Anxiety disorder

Anxiety disorders include a constellation of disorders in which anxiety and associated symptoms are irrational or experienced at a level of severity that impairs functioning. The characteristic features are anxiety and avoidance. 

Noradrenergic model. This model suggests that the autonomic nervous system of anxious patients is hypersensitive and overreacts to various stimuli. The locus ceruleus may have a role in regulating anxiety, as it activates norepinephrine release and stimulates the sympathetic and parasympathetic nervous systems. Chronic noradrenergic overactivity down regulates 02-adrenoreceptors in patients with generalized anxiety disorder (GAD) and posttraumatic stress disorder (PTSD). Patients with social anxiety disorder (SAD) appear to have a hyperresponsive adrenocortical response to psychological stress. 

Functional neuroimaging studies suggest that frontal and occipital brain areas are integral to the anxiety response. Patients with panic disorder may have abnormal activation of the parahippocampal region and prefrontal cortex at rest. Panic anxiety is associated with activation of brain stem and basal ganglia regions. GAD patients have an abnormal increase in cortical 

The clinical presentation of GAD is shown in Table 68-1. The diagnostic criteria require persistent symptoms most days for at least 6 months. The anxiety or worry must be about a number of matters and is accompanied by at least three psychological or physiologic symptoms. The illness has a gradual onset at an average age of 21 years. The course of illness is chronic, with multiple spontaneous exacerbations and remissions. There is a high percentage of relapse and a low rate of recovery. 

Symptoms usually begin as a series of unexpected panic attacks. These are followed by at least 1 month of persistent concern about having another 

Before outlining the main features of each anxiety disorder, it is necessary to define two terms panic attacks and anxiety symptoms. Panic attacks are very brief but extremely intense surges of anxiety. The major differences between a panic attack and more generalized anxiety symptoms are differences in the onset, duration, and intensity (see figure 7-A). Panic attacks often come out of the blue that is, they are not necessarily provoked by stress. They come on suddenly, are extremely intense, and last anywhere from 1 to 30 minutes and then subside. Tlie patient feels as if he or she will actually die or go crazy as we are not talking about uneasiness but fullblown panic. 

The person may continue to feel nervous or upset for several hours, but the attack itself lasts only a matter of minutes. If a patient says, Tve had a continuous panic attack for the past three days, he or she may be having intense anxiety symptoms, but not a true panic attack. In anxiety disorders without panic attacks, the anxiety symptoms can be very unpleasant, but are much less intense they also can be prolonged or generalized—that is, present most of the day and lasting from days to years. The distinction between anxiety and panic is very important when it comes to making an accurate diagnosis and choosing appropriate treatments. The symptoms of anxiety are as follows  

Trembling, feeling shaky, restlessness, muscle tension Shortness of breath, smothering sensation Tachycardia (rapid heartbeat) 

Sweating and cold hands and feet Lightheadedness and dizziness Paresthesias (tingling of the skin) 

Diarrhea, frequent urination, or both Feelings of unreality (derealization) 

Recent studies have shown that African Americans with various anxiety disorders are also likely to be given a misdiagnosis of psychosis and are more likely to receive antipsychotic treatment. Pan- 

Obsessive-compulsive disorder is rarely diagnosed in African Americans (Friedman et al. 1993 Hatch et al. 1992 Paradis et al. 1994). Although there are no definitive studies, case reports suggest that many of these patients are diagnosed as being psychotic (Lawson 1999). The ego-dystonic obsessions in obsessive-compulsive disorder may easily be misinterpreted as delusions or a thought disturbance, and the compulsions may be mistaken for psychotic behavior (Hwang and Hollander 1993). 

Recent studies have shown that posttraumatic stress disorder (PTSD) in African Americans may be associated with different symptoms and maybe misdiagnosed, with the consequent greater likelihood of antipsychotic treatment (Lawson 1999). In all populations, typical symptoms in PTSD may easily be mistaken for psychotic symptoms. Flashbacks in patients with PTSD may be mistaken for hallucinatory experiences, emotional blunting for a flattened affect, and hyperreactivity for psychotic excitement. Consequently, patients are at risk of being misdiagnosed with schizophrenia (Allen 1996). 

