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BACKGROUND: Anxiety is a common and disabling condition that significantly impacts quality of life. Subsyndromal anxiety (SSA) refers to anxiety symptoms that do not meet the full diagnostic criteria for an anxiety disorder but pose a risk for developing such disorders. We aimed to provide practical recommendations for the treatment of SSA in primary care settings. METHODS: A narrative review was conducted to identify strategies for recognizing and treating patients with SSA. RESULTS: The recommendations for treating SSA include lifestyle modifications such as exercise and stress reduction techniques, psychotherapy, and pharmacological treatments, including natural compounds like the lavender oil extract Silexan. Regular follow-up care is essential to monitor treatment response and address ongoing symptoms. Additionally, the use of the GAD-7 tool is recommended for accurately identifying patients with SSA. CONCLUSION: Implementing these recommendations in primary care can lead to effective treatment of SSA, preventing the development of more severe anxiety disorders. An integrative approach, combining lifestyle modifications, psychotherapy, and pharmacotherapy, including natural compounds, offers significant benefits for managing anxiety.
Anxiety is prevalent and disablingSubsyndromal anxiety is a risk factor for anxiety disordersSubsyndromal anxiety can be assessed with the GAD-7 (Generalised Anxiety Disorder-7 scale)Subsyndromal anxiety can be treated with life-style modification, psychotherapy and pharmacological treatment, including silexan, a natural compound.
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Starting in 2019, the 2014 German Guidelines for Anxiety Disorders (Bandelow et al. Eur Arch Psychiatry Clin Neurosci 265:363-373, 2015) have been revised by a consensus group consisting of 35 experts representing the 29 leading German specialist societies and patient self-help organizations. While the first version of the guideline was based on 403 randomized controlled studies (RCTs), 92 additional RCTs have been included in this revision. According to the consensus committee, anxiety disorders should be treated with psychotherapy, pharmacological drugs, or their combination. Cognitive behavioral therapy (CBT) was regarded as the psychological treatment with the highest level of evidence. Psychodynamic therapy (PDT) was recommended when CBT was not effective or unavailable or when PDT was preferred by the patient informed about more effective alternatives. Selective serotonin reuptake inhibitors (SSRIs) and serotonin-noradrenaline reuptake inhibitors (SNRIs) are recommended as first-line drugs for anxiety disorders. Medications should be continued for 6-12 months after remission. When either medications or psychotherapy were not effective, treatment should be switched to the other approach or to their combination. For patients non-responsive to standard treatments, a number of alternative strategies have been suggested. An individual treatment plan should consider efficacy, side effects, costs and the preference of the patient. Changes in the revision include recommendations regarding virtual reality exposure therapy, Internet interventions and systemic therapy. The recommendations are not only applicable for Germany but may also be helpful for developing treatment plans in all other countries.
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Terapia Cognitivo-Conductual , Intervención basada en la Internet , Trastornos de Ansiedad/tratamiento farmacológico , Humanos , Psicoterapia , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéuticoRESUMEN
BACKGROUND: During the COVID-19 pandemic, internet-delivered psychotherapeutic interventions (IPI) move increasingly into the focus of attention. METHOD: We reviewed 39 randomized controlled studies of IPIs with 97 study arms (n = 4122 patients) for anxiety disorders (panic disorder/agoraphobia, generalized anxiety disorder, and social anxiety disorder) and performed a meta-analysis. Most studies were conducted with cognitive behavioural approaches (iCBT). Results were compared with a previous meta-analysis examining medications and face-to-face (F2F) psychotherapy. RESULTS: In direct comparisons, IPIs were as effective as F2F-CBT and superior to waitlist controls. Programs with more intensive therapist contact yielded higher effect sizes (ES). We compared the obtained ES with a previous comprehensive meta-analysis of 234 studies. In this comparison, iCBT was less effective than individual F2F-CBT and medications, not different from pill placebos, and more effective than psychological placebo and waitlist (p > .0001 for all comparisons). ES of IPIs may be overestimated. Treatments were only compared to waitlist, which is not a sufficient control condition. 97% of the studies were not blinded with regard to the main outcome measure. 32% of the participants received antianxiety drugs during the trials. In 89%, participants were recruited by advertisements rather than from clinical settings, and 63% of the participants had an academic background (students or university employees) which might affect the generalizability of the findings. Remote diagnoses were often made by students without completed training in psychotherapy. In only 15% of the studies, diagnoses were made in personal contact with a psychiatrist or psychologist. In 44% of the studies, the 'therapists' maintaining remote contact with the participants were mostly students without completed psychotherapy education. CONCLUSIONS: IPIs may be a useful tool when face-to-face psychotherapy is not easily available, or as an add-on to standard psychotherapeutic or psychopharmacological treatments but should perhaps not be used as monotherapy. We have suggested standards for future research and the practical use of IPIs.
