Panic disorder

Abstracts

OBJETIVOS: Revisar o transtorno do pânico (TP), considerando seus aspectos clínicos, epidemiológicos, diagnósticos e etiológicos, bem como os avanços no tratamento, uma vez que o TP é uma entidade nosológica acompanhada de importante prejuízo psíquico e funcional. MÉTODO: Foi realizada uma revisão narrativa da literatura nas principais bases de dados existentes (MEDLINE, PsychINFO e SciELO) e em livros-textos atualizados. RESULTADOS: Devido à sintomatologia predominantemente física desse transtorno, os pacientes geralmente procuram vários atendimentos clínicos até que o diagnóstico seja feito. Em função desses aspectos e da sua cronicidade, o TP está associado a elevados custos econômicos. O tratamento do TP pode ser feito com psicoterapia e/ou psicofármacos. As diversas abordagens terapêuticas são apresentadas com o nível de evidência de cada recomendação. Em virtude da cronicidade e morbidade do TP, pesquisas têm se voltado para o estudo de estratégias de prevenção já na infância. CONCLUSÕES: O TP é um transtorno crônico e com baixas taxas de remissão dos sintomas em longo prazo. Sendo assim, sugere-se que sejam delineados novos estudos para tratamento precoce dos transtornos de ansiedade ou mesmo para prevenção em crianças de risco.

Transtorno do pânico; transtornos de ansiedade; diagnóstico; tratamento; farmacoterapia; psicoterapia

Panic disorder

Giovanni Abrahão Salum^I; Carolina Blaya^II; Gisele Gus Manfro^III

^IScholarship holder, Undergraduate Research, National Council of Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq) Researcher, Program in Child and Adolescent Anxiety Disorders, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, RS, Brazil

^IIMSc, PhD, Medical Sciences, Psychiatry, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil. Researcher, Program in Anxiety Disorders, HCPA, Porto Alegre, RS, Brazil

^IIIAssociate professor, Department of Psychiatry and Legal Medicine, UFRGS, Porto Alegre, RS, Brazil. Coordinator, Program in Anxiety Disorders and Program in Child and Adolescent Anxiety Disorders, HCPA, Porto Alegre, RS, Brazil. Researcher, National Council of Scientific and Technological Development (Conselho Nacional de Desenvolvimento Científico e Tecnológico - CNPq)

Correspondence

ABSTRACT

OBJECTIVE: To review panic disorder (PD) considering its clinical, epidemiological, diagnostic, and etiologic aspects, as well as the advances in its treatment, since PD is a nosologic entity characterized by important psychiatric and functional impairment.

METHODS: A review of the literature was carried out using the main databases available (MEDLINE, PsychINFO and SciELO) and up-to-date textbooks.

RESULTS: Due to the prevalence of physical symptoms in this disorder, patients usually have to seek clinical care for several times before the diagnosis is established. As a result of these aspects and because of its chronicity, PD is associated with high economic costs. PD treatment may include psychotherapy and/or use of psychotropic drugs. In this review, we present several different therapeutic approaches, as well as the levels of evidence of each recommendation. Due to PD chronicity and morbidity, researches have been focused on the study of strategies to prevent PD since childhood.

CONCLUSIONS: PD is a chronic disorder with low long-term remission rates. Therefore, we suggest that new studies should be designed concerning the early treatment of anxiety disorders or even the prevention of this disorder in children at risk.

Keywords: Panic disorder, anxiety disorder, diagnosis, treatment, pharmacotherapy, psychotherapy.

INTRODUCTION

Panic disorder (PD) is characterized by recurrent panic attacks consisting of intense fear and discomfort followed by physical and cognitive symptoms with a sudden onset, reaching their maximum intensity in up to 10 minutes. Such attacks result in continual concerns or important changes in the individual's behavior regarding the possibility of having new anxiety attacks.

Patients with PD usually follow a long pattern (which can last for up to one decade) of visits to emergency rooms before the diagnostic is established looking for the organic cause of their symptoms.¹ Therefore, besides psychiatrists, physicians of all specialties, and mainly those working with primary health care and medical emergency services should be familiar with PD diagnostic criteria. These professionals' knowledge is extremely important due to the high prevalence of panic attacks in the general population; therefore they the need to be able to distinguish single panic attacks from the complete syndrome (PD) and from other medical conditions that may manifest as an anxiety crisis.