Symptom presentation may differ in African Americans with combat-related PTSD compared with Caucasians and Hispanics with the disorder (Allen 1996 Penk and Allen 1991). African American substance abusers with heavy-combat exposure were reported to be more disturbed than a similar group of whites and scored higher on the MMPI scales for paranoid and psychotic symptoms (Penk et al. 1989). A later study found higher levels of psychotic symptoms and paranoid ideation among blacks with PTSD compared with whites with the disorder, using the MMPI-2 groups (Frueh et al. 1996). Unlike the older MMPI, the MMPI-2 (Hathaway and McKinley 1989) was normed on diverse ethnic groups. 

Consistent with these findings, African American veterans reportedly received more neuroleptic medication than did Hispan- 

Before we discuss treatment issues unique to some of the most prevalent anxiety disorders, it is important to review some concepts common to all of them. 

Several neurochemical hypotheses have been set forth to explain the mechanisms leading to the clinical manifestations of anxiety disorders. Although a detailed account goes beyond the scope of this book, it is enough to state that norepinephrine, serotonin, and GABA (gamma-aminobutyric acid) are three of the neurotransmitters most often implicated. The medications found to be most useful for the treatment of anxiety disorders—SSRIs, TCAs, MAOIs, and benzodiazepines—have profound effects on these neurotransmitters and their respective neuroreceptors. 

Anxiety disorders include a range of diagnoses in which panic or disabling anxiety is a prominent feature. These include panic disorder with and without agoraphobia, specific phobias, PTSD, social phobia, OCD, and generalized anxiety disorder (GAD) (Table 4.1). 

several other psychiatric disorders have anxiety as a prominent feature. For example, approximately two-thirds of depressed patients suffer from anxiety as a significant part of their symptomatology. Because there is considerable overlap in symptoms, diagnosis can be tricky, but a correct diagnosis can make a big difference in whether a patient is referred for medication and which medication regimen a physi- 

Anxiety disorder due to a general medical condition Substance-induced anxiety disorder Anxiety disorder not otherwise specified 

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Anxiety disorders and insomnia represent relatively common medical problems within the general population. These problems typically recur over a person s lifetime (3,4). Epidemiological studies in the United States indicate that the lifetime prevalence for significant anxiety disorders is about 15%. Anxiety disorders are serious medical problems affecting not only quaUty of life, but additionally may indirecdy result in considerable morbidity owing to association with depression, cardiovascular disease, suicidal behavior, and substance-related disorders. 

Benzodiazepines, ie, the hiU BZR agonists, are prescribed for anxiety, insomnia, sedation, myorelaxation, and as anticonvulsants (97). Those benzodiazepines most commonly prescribed for the treatment of anxiety disorders are lorazepam (19), alprazolam (20), diazepam (21), bromazepam (22), chlorazepate (23), and oxazepam (24). These dmgs together represent about 70% of total... 

Buspirone. Buspirone (3) hydrochloride has been approved for the symptomatic management of generali2ed anxiety disorder (Table 3). This dmg is of special iaterest because it does not exert its therapeutic actions via modulation of the GABA receptor complex. This compound is stmcturaHy... 

Glassification of Substance-Related Disorders. The DSM-IV classification system (1) divides substance-related disorders into two categories (/) substance use disorders, ie, abuse and dependence and (2) substance-induced disorders, intoxication, withdrawal, delirium, persisting dementia, persisting amnestic disorder, psychotic disorder, mood disorder, anxiety disorder, sexual dysfunction, and sleep disorder. The different classes of substances addressed herein are alcohol, amphetamines, caffeine, caimabis, cocaine, hallucinogens, inhalants, nicotine, opioids, phencyclidine, sedatives, hypnotics or anxiolytics, polysubstance, and others. On the basis of their significant socioeconomic impact, alcohol, nicotine, cocaine, and opioids have been selected for discussion herein. 

Antidepressants are small heterocyclic molecules entering the circulation after oral administration and passing the blood-brain barrier to bind at numerous specific sites in the brain. They are used for treatment of depression, panic disorders, generalized anxiety disorder, social phobia, obsessive compulsive disorder, and other psychiatric disorders and nonpsychiatric states. 

Anxiolytics are drugs used for the treatment of anxiety disorders. Apart from benzodiazpines, a frequently used anxiolytic is the 5HT1A (serotonin) receptor agonist buspiron, which has no sedative, amnestic or muscle-relaxant side effects, but whose action takes about a week to develop. Furthermore, it is less efficaceous than the benzodiazepines. Buspiron s mechanism of action is not fully understood. 

Benzodiazepines are amongst the most frequently prescribed drugs they have well-established uses in the treatment of anxiety disorders (anxiolytics) and insomnia, preanaesthetic sedation, suppression of seizures, and muscle relaxation. 

