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.

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.

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.

Lugar de los antipsicóticos de segunda generación en el tratamiento del trastorno bipolar: [revisión] / Second-generation antipsychotics in treating bipolar disorder: [review]

A pesar del entusiasmo creciente por el uso de los antipsicóticos de segunda generación (ASG) en pacientes bipolares, una revisión sistemática publicada en 2007 generó varias dudas sobre la efectividad de estos medicamentos, tanto para el tratamiento de episodios agudos como para la prevención de los cambios del estado de ánimo. Existe, por lo tanto, la necesidad de verificar si durante los dos últimos años se han realizado nuevos estudios que validen la inclusión de los ASG entre las opciones farmacológicas de primera línea para el tratamiento del trastorno bipolar. Sin embargo, desafortunadamente, los estudios más recientes resultaron inadecuados cualitativa y cuantitativamente para reducir las dudas sobre la seguridad y eficacia de los ASG en esos pacientes. Por esta razón, en la actualidad, los ASG deberían considerarse agentes de cuarta línea en todas las diferentes fases que caracterizan el curso fluctuante de este trastorno. De hecho, el uso de estos fármacos debería sólo considerarse en el caso de que los estabilizadores del estado de ánimo, los anticonvulsivos, los antidepresivos o los antipsicóticos de primera generación (APG) fallaran. Si a pesar de ello los clínicos insisten que es indispensable el tratamiento de estos pacientes con ASG, se debería preferir la olanzapina, a pesar de sus limitaciones en cuanto a seguridad, porque esta droga presenta el mayor número de estudios bien diseñados con resultados tranquilizadores en cuanto a su eficacia.

[Research progress in neuropsychopharmacology updated for the post-genomic era].

Neuropsychopharmacological research in the post genomic (genomic sequence) era has been developing rapidly through the use of novel techniques including DNA chips. We have applied these techniques to investigate the anti-tumor effect of NSAIDs, isolate novel genes specifically expressed in rheumatoid arthritis, and analyze gene expression profiles in mesenchymal stem cells. Recently, we have developed a novel system of quantitative PCR for detection of BDNF mRNA isoforms. By using this system, we identified the exon-specific mode of expression in acute and chronic pain. In addition, we have made gene expression profiles of KO mice of beta2 subunits in acetylcholine receptors.

[Therapeutic and cosmetic psychopharmacology. Risks and limits]. / Psicofarmacología terapéutica y cosmética. Riesgos y límites.

In this paper, I analyze risks and limits of the current psychopharmacology and how both are promoting a new social interpretation of health concept. Besides, I show how such interpretation can be detected in four issues related to safety, equality, psychiatrization of human condition, and autonomy. In the conclusions, I defend, first, the obligation of physician to inform patients about the important long-term uncertainties around psychopharmacology. Second, I justify the necessity of promote more prolonged monitoring of patients treated with such kind of drugs. Third, I insist in the relevance of increasing research about drugs ' adverse effects extended over a long time. And forth, I bring up the utility of health concept to avoid the subjective stigmatization of cognitive or affective traits, to prevent potential problems of inequality and coercion, and to keep from mental disorders caused by attempts of getting psychical states supposedly optimized.

Se escucha hablar de psicofarmacología de género: ¿estaremos escuchando bien? / One hears talk of gender psychopharmacology: are they listening well?

El titulo "psicofarmacología de género", que encabeza una cantidad creciente de artículos de la especialidad, carece, en conjunto, de la más mínima coherencia. Los autores de este ensayo presentan una discusión acerca de este fenómeno, que en el mejor de los casos puede ser calificado como un malentendido.

The heading "Gender Psychopharmacology", presiding growing quantities of papers on the speciality, lacks coherence, all together. The authors of the present essay discuss this phenomenon, that can be characterized as a misunderstanding, at best.

Therapeutic drug monitoring in neuropsychopharmacology: does it hold its promises?

