The focus of this Special Report on anxiety disorders is not accidental. Anxiety disorders are, probably next to substance abuse, the most common mental disorders in the general population, and definitely the most common mental disorders among children and adolescents. Over the last several decades, we have seen tremendous developments in conceptualization, classification and treatment of these disorders. The time when benzodiazepines occupied the central stage in the treatment of these disorders is gone. Selective serotonin reuptake inhibitors and various forms of therapy, especially cognitive-behavioral therapy (CBT) are now considered first-line treatments in many, if not all, anxiety disorders. As child and adolescent psychopharmacology is coming of age, a large body of research data is emerging, and we are approaching treatment of children and adolescents more systematically. Research into anxiety disorders is focusing on the role of serotonin, amygdala, early experiences and many other issues.

The articles in this Special Report illustrate these developments, covering important problems such as: treating anxiety disorders during various stages of life; the relationship between pediatric anxiety disorders and adult psychopathology; differences between childhood and adolescent anxiety presentation from that in adults; issues associated with risk of relapse in panic disorder; the rational treatment for pediatric obsessive-compulsive disorder; tools for assessing severity of generalized anxiety disorder; and treatment options and considerations for late-life anxiety. The articles present a wealth of clinical material and lot of food for thought.

Nonetheless, brooding over the articles evokes more questions. Where does the universal experience of normal anxiety end and pathological anxiety begin? How does one decide whether to use CBT or medication in children and adolescents (especially since no medication is approved by the U.S. Food and Drug Administration for pediatric anxiety disorders)? Do benzodiazepines, especially the old ones, deserve the bad name they have received? What is the role of anxiety in healthy development? What is the social function of anxiety? How much does personality makeup contribute to the experience of and coping with anxiety? And there are certainly many others.

Hopefully, this Special Report will help the reader address some of the important decisions in the management of anxiety disorders. It may also help in finding answers to some of the aforementioned questions raised. It reminds us how little we know, how much still has to be done, and how much more our approach to treatment selection still reflects art rather than science.

Articles

The focus of this Special Report on anxiety disorders is not accidental. Anxiety disorders are, probably next to substance abuse, the most common mental disorders in the general population, and definitely the most common mental disorders among children and adolescents.

Special Report: Anxiety Disorders Across the Life Span

Han Shan was a Taoist/Buddhist hermit-poet who lived in China's Tientai Mountains 1,200 years ago. An immortal figure in Chinese literature and Zen, his name means Cold Mountain, which he used to refer to himself and the mountain retreat where he lived.

A Psychiatrist Waits for His 10 O'clock Patient and Imagines He is Han Shan

Generalized anxiety disorder (GAD) is a chronic, impairing and highly comorbid psychiatric condition afflicting an estimated 2.1% to 3.1% of the U.S. population during any given 12-month period (Grant et al., 2005; Kessler et al., 2005). Although historically neglected relative to other anxiety disorders, recent years have witnessed increasing attention and interest in the nature and treatment of GAD. A number of factors have contributed to these developments including elimination of GAD's status as a residual category in the DSM-III-R and several empirically based refinements in the diagnostic criteria for GAD. Among the most consequential of these revisions has been the designation of uncontrollable worry (apprehensive expectation) as the hallmark feature of the disorder and the specification of six key associated symptoms, primarily centering on motor tension (e.g., muscle tension, aches or soreness, restlessness) and vigilance (e.g., feeling keyed up or on edge, difficulty concentrating).

As currently defined in the DSM-IV-TR, a diagnosis of GAD involves excessive anxiety and worry about a number of events or activities, which occur more days than not for at least six months. The worrying is difficult to control, and the individual experiences three or more associated symptoms, including restlessness, fatigue, difficulty concentrating, irritability, muscle tension and sleep disturbance. The focus of worry is not on a situation that could be more parsimoniously subsumed under another anxiety disorder (e.g., fear of embarrassment or humiliation in social situations, as in social anxiety disorder). Additionally, there must be evidence of clinically significant functional impairment.

