Can Long-Term Pharmacotherapy Prevent Relapses in Generalized Anxiety Disorder? A Systematic Review.

BACKGROUND AND OBJECTIVES: Generalized anxiety disorder (GAD) is a persistent anxiety disorder with a high rate of relapse. While several trials have demonstrated the efficacy of pharmacotherapy for GAD treatment, fewer studies have investigated its efficacy in preventing symptom relapse in long-term treatment. The aim of this study is to evaluate if long-term pharmacotherapy may prevent relapses in GAD patients. METHODS: This is a systematic review of the relapse prevention trials with GAD patients. RESULTS: Eight trials were included in this review with 5304 patients in total. All patients showed a higher risk of relapse if treatment was not maintained for at least 6 months after remission, with hazard ratios ranging from 0.12 to 0.58 and mostly moderate effect sizes (0.19-1.06). CONCLUSION: Long-term pharmacotherapy may prevent symptom relapse in GAD patients. As the relapse rate is very high, the data support the continuation of pharmacotherapy for as long as possible.

Treatment effect on temperament and character in panic disorder: a prospective randomized double-blind study / Efeito de tratamento sobre temperamento e caráter no transtorno de pânico: estudo randomizado prospectivo duplo-cego

OBJECTIVE: The present study aims to analyze the effect of pharmacological treatment for panic disorder on temperament and character dimensions and to compare the effect of imipramine and fluoxetine on this outcome. METHOD: Temperament and character dimensions were evaluated in panic disorder patients before and after six months of pharmacological treatment with imipramine and fluoxetine, using the Temperament and Character Inventory-Revised. Patients were randomized between groups and both (patient and investigators) were blinded to the intervention drug. Furthermore, 34 non-panic controls answered the revised Temperament and Character Inventory through an Internet survey. RESULTS: Panic disorder patients showed higher scores for Harm Avoidance and lower scores for Persistence, Self-Directedness, and Cooperativeness than controls at baseline, but only the low Persistence value remained different from controls after treatment. Responder patients presented significant reduction in Harm Avoidance scores and a significant increase in Self-Directedness scores, whereas non-responders showed a significant increase of Harm Avoidance levels. Fluoxetine and Imipramine showed similar effects on the revised Temperament and Character Inventory dimensions. CONCLUSION: High Harm Avoidance and low Self-Directedness, Persistence, and Cooperativeness are associated with panic disorder. Treatment of acute panic disorder symptoms lead to the reduction of Harm Avoidance and to an increase in Self-Directedness scores. However, there was no difference between treatment with fluoxetine and imipramine for the effect on the revised Temperament and Character Inventory dimensions.

OBJETIVO: O presente estudo tem como objetivo analisar o efeito do tratamento farmacológico do transtorno do pânico nas dimensões de temperamento e caráter, comparando os efeitos das medicações imipramina e fluoxetina neste desfecho. METODOLOGIA: As dimensões de temperamento e caráter foram avaliadas em pacientes com transtorno do pânico antes e depois de seis meses de tratamento com imipramina ou fluoxetina, utilizando-se o "Temperament and Character Inventory- Revised" (TCI-R). O estudo foi randomizado e duplo-cego. Além disso, 34 controles sem transtorno do pânico responderam ao TCI-R via internet. RESULTADOS: Pacientes com transtorno do pânico apresentaram maior pontuação para "Harm Avoidance" e menor pontuação para "Persistence", "Self-Directedness" e "Cooperativeness" que os controles antes do tratamento, mas apenas "Persistence" manteve a diferença após o tratamento. Pacientes respondedores apresentaram redução significativa da pontuação para "Harm Avoidance" e aumento significativo para "Self-Directedness" após o tratamento, enquanto os não-respondedores mostraram aumento significativo na pontuação para "Harm Avoidance". A fluoxetina e a imipramina apresentaram efeitos semelhantes nas dimensões do TCI-R. CONCLUSÃO: Alta pontuação para "Harm Avoidance" e baixa para "Persistence", "Self-Directness" e "Cooperativeness" estão associados ao transtorno do pânico. O tratamento sintomático do transtorno do pânico leva a redução da pontuação para "Harm Avoidance" e aumento de pontuação para "Self-Directedness". No entanto, não há diferença entre os efeitos da imipramina e da fluoxetina nestas dimensões do TCI-R.