To produce its characteristic effects, a drug must be present in appropriate concentrations at its sites of action. The latter is not only a function of the dose administered, but also of the extent and rate of drug absorption, distribution, tissue binding, biotransformation, and excretion, which can vary markedly between individual patients due to differences in gender, age, morbidity, smoking or eating habits, differential expression of drug metabolising enzymes or drug transporters or other factors. Therefore drug concentrations in blood resulting after a given dose differ by tenfold or more between individual patients. For psychoactive drugs, animal studies have shown that plasma concentrations of psychotropic drugs correlate well with concentrations in the target organ, the brain. In the brain of patients treated with antipsychotic or antidepressant drugs clear-cut relationships were found between plasma concentrations of the drug and occupancy of dopamine receptors or serotonin uptake sites by positron emission tomography (PET). Monitoring concentrations of psychoactive drugs in plasma of patients, so called therapeutic drug monitoring (TDM), is therefore useful to adjust dosages for optimal "receptor" blockade. TDM is well established for mood stabilizers and anticonvulsant drugs. For other neuropsychiatric drugs, however, "routine" TDM is rare. Optimal target concentrations are unclear for many drugs, and the number of laboratories that use reliable methods to measure the low concentrations of the drugs within a single day is quite limited. Moreover, the use of TDM in practice is far from optimal. The TDM group of the Arbeitsgemeinschaft für Neuropsychopharmakologie und Pharmakopsychiatrie (AGNP see http://www.agnp.de/) has published literature-based guidelines for optimal use of TDM in psychiatry. TDM can be most informative to solve problems underlying the treatment of an individual patient. It can be clarified if suggested non-compliance or insufficient response in spite of recommended doses is due to rapid metabolism of the drug. Moreover, many drug interactions have been detected by using TDM. In conclusion, TDM is a reliable tool to optimise psychopharmacotherapy. When used adequately it is helpful for many psychiatric patients and in many situations.

Clinical implications of antipsychotic-induced hyperprolactinemia in patients with schizophrenia spectrum or bipolar spectrum disorders: recent developments and current perspectives.

Hyperprolactinemia is increasingly studied as a frequent and potentially important consequence of antipsychotic medication treatment. Some individuals presenting with hyperprolactinemia remain asymptomatic, but others may exhibit a wide range of clinical symptoms resulting from either the direct effects of prolactin on body tissues (galactorrhea, gynecomastia) or endocrine-related secondary effects (sexual and reproductive dysfunction in the short term, and possibly the risk of tumorigenesis and osteoporosis in the longer term). Short-term side effects may negatively impact medication compliance, and long-term effects have the potential for serious health consequences. Antipsychotic medications have differing propensities to cause prolactin elevation. The first-generation antipsychotics, as well as the second-generation antipsychotic risperidone and its active metabolite paliperidone, have been shown to cause marked and sustained elevations in prolactin levels, whereas others of the second-generation antipsychotics appear to have little or no effect on prolactin levels or may decrease prolactin. A comprehensive overview of antipsychotics and hyperprolactinemia is presented together with a review of emerging evidence about the short- and long-term health risks of hyperprolactinemia.

Pharmacogenomics, informatics, and individual drug therapy in psychiatry: past, present and future.

The modern era of psychopharmacology began in the 10 year period from the late 1940s to the late 1950s. During this period, the first antidepressants, antipsychotics, anxiolytics and mood stabilizers were all discovered. In the 1960s, the pharmacology of these drugs was elucidated and theories about the mechanisms of action proposed. In the 1970s and 1980s, new, more selective compounds were developed based on improved structure-activity relationships derived from in vitro receptor binding studies and animal models. These compounds entered clinical testing in the 1980s and began to be marketed in the late 1980s and 1990s. All of these agents were approved to treat psychiatric syndromes which are conditions defined by a cluster of signs and symptoms. None of these agents was developed based on an understanding of the pathophysiology of the illnesses being treated. None of these agents are curative and virtually all have limited clinical efficacy. In the earliest days of the modern era, there were few drugs available to combine and many had such broad actions that they were often marginally tolerated or unsafe when used in combination (tricyclic antidepressants and monoamine oxidase inhibitors). With the advent of more medications, the frequency and extent of polypharmacy has exploded. In addition to simply having more drugs from which to select with different pharmacological profiles, many newer medications are also more selective in their pharmacological actions and thus are often better tolerated and safer when used in combination. In addition, there is the concern that the trade-off for more selective pharmacology may have been better tolerability at the expense of reduced efficacy, which clinicians then compensate for by using more medications in combination. For all of the above reasons, polypsychopharmacology has been present from the beginning of the modern era of psychopharmacotherapy and continues to be the rule rather than the exception. In fact, the frequency and the complexity of such polypsychopharmacology are both enormous and increasing. The percentage of patients being discharged from the Biological Branch of the National Institute of Mental Health on more than three psychiatric medications increased more than ten times between 1974-79, and 1990-95. The majority of patients seen in the Veterans Administration Medical System in the United States are on unique combinations of medications and the frequency and complexity of such polypharmacotherapy is increased in patients on psychiatric medications. Throughout the modern era, there have been attempts to determine whether there are populations of patients selectively responsible to specific agents (e.g. serotonin versus norepinephrine reuptake inhibitors). However, no compelling data have so far emerged. Instead, clinicians generally resort to combining drugs on the basis of symptoms such as psychosis and depression or anxiety and depression. Science has primarily informed the clinician about safety concerns rather than efficacy concerns when using such combinations. That will change in the future with a better understanding of the pathophysiology of psychiatric illnesses which in turn will lead to improved therapies and the potential for more rationally derived combination treatments.