Given its prevalence and associated impairment, the significant burden imposed on health care resources, accurate assessment of GAD and its severity by mental health and primary care clinicians is an increasingly important goal. Reliable diagnosis and assessment of disorder severity can guide the nature, frequency and duration of therapeutic interventions. Moreover, accurate assessment of initial disorder severity provides a benchmark from which ongoing evaluation of treatment effectiveness can proceed.

Assessing the severity of GAD can be done quantitatively (e.g., a 0-10 rating scale), qualitatively (e.g., categorical classifications such as mild, moderate or severe), or with some combination of these approaches. It should apply to relevant domains (e.g., worry, associated symptoms, subjective distress, impairment in role-functioning). In the recent National Comorbidity Survey-Replication study, severity of 12-month GAD cases was evaluated among a large representative community sample (Kessler et al., 2005). Findings revealed that 32.3% of individuals with GAD were classified as serious, 44.6% of cases as moderate and 23.1% as mild, with severity defined by the consequences of GAD in several domains of functioning. Serious cases were defined by: a recent suicide attempt; substantial work limitation; substance dependence with serious role impairment; or 30 or more days out of role in the year. Moderate cases were defined by: a suicide gesture, plan or ideation; substance dependence without serious role impairment; and moderate work limitation or moderate role impairment. Disorders not meeting the criteria for serious or moderate severity were classified as mild.

A complementary way to assess the severity of GAD is to focus on the specific symptoms constituting the disorder. A number of psychometrically sound instruments designed toward this end have been reported in the anxiety disorder and GAD research literature (

). (For more comprehensive reviews see Roemer and Medaglia [2001] and Turk et al. [2004]).

The Hamilton Anxiety Rating Scale (HAM-A) is a widely used interview measure designed to assess anxiety. Although it predates current conceptualizations of GAD, it assesses several of the associated symptoms of GAD. The HAM-A features both psychic and somatic anxiety subscales. The psychic subscale, which is comprised of items that address the more subjective cognitive and affective components of anxious experience (e.g., anxious mood, tension, fears, difficulty concentrating), is particularly useful in assessing the severity of GAD. In contrast, the somatic subscale emphasizes features of GAD that are somewhat less typical, including autonomic arousal, respiratory and cardiovascular symptoms. The HAM-A has become an industry standard in clinical trials of pharmacotherapy and psychotherapy for GAD. Full-scale pretreatment scores of 18 to 20 or greater are a common index of severity required for entry into a clinical trial. A 40% to 50% reduction in the HAM-A total score (i.e., a full-scale score in the range of 8 to10 or less) is a typical criterion for defining treatment response (Gelenberg et al., 2000; Rickels et al., 2005). One notable limitation in using the HAM-A to assess GAD severity is that it does not evaluate excessive or difficult-to-control worry, which is recognized as the central feature of GAD in current conceptualizations (e.g., DSM-IV-TR).

Recently, Shear and colleagues (in press) have developed the Generalized Anxiety Disorder Severity Scale (GADSS). The GADSS was explicitly designed to be a specific measure of GAD severity, and it facilitates probing of typical domains of worry (e.g., future, health, finances, relationships) and detection of the six associated symptoms defining GAD. Severity is assessed by ratings of frequency and distress due to worrying, the associated symptoms of GAD, and impairment/interference in social and work functioning. Preliminary evaluation has shown that the GADSS has good reliability, validity and treatment sensitivity.

Self-report measures have the advantages of brevity, ease of administration and scoring, and a decreased demand on human resources, which are often limited in high-volume outpatient clinics and private practice settings. The Beck Anxiety Inventory (BAI) and the Trait Anxiety subscale of the State-Trait Anxiety Inventory (STAI-T) are among the most widely used self-report measures of anxiety, although each has limitations. The BAI is biased toward somatic and panic-like symptoms of anxiety, which have been shown to be less characteristic of GAD, whereas the STAI-T appears to confound anxiety and depression and may be more a measure of general negative affectivity than anxiety. Despite this limitation, the STAI-T has demonstrated sensitivity to treatment change in studies of cognitive-behavioral therapy for GAD.