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COVID-19 , Pandemias , Agorafobia/terapia , Trastornos de Ansiedad/psicología , Trastornos de Ansiedad/terapia , Humanos , Internet , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del TratamientoRESUMEN
OBJECTIVE: The endogenous opioid system is assumed to be involved in the pathophysiology of borderline personality disorder (BPD), and opioid antagonists may improve core features of BPD. The aim of this retrospective chart analysis was to evaluate the relative contribution of the opioid antagonist naltrexone and other psychotropic drugs in the improvement of overall symptomatology in BPD. METHODS: One hundred sixty-one inpatients with BPD treated between January 2010 and October 2013 were classified as either treatment responders or non-responders. Treatment responders were defined as subjects with significant improvements in four or more symptoms from a defined symptom list. The relative contribution of all psychotropic drugs to improvement of BPD symptomatology was assessed by means of a stepwise logistic regression. RESULTS: None of the drugs applied contributed significantly to improvement, with the exception of naltrexone (odds ratio [OR] 43.2, p ≤ 0.0001). Patients treated with naltrexone (N = 55, 34%) recovered significantly more often. Higher doses of naltrexone were more effective (OR 791.8, p ≤ 0.0001) than lower doses (OR 26.6, p ≤ 0.0001); however, even low-dose treatment was better than any other pharmacological treatment. CONCLUSIONS: Naltrexone was associated with improvement in BPD in a dose-dependent manner. The present study provides additional evidence that dysregulation of the endogenous opioid system is implicated in the pathophysiology of BPD symptoms.
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Trastorno de Personalidad Limítrofe , Naltrexona , Trastorno de Personalidad Limítrofe/diagnóstico , Trastorno de Personalidad Limítrofe/tratamiento farmacológico , Humanos , Pacientes Internos , Naltrexona/uso terapéutico , Antagonistas de Narcóticos/uso terapéutico , Estudios RetrospectivosRESUMEN
The mean age and gender distribution of patients seeking help for mental disorders have not yet been investigated systematically. Epidemiological surveys can provide data on gender distribution of disorders and an age range in which a disorder is most frequent, but do not offer data on the average help-seeking patient, and they are usually conducted by lay interviewers with non-clinical subjects. However, this information on age and gender can be simply extracted from randomized clinical trials (RCTs) in which consecutive clinical patients are included. As it can be assumed that the average patient tends to participate in a clinical trial when her/his illness severity has reached its highpoint, the mean age of patients in RCTs is a good estimator of the peak severity of a disorder. In RCTs, diagnoses are made by psychiatrists and only clinical patients fulfilling a minimum degree of severity are included. From 10.465 records found by electronic and hand search, we extracted 832 eligible RCTs with 151,336 patients with the 19 most relevant mental disorders. We provide a table with the mean age, standard deviation and gender distributions of all major mental disorders. These results can be used in scientific articles and educational materials and can help health care providers or researchers planning treatment programs. Patients can be informed about the natural course of the disorder. By determining the reasons why some disorders occur predominantly in a certain age or have an unbalanced gender distribution information the aetiology of these disorders may further be elucidated.
