Anxiety disorders limitations

There has been little formal study of maintenance therapy for social anxiety disorder. Limited data indicates that continued pharmacotherapy provides significant prophylactic protection against relapse. Furthermore, growing evidence indicates that patients with social anxiety disorder experience a high rate of relapse after treatment discontinuation. CBT, however, may afford continued prophylactic benefit long after conclusion of the therapy, though the data to support this contention is limited. 

Often occurs in context of other anxiety disorders. The feared social or performance situation can be limited to a specific social interaction (e.g., public speaking) or generalized to most any social interaction. Differs from specific phobia, in which the fear and anxiety are limited to a particular object or situation (e.g., insects, heights, public transportation). 

Buspirone (Buspar). The first nonsedating, nonbenzodiazepine specifically introduced as an anxiolytic, buspirone is FDA approved for the treatment of GAD. This medication acts as a partial agonist at the postsynaptic serotonin (5HT)-1A receptor. Like the antidepressants, buspirone has a delayed onset of action and effectively relieves the intrapsychic symptoms of GAD. Devoid of the muscle-relaxing properties of benzodiazepines, buspirone does not as effectively relieve the physical symptoms of GAD. Buspirone is not effective in the treatment of depression. Furthermore, its utility for the treatment of anxiety disorders other than GAD appears to be limited. 

The etiology of social anxiety remains unclear however, evidence suggests that developmental and genetic factors may predispose some individuals to social anxiety disorder. Adults with social anxiety disorder are more likely to report a history of childhood shyness and separation anxiety, limited social interaction during adolescence, and having had parents who placed great emphasis on the importance of the opinion of others. 

Psychosurgery. Case series have been reported of patients with severe treatment resistant social anxiety disorder undergoing surgical procedures including capsu-lotomy and endoscopic transthoracic sympathectomy. Given the limited evidence... 

Individual characteristics can determine how a person reacts to a trauma and thereby contribute to the risk for developing PTSD. These include neurosis, limited social support, a family history of an anxiety disorder, and a personal history of previous significant stressors, particularly childhood sexual or physical abuse. 

Tricyclic Antidepressants (TCAs). Because of their effectiveness not only for depression but for anxiety disorders such as panic disorder as well, TCAs were the first medications formally tested in the treatment of PTSD. Three TCAs, amitriptyline, imipramine, and desipramine, have been studied in small trials, producing modest benefit for reexperiencing and hyperarousal symptoms, without any relief of avoidance/numbing symptoms. Given this limited benefit in conjunction with the side effect burden and potential for toxicity in a suicide prone population, TCAs are infrequently used in the treatment of PTSD. Please refer to Chapter 3 for more information regarding TCAs. 

There is also evidence for both the familial aggregation and heritability of generalized anxiety disorder (GAD) in a limited number of studies. There is a five-fold average increase in the rister of GAD among relatives of probands with GAD compared to that among relatives of controls 5 (Mendlewicz et al. 1993 Noyes et al. 1987) and the heritability of GAD among female twins is 0.32 (Kendler et al. 1992). 

For much of the second half of the twentieth century the benzodiazepines were the mainstay of the treatment of anxiety. Despite well-publicised concerns about their long-term safety, they remain an important therapeutic option. The anticonvulsants contain a number of drugs that act via GABA or glutamate neurotransmission and have a limited but interesting role in the treatment of particular anxiety disorders. 

Although promising in preclinical models of anxiety, the 5-HT3 receptor antagonist ondansetron has limited efficacy in panic disorder (Schneier et al. 1996) however, at higher doses (1 mg), ondansetron was superior to placebo in a study of patients with generalized anxiety disorder (Freeman et al. 1997). 

The terms social phobia or social anxiety disorder refer to a pattern of recurrent fear and apprehension in social situations or scenarios where an individual may be scrutinized. Before modifications in the Diagnostic and Statistical Manual of Mental Disorders, 4th ed. (DSM-IV), identification of social phobia in childhood was limited by having the condition closely aligned to both... 

Although social attachment and impairment of social behaviors are evident in a wide range of psychopathology, including childhood trauma, personality disorders, and anxiety disorders, an extensive review of this subject is beyond the scope of this chapter. The focus of this section will thus be primarily limited to the neurobiology of affiliation as it relates to autism spectrum disorders. 

Several controlled studies of IMI involved less homogeneous samples of anxious children. Neither IMI nor alprazolam (a BZ) was superior to placebo in an 8-week study of 24 children (ages 7-18 years) with school refusal, which included subjects with anxiety and depression (Bernstein et ah, 1990). A more recent placebo-controlled study of IMI -I- CBT for 47 adolescents (ages 12-18 years) with school refusal, anxiety, and/or depression was designed to address the limitations of previous studies of TCA treatment for pediatric anxiety disorders (Bernstein et ah, 2000). Accordingly, sample size was based on proposed power analysis IMI dose and serum level were monitored to ensure adequate exposure (mean IMI dose 180 mg/day mean serum IMI180 pg/L and mean IMI -I- DMI 250 pg/L at week 3 and week 8) and CBT was manual based and closely monitored. Fifty-four percent of subjects treated with IMI -I- CBT met remission criteria (defined as > 75% school attendance at the end of the study), compared to 17% of subjects treated with placebo -I- CBT. No between-group differences were noted... 

The extent of Buspirone experience in children and adolescents is limited to open studies and case reports. There are no published double-blind placebo-controlled studies of Buspirone for pediatric anxiety disorders or any other psychiatric disorder. Results of a recently completed large (n = 350 ages 6-17 years), industry-sponsored, multisite study of Buspirone for children (15-30 mg/day) and adolescents (45-60 mg/ day) with GAD have not been published or presented at open academic conferences. Until such data are made available, the use of Buspirone for treatment of pediatric anxiety disorders remains speculative. 

Despite these limitations, CBT treatments have proven to be efficacious for a majority of child and adolescent subjects with anxiety disorders. Indeed,... 

The parallel-group, double-blind, placebo-controlled study design represents the golden standard of acute treatment trials of depression, mania and anxiety disorders. This design is intended to limit bias, in particular selection and measurement bias. Trials based on this design are expected to provide information about the effect size of a new compound and its side-effect profile. 

This design may help to screen out placebo responders as well as bipolar depressed patients with transient exacerbations of symptoms, or subjects suffering from anxiety disorders in response to environmental psychological stressors. However, the value of this design is limited because it will not reduce potential investigator bias, i.e. the expectation of pharmacological effects after a given time. 

Social anxiety disorder is an uncommonly diagnosed but a fairly common condition in which the patient experiences severe anxiety in social interactions. This anxiety may limit their ability to function adequately in their jobs or interpersonal relationships. Several SSRIs and venlafaxine are approved for the treatment of social anxiety. The efficacy of the SSRIs in the treatment of social anxiety is greater in some studies than their efficacy in the treatment of MDD. 

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