Relapse prevention in panic disorder with pharmacotherapy: where are we now?

Introduction: A substantial number of patients with PD experience relapse after the discontinuation of effective pharmacotherapy, leading to detrimental effects on the individuals and considerable societal costs. This suggests the need to optimize pharmacotherapy to minimize relapse risk. Area covered: The present systematic review examines randomized, double-blind, placebo-controlled relapse prevention studies published over the last 20 years involving recommended medications. The authors aim to provide an overview of this topic and evaluate whether recent advances were achieved. Only seven studies were included, providing limited results. One-year maintenance pharmacotherapy with constant doses had protective effects against relapse in patients who had previously exhibited satisfactory responses to the same medication at the same doses. The duration of maintenance treatment did not influence relapse risk. No data were available concerning the use of lower doses or the predictors of relapse. Expert opinion: Relapse prevention in PD has received limited attention. Recent progress and conclusive indications are lacking. Rethinking pharmacological research in PD may be productive. Collecting a wide range of clinical and individual features/biomarkers in large-scale, multicenter long-term naturalistic studies, and implementing recent technological innovations (e.g., electronic medical records/'big data' platforms, wearable devices, and machine learning techniques) may help identify reliable predictive models.

Short-Term Psychiatric Rehabilitation in Major Depressive and Bipolar Disorders: Neuropsychological-Psychosocial Outcomes.

OBJECTIVE: Our pilot study aims to investigate the efficacy of a Short-Term (4 weeks) Psychiatric Rehabilitation Program (S-T PsyRP), without specific cognitive remediation trainings, on the neuropsychological performance and psychosocial functioning of inpatients with Major Depressive Disorder (MDD) or Bipolar Disorder (BD). Published studies with similar aims are lacking. METHODS: Fifty-three inpatients with MDD and 27 with BD (type I/II) were included. The S-T PsyRP was usually performed as clinical practice at Villa San Benedetto Menni Hospital and included a variety of activities aimed at promoting personal autonomies, interpersonal/social skills, and self-care. At the beginning and the end of the hospitalization we evaluated: neuropsychological performance (cognitive tests on verbal/visual working memory, attention, visual-constructive ability, language fluency, and comprehension); psychosocial functioning by the Rehabilitation Areas Form (RAF, handbook VADO); illness severity by the Brief Psychiatric Rating Scale (BPRS). Repeated-measure ANOVA and Pearson's linear correlation were used. RESULTS: We found significant improvement (p<0.01) in all the neuropsychological tests except for one, in 4 out of 6 RAF psychosocial areas ("involvement in ward activities", "autonomies", "self-care", and "self-management of health") and in clinical symptoms severity. No associations were found between the amelioration of clinical symptoms and neuropsychological or psychosocial improvement. CONCLUSION: A S-T PsyRP without specific cognitive remediation trainings may improve several cognitive/functional domains in MDD or BD inpatients, probably by offering opportunities to engage in demanding problem-solving conditions and cognitively stimulating activities.

Long-Term Pharmacological Treatments of Anxiety Disorders: An Updated Systematic Review.

Many aspects of long-term pharmacological treatments for anxiety disorders (AnxDs) are still debated. We undertook an updated systematic review of long-term pharmacological studies on panic disorder (PD), generalized anxiety disorder (GAD), and social anxiety disorder (SAD). Relevant studies dating from January 1, 2012 to August 31, 2015 were identified using the PubMed database and a review of bibliographies. Of 372 records identified in the search, five studies on PD and 15 on GAD were included in the review. No studies on SAD were found. Our review confirms the usefulness of long-term pharmacological treatments for PD and GAD and suggests that they can provide further improvement over that obtained during short-term therapy. Paroxetine, escitalopram, and clonazepam can be effective for long-term treatment of PD. However, further studies are needed to draw conclusions about the long-term benzodiazepine use in PD, particularly for the possible cognitive side-effects over time. Pregabalin and quetiapine can be effective for long-term treatment of GAD, while preliminary suggestions emerged for agomelatine and vortioxetine. We did not find any evidence for determining the optimal length and/or dosage of medications to minimize the relapse risk. Few investigations have attempted to identify potential predictors of long-term treatment response. Personalized treatments for AnxDs can be implemented using predictive tools to explore those factors affecting treatment response/tolerability heterogeneity, including neurobiological functions/clinical profiles, comorbidity, biomarkers, and genetic features, and to tailor medications according to each patient's unique features.

Cardiorespiratory response to physical exercise and psychological variables in panic disorder.