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Trastornos Mentales/epidemiología , Trastornos Mentales/terapia , Aceptación de la Atención de Salud/estadística & datos numéricos , Selección de Paciente , PubMed/estadística & datos numéricos , Ensayos Clínicos Controlados Aleatorios como Asunto/estadística & datos numéricos , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Humanos , Masculino , Persona de Mediana Edad , Distribuciones Estadísticas , Adulto JovenRESUMEN
Anxiety disorders, including panic disorder/agoraphobia (PDA), generalized anxiety disorder (GAD), social anxiety disorder (SAD), and others, are the most prevalent mental disorders. In this paper, recommendations are given for the psychopharmacological treatment of these disorders which are based on comprehensive treatment guidelines, meta-analyses, and systematic reviews of available randomized controlled studies. Anxiety disorders can effectively be treated with psychotherapy, pharmacotherapy, or a combination of both. First-line drugs are the selective serotonin reuptake inhibitors (SSRIs) and serotonin-norepinephrine reuptake inhibitors (SNRIs). Benzodiazepines are not recommended for routine use due to their possible addiction potential. Other treatment options include the calcium modulator pregabalin, tricyclic antidepressants, buspirone, moclobemide, and others. Drug treatment can be combined with psychological treatments. Novel treatment strategies include medications that act on GABA, glutamate, and other neurotransmitter systems. After remission, medications should be continued for 6 to 12 months.
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Ansiolíticos/uso terapéutico , Trastornos de Ansiedad/tratamiento farmacológico , Inhibidores Selectivos de la Recaptación de Serotonina/uso terapéutico , Inhibidores de Captación de Serotonina y Norepinefrina/uso terapéutico , Humanos , PsicoterapiaRESUMEN
BACKGROUND: Depression is considered to have the highest disability burden of all conditions. Although treatment-resistant depression (TRD) is a key contributor to that burden, there is little understanding of the best treatment approaches for it and specifically the effectiveness of available augmentation approaches.AimsWe conducted a systematic review and meta-analysis to search and quantify the evidence of psychological and pharmacological augmentation interventions for TRD. METHOD: Participants with TRD (defined as insufficient response to at least two antidepressants) were randomised to at least one augmentation treatment in the trial. Pre-post analysis assessed treatment effectiveness, providing an effect size (ES) independent of comparator interventions. RESULTS: Of 28 trials, 3 investigated psychological treatments and 25 examined pharmacological interventions. Pre-post analyses demonstrated N-methyl-d-aspartate-targeting drugs to have the highest ES (ES = 1.48, 95% CI 1.25-1.71). Other than aripiprazole (four studies, ES = 1.33, 95% CI 1.23-1.44) and lithium (three studies, ES = 1.00, 95% CI 0.81-1.20), treatments were each investigated in less than three studies. Overall, pharmacological (ES = 1.19, 95% CI 1.80-1.30) and psychological (ES = 1.43, 95% CI 0.50-2.36) therapies yielded higher ESs than pill placebo (ES = 0.78, 95% CI 0.66-0.91) and psychological control (ES = 0.94, 95% CI 0.36-1.52). CONCLUSIONS: Despite being used widely in clinical practice, the evidence for augmentation treatments in TRD is sparse. Although pre-post meta-analyses are limited by the absence of direct comparison, this work finds promising evidence across treatment modalities.Declaration of interestIn the past 3 years, A.H.Y. received honoraria for speaking from AstraZeneca, Lundbeck, Eli Lilly and Sunovion; honoraria for consulting from Allergan, Livanova and Lundbeck, Sunovion and Janssen; and research grant support from Janssen. In the past 3 years, A.J.C. received honoraria for speaking from AstraZeneca and Lundbeck; honoraria for consulting with Allergan, Janssen, Livanova, Lundbeck and Sandoz; support for conference attendance from Janssen; and research grant support from Lundbeck. B.B. has recently been (soon to be) on the speakers/advisory board for Hexal, Lilly, Lundbeck, Mundipharma, Pfizer, and Servier. No other conflicts of interest.
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Antidepresivos/uso terapéutico , Trastorno Depresivo Resistente al Tratamiento/terapia , Psicoterapia , Trastorno Depresivo Resistente al Tratamiento/tratamiento farmacológico , Humanos , Resultado del TratamientoRESUMEN
BACKGROUND: The purpose of this study was to assess the pharmacological treatment strategies of inpatients with borderline personality disorder between 2008 and 2012. Additionally, we compared pharmacotherapy during this period to a previous one (1996 to 2004). METHODS: Charts of 87 patients with the main diagnosis of borderline personality disorder receiving inpatient treatment in the University Medical Center of Goettingen, Germany, between 2008 and 2012 were evaluated retrospectively. For each inpatient treatment, psychotropic drug therapy including admission and discharge medication was documented. We compared the prescription rates of the interval 2008-2012 with the interval 1996-2004. RESULTS: 94% of all inpatients of the interval 2008-2012 were treated with at least one psychotropic drug at time of discharge. All classes of psychotropic drugs were applied. We found high prescription rates of naltrexone (35.6%), quetiapine (19.5%), mirtazapine (18.4%), sertraline (12.6%), and escitalopram (11.5%). Compared to 1996-2004, rates of low-potency antipsychotics, tri-/tetracyclic antidepressants and mood stabilizers significantly decreased while usage of naltrexone significantly increased. CONCLUSIONS: In inpatient settings, pharmacotherapy is still highly prevalent in the management of BPD. Prescription strategies changed between 1996 and 2012. Quetiapine was preferred, older antidepressants and low-potency antipsychotics were avoided. Opioid antagonists are increasingly used and should be considered for further investigation.
