Modifiable risk and protective factors for anxiety disorders among adults: A systematic review.

Anxiety disorders are highly prevalent in the general population and associated with high rates of impairment and disability. This burden highlights the need to identify risk factors that individuals can modify without professional intervention. A systematic review was conducted to identify studies that examined modifiable risk and protective factors for anxiety disorders among adults in the general population. Searches were conducted in PubMed, PsycINFO and MEDLINE using medical subject headings and text words related to risk factors, protective factors, and each anxiety disorder. Screening, data extraction, and quality assessment were performed by three study authors. Modifiable risk and protective factors from 19 studies across seven countries were identified. Risk factors identified included cigarette smoking, alcohol use, cannabis use, negative appraisals of life events, avoidance, and occupational factors. Protective factors included social support, coping, and physical activity. Cigarette smoking was the most studied risk factor. Support was found for cigarette smoking as a risk factor for agoraphobia and panic disorder. Mixed results were found for generalized anxiety disorder and specific phobia. Across disorders, smoking frequency was associated with greater risk. Results indicate an important gap in the literature in that few studies have examined modifiable risk factors for anxiety disorders.

Physical activity protects from incident anxiety: A meta-analysis of prospective cohort studies.

BACKGROUND: Prospective cohorts have suggested that physical activity (PA) can decrease the risk of incident anxiety. However, no meta-analysis has been conducted. AIMS: To examine the prospective relationship between PA and incident anxiety and explore potential moderators. METHODS: Searches were conducted on major databases from inception to October 10, 2018 for prospective studies (at least 1 year of follow-up) that calculated the odds ratio (OR) of incident anxiety in people with high PA against people with low PA. Methodological quality was assessed using the Newcastle-Ottawa Scale (NOS). A random-effects meta-analysis was conducted and heterogeneity was explored using subgroup and meta-regression analysis. RESULTS: Across 14 cohorts of 13 unique prospective studies (N = 75,831, median males = 50.1%) followed for 357,424 person-years, people with high self-reported PA (versus low PA) were at reduced odds of developing anxiety (adjusted odds ratio [AOR] = 0.74; 95% confidence level [95% CI] = 0.62, 0.88; crude OR = 0.80; 95% CI = 0.69, 0.92). High self-reported PA was protective against the emergence of agoraphobia (AOR = 0.42; 95% CI = 0.18, 0.98) and posttraumatic stress disorder (AOR = 0.57; 95% CI = 0.39, 0.85). The protective effects for anxiety were evident in Asia (AOR = 0.31; 95% CI = 0.10, 0.96) and Europe (AOR = 0.82; 95% CI = 0.69, 0.97); for children/adolescents (AOR = 0.52; 95% CI = 0.29, 0.90) and adults (AOR = 0.81; 95% CI = 0.69, 0.95). Results remained robust when adjusting for confounding factors. Overall study quality was moderate to high (mean NOS = 6.7 out of 9). CONCLUSION: Evidence supports the notion that self-reported PA can confer protection against the emergence of anxiety regardless of demographic factors. In particular, higher PA levels protects from agoraphobia and posttraumatic disorder.

Influence of vulnerability factors in panic disorder severity / Influencia de factores de vulnerabilidad en la gravedad del trastorno de pánico

BACKGROUND: we studied herein the predictive value for panic severity of three well-based vulnerability factors: personality traits (neuroticism and extraversion; NEO-PI-R), anxiety sensitivity (ASI), and perceived control (ACQ-R). METHOD: the sample was composed of 52 participants diagnosed with panic disorder, with or without agoraphobia, according to DSM-IV-TR criteria. RESULTS: our results revealed that the anxiety facet is a better predictor of panic severity than neuroticism. Anxiety sensitivity increases the predictive value for panic severity and, finally, perception of control of emotions is the only perception control subscale that increases the predictive value for panic severity more than the anxiety facet and anxiety sensitivity. CONCLUSIONS: this finding supports the assumption of the importance of taking into account the assessment of the lower order dimensions of the vulnerability factors in the field of psychopathology studies. Furthermore, the predictive value of perception of control of emotions indicates the importance of this specific vulnerability factor in the etiology of panic disorder (with or without agoraphobia) and, thus, shows the necessity to include emotion regulation strategies in the psychological treatments