The Penn State Worry Questionnaire (PSWQ) measures a general trait-like tendency to worry excessively. As such, it is an especially useful instrument to assess the severity of pathological worry characteristic of GAD. It has been shown to discriminate among the anxiety disorders, as individuals with GAD score significantly higher on the PSWQ than any other anxiety disorder group, and it is also sensitive to change in studies of cognitive-behavioral therapy for GAD (Molina and Borkovec, 1994). The Generalized Anxiety Disorder Questionnaire-IV (GADQ-IV) is a brief measure designed to screen for the presence of GAD, based on DSM-IV diagnostic criteria.

Several other dimensions of individual functioning also warrant attention during assessment, as these may significantly impact and/or contribute to overall severity of GAD (

). Among these, people with GAD often have maladaptive beliefs about worry, including the assumption that worry serves a protective function or that worry will prevent negative and feared outcomes from occurring. Asking a patient to describe their beliefs about the effects of worry may identify targets to address in treatment.

Emotional functioning is another important area to examine, as it has been shown that people with GAD have difficulty identifying their emotions or may consciously attempt to avoid experiencing emotions by using worry as a cognitive avoidance strategy. In such cases, interventions aimed at improving emotion regulation may be of benefit. While overt avoidance may not be as common in GAD as in phobic disorders, subtle behavioral avoidance is often present and may serve as a maintaining factor.

Careful probing during the clinical evaluation and between-session patient self-monitoring can help to identify areas of avoidance to target in treatment. Interpersonal functioning may also be impaired, and social or intimate relationships are often a major focus of patient's excessive worrying. Fears of disapproval, negative evaluation and appearing incompetent are common in patient's clinical presentation and need to be addressed.

Finally, careful assessment of comorbid Axis I and Axis II psychopathology is crucial, as GAD has been found to be a highly comorbid disorder with 30-day and lifetime comorbidity rates estimated at 66.3% and 90.4%, respectively (Wittchen et al., 1994). Comorbid psychopathology has been shown to be associated with increased severity of GAD. Among the most common co-occurring conditions are other anxiety disorders, depressive disorders and substance use disorders.

As public awareness and recognition of GAD continues to grow, clinicians will likely evaluate and treat these patients with increasing frequency. Accurate detection, diagnosis and assessment of disorder severity can inform the clinician's interventions and improve treatment effectiveness. A small but sufficient group of empirically supported instruments to assess the severity of GAD are now available and should be judiciously combined with one's clinical acumen.

Dr. Belzer is a research fellow in affective, anxiety and related disorders, Department of Psychiatry, Columbia University College of Physicians and Surgeons and the Anxiety Disorders Clinic of New York State Psychiatric Institute. He has indicated he has nothing to declare.

Gelenberg AJ, Lydiard RB, Rudolph RL et al. (2000), Efficacy of venlafaxine extended-release capsules in nondepressed outpatients with generalized anxiety disorder: A 6-month randomized controlled trial. JAMA 283(23):3082-3088.		
 

Grant BF, Hasin DS, Stinson FS et al. (2005), Prevalence, correlates, co-morbidity, and comparative disability of DSM-IV generalized anxiety disorder in the USA: results from the National Epidemiologic Survey on Alcohol and Related Conditions. Psychol Med 35(12):1747-1759.
 

Kessler RC, Chiu WT, Demler O et al. (2005), Prevalence, severity, and comorbidity of 12-month DSM-IV disorders in the National Comorbidity Survey Replication. [Published erratum Arch Gen Psychiatry 62(7):709. Merikangas, KR (added).] Arch Gen Psychiatry 62(7):617-627 [see comment].
 