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Trastorno de Personalidad Limítrofe/tratamiento farmacológico , Trastorno de Personalidad Limítrofe/epidemiología , Psicotrópicos/uso terapéutico , Adulto , Anticonvulsivantes/uso terapéutico , Antidepresivos/uso terapéutico , Antimaníacos/uso terapéutico , Antipsicóticos/uso terapéutico , Trastorno de Personalidad Limítrofe/psicología , Femenino , Alemania/epidemiología , Hospitalización/tendencias , Humanos , Masculino , Persona de Mediana Edad , Antagonistas de Narcóticos/uso terapéutico , Prevalencia , Estudios Retrospectivos , Factores de Tiempo , Adulto JovenRESUMEN
BACKGROUND: It is a widespread opinion that after treatment with psychotherapy, patients with anxiety disorders maintain their gains beyond the active treatment period, whereas patients treated with medication soon experience a relapse after treatment termination.AimsWe aimed to provide evidence on whether enduring effects of psychotherapy differ from control groups. METHOD: We searched 93 randomised controlled studies with 152 study arms of psychological treatment (cognitive-behavioural therapy or other psychotherapies) for panic disorder, generalised anxiety disorder and social anxiety disorder that included follow-up assessments. In a meta-analysis, pre-post effect sizes for end-point and all follow-up periods were calculated and compared with control groups (medication: n = 16 study arms; pill and psychological placebo groups: n = 17 study arms). RESULTS: Gains with psychotherapy were maintained for up to 24 months. For cognitive-behavioural therapy, we observed a significant improvement over time. However, patients in the medication group remained stable during the treatment-free period, with no significant difference when compared with psychotherapy. Patients in the placebo group did not deteriorate during follow-up, but showed significantly worse outcomes than patients in cognitive-behavioural therapy. CONCLUSIONS: Not only psychotherapy, but also medications and, to a lesser extent, placebo conditions have enduring effects. Long-lasting treatment effects observed in the follow-up period may be superimposed by effects of spontaneous remission or regression to the mean.Declaration of interestIn the past 12 months and in the near future, Dr Bandelow has been/will be on the speakers/advisory board for Hexal, Mundipharma, Lilly, Lundbeck, Pfizer and Servier. Dr Wedekind was on the speakers' board of AstraZeneca, Essex Pharma, Lundbeck and Servier. All other authors have nothing to declare.
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Ansiolíticos/uso terapéutico , Trastornos de Ansiedad/terapia , Evaluación de Resultado en la Atención de Salud/estadística & datos numéricos , Psicoterapia/estadística & datos numéricos , Trastornos de Ansiedad/tratamiento farmacológico , Estudios de Seguimiento , HumanosRESUMEN
Anxiety disorders are the most prevalent mental disorders and are associated with substantial healthcare costs and a high burden of disease. In this article, changes in the new Diagnostic and Statistical Manual for Mental Disorders (the DSM-5) with respect to panic disorder/agoraphobia, generalized anxiety disorder, social anxiety disorder, specific phobias, and selective mutism are compared with the International Classification of Diseases (ICD-10) system.