In addition to the psychic suffering and functional impairment experience by patients with PD, this disorder is associated with several other outcomes that empirically explain why it should be considered a public health problem. Patients with PD have higher rates of work absence and lower productivity;²; higher rates of use of health care services, procedures and laboratory tests;³ increased risk of suicidal ideation and suicide attempt, regardless of the comorbidity;^4,5 and, in post-menopausal women, it seems to be related to cardiovascular morbidity and mortality.⁶ However, it is important to emphasize that the association between PD and cardiovascular mortality remains controversial and may be restricted to a specific population.⁷

The objective of the present update article is to review PD considering its aspects related to clinical factors, prevalence, diagnosis, and etiology, as well as the advances in its treatment. With that purpose, a review of the literature was carried out using the main databases available (MEDLINE, PsychINFO, and SciELO) and up-to-date textbooks.

REVIEW OF THE LITERATURE

Although PD was established as a diagnostic entity more than 19 years ago with the publication of the Diagnostic Statistical Manual of Mental Disorders (DSM) III,⁸ references to this clinical entity were available much earlier (e.g., soldier's heart, by Da Costa,⁹ neurocirculatory asthenia, by Wheeler,¹⁰ and effort syndrome, by Lewis¹¹). In addition to the paroxistic activity of the autonomic nervous system (ANS) and catastrophic cognitions, these syndromes included symptoms of severe fatigue, which are not included in the current diagnostic criteria. Among all anxiety disorders, PD has been the most often studied disorder during the last 25 years; however, some important gaps still remain in terms of diagnosis and classification, etiology and treatment of this clinical condition.

PREVALENCE

The prevalence of panic attacks is very high. The National Comorbidity Survey (NCS) Replication,¹² which involved a representative sample of the U.S. population, estimated that 23% of the this population met the criteria for at least one single panic attack throughout their lives. The PD prevalence, however, is less common, since, during a lifetime, 5% (4% without agoraphobia, and 1% with agoraphobia) of the respondents met the criteria for the disorder, reaching around 1% in the last year. The prevalence of agoraphobia combined with panic attacks without meeting the criteria for PD was also of approximately 1%. The presence of agoraphobia makes clinical disability and severity even worse: more than 95% of the individuals interviewed had moderate to severe disabilities related to the disorder, while only 21% of the patients with single panic attacks had moderate to severe disabilities.¹²

There are no data on a representative sample of the Brazilian population. A study conducted in São Paulo (SP) found a prevalence of 1.6% for PD throughout life and 1% during 1 year.¹³ There seems not be a variation in the worldwide prevalence, but it is not possible to draw a definite conclusion about it due to the different methodological approaches used in several studies. PD is approximately twice more common in women than in men, and it usually has its onset at the end of adolescence or in the beginning of adulthood, generally occurring between 20 and 30 years; there are rare cases during childhood.^12,14

Psychiatric comorbidity is a rule in PD not an exception. Almost 100% of the patients with PD with agoraphobia and around 83% of the patients with PD without agoraphobia have at least one psychiatric comorbidity. Considering PD with agoraphobia, 95% of the patients have at least another anxiety disorder, 64% have at least one mood disorder, 63% have one impulse control disorder, and 31% have alcohol and drug abuse or dependence. Among anxiety disorders, specific phobia is the most common comorbidity (present in 74% of the cases), followed by social anxiety disorder (66%), generalized anxiety disorder (32%), and separation anxiety (13%). Among mood disorders, almost 50% meet the criteria for major depression, 16% for bipolar mood disorder (types I and II), and 10% for dysthymia. Considering alcohol and drug dependence, 14% met the criteria for only alcohol dependence, and 11% for drug dependence.¹²

ETIOLOGY

Several factors have been identified as part of the etiology of PD, and both genetic and environmental factors seem to contribute to the occurrence of this disorder.¹⁵

Anxiety disorders usually occur in the same families.¹⁶ Studies involving families with PD showed a family pattern, with PD risk, in the first-degree relatives of patients with this disorder approximately eight times higher than in the control group.¹⁷ Studies with twins also confirmed these findings, showing a higher agreement rate of PD in monozygotic twins compared with dizygotic twins, with an estimate heritability rate of approximately 43%.¹⁶

