findings to understand the therapeutic effects of medications in neuropsychiatric disorders, as well as facilitating future drug discovery.