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Trastornos de Ansiedad/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Clasificación Internacional de Enfermedades , HumanosRESUMEN
According to ICD-10 criteria, mixed anxiety and depressive disorder (MADD) is characterized by co-occurring, subsyndromal symptoms of anxiety and depression, severe enough to justify a psychiatric diagnosis, but neither of which are clearly predominant. MADD appears to be very common, particularly in primary care, although prevalence estimates vary, often depending on the diagnostic criteria applied. It has been associated with similarly pronounced distress, impairment of daily living skills, and reduced health-related quality of life as fully syndromal depression and anxiety. Although about half of the patients affected remit within a year, non-remitting patients are at a high risk of transition to a fully syndromal psychiatric disorder. The validity and clinical usefulness of MADD as a diagnostic category are under debate. It has not been included in the recently released DSM-5 since the proposed diagnostic criteria turned out to be not sufficiently reliable. Moreover, reviewers have disputed the justification of MADD based on divergent results regarding its prevalence and course, diagnostic stability over time, and nosological inconsistencies between subthreshold and threshold presentations of anxiety and depressive disorders. We review the evidence in favor and against MADD and argue that it should be included into classification systems as a diagnostic category because it may enable patients to gain access to appropriate treatment early. This may help to reduce patients' distress, prevent exacerbation to a more serious psychiatric disorder, and ultimately reduce the societal costs of this very common condition.
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Trastornos de Ansiedad , Trastorno Depresivo , Trastornos de Ansiedad/clasificación , Trastornos de Ansiedad/diagnóstico , Trastornos de Ansiedad/epidemiología , Trastorno Depresivo/clasificación , Trastorno Depresivo/diagnóstico , Trastorno Depresivo/epidemiología , Humanos , Clasificación Internacional de Enfermedades , Escalas de Valoración PsiquiátricaRESUMEN
A consensus group consisting of 36 experts representing 20 leading German specialist societies and patient self-help organizations developed evidence-based recommendations for the treatment of anxiety disorders in Germany. These were based on a systematic review of randomized controlled trials on anxiety disorders (n = 403) and on preexisting German and international guidelines. According to the consensus committee, anxiety disorders should be treated with psychotherapy or pharmacological drugs or a combination of both. Cognitive behavioral therapy (CBT) was regarded as the psychological treatment with the highest level of evidence. Psychodynamic therapy (PDT) was recommended for cases in which CBT was not effective or not available or in which PDT was the informed patient's preferred option. First-line drugs for anxiety disorders include selective serotonin reuptake inhibitors and serotonin-noradrenaline reuptake inhibitors. After remission, medications should be continued for 6-12 months. When either drug or psychotherapy was not effective, treatment should be switched to the other approach or to a combination of both. For patients non-responsive to standard treatments, alternative strategies are suggested. When developing a treatment plan, efficacy, side effects, costs and the preference of the patient should be considered. A large amount of data available from randomized controlled trials permit the formulation of robust evidence-based recommendations for the treatment of anxiety disorders. The recommendations were not only developed for the special situation in Germany, but may also be helpful for developing treatment plans in other countries.
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Ansiolíticos/normas , Ansiolíticos/uso terapéutico , Trastornos de Ansiedad/terapia , Terapia Cognitivo-Conductual/métodos , Terapia Cognitivo-Conductual/normas , Guías como Asunto/normas , Trastornos de Ansiedad/diagnóstico , Alemania , HumanosRESUMEN
Part 1 of this paper discussed several more general aspects of Diagnostic and Statistical Manual of Mental Disorders (DSM-5) and offered a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. This second part focusses on several other disorders, including bipolar and schizophrenia spectrum disorders. The respective changes and their possible consequences are discussed under consideration of traditional psychiatric classification, particularly from the perspective of European traditions and on the basis of a PubMed search and review papers. The general conclusion is that even seemingly small changes such as the introduction of the mixed feature specifier can have far-reaching consequences. Contrary to the original plans, DSM-5 has not radically changed to become a primarily dimensional diagnostic system but has preserved the categorical system for most disorders. The ambivalence of the respective decision-making becomes apparent from the last minute decision to change the classification of personality disorders from dimensional back to categorical. The advantages and disadvantages of the different approaches are discussed in this context. In DSM-5, only the chapter on addictive disorders has a somewhat dimensional structure. Also in contrast to the original intentions, DSM-5 has not used a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses. Even in the most advanced field in terms of biomarkers, the neurocognitive disorders, the primarily symptom-based, descriptive approach has been preserved and the well-known amyloid-related and other biomarkers are not included. This is because, even after so many years of biomarker research, the results are still not considered to be robust enough to use in clinical practice.