OBJECTIVE: To investigate the possible influence of psychological variables on cardiorespiratory responses and perceived exertion of patients with Panic Disorder (PD) during a submaximal exercise test. METHOD: Ten outpatients with PD and 10 matched healthy subjects walked up on a treadmill slope at a speed of 4 km/h in order to reach 65% of their maximum heart rate. Cardiorespiratory variables were continuously recorded. Before the exercise, the state and trait anxiety (State-Trait Anxiety Inventory scores), fear of physical sensations (Body Sensation Questionnaire scores), and fear of autonomic arousal (Anxiety Sensitivity Index scores) were assessed; during the exercise, levels of anxiety (VAS-A) and exertion (Borg Scale CR 10) were measured. RESULTS: Compared to controls, patients reached earlier the target HR and the ventilatory threshold, showed lower oxygen consumption, higher HR and lower within-subject standard deviations of HR (a measure of cardiac variability). Exertion was also higher, and there was a significant correlation between breathing frequency, tidal volume and HR. No significant associations were found between cardiorespiratory response, perceived exertion, and psychological variables in patients with PD. CONCLUSION: Although patients with PD presented poor cardiorespiratory fitness and were required to spend more effort during physical exercise, this did not appear to be related to the psychological variables considered. Further studies with larger groups are warranted.

Cardiorespiratory response to physical exercise and psychological variables in panic disorder / A resposta cardiorrespiratória ao exercício e variáveis psicológicas no transtorno do pânico

OBJECTIVE: To investigate the possible influence of psychological variables on cardiorespiratory responses and perceived exertion of patients with Panic Disorder (PD) during a submaximal exercise test. METHOD: Ten outpatients with PD and 10 matched healthy subjects walked up on a treadmill slope at a speed of 4 km/h in order to reach 65 percent of their maximum heart rate. Cardiorespiratory variables were continuously recorded. Before the exercise, the state and trait anxiety (State-Trait Anxiety Inventory scores), fear of physical sensations (Body Sensation Questionnaire scores), and fear of autonomic arousal (Anxiety Sensitivity Index scores) were assessed; during the exercise, levels of anxiety (VAS-A) and exertion (Borg Scale CR 10) were measured. RESULTS: Compared to controls, patients reached earlier the target HR and the ventilatory threshold, showed lower oxygen consumption, higher HR and lower within-subject standard deviations of HR (a measure of cardiac variability). Exertion was also higher, and there was a significant correlation between breathing frequency, tidal volume and HR. No significant associations were found between cardiorespiratory response, perceived exertion, and psychological variables in patients with PD. CONCLUSION: Although patients with PD presented poor cardiorespiratory fitness and were required to spend more effort during physical exercise, this did not appear to be related to the psychological variables considered. Further studies with larger groups are warranted.

OBJETIVO: Investigar a possível influência de variáveis psicológicas na resposta cardiorrespiratória e percepção de esforço dos pacientes com Transtorno do Pânico (TP) durante exercício físico de intensidade submáxima. MÉTODO: Dez pacientes ambulatoriais com TP e dez controles saudáveis foram submetidos a uma caminhada na velocidade de 4 km/h em uma rampa inclinada. A inclinação da rampa foi aumentada até que fosse atingida 65 por cento da frequência cardíaca máxima (FC alvo). Variáveis cardiorespiratorias foram monitoradas continuamente. Antes do exercício o Inventário de Estado-Traço de Ansiedade, o Índice de Sensibilidade à Ansiedade e o Questionário de Sensações Corporais foram aplicados. Durante o exercício, o nível de ansiedade (Escala Análoga Visual para Ansiedade - VAS-A) e esforço (Escala Borg CR 10) foram medidos. RESULTADOS: Comparados aos controles, os pacientes atingiram a FC alvo e o limiar respiratório mais rápido, tiveram menor consumo de oxigênio, FC mais alta e menor desvio padrão da FC em cada sujeito (medida de variabilidade cardíaca). O esforço também foi maior e houve uma correlação significativa entre frequência respiratória, volume corrente e FC. Nenhuma associação significativa foi encontrada entre cardiorrespiratória resposta, percepção de esforço e variáveis psicológicas em pacientes com TP. CONCLUSÃO: Pacientes com TP mostrou baixa aptidão cardiorrespiratória e maior esforço durante o exercício físico que não pareceu estar relacionada com as variáveis psicológicas consideradas. Mais estudos em grupos maiores são necessários.