A systematic review of fMRI studies in generalized anxiety disorder: evaluating its neural and cognitive basis.

BACKGROUND: Generalized anxiety disorder (GAD) is a prevalent anxiety disorder, but its neurobiological basis has been poorly studied. A few cognitive models have been proposed for understanding GAD development and maintenance. The aim of this study is to review functional Magnetic Resonance Image (fMRI) studies conducted with GAD patients and evaluate if they support and underpin the theoretical cognitive models proposed for this anxiety disorder. METHODS: A literature systematic review was undertaken in PubMed and ISI databases with no time limits. RESULTS: From the studies included in this review, 10 explored the "emotional dysregulation model", showing, prefrontal cortex (PFC) and anterior cingulate cortex (ACC) hypofunction and deficient top-down control system during emotion regulation tasks, despite conflicting techniques and results. Only one study explored the "conditioned fear overgeneralization theory", other the "intolerance of uncertainty model" and two studies were unspecific (worry induction tasks). Between those, there were 4 studies evaluating pre- and post-treatment with antidepressants or "mindfulness". LIMITATIONS: The studies׳ methodologies differ between one another making it difficult to identify a common finding. CONCLUSION: Emotion dysregulation seems to be an important cognitive dysfunction in GAD patients and fMRI studies suggest that it is related to PFC and ACC hypofunction as well as a deficient cortex-amygdala functional connectivity.

Temperament and character dimensions and their relationship to major depression and panic disorder.

INTRODUCTION: Since the first publication of Cloninger's psychobiological model of personality, the relationship between temperament and character dimensions and psychiatric disorders has been widely studied. The exact nature of this interaction, however, is still unclear. Different models have been proposed (state-dependency, vulnerability, continuous spectrum etc). OBJECTIVE: To analyze the relationship between temperament and character dimensions with depression and panic disorder. METHOD: Systematic review on interventional studies published up until December 2011 on MEDLINE and ISI databases. Also, a brief review on genetic studies is hereby undertaken, aiming to discuss the gene-environment interaction in relation to this topic. RESULTS: Thirteen studies were included: 10 related to depression and 3 to panic disorder (or unspecific anxiety symptoms). All of them showed association between high harm avoidance (HA) and low self-directedness (SD) with depression and anxiety symptoms. Longitudinal studies demonstrated that these traits may not be just state-dependent. CONCLUSIONS: HA and SD dimensions are associated with both the occurrence of depressive and anxiety symptoms. There is also some evidence to suggest that high HA and low SD indicates susceptibility to depression. Longitudinal studies are not sufficient to affirm the same about panic disorder up to the present moment.

Transtornos de ansiedade / Anxiety disorders

Os transtornos de ansiedade apresentam alta prevalência na população e provocam grande prejuízo a pacientes e familiares. Existem diversos subtipos de transtornos de ansiedade e seu diagnóstico correto se baseia na avaliação clínica cuidadosa. Neste artigo descrevemos como diagnosticar e tratar o transtorno de ansiedade generalizada, o transtorno do pânico e o transtorno de ansiedade social, três dos mais frequentes transtornos de ansiedade.

Selective serotonin-reuptake inhibitors in the treatment of panic disorder: a systematic review of placebo-controlled studies.

The selective serotonin-reuptake inhibitors are widely used in clinical practice in the treatment of panic disorder (PD). This article undertakes an up-to-date, systematic review of the published double-blind, placebo-controlled, randomized, short-term studies with currently available selective serotonin-reuptake inhibitors in the treatment of PD. Sertraline, paroxetine, citalopram, escitalopram, fluoxetine and fluvoxamine have all been proven to be superior to pill-placebo, although the placebo effect has been shown to be extremely important in patients with PD. The authors also explore the anxiolytic mechanism of action of this antidepressant drug class and the preclinical studies that are being developed to clarify the etiopathogenic mechanisms of PD and, more precisely, the role of the serotoninergic system in this pathogenesis. These steps are considered fundamental for the improvement of pharmacological treatment of PD.