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Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastornos Mentales/clasificación , Trastornos Mentales/diagnóstico , Trastornos Relacionados con Sustancias/diagnóstico , Bases de Datos Factuales/estadística & datos numéricos , Humanos , Trastornos PsicofisiológicosRESUMEN
DSM-5 was published in 2013 after about 10 years of preparation. Part 1 of this paper discusses several more general aspects of DSM-5 and offers a detailed, paradigmatic analysis of changes made to the chapter on depressive disorders. The background for the changes is analysed on the basis of a PubMed search and review papers on the classification of mental disorders in general and on empirical knowledge about individual disorders. Contrary to the original plans, DSM-5 has not introduced a primarily dimensional diagnostic system but has widely preserved the categorical system of disorders. Also, it has not adopted a more neurobiological approach to disorders by including biological markers to increase the objectivity of psychiatric diagnoses but has maintained the primarily symptom-based, descriptive approach. The criteria for some disorders have been changed, including affective, schizophrenic and addiction disorders, and a few new disorders have been added. A minimal version of the dimensional approach was realised through the introduction of several transnosological specifiers and the option to make symptom- or syndrome-related severity and dimensional assessments. These specifiers and assessments might allow a more individualised description of a patient's psychopathological state and more personalised treatment. However, most of the symptom- and syndrome-related assessments are not mandatory and therefore may not be used in clinical practice.
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Trastorno Depresivo/diagnóstico , Manual Diagnóstico y Estadístico de los Trastornos Mentales , Trastorno Depresivo/clasificación , Humanos , Evaluación de SíntomasRESUMEN
Around half the inmates in prison institutions have antisocial personality disorder (ASPD). A recent theory has proposed that a dysfunction of the endogenous opioid system (EOS) underlies the neurobiology of borderline personality disorder (BPD). In the present theoretical paper, based on a comprehensive database and hand search of the relevant literature, this hypothesis is extended to ASPD, which may be the predominant expression of EOS dysfunction in men, while the same pathology underlies BPD in women. According to evidence from human and animal studies, the problematic behaviours of persons with antisocial, callous, or psychopathic traits may be seen as desperate, unconscious attempts to stimulate their deficient EOS, which plays a key role in brain reward circuits. If the needs of this system are not being met, the affected persons experience dysphoric mood, discomfort, or irritability, and strive to increase binding of endogenous opioids to receptors by using the rewarding effects of aggression by exertion of physical or manipulative power on others, by abusing alcohol or substances that have the reward system as target, by creating an "endorphin rush" by self-harm, by increasing the frequency of their sexual contacts, or by impulsive actions and sensation seeking. Symptoms associated with ASPD can be treated with opioid antagonists like naltrexone, naloxone, or nalmefene.
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Trastorno de Personalidad Antisocial/fisiopatología , Péptidos Opioides/metabolismo , Receptores Opioides/metabolismo , Agresión/psicología , Animales , Trastorno de Personalidad Limítrofe/fisiopatología , Femenino , Humanos , Masculino , Prisioneros/psicología , RecompensaRESUMEN
Accumulating evidence from mouse models points to the G protein-coupled receptor RGS2 (regulator of G-protein signaling 2) as a promising candidate gene for anxiety in humans. Recently, RGS2 polymorphisms were found to be associated with various anxiety disorders, e.g., rs4606 with panic disorder (PD), but other findings have been negative or inconsistent concerning the respective risk allele. To further examine the role of RGS2 polymorphisms in the pathogenesis of PD, we genotyped rs4606 and five additional RGS2 tag single nucleotide polymorphisms (SNPs; rs16834831, rs10801153, rs16829458, rs1342809, rs1890397) in two independent PD samples, comprising 531 matched case/control pairs. The functional SNP rs4606 was nominally associated with PD when both samples were combined. The upstream SNP rs10801153 displayed a Bonferroni-resistant significant association with PD in the second and the combined sample (P = 0.006 and P = 0.017). We furthermore investigated the effect of rs10801153 on dimensional anxiety traits, a behavioral avoidance test (BAT), and an index for emotional processing in the respective subsets of the total sample. In line with categorical results, homozygous risk (G) allele carriers displayed higher scores on the Agoraphobic Cognitions Questionnaire (ACQ; P = 0.015) and showed significantly more defensive behavior during fear provoking situations (P = 0.001). Furthermore, significant effects on brain activation in response to angry (P = 0.013), happy (P = 0.042) and neutral faces (P = 0.032) were detected. Taken together, these findings provide further evidence for the potential role of RGS2 as a candidate gene for PD.