ANTECEDENTES: en este trabajo se estudia el valor predictivo sobre la gravedad del pánico de tres factores de vulnerabilidad bien establecidos: rasgos de personalidad (neuroticismo y extraversión; NEO-PI-R), sensibilidad a la ansiedad (ASI) y percepción de control (ACQ-R). MÉTODO: la muestra fue de 52 participantes con diagnóstico de trastorno de pánico, con o sin agorafobia, según criterios DSM-IV-TR.RESULTADOS: nuestros resultados revelan que la faceta de ansiedad es mejor predictor de la gravedad del pánico que el neuroticismo. La sensibilidad a la ansiedad aumenta el valor predictivo sobre la gravedad del pánico y, finalmente, la percepción de control de las emociones es la única subescala de la percepción de control que aumenta la capacidad predictiva más allá de la faceta de ansiedad y la sensibilidad a la ansiedad. CONCLUSIONES: estos resultados apoyan el supuesto sobre la importancia de evaluar las dimensiones de orden inferior de los factores de vulnerabilidad en los estudios psicopatológicos. Además, el valor predictivo de la percepción de control de las emociones indica la importancia de este factor específico de vulnerabilidad en la etiología del trastorno de pánico (con o sin agorafobia) lo que muestra la necesidad de incluir estrategias de regulación emocional en los tratamientos psicológicos

Relapse following combined treatment discontinuation in a placebo-controlled trial for panic disorder.

A recent double-blind, placebo-controlled trial (Barlow et al., 2000 JAMA. 283:2529-2536) examined separate and synergistic effects of psychological and pharmacological treatments for panic disorder. One finding warranting further investigation involved relatively high relapse rates of participants who received cognitive-behavioral therapy (CBT) + imipramine when compared with those receiving CBT + placebo. In this article, we investigate why CBT was less effective in protecting against relapse for individuals in the active drug condition. We hypothesized that participants correctly deduced treatment assignments and, for those taking imipramine, this was associated with the belief that they were no longer taking active drug after discontinuation, accounting for increased relapse rates. Contrary to hypothesis, there were no group differences in frequencies of guessing drug or placebo, nor were specific beliefs about taking drug or placebo differentially associated with relapse. Other possible reasons for differential relapse rates and treatment implications are discussed.

Revisión clínica del tratamiento de los Trastornos de Ansiedad / Clinical review of the treatment of Anxiet y Disorders

La ansiedad es patológica cuando se produce ante estímulos inadecuados o inexistentes, o cuando éstos existen o son adecuados, pero la intensidad y/o la duración de la respuesta supera los límites adaptativos. Es el síntoma común de un conjunto de cuadros clasificados como trastornos de ansiedad. Nos ocuparemos en la presente revisión de los más frecuentes y con mayor trascendencia en la calidad de vida de los pacientes. Revisamos las pruebas actualmente disponibles sobre efectividad y seguridad de las opciones terapéuticas utilizadas para el abordaje del trastorno de angustia, el trastorno de ansiedad generalizado, la fobia social y simple o específica y el nivel asistencial más eficiente para su tratamiento. Se trata de una revisión de la bibliografía seleccionada (guías basadas en la evidencia y revisiones sistemáticas y clínicas), considerando básicamente la validez y consistencia de los estudios, importancia de los resultados y su aplicabilidad. Los grados de recomendación se fundamentan en los niveles de evidencia existentes (AU)

Anxiety is pathological when it is produced in the absence of stimuli or with inadequate stimuli, or when stimuli do exist and are appropriate but the intensity and duration of the response exceed adaptive limits. This is the common symptom of a group of disorders classified as anxiety disorders. In this review, we focus on the most frequent of these and those with the greatest repercussions on the patients’ quality of life. We review currently available tests of efficacy and safety of the therapeutic options available to treat panic attacks, generalised anxiety disorder, specific or simple social phobia and the most efficient healthcare levels for their treatment. This paper reviews the literature selected (evidence-based guidelines and systematic and clinical reviews), basically considering the validity and consistency of the studies, the importance of the results and their applicability. The recommendations are based on existing levels of evidence (AU)

Anxiety disorders and older women.

Anxiety is a problem for millions of Americans. It poses special challenges for women as they grow into advanced age. This paper provides a general overview of anxiety disorders, including panic disorder, agoraphobia, specific phobia, social phobia, obsessive compulsive disorder, and generalized anxiety disorder. Etiology, assessment and treatment strategies are then addressed. Special focus is directed at biological and psychosocial issues as they relate to older women in the development, experience, treatment and prevention of anxiety disorders.

Screening for anxiety in an epidemiological sample: predictive accuracy of questionnaires.