Molina S, Borkovec TD (1994), The Penn State Worry Questionnaire: psychometric properties and associated characteristics. In: Worrying: Perspectives on Theory, Assessment and Treatment, Davey GCL, Tallis F, eds. New York: Wiley, pp265-283.
 

Rickels K, Pollack MH, Feltner DE et al. (2005), Pregabalin for treatment of generalized anxiety disorder: a 4-week, multicenter, double-blind, placebo-controlled trial of pregabalin and alprazolam. Arch Gen Psychiatry 62(9):1022-1030.
 

Roemer L, Medaglia E (2001), Generalized anxiety disorder: a brief overview and guide to assessment. In: Practitioner's Guide to Empirically Based Measures of Anxiety, Antony MM, Orsillo SM, Roemer L, eds. New York: Kluwer Academic/ Plenum Publishers, pp189-195.
 

Shear K, Belnap BH, Mazumdar S et al. (in press), The Generalized Anxiety Disorder Severity Scale (GADSS): a preliminary validation study. Depress Anxiety.
 

Turk CL, Heimberg RG, Mennin DS (2004), Assessment. In: Generalized Anxiety Disorder: Advances in Research and Practice, Heimberg RG, Turk CL, Mennin DS, eds. New York: Guilford Press, pp219-247.
 

Wittchen HU, Zhao S, Kessler RC, Eaton WW (1994), DSM-III-R generalized anxiety disorder in the National Comorbidity Survey. Arch Gen Psychiatry 51(5):355-364.

Generalized anxiety disorder (GAD) is a chronic, impairing and highly comorbid psychiatric condition. A small but sufficient group of empirically supported instruments to assess the severity of GAD are now available.

Tools for Assessing Generalized Anxiety Disorder

Despite high prevalence and negative consequences of anxiety disorders in later life, this area has received little research attention. A relatively small number of outcome investigations on late-life anxiety have focused on the impact of pharmacological and psychotherapeutic treatments.

Community prevalence rates for anxiety disorders in older adults range from 3.5% to 10.2%, suggesting a higher prevalence than for late-life depression (Beekman et al., 1998; Bland et al., 1988). Anxiety disorders are even more common among older adults with medical illness and in senior housing facilities (Junginger et al., 1993; Tolin et al., 2005). Generalized anxiety disorder (GAD) is one of the most common anxiety disorders, with community prevalence rates ranging from 1.9% to 7.3% (Beekman et al., 1998; Blazer et al., 1991). Anxiety symptoms that do not meet DSM criteria are even more prevalent, with rates from 15% to 20% in community samples and even higher in medically ill populations (Himmelfarb and Murrell, 1984; Mehta et al., 2003; Wittchen et al., 2002). For example, panic attacks, but not necessarily DSM-diagnosable panic disorder, are common in chronic obstructive pulmonary disease (COPD). Anxiety symptoms and disorders are associated with many negative consequences such as decreased physical activity and functional status, poorer self-perceptions of health, decreased life satisfaction, increased loneliness, increased physical disability, decreased quality of life, and increased service utilization (Brenes et al., 2005a, 2005b; Lenze et al., 2001; Stanley et al., 2001; van Balkom et al., 2000).

The first line of treatment for anxiety in later life is typically pharmacological. Benzodiazepines are the most commonly used anxiety management medication, followed by serotonergic antidepressants, buspirone (BuSpar), and venlafaxine (Effexor) (Mamdani et al., 2005). Recent research has also examined the impact of psychotherapy, typically cognitive-behavioral therapy (CBT), for late-life anxiety.

