Juan Carlos Martínez-Aguayo

Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review

Background The United States Food and Drug Administration (FDA) has warned about the increased suicidality risk associated with the use of selective serotonin reuptake inhibitors (SSRI) and venlafaxine in children and adolescents. Objectives To critically appraise the available evidence supporting the FDA Black box warning concerning to the use of antidepressants in child and adolescents. Methods A critical review of articles in Medline/PubMed and SciELO databases regarding the FDA Black box warning for antidepressants, and the impact of FDA warnings on antidepressant prescriptions and suicide rates. Results The warning was based on surveys that did not report either cases of suicide nor a significant difference supporting an increased suicidality rate. The concept was defined in an ambiguous way and there is currently more available evidence to support such definition. The use of SSRI and venlafaxine has been associated to lower suicidality rates, but the prescription fall due to the warning increased suicide rates. Discussion Suicidality is an inherent feature of depressive disorders so it would be desirable to consider how much of the phenomenon may be attributed to antidepressants per se. It would be appropriate to consider that suicide rates might increase also as a consequence of the warning.

Trypophobia: What Do We Know So Far? A Case Report and Comprehensive Review of the Literature

In this article, we describe the case of a girl who suffers from a phobia to repetitive patterns, known as trypophobia. This condition has not yet been recognised by diagnostic taxonomies such as the Diagnostic and Statistical Manual of Mental Disorders. Trypophobia usually involves an intense and disproportionate fear towards holes, repetitive patterns, protrusions, etc., and, in general, images that present high-contrast energy at low and midrange spatial frequencies. It is commonly accompanied by neurovegetative symptoms. In the case we present here, the patient also suffered from generalised anxiety disorder and was treated with sertraline. After she was diagnosed, she showed symptoms of both fear and disgust towards trypophobic images. After some time following treatment, she only showed disgust towards said images. We finish this case report presenting a comprehensive literature review of the peer reviewed articles we retrieved after an exhaustive search about trypophobia, we discuss how this case report contributes to the understanding of this anxiety disorder, and what questions future studies should address in order to achieve a better understanding of trypophobia.

Efectos neurobiológicos del estrés prenatal sobre el nuevo ser

Prenatal stress (PS) has been mainly investigated in animal models. It could trigger permanent neurobiological changes in the offpring through fetal programming, displayed as behavioral, cognitive, anxious, affective and psychotic disorders during infancy and adulthood. Main effects of PS have been related to the functioning of hypothalamic-pituitary-adrenal axis (HPA), serotonergic, glutamatergic and GABAergic systems, cortical (prefrontal, temporal and insular cortex) and subcortical structures (amygdala, hippocampus), cerebellum and placenta. Glucocorticoids are the most recognized transmission factors of maternal-fetal stress, with distinctive effects according to the moment of action, developmental stage and fetal gender. Alteration pattern of the HPA axis by PS would be similar to the one observed in some mental disorders. Other neuromodulators involved in the neurotoxicity of PS are nitric oxide and brain derived neurotrophic factor, associated to synaptic potentiation and depression. Also, serotonergic system has an important relationship with HPA axis, verifying a decreased number of serotonin transporters and an impaired placental synthesis of the neurotransmitter, essential for fetal neurodevelopment. Other epigenenomic mechanisms would be the modulation of synaptic plasticity by neurotrophins, adhesion and membrane molecules. Treatment with selective serotonin reuptake inhibitors has shown controversial outcomes. PS would affect fetal programming causing significant and permanent neurobiological alterations with clinical manifestations. This complex phenomenon must be further investigated, especially in human models.

Estado actual de los trastornos somatomorfos y conversivos en niños y adolescentes

Somatoform (SD) and conversion (CD) disorders have increased their incidence during the last two decades in children and adolescents, although both are curre...

Psicofarmacología del suicidio II parte: Estabilizadores del ánimo y suicidio

Resumen El litio y los anticonvulsivantes han sido ampliamente empleados como estabilizadores del animo (EA) en el trastorno afectivo bipolar (TAB), demostrando ademas una reduccion del riesgo de suicidio. En el caso particular del litio, dicho efecto seria independiente de su accion estabilizadora. Si bien los mecanismos de accion de la droga no son completamente conocidos y la investigacion clinica se ve dificultada debido a la heterogeneidad de las muestras estudiadas, se han propuesto distintas vias que explicarian su efecto, relacionadas con el metabolismo de los neurotransmisores y con factores neurotroficos y neuroprotectores. Pese a la disminucion actual en el uso del litio como EA, continua siendo el farmaco antisuicida de eleccion en pacientes bipolares. Palabras clave: Estabilizador del animo, litio, anticonvulsivante, suicidio, trastorno afectivo bipolar. during lithium maintenance treatment. J Clin Psychiatry 2000; 61: 97-104.8. Lauterbach E, Felber W, Muller-Oerlinghausen B, Ahrens B, Bronisch T, Meyer T,

Study 329 and the use of paroxetine in child and adolescent unipolar depression

Dear Editor, We have recently published the article “Ten years after the FDA black box warning for antidepressant drugs: a critical narrative review” regarding the warning issued in 2003 by the United States Food and Drug Administration (FDA) about the use of serotonin reuptake inhibitors and venlafaxine for the treatment of child and adolescent depression, and its association to an increased suicidality risk1. However, considering the new evidence emerged on the topic, we would like to update our article using new available information regarding paroxetine use, a serotonin reuptake inhibitor involved in FDA’s warning as well. In 2001, Keller et al. published the study “Efficacy of paroxetine in the treatment of adolescent major depression: a randomized, controlled trial”2 (Study 329), sponsored and conducted by SmithKline Beecham (which later became Glaxo SmithKline), concluding that paroxetine is generally well tolerated and effective for unipolar major depression in adolescents when compared with placebo. The “ghostwritten” published results of Study 329 were used for a marketing campaign characterizing paroxetine as remarkably effective and safe. After the campaign, over 2 million off-label prescriptions were written. In 2012, Glaxo SmithKline was fined a record

Antipsicóticos y suicidio

3 billion for dishonest encouragement of paroxetine use3. Additionally, the manuscript was made by a medical writer hired by the laboratory, and all the 22 authors in the manuscript denied having participated in writing the draft3. Recently, the British Medical Journal has published the reanalysis of Study 329, carried out by independent researchers4, using Clinical Data Records, in the context of the RIAT initiative “Restoring Invisible and Abandoned Trials,” and in order to check whether access to and reanalysis of a full dataset from a randomized controlled trial would have clinically relevant implications for evidence based medicine. The authors demonstrated that the antidepressant is neither safe nor effective in adolescent depression. Indeed, the effect of paroxetine was not significantly different from placebo for primary or secondary outcome measure. There were significant increases in harms, suicidal ideation and behavior in paroxetine group, while imipramine group displayed cardiovascular problems. The authors highlighted the need of making primary trial data and protocols available to increase the thoroughness of the evidence. In our study, Study 329 was not included, and neither was its reanalysis1. We consider of utmost relevance to take this case into account, especially when considering that the outcome of a clinical intervention is directly related to suicide spectrum. Although in our article we showed some criticism about the ambiguity of the FDA warning, we do not support, in whatever way, these type of practices, which discredit the medical community and science in general.