The study examined the predictive accuracy of selected questionnaires when screening for anxiety in a representative epidemiological sample of young female adults (N = 1877). All participants were diagnosed using a structured diagnostic interview. Anxiety questionnaires included global as well as specific measures (Beck Anxiety Inventory (BAI), Symptom Checklist, Anxiety Sensitivity Index (ASI), Fear Questionnaire (FQ), Mobility Inventory (MI)). Sensitivity, specificity, positive and negative predictive power were computed for two screening decisions: (1) identifying any anxiety disorder or (2) identifying a specific anxiety disorder (agoraphobia) within the total sample and the clinical subsample. Due to naturalistic (low) base rates in epidemiological samples, diagnostic indices were lower than those previously reported. However, questionnaire data proved useful when a specific disorder was targeted (agoraphobia) and specific symptoms were operationalized.

Estudio de un caso de pánico-agorafobia detectado mediante la acción preventiva / Study of a case of panic-agoraphobia detected by means of preventive action

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Application of a new statistical approach to evaluate a clinical trial with panic disorder patients.

In clinical trials in psychiatry, changes in severity are usually measured with ordinal level scales which are applied repeatedly during the trial, showing a constant decline in psychopathology scores as treatment leads to improvement. Previous non-parametric tests for repeated measures in factorial designs did not test the hypothesis that scale scores decrease constantly during the trial. A recently developed "rank test for ordered alternatives in a mixed model" was developed and applied to the data of a clinical trial in panic disorder. Thirty-seven outpatients with panic disorder and agoraphobia (PDA) were treated with imipramine (75-150 mg/day) in an 8-week open, prospective trial. Patients with intercurrent agoraphobia were instructed in practising self-exposure in their agoraphobic situations. The total score on the Panic and Agoraphobia Scale, the Hamilton Anxiety Scale (HAMA) and the Clinical Global Impression Scale (CGI) were used as the main efficacy measures. The new rank test showed significant treatment results in all scales applied. Treatment results were excellent, as was shown by a decrease in the average Panic and Agoraphobia Scale severity scores from 28.9 (range 14-45) to 13.3 (range 0-37; rank statistic Tn = 6.7; p < 0.0001). The largest effect size r(w) of all clinician-rated scales was seen with the observer-rated version of the Panic and Agoraphobia Scale, although closely followed by the CGI and the HAMA. Among the self-rated scales, the Panic and Agoraphobia Scale also showed the largest effect size. All five subscores of the Panic and Agoraphobia Scale showed significant improvements. The highest treatment effect sizes were seen in the "panic attacks" subscore, followed by the "anticipatory anxiety" subscore. The new statistical test applied in this study, which has some advantages in comparison with previously applied tests, is suitable for psychiatric treatment evaluations since it can also be applied in the case of discrete repeated measurements.

Long-term maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia.

BACKGROUND: There has been little systematic work done regarding the long-term treatment of panic disorders. The aim of the present study was to assess the 12-month cumulative risk of relapse specifically due to discontinuation of imipramine and to test the hypothesis that maintenance treatment with imipramine protects patients with panic disorder and agoraphobia from such reversals. METHOD: Following an acute-phase open trial with imipramine (2.25 mg/kg per day) involving 110 patients for 6 months, the 56 patients who were in stable remission, did not require additional treatment, and consented to be randomly assigned to double-blind maintenance (n = 29) or discontinuation (n = 27) conditions were followed up with planned assessments every 2 months during a 1-year period. There were no behaviorally oriented interventions or instructions at any time during the 18 months of the study. RESULTS: Maintenance treatment (1 relapse) and discontinuation (10 relapses) conditions had significantly different survival curves (Mantel-Cox statistic chi(2)1 = 10.47, P = .001). None of the additional 10 variables from demographic, clinical, and open-treatment domains considered in the proportional hazard model disrupted the significant relationship between experimental drug condition and relapse; other things being equal, a patient receiving imipramine maintenance was 92.5% lower in the hazard rate of relapse than a patient receiving placebo. CONCLUSION: The results confirm the very high degree of prophylactic effectiveness of maintenance imipramine treatment and demonstrate that relapse, although substantial, occurs in a minority of patients with panic disorder and agoraphobia who are in stable remission prior to treatment discontinuation.

Rational treatment of panic disorder with antidepressants.

Rational treatment of panic disorders with antidepressants rests on decisions of drug choice, dosage, and duration of treatment. In this paper, we selectively review the author's research with the standard antidepressant, imipramine, in the treatment of panic disorder with agoraphobia as it relates to practical issues. We develop general guidelines for treatment, suggest researchable ways of increasing the net effectiveness of treatment with this class of drugs, and discuss limited generalizations to the extant literature on selective serotonin reuptake inhibitors in panic disorders.