Approximately half of older patients diagnosed with an anxiety disorder in primary care are prescribed an anxiolytic or antidepressant medication (Stanley et al., 2001). All pharmacological interventions reviewed are approved treatment options for anxiety disorders. Benzodiazepines are the most frequently prescribed medications for anxiety in later life, with usage rates of 10% to as high as 43% for individuals with persistent anxiety (Gleason et al., 1998; Gray et al., 2003; Mamdani et al., 2005; Schuurmans et al., 2005). However, benzodiazepines can lead to an increased risk of falls, and possibly increased cognitive decline, in older people (Paterniti et al., 2002).

 Only three randomized controlled trials have investigated the efficacy of benzodiazepines for anxiety disorders in later life. Two of these focused on GAD (Bresolin et al., 1988; Frattola et al., 1992) and one on an earlier, comparable category of anxiety neurosis (Koepke et al., 1982). The data from these trials suggest the utility of benzodiazepines for anxiety disorders in older adults. Despite the results demonstrating efficacy, limited and short-term use of benzodiazepines is recommended given the possible negative consequences (Sheikh and Cassidy, 2000).

. Five pharmacotherapy studies of late-life anxiety disorders have tested antidepressant medications. Two of these studies included patients with panic disorder (PD), one included a mixed group of patients with GAD, PD or obsessive-compulsive disorder (OCD), and two included patients with GAD. Sheikh and Swales (1999) found promising results when comparing the efficacy of imipramine (Janimine, Tofranil), alprazolam (Xanax) and placebo in patients with PD. A follow-up investigation demonstrated improvement in anxiety symptoms in patients with PD using sertraline (Zoloft) (Sheikh et al., 2004). A sample with mixed anxiety disorders showed high response rates to fluvoxamine (Luvox) (Wylie et al., 2000). Interestingly, none of the three patients with PD responded to treatment. Katz and colleagues (2002) conducted a secondary analysis of data from patients age 60 years and older who participated in five randomized clinical trials of venlafaxine for GAD. Venlafaxine demonstrated superiority to placebo in this investigation. In the only prospective, randomized trial to date of a serotonergic antidepressant, Lenze and colleagues (2005), found citalopram (Celexa) superior to placebo, and these gains were maintained at 32-week follow-up for patients who continued taking the medication (Blank et al., in press).

Most psychotherapy studies of late-life anxiety have used CBT with patients with GAD. We found evidence for the efficacy of CBT for GAD in seven studies. The CBT protocols in these investigations typically consisted of education about anxiety, relaxation training, cognitive therapy and systematic desensitization to worry-provoking thoughts and situations, most commonly administered in a group format. Control conditions included waiting list, minimal contact control, usual care, supportive therapy and a discussion group attention placebo. Data suggest that at follow-up, gains are maintained, particularly when booster sessions are given.

One study found that supportive therapy (which emphasized empathic listening) and CBT were equally effective in reducing anxiety and depressive symptoms (Stanley et al., 1996). Another investigation compared CBT to a minimal contact control condition and demonstrated superiority of CBT, even at 12-month follow-up (Stanley et al., 2003a). Wetherell and colleagues (2003), compared active (CBT and discussion group attention placebo ) and inactive (waiting list) conditions and demonstrated roughly equal efficacy in active conditions compared to waiting list. Interestingly, CBT was only superior to discussion group placebo on one measure of anxiety, and this finding was no longer significant at six-month follow-up. A small study of primary care patients demonstrated the effectiveness of individually administered CBT compared to usual care (Stanley et al., 2003b). This investigation was an important initial effort to disseminate anxiety treatment options into a primary care setting, where the majority of older adults with GAD present for treatment.

Other approaches to the treatment of late-life anxiety have added techniques to the standard CBT protocol. One approach used an enhanced form of individually administered CBT (Mohlman et al., 2003). Enhanced CBT included the standard CBT elements as well as additional memory aids (e.g., reminder phone calls, weekly review of concepts and techniques). Overall, results suggest that CBT enhancements improved treatment outcome compared to waiting list. A follow-up investigation compared enhanced CBT to a waiting list among patients with varying levels of executive functioning (Mohlman and Gorman, 2005). Results suggested that individuals with impaired executive functioning did not respond to CBT whereas those with intact and improved executive functioning were more likely to respond. Another approach used a CBT protocol based on the concept of intolerance of uncertainty as the key feature of GAD (Ladouceur et al., 2004). The majority of patients in this study no longer met criteria for GAD upon completion of treatment.

