Anxiety disorders (see 6.04 Anxiety) are characterized by an abnormal or inappropriate wariness. There are several disorders that fall under the heading of anxiety including panic disorders, phobias, generalized anxiety disorder (GAD), acute stress disorder, and posttraumatic stress disorder (PTSD). Panic disorder is characterized by rapid and unpredictable attacks of intense anxiety that are often without an obvious trigger. Phobias are examples of life-disrupting anxiety or fear associated with an object or situation, including social phobias. GAD develops over time and involves the generalization of fears and anxieties to other, usually inappropriate situations until they ultimately result in an overwhelming anxiety regarding life in general. Acute stress disorder involves the response to a threatened or actual injury or death and is characterized by dissociation, detachment, and depersonalization. Acute stress disorder usually resolves within a few weeks; however it can progress into more severe anxiety disorders such as PTSD. PTSD is characterized by intrusive, anxiety-provoking memories of a stress or trauma (death or injury, terrorist attack, combat experience) that recur and become disruptive to daily function. The symptoms of PTSD include nightmares, obsessive thoughts, flashbacks (re-experiencing the trauma), and avoidance of situations associated with the stressor and a generalization of anxiety.
All of these categories of anxiety can produce crippling and overwhelming emotional and physical symptoms. Anxiety disorders are common with as many as 25% of adults suffering from some form of clinical anxiety at some point in their life with 19 million individuals affected in the USA. Anxiety is estimated to cost worldwide approximately $40 billion annually.
Diagnosis of anxiety disorders is based upon interview with a psychologist or psychiatrist. While a considerable progress has been made in the understanding of the neuronal circuitry underlying fear responses, the biological basis of anxiety disorders is not well understood. Findings of a modest genetic influence including polymorphisms in COMT (catechol O-methyl transferase), the serotonin transporter gene SLC6A4, and 5HT receptors indicate the need for additional genetic linkage studies; however there is a marked environmental/epigenetic component, especially stress in early life, that appears to play a greater role in determining if an individual will develop an anxiety disorder.
Current treatments for anxiety disorders vary depending on the diagnosis. Acute stress disorder can be treated successfully with psychotherapy, and will often resolve itself. Phobias are also successfully treated through behavioral therapy and seldom require medication. The remaining disorders are treated with a combination of therapy and anxiolytic drugs. The earliest anxiolytics were barbiturates, which have now largely been replaced by the benzodiazepines (BZs), e.g., diazepam, clonazepam, etc. While BZs are highly efficacious and have a greater safety margin, there are still significant issues with sedation, withdrawal, dependence liability, and possible overdose. Antidepressants including SSRIs, SNRIs, and 5HT antagonists have also been used with mixed success.
While defined as an anxiety disorder, obsessive compulsive disorder (OCD) has several distinct features that set it apart. It is characterized by an overwhelming sense that negative consequences will arise from the failure to perform a specific ritual. The rituals are repetitive, taking a variety of forms including hand washing, checking to see if the stove is turned off, or the recitation of particular words or phrases. DSM-IV-TR criteria require that the symptoms include obsessions or compulsions that cause marked distress and occupy at least 1 h per day. OCD interferes with normal routine and produces a social impairment equivalent to schizophrenia. In addition to the disabling effect OCD has on the patient, it also produces a significant strain on family relations as relatives become caregivers and are drawn into a routine of providing reassurance and ritual maintenance. OCD becomes apparent at between 22 and 36 years, affecting males and females equally. OCD is highly prevalent, affecting 2-3% of the US population, yet in spite of its clear negative impact on quality of life, OCD is typically underdiagnosed. This is due to a combination of the lack of familiarity of a physician with OCD symptoms and patients tending to be embarrassed and hiding their symptoms.
In contrast to many other psychiatric disorders, OCD patients often have insight into the illogical and extreme nature of their behaviors. Unfortunately there is still reluctance to admit to the symptoms, and it is necessary that the physician probe carefully in order to make an appropriate diagnosis. Positron emission tomography (PET) and single positron emission computed tomography (SPECT) imaging studies suggest a role for increased activity in the orbitofrontal cortex, the cingulated cortex, and the caudate nucleus. Interestingly, these regions have been found to further activate when patients are confronted with a stimulus known to provoke symptoms, and show a decrease activity in response to therapy. While imaging methods are not routinely employed, these studies suggest that an objective diagnostic test is feasible.
Current treatment strategies for OCD include the use of the TCA, clomipramine or the SSRIs, fluoxetine or fluvoxamine at doses higher than those typically used in depressed patients. This approach is effective in 40-60% of patients; however, it only produces a modest 20-40% improvement in symptoms. Therefore, it is critical that patients also undergo behavioral therapy. The pharmacological approach has been found to greatly enhance the success rate of behavioral therapy, and the combined therapies have a much lower relapse rate than either when used alone. For refractory patients, SSRIs can be augmented by the addition of other drugs, e.g., dopamine antagonists. Neurosurgical approaches are available for severely affected patients that do not respond to combined pharmacological and behavioral therapy; however, this approach has not been extensively validated and the overall success rate is less than 50%.
While the prognosis for OCD has improved dramatically with the SSRIs, the overall outlook ranges from moderate to poor. At least 40% of patients are refractory to treatment, and those that respond often experience an incomplete decrease in symptoms and a significant propensity for relapse.
The prognosis for an individual with an anxiety disorder is dependent on the category and severity of the disorder. However, with combined pharmacological and behavioral interventions, the outlook is moderate to good even with the most severe cases of GAD. To satisfy current unmet medical need, efforts are being focused on new chemical entities (NCEs) that have the efficacy of BZs but lack the associated adverse effects. Such agents include g-amino-butyric acid (GABAa) receptor subunit selective 'BZ-like' NCEs12 including neurosteroids (e.g., ganaxolone), direct acting GABAa agonists like gaboxadol, and newer approaches to anxiety including cannabinoids, metabotropic glutamate receptor modulators, nicotinic receptor agonists, and modulators of the corticotrophin-releasing factor (CRF) family of receptors.
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It seems like you hear it all the time from nearly every one you know I'm SO stressed out!? Pressures abound in this world today. Those pressures cause stress and anxiety, and often we are ill-equipped to deal with those stressors that trigger anxiety and other feelings that can make us sick. Literally, sick.