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Trastornos de Ansiedad/etiología , Biomarcadores/análisis , Predisposición Genética a la Enfermedad , Trastorno de Pánico/genética , Polimorfismo de Nucleótido Simple/genética , Proteínas RGS/genética , Adulto , Trastornos de Ansiedad/psicología , Mapeo Encefálico , Estudios de Casos y Controles , Emociones/fisiología , Femenino , Estudios de Seguimiento , Genotipo , Haplotipos , Humanos , Procesamiento de Imagen Asistido por Computador , Masculino , Trastorno de Pánico/complicaciones , Trastorno de Pánico/psicología , Personalidad , Fenotipo , Proyectos Piloto , Pronóstico , Pruebas PsicológicasRESUMEN
Anxiety disorders are very prevalent and often persistent mental disorders, with a considerable rate of treatment resistance which requires regulatory clinical trials of innovative therapeutic interventions. However, an explicit definition of treatment-resistant anxiety disorders (TR-AD) informing such trials is currently lacking. We used a Delphi method-based consensus approach to provide internationally agreed, consistent and clinically useful operational criteria for TR-AD in adults. Following a summary of the current state of knowledge based on international guidelines and an available systematic review, a survey of free-text responses to a 29-item questionnaire on relevant aspects of TR-AD, and an online consensus meeting, a panel of 36 multidisciplinary international experts and stakeholders voted anonymously on written statements in three survey rounds. Consensus was defined as ≥75% of the panel agreeing with a statement. The panel agreed on a set of 14 recommendations for the definition of TR-AD, providing detailed operational criteria for resistance to pharmacological and/or psychotherapeutic treatment, as well as a potential staging model. The panel also evaluated further aspects regarding epidemiological subgroups, comorbidities and biographical factors, the terminology of TR-AD vs. "difficult-to-treat" anxiety disorders, preferences and attitudes of persons with these disorders, and future research directions. This Delphi method-based consensus on operational criteria for TR-AD is expected to serve as a systematic, consistent and practical clinical guideline to aid in designing future mechanistic studies and facilitate clinical trials for regulatory purposes. This effort could ultimately lead to the development of more effective evidence-based stepped-care treatment algorithms for patients with anxiety disorders.
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Effects of once-daily extended-release quetiapine fumarate (quetiapine XR) monotherapy on sleep quality and disturbance in patients with major depressive disorder (MDD) were evaluated. Pooled data from four 6- or 8-wk placebo-controlled quetiapine XR (50-300 mg/d) monotherapy studies (D1448C00001; D1448C00002; D1448C00003; D1448C00004) were analysed. Primary efficacy end-point was change from randomization in Montgomery Åsberg Depression Rating Scale (MADRS) score. Post hoc analyses of secondary end-points were conducted for change from randomization in: MADRS item 4 (reduced sleep); Hamilton Rating Scale for Depression (HAMD) items 4 (insomnia-early), 5 (insomnia-middle), 6 (insomnia-late) and sleep disturbance factor (items 4 + 5+6) scores; Pittsburgh Sleep Quality Index (PSQI) global scores. MADRS total score change was also evaluated in patients experiencing high and low baseline sleep disturbance (HAMD sleep disturbance factor scores ⩾4 and < 4, respectively). In total, 1808 patients were randomized to quetiapine XR or placebo across four studies. At last assessment, quetiapine XR reduced MADRS item 4, HAMD items 4, 5 and 6, HAMD sleep disturbance factor score and PSQI global scores from baseline vs. placebo (p < 0.001). For those experiencing high sleep disturbance (n = 865, quetiapine XR; n = 514, placebo), quetiapine XR improved MADRS total score vs. placebo at all visits (p < 0.001). For those with low sleep disturbance (n = 252, quetiapine XR; n = 121, placebo), quetiapine XR improved MADRS total score vs. placebo at weeks 2 (p < 0.001), 4 and 6 (both p < 0.05). In conclusion, quetiapine XR (50-300 mg/d) monotherapy improved symptoms of sleep disturbance vs. placebo in patients with MDD, including those with either high or low baseline sleep disturbance levels.