Much less research has been conducted in older adult populations with anxiety disorders other than GAD. Some research suggests the effectiveness of CBT for PD, agoraphobia, OCD, specific phobia and social phobia. There have been no randomized, controlled psychosocial interventions conducted exclusively with older adults with PD. However, a non-controlled study produced promising results demonstrating the effectiveness of CBT in older PD patients (Swales et al., 1996). A retrospective chart review of older inpatients treated for OCD using exposure and response prevention, along with other elements (e.g., pharmacotherapy, milieu therapy) showed that staff and self-report improvement ratings were high (Carmin et al., 1998).

Several studies have demonstrated the effectiveness of CBT in samples with mixed anxiety disorder diagnoses. Radley and colleagues (1997), found efficacy for CBT in a multiple baseline design in a small sample of patients with a variety of anxiety disorders.

A small case series of patients with various anxiety disorder diagnoses also found improvement in anxiety symptoms following CBT (King and Barrowclough, 1991). Another study used a home-based individual format, which demonstrated significant effects for CBT relative to supportive therapy (Barrowclough et al., 2001). Gains were maintained at 12-month follow-up. Gorenstein and colleagues (2005) found equivalent effects for CBT plus medication management relative to medication management alone.

Overall, available data suggest the potential utility of both pharmacological and psychotherapeutic treatments for late-life anxiety disorders, especially GAD. The CBT literature has demonstrated the effectiveness of CBT compared to no treatment, but evidence does not consistently support the benefits of CBT relative to other psychosocial treatment options (e.g., supportive therapy). Pharmacological treatment is more effective than placebo in the treatment of late-life anxiety, and some evidence suggests that it is more effective than CBT (Wetherell et al., 2005).

Limitations of this literature include homogeneous and unrepresentative samples in terms of age, functional status, ethnicity, education, or medical health; neglect of anxiety disorders other than GAD; and a relative dearth of research on treatment in settings more typically used by anxious older adults (e.g., primary care). Another concern is the failure to investigate long-term maintenance. In most CBT studies, follow-up is limited to 12 months or less. Pharmacological trials have typically not examined the nature and efficacy of various maintenance options.

Psychotherapy attrition rates are higher among older adults (21% to 39%) than among younger adults (approximately 10%) (Gould et al., 2004). Attrition from pharmacotherapy trials is somewhat lower (15% to 23%) and is consistent with attrition rates in younger adults with anxiety disorders (Katz et al., 2002; Lenze et al., 2005). Psychotherapy trials typically analyze data only from completers, whereas pharmacological trials more often analyze on an intent-to-treat basis. Furthermore, psychotherapy studies typically use multiple outcome measures, which complicate the interpretation of inconsistent results across measures. Finally, there is no psychotherapy comparison condition equivalent to a pill placebo.

Although initial results point to the efficacy of pharmacological and psychotherapeutic treatment for geriatric anxiety disorders, more research is needed on other intervention techniques, patient samples, and anxiety disorder diagnoses. More research is also needed to determine whether medication is an acceptable and effective long-term management tool for these chronic disorders. Long-term follow-up of patients and creative methods for the dissemination of these treatments remain important goals for future research, as do combinations of pharmacological and psychotherapeutic treatment and stepped care approaches.

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Psychiatric Times Vol 23 No 3

Special Report: Anxiety Disorders Across the Life Span

A Psychiatrist Waits for His 10 O'clock Patient and Imagines He is Han Shan

Tools for Assessing Generalized Anxiety Disorder

Treating Late-Life Anxiety