The definition of desired therapeutic and side effects in the case of the benzodiazepines very much depends on the clinical problem in question. The sedative and hypnotic actions are desired effects in the treatment of insomnia, but undesired effects in the treatment of anxiety disorders. Effects that are usually undesired include daytime drowsiness, potentiation of the sedative effects of ethanol, and anterograde amnesia. They are mediated via the benzodiazepine site of GABAa receptors, since they can be antagonized with flumazenil. 

Up to 30% of COPD patients suffer from anxiety disorder or depression, and should be treated with conventional pharmacotherapy. 

Holmes A, Picciotto MR (2006) Galanin a novel therapeutic target for depression, anxiety disorders and drag addiction CNS Neurol Disord Drag Targets 5 225-232... 

Indeed, 5-HT is also a substrate for the 5-HT transporter, itself an important player in the treatment of depression, and more recently for the whole range of anxiety disorders spectrum (GAD, OCD, social and other phobias, panic and post-traumatic stress disorders). It is the target for SSRIs (selective serotonin reuptake inhibitors) such as fluoxetine, paroxetine, fluvoxamine, and citalopram or the more recent dual reuptake inhibitors (for 5-HT and noradrenaline, also known as SNRIs) such as venlafaxine. Currently, there are efforts to develop triple uptake inhibitors (5-HT, NE, and DA). Further combinations are possible, e.g. SB-649915, a combined 5-HTia, 5-HT1b, 5-HT1d inhibitor/selective serotonin reuptake inhibitor (SSRI), is investigated for the treatment of major depressive disorder. 

Tranquilizers (also called antianxiety drugs) are used to treat a variety of psychiatric disorders which go along with anxiety (anxiety disorders). Serotonin-reuptake inhibitors and the benzodiazepines are the most commonly employed drugs for the treatment of common clinical anxiety disorders. 

Antianxiety drugp are used in the management of anxiety disorders and short-term treatment of the symptoms of anxiety. Long-term use of these dru is usually not recommended because prolonged therapy can result in drug dependence and serious withdrawal symptoms. 

OCD, panic disorder, general anxiety disorder, social anxiety disorder, post-traumatic stress syndrome Depression, OCD, panic disorders, post-traumatic stress disorder... 

Grant BF, Stinson FS, Dawson DA, et al Prevalence and co-occurrence of substance use disorders and independent mood and anxiety disorders results from the National Epidemiologic Survey on Alcohol and Related Conditions. Arch Gen Psychiatry 61 807-816, 2004b... 

Iwata N, Cowley DS, Radel M, et al Relationship between a GABA alpha g Pro385Ser substitution and benzodiazepine sensitivity. Am] Psychiatry 156 1447—1449,1999 Jacobson AF, Dominguez RA, Goldstein B, et al Comparison of buspirone and diazepam in generalized anxiety disorder. Pharmacotherapy 5 290—296, 1985 Jaffe JH, Ciraulo DA, Nies A, et al Abuse potential of halazepam and diazepam in patients recently treated for acute alcohol withdrawal. Clin Pharmacol Ther 34 623-630, 1983... 

Anxiety disorders are common in the population of opioid-addicted individuals however, treatment studies are lacking. It is uncertain whether the frequency of anxiety disorders contributes to high rates of illicit use of benzodiazepines, which is common in methadone maintenance programs (Ross and Darke 2000). Increased toxicity has been observed when benzodiazepines are co-administered with some opioids (Borron et al. 2002 Caplehorn and Drummer 2002). Although there is an interesting report of clonazepam maintenance treatment for methadone maintenance patients who abuse benzodiazepines, further studies are needed (Bleich et al. 2002). Unfortunately, buspirone, which has low abuse liability, was not effective in an anxiety treatment study in opioid-dependent subjects (McRae et al. 2004). Current clinical practice is to prescribe SSRIs or other antidepressants that have antianxiety actions for these patients. Carefully controlled benzodiazepine prescribing is advocated by some practitioners. 

Medical use of benzodiazepines has been declining. Prescribing trends show an overall decline in the number of all benzodiazepine prescriptions written, with a market shift to increased prescribing of short elimination half-life agents (lorazepam, alprazolam), compared with long-elimination half-life agents (diazepam, chlordiazepoxide) (Ciraulo et al. 2004). In 2001, alprazolam was the most widely prescribed benzodiazepine (Ciraulo et al. 2004), and it also was the most widely prescribed psychiatric medication in that year for mood and anxiety disorders (Stahl 2002). 

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