[The first panic attack: a missed chance for prevention of panic disorder and its complications]. / Die erste Panikattacke: eine ungenützte Chance zur Prävention der Panikstörung und ihrer Komplikationen.

OBJECTIVE: Assessment and analysis of first medical consultations and their significance in panic disorder patients. METHODS: 90 panic disorder patients were interviewed concerning their experiences with the medical system at the time of their first panic attack. RESULTS: Panic disorder patients contacted mostly non-psychiatric medical services at the time of their first panic attack. The correct diagnosis was established in only 4 cases (5.6%). CONCLUSIONS: An important chance for secondary prevention of the development of panic disorder is missed, probably due to the poor education of physicians on panic attacks.

Maintenance drug treatment of panic disorder. I. Results of a prospective, placebo-controlled comparison of alprazolam and imipramine.

One hundred six patients diagnosed according to DSM-III as suffering from agoraphobia with panic disorder, panic disorder with limited phobic avoidance, or uncomplicated panic disorder entered an acute 8-week treatment phase. Patients who improved received an additional 6 months' maintenance treatment. Significantly more patients treated with alprazolam than with imipramine hydrochloride or placebo remained in therapy and experienced panic attack and phobia relief during the acute treatment phase. During the maintenance phase, neither tolerance nor daily dose increase was observed. All patients who completed the maintenance phase (27 in the alprazolam group, 11 in the imipramine group, and 10 in the placebo group) were panic free at the end of 8 months of study treatment. Alprazolam therapy was effective and well tolerated at a mean daily dose of 5.7 mg. Imipramine hydrochloride (175 mg/d) also produced significant panic relief but was associated with poor patient acceptance.

Protective effects of imipramine maintenance treatment in panic disorder with agoraphobia.

OBJECTIVE: This study was designed to assess and compare the differential relapse rates of patients with panic disorder and agoraphobia after discontinuation of acute treatment (6 months) or acute plus maintenance treatment (18 months) with imipramine. METHOD: Sixteen patients with panic disorder and agoraphobia who had shown marked and stable response to 6 months of acute imipramine treatment and a comparable group of 14 patients who had been in remission during an additional year of half-dose imipramine maintenance treatment entered a 3-month, double-blind discontinuation study followed by a 3-month drug-free period. Assessments of the patients were made according to operationalized response/relapse criteria, and plasma drug concentrations were monitored. RESULTS: Survival analysis revealed significantly different cumulative probabilities of continued response 6 months after discontinuation of imipramine treatment between the patients who had received only acute treatment and those who had received acute and maintenance treatment. CONCLUSIONS: The results support the hypothesis that successful imipramine maintenance treatment of patients with panic and agoraphobia can have protective effects against relapse, at least in the first 6 months after the maintenance treatment period.

Clinical experiments in maintenance and discontinuation of imipramine therapy in panic disorder with agoraphobia.

Several issues remain to be ascertained beyond the acute response to imipramine hydrochloride in patients with panic disorder. Study 1 consisted of a prospective, systematic characterization of half-dose 12-month maintenance in patients with panic disorder with agoraphobia who had shown marked and stable response to 6 months of acute-phase treatment with imipramine. Study 2 assessed the 6-month cumulative relapse rate following discontinuation of acute-phase imipramine treatment in a comparable sample of patients. The same assessment battery was used in both studies, and the integrity of experimental drug conditions was verified by plasma drug level determinations. In contrast to the high relapse rate following discontinuation of acute-phase treatment, none of the patients showed relapse or had sustained worsening in panic or phobia measures during the half-dose maintenance period. The results underscore the importance of pharmacological prophylaxis and provide empirical guidelines for a successful low-dose maintenance regimen for patients with panic disorder and agoraphobia who respond markedly to imipramine.

Maintenance treatment with antidepressants in panic disorder.

Because panic disorder is a chronic illness, patients may require long-term pharmacologic treatment. Unfortunately, the benefits and risks of such therapy have received little study. At least two classes of antidepressants, the tricyclic antidepressants and the monoamine oxidase inhibitors, are effective for the treatment of panic disorder, but because relapse is common when these drugs are discontinued, many patients require maintenance treatment. However, such long-term use of tricyclic antidepressants and monoamine oxidase inhibitors exposes patients to risks that include potentially fatal overdoses and hypertensive crises. Patients should be aware of the risks involved and should weigh them against the benefits of long-term use. They should reduce the dose to the lowest effective level, from time to time gradually taper medications to assess continuing need, and avail themselves of other therapies rather than rely solely on drug treatment. Above all, more research should be done on the long-term risks and benefits of antidepressant drugs.