Previous studies have associated traumatic experiences during childhood^18-20 with the development of PD in adulthood. Stressful events taking place during adulthood are also related to the development of anxiety disorders²¹ and to PD,²² and about 80% of the patients reported stressful life events during the 12 months prior to the onset of the disorder. Scocco et al.²³ described that approximately 90% of the patients with PD experience role transition and that 40% had losses in the year before PD onset. Socioeconomic factors such as ethnicity, marital status, educational level, and income do not seem to play an important role in the association with PD.¹² Smoking and nicotine dependence during adolescence have been suggested as risk factors for PD in adulthood, but the causality of such association remains controversial.²⁴

With regard to anxiety disorders and, more specifically, with respect to PD, it is expected that genes play a role closely related to the determination of intermediate phenotypes, that is, characteristics that are common, to a higher or lower extent, to all individuals, and that are associated with one or more psychiatric disorders in an specific or unspecific manner. Among the intermediate phenotypes of childhood anxiety disorders, one can mention inhibited behavior (inhibition of behavior associated with fear of strangers) and anxiety sensitivity (fear and concerns related to distorted interpretations of normal body reactions). During adulthood, neuroticism (anxiety, depression, tension, irrationality, emotion, low self-esteem, and tendency to feelings of guilt) and some specific temperaments, such as harm avoidance (tendency to avoid situations including any kind of risk, or that cause or may cause damage), are related to anxiety disorders. Although some studies have demonstrated that inhibited behavior during childhood could be connected to PD throughout life, this association remains controversial, and this type of intermediate phenotype seems to be consistently associated with social anxiety disorder. Anxiety sensitivity in childhood seems to be a specific phenotype of PD; however, it can explain only a small portion of the cases. Neuroticism and harm avoidance are also high in patients with PD, but these are not unspecific phenotypes connected to other anxiety and mood disorders.^25,26

Several polymorphisms in candidate genes have been investigated regarding the association with PD and with the intermediate phenotypes connected to them, but none of the findings was consistently replicated by other studies; therefore, there is not convincing evidence of any gene specifically connected to PD with a magnitude that has clinical relevance. It is worth mentioning that in addition to investigating the heritability of specific genes bringing risk for psychiatric psychopathology, current psychiatry has focused its attention on the study of epigenetics, that is, the study of key cell processes that are part of several environmental stimuli to cause dramatic and often long-lasting changes in the genic expression by regulating the chromatin structure, in other words, "by choosing what will be codified in the genetic code".²⁷ It is expected that the advances in studies of epigenetics are the key for the understanding of several disorders with multifactorial and complex etiology such as PD.

Some structural neuroimaging studies have found some differences between the brains of patients with PD and controls. A reduced volume in the temporal lobes and in the amygdala has been found among patients with PD. Other studies have detected a reduction in the grey matter in the left parahippocampal gyrus, bilateral reduction in the grey matter of the putamen, and an increase in the brain stem, specifically in rostral sites, in the left insula and left upper temporal gyrus, midbrain, and pons.²⁸ Functional neuroimaging studies are not conclusive due to the difficulty in finding valid paradigms for this disorder.

Considering the theoretical grounding for the understanding of PD from a psychological point of view, one of the theories more widely accepted and with great practical usefulness is based on the behavioral-cognitive theory. According to Clark,²⁹ panic attacks are the result of dysfunctional catastrophic interpretations of certain body manifestations. The assumption is focused on the inadequate processing of information originated from an external stimulus (noise, light) or an internal stimulus (sensation of tachycardia, sweating, dizziness). The interpretation is that there is imminent danger, which triggers and intensifies body sensations, confirming the presence of "danger" and thus generating catastrophic interpretations and anxiety in a growing and fast swirl of events. The model suggested by Barlow³⁰ expands this concept. According to this model, the initial panic attack is a false alarm that can be triggered when there is an occasional increase in the levels of stress in the life of individuals who are biologically or psychologically vulnerable. After the first attack, the individual becomes concerned about future attacks. For Barlow,³⁰ the primary fear in the PD is the fear of physical sensations, mainly those associated with autonomic activity, being influenced by sociocultural factors.

