Tapas Banerjee

Introduction
Anxiety is an unpleasant emotional experience characterized by apprehension disproportionate to the severity of stressful factors in the environment or without any cause in reality. This is usually accompanied by distressing somatic symptoms caused by hyperactivity of the autonomic nervous system (ANS). Anxiety is thought to be a part of the evolutionary fight-flight response to stress. An optimum level of anxiety is helpful for improving performance but anxiety of severe nature (pathological anxiety) is often detrimental. It takes the form of a disorder or disease when it persist for a prolonged period of time, outlasting the stressor, and begins to affect the well-being of the individual in every respect.

Classification
Anxiety should be differentiated from fear, which presents with symptoms proportionate to the cause in reality. Previously, anxiety was referred to as generalized anxiety disorder and encompassed different varieties which were not clearly defined. Present classification systems (see Table 1) categorize anxiety into different subtypes, preserving a residual category of generalized anxiety disorders. Distinction between the subtypes is important as management differs.

Table 1. Classification of anxiety

DSM-IV = American Psychiatry Association's Diagnostic and Statistical Manual for Mental Disorders, 4th Edition; ICD-10 = World Health Organization’s International Classification of Diseases 10th edition (ICD - 10).

There are minor differences in the two classification systems. For instance, in ICD-10, panic disorder is classified into two different systems whereas in DSM IV, OCD has been classified as a type of anxiety disorder. Mixed anxiety and depressive disorder has been included in ICD-10 but is absent in DSM-IV.

Clinical Features
Epidemiology: The lifetime prevalence for panic disorders is 1.5 to 4% of the population whereas it is 3 to 5% for phobias. About 2 to 3% of the general population can suffer from GAD or OCD in their lifetime, whereas the lifetime prevalence of PTSD is 1 to 3%. Epidemiological studies have revealed certain interesting facts regarding the gender distribution of anxiety disorders in the general population. An equal number of males as females seem to suffer from panic disorders without agoraphobia while nearly twice as many women suffer in their lifetime from panic disorders with agoraphobia, other phobias or PTSD, as compared to men. GAD may have a slight female predominance.
Anxiety disorders can occur at different ages. Panic disorders generally develops in late 20s and seldom after mid-40s whereas phobic disorders mostly start in late childhood with a second peak of onset in people in the mid-20s. OCD usually develops in the adolescence or early adulthood. PTSD can occur following severe stress at any age including childhood. GAD develops usually in adulthood. A familial association may be noted in GAD and specific phobias.

Clinical Manifestations: Anxiety manifests through psychological as well as physical signs and symptoms. The former include apprehension, worries, dreadful feelings, decrease in concentration, getting up from bed in the middle of the night (middle insomnia), a sense of a lump in the throat, fluttering (butterfly) sensations in the stomach and thirst. Phobias are distinguished by irrational fear of some object or situation with a tendency on the part of the subject to avoid it. Various physical signs-symptoms noted include tremors, increased muscle tension, muscle twitching, generalized bodyache, short rapid breathing, flushing, palpitations, dryness of the mouth, pupillary dilatation and other features of autonomic overactivity. The cardinal diagnostic clues to various types of anxiety disorders is presented in