Nicotine: from molecular mechanisms to behaviour.

The addictive potential of nicotine is clearly recognized by the tenacity of tobacco smoking for most users, and has prompted extensive psychopharmacological studies in animals. In parallel, the interaction of nicotine with the many subtypes of its eponymous receptor has been the focus of molecular and cellular investigations. More recently, a convergence of these approaches has been stimulated by the generation of transgenic animals, which facilitates analysis of the impact of molecular changes on behaviour. Nicotine, like other addictive drugs including psychomotor stimulants, promotes dopamine release in the nucleus accumbens. This transmitter system has been a major focus of both neurochemical and behavioural investigations, although recently the pre-eminence of this system in nicotine dependence has been challenged. Complexities in the brain circuitry (including the subdivisions of the nucleus accumbens) and differences between behavioural models help to rationalise the current controversy.

A pre-clinical study showing how dopaminergic drugs administered during pre-exposure can impair or facilitate latent inhibition.

RATIONALE: It has been suggested that, in classical conditioning, dopamine (DA) codes for (a) attention to the conditioned stimulus (CS) or (b) the intensity of the unconditioned stimulus. OBJECTIVES: To clarify the role of DA in pre-clinical classical conditioning studies. METHODS: An existing model of classical conditioning presented by Schmajuk, Lam, and Gray (J Exp Psychol Anim Behav Process 22:321-349, 1996) suggests that DA cells in the ventral midbrain area code for the attentionally modulated internal representation of the CS. It is assumed that this representation is increased by dopaminergic agonists and decreased by dopaminergic antagonists. Computer simulations with the model describe the effect of nicotine and haloperidol on latent inhibition. RESULTS: Simulations replicate experimental results demonstrating that both nicotine and haloperidol affect latent inhibition when administered during the pre-exposure phase. In addition, the model reproduces data showing that administration of nicotine or haloperidol results in the impairment or facilitation of latent inhibition depending on the duration of CS or the number of CSs. CONCLUSIONS: The model demonstrates that pre-clinical experimental results, including cell activity and pharmacological data, are consistent with an attentional role for DA in classical conditioning.

Tobacco smoking and nicotine neuropsychopharmacology: some future research directions.

Although nicotine is acknowledged as the major pharmacologically active chemical in tobacco that accounts for its continued use, there is a need for much further research. It is necessary to systematically compare the complex pharmacological actions of pure nicotine with those of tobacco, using different routes of administration and, therefore, rates of absorption. Tobacco smoking produces several important behavioral and central nervous system effects. More research is needed to determine the role of nicotine versus the many other substances present in tobacco smoke. Although nicotine is the primary pharmacological agent in tobacco that maintains its use, other chemicals and their biological mechanisms involved in tobacco smoking need to be studied further.

New directions in clinical psychopharmacology.

This paper reviews the current clinical use of psychotropic drugs and suggests new directions for future drug development. The author reviews the contemporary pharmacotherapy of depression, anxiety disorders, schizophrenia, and bipolar disorder and summarizes current trends in the drug treatment of psychiatric aspects of HIV disease. The increasing use of combination pharmacotherapy is discussed, as well as the impact of pharmacokinetics in clinical psychopharmacology. The use of botanical products for psychiatric disorders and tobacco use in the psychiatric patient are also addressed. Current research is producing drugs that have greater specificity in their mechanism of action effecting faster clinical response with minimum adverse effects.