Other authors have investigated the psychodynamic factors associated with the onset of PD or the higher psychological vulnerability to the disorder.³¹ Patients with PD often describe themselves as fearful, nervous, and shy children, and they also mention discomfort with aggressive feelings, chronic feelings of low self-esteem, frustration, and resentment prior to PD onset. Quality of the parental relationship is a risk factor for PD.³² For instance, PD patients often describe their parents as nervous, intimidating, controlling people who are always criticizing others.³³ The psychodynamic theory considers the assumption that unconscious internal conflicts are closely related to anxiety manifestations; therefore, frustrations, resentments, and childish relationships are essential for the therapeutic approach of this disorder, in addition to a detailed assessment of the individual's underlying personality structure.

The biological bases, both genetic and neuroanatomic, and the psychological theories, both behavioral-cognitive and psychodynamic, are constantly evolving: they are subject to periodic updating and conceptual evolution and, in contrast to what one should expect, they do not exclude one another but complement each other. A complex disorder such as PD can only be fully understood based on a broad theoretical framework encompassing aspects from several lines of thought.

DIAGNOSIS

PD is classified in the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR)³⁴ within the group of anxiety disorders, and the criteria defined by the DSM-IV-TR are very similar to those found in the International Classification of Diseases (ICD-10).

PD diagnosis is essentially clinical. The diagnostic criteria for PD according to the DSM-IV-TR are shown in Table 1.

Several authors have suggested subtypes of PD based on the symptoms of the attack (cardiorespiratory, autonomic/somatic, cognitive types), period of the day when the attack takes place (day time attack, night attack), age of onset (early or late), course (limited, chronic), etc. However, consistency regarding the definition of these subtypes has not been reached, mainly due to their similar therapeutic management.²⁴

DIFFERENTIAL DIAGNOSIS

One of the key aspects in the assessment of patients with panic attacks is the differential diagnosis, especially because of the interface between this manifestation and other clinical health conditions. Thus, even though the diagnosis of PD is essentially clinical, several clinical and psychiatric situations have manifestations that include panic attacks or that are similar to panic attacks. Therefore, the assessment algorithm of panic attacks includes: attacks secondary to a clinical condition (e.g., hyperthyroidism , pheochromocytoma), substance use or abstinence (e.g., use of cocaine, alcohol abstinence), anxiety disorders (such as PD), and other psychiatric disorders.

Due to the acute characteristic of the panic attack, its differential diagnosis is extremely important during emergency care and should be established based on the clinical presentation. Assessment of clinical diseases according to the symptoms presented is crucial for an efficient management of the attacks. Abuse of stimulants, as well as abstinence of central nervous system depressive drugs, must be assessed during anamnesis as possible attacks. A detailed history of the medications and drugs used by the patients must be collected, mainly regarding the history of use of alcohol, caffeine, cocaine, nicotine, bronchodilators, and sedative hypnotics. In case the attack cannot be explained in more detail based on any clinical conditions or due to substance use or abstinence, the diagnostic investigation must be aimed at psychiatric disorders, with special attention to anxiety disorders and, mainly, PD. Figure 1 shows a algorithm of diagnostic assessment of panic attacks.

TREATMENT

Management of panic attacks

The emergency management of panic crises is mainly based on the procedure of calming down the patients by explaining that their symptoms are originated from an anxiety attack, not being a severe clinical condition with imminent risk of death (regarding attacks related to psychiatric disorders), emphasizing that the crisis is really intense, very unpleasant, resulting in a very acute uncomfortable feeling. It is important to reinforce that the attack is transitory (lasting for about 10 to 30 minutes) and it is especially important to tell patients to breathe through their nose avoiding mouth breathing, highlighting the importance of trying to control the rate of inhalations with the purpose of avoiding hyperventilation. Most of the time, the fast calming down procedure and the self-restricted characteristic of the symptoms are enough to solve the crisis. In patients with prevalent breathing symptoms, probably related to hyperventilation, the patients are instructed to breathe using their diaphragm, restricting the use of the intercostal muscles. Patients should be stimulated to breathe slowly until hyperventilation symptoms cease. Some deep breathing techniques may also be used. For instance, patients can be instructed to remain laying down, keep their eyes closed, breath slowly and deeply, trying to relax different muscle groups and concentrating on a calm mental scene. However, if the crisis is very intense or long-lasting, the use of psychotropic drugs may be recommended. Short-acting benzodiazepines are the first choice in such cases, and, in spite of the lack of evidence supporting more encouraging statements, these psychotropic drugs are often used in the clinical practice. There is evidence of the usefulness of benzodiazepines especially regarding cardiac and non-cardiac thoracic pain, showing that this type of medication reduces anxiety, pain, and cardiovascular activation. These studies have shown that benzodiazepines were safe to be administered isolated or in combination with other medications.³⁵Figure 2 shows an algorithm for this assessment and management.

Treatment of panic disorder with or without agoraphobia

Early treatment of PD is essential to reduce suffering and harm associated with the disorder and with the purpose of preventing the occurrence of complications and comorbidities, as well as social costs. In addition, PD treatment significantly reduces social costs because, even though it increases direct costs with medical visits and psychiatric medications, there is an important reduction in the number of emergency room visits and non-psychiatric medical visits.³⁶

Prevention of new crises and reduction of associated complications, such as anticipatory anxiety and phobic avoidance, are key aspects of PD treatment. It is important to draw special attention to the comorbidities such as mood disorders and use of substances. In general, there are three types of PD treatment: psychopharmacological treatment, psychotherapeutic treatment, and a combination of both.

Psychotropic drugs

The levels of evidence of each recommendation are assigned by the symbols: ^ALevel of recommendation A (well established recommendation - resulting from more than one high-quality randomized clinical trial); ^B Level of recommendation B (established recommendation, but might need further investigations - resulting from one randomized clinical trial that has not been replicated); ^C Level of recommendation C ( weak recommendation - resulting from non-controlled studies^C1, case reports, and experts' opinion^C2); and ^D Level of recommendation D (inconsistent recommendation - with similar amount of evidence showing ineffectiveness and benefit of medication).³⁷

Among the psychotropic drugs, the selective serotonin reuptake inhibitors (SSRIs) (fluoxetine^A, sertraline^A, paroxetine^A, fluvoxamine^A, citalopram^A, and escitalopram^A) and venlafaxine^A, a serotonin and noradrenaline reuptake inhibitor (SNRI), are the first pharmacologic choice for PD. Tricyclic drugs (clomipramine^A and imipramine^A) are similarly efficient, but they are less tolerated than the SSRIs and can be lethal in case of overdose; therefore, these medications can be used as a second choice in the PD treatment. There is no difference in the effectiveness of the first-line agents previously mentioned.^37-40 The use of benzodiazepines (alprazolam^A, clonazepam^A, diazepam^A, and lorazepam^A) is controversial, and some international guidelines recommend their use for refractory cases in patients without history of drug dependence and allow their concomitant use during the first weeks of treatment with SSRIs due to their short-term efficacy – from 1 day to 1 week^37-39–, while other guidelines do not recommend their use⁴⁰ due to the risk of dependence. In the clinical practice, their use is common and can be useful for the management of PD patients. However, it is important to bear in mind that there is risk of dependence throughout the treatment of any patient.³⁷

Some studies have demonstrated the efficacy of monoamine oxidase inhibitors^B (MAOIs), but one should be attentive to the possibility of severe adverse effects due to drug and food interactions. Phenelzine, a MAOI, should only be prescribed after failure of first-line agents or due to intolerance to the previously mentioned medications. These are some of the medications that have shown to be effective for PD: ondansetron^B, bupropion^B, tiagabine^B, vigabatrin^B, milnacipran^B, combinations of SSRIs and tricyclic drugs^B, olanzapine in monotherapy^B, olanzapine added to a SSRI^B, pindolol added to a SSRI^B, and a combination of valproate and clonazepam^B.³⁷ In addition, there is preliminary evidence supporting the use of duloxetine^C, another SNRI for the PD treatment.⁴¹

For resistance cases, olanzapine in monotherapy^C1, fluoxetine added to a tricyclic drug^C1, a tricyclic drug added to fluoxetine^C1, olanzapine added to a SSRI^C1 can be used according to open trials. Lithium added to clomipramine^C2 , or a combination of clonazepam and valproate^C2were effective according to some case reports. Monoclobemide^D and reboxetine^D have shown inconsistent results.³⁷

A period of 12 weeks is the cutoff point expected for a new therapeutic approach and for considering the first attempt a failure. Some authors have suggested that a response lower than 25% regarding the reduction of symptoms during the first 8 weeks of treatment are enough for a second attempt. However, clinical decisions must be taken based on individual analysis according to the clinical experience, considering the lack of evidence in this field. The guidelines recommend that maintenance treatment lasts for approximately 1 to 2 years.³⁷

Psychotherapy

Cognitive-behavioral therapy (CBT) is the type of treatment showing the most consistent results for PD, with better results than the therapies of psychosocial attention control and placebo in most studies and having good acceptability and compliance rates, fast beginning of effects, and good cost-benefit relation.⁴² Both group and individual CBT present similar results. Two large meta-analysis have reported significant effects of 1.55 (63% of response)⁴³ and 0.90⁴⁴ for CBT in PD treatment. CBT is also a rescue strategy for patients showing poor previous response to medications, being quite effective for PD comorbid conditions.^37-40 Recent studies have investigated the effectiveness of CBT administered via computer or the internet, also showing promising results comparable to those of the regular therapy.^45,46

PD treatment using CBT consists in psychoeducation on PD with the purpose of correcting wrong interpretations regarding PD, learning techniques to reduce anxiety using diaphragmatic breathing and muscle relaxation, cognitive restructuring to identify and correct thought distortions, interoceptive exposure so that the patient learns how to deal with the physical symptoms of panic attack and in vivo exposure to stimulate patients to face the main situations they are afraid of because they fear they will feel bad and will not be able to solve the problem and get help.

There is preliminary evidence of the effectiveness of brief psychodynamic treatments focused on PD.⁴⁷ In spite of the shortage of evidence, psychoanalytical treatment and psychoanalytical psychotherapy are very often used in the clinical practice at some centers.³⁷ The following are some of the reasons for the lack of evidence: long-lasting treatment, studies focused on other outcomes different from the symptoms and structured diagnoses provided by the DSM-IV-TR. In spite of that, this type of psychotherapy seems to offer long-lasting results and lower relapse rates, as well as advantages in unconventional outcomes, such as the use of more mature defensive styles, improvement of interpersonal relationships and intrapsychic conflicts and, as a consequence, better quality of life in terms of psychosocial functioning.

Combined therapies

A meta-analysis involving approximately 21 randomized clinical trials that included more than 1,700 patients with PD with or without agoraphobia showed that the combined treatment with antidepressives and psychotherapy was more effective than these two types of treatment as monotherapies during the acute phase of the disorder. After the end of the treatment, those patients who received combined treatment continued to enjoy its benefits in comparison with those who received only medication, but there was no difference regarding those patients who were treated only with psychotherapy, with an evident advantage for the techniques based on behavioral-cognitive principles.⁴⁸ Therefore, although there is little evidence comparing the therapeutic modalities for PD, the inclusion of the cognitive therapy at some point of the treatment will probably improve long-term outcomes.²⁴

From the public health point of view, some guidelines^37,39 recommend that at least two attempts using first-line treatment should be made with a general practitioner before referring to a specialized psychiatrist. Obviously, this recommendation should consider each case individually based on the peculiarities of the clinical practice and the specific characteristics of the medical practice in each region.

PROGNOSIS AND PREVENTION

For a large portion of the patients, PD has the prognosis of a chronic disorder with relapses and frequent exacerbations, usually associated with stressful life events, characterized by phases of partial or complete remission of symptoms. Several studies have clearly demonstrated that the discontinuation of medications results in relapse for a significant number of patients with rates ranging from 25-50% within 6 months. Although the rates are lower for CBT, a large number of patients also have relapses when being treated with these therapeutic approaches, and this contributes to the fact that PD is considered a chronic disorder for many patients. Furthermore, SSRIs, tricyclic drugs, SNRIs, and benzodiazepines are associated with withdrawal syndrome (much worse for benzodiazepines), which may become an interoceptive stimulus that triggers PD relapses and favors chronicity.

Due to the chronic characteristic of mental disorders, psychiatry has focused on the investigation of prevention strategies. Some recent strategies have found promising results with therapeutic protocols used in subjects who had subclinical symptoms of the disorder.⁴⁹ In addition, one of the main risk factors for anxiety disorders in adulthood is the presence of anxiety disorders or traits during childhood and adolescence.²⁶ In that sense, in an increasingly early manner, current researches have been focusing on the early treatment of anxiety disorders or even in the prevention with children at risk, such as children of parents with anxiety disorder. There are few studies investigating the effectiveness of these prevention strategies; however, this is a promising field for further research.

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Publication Dates

• Publication in this collection
  18 Mar 2010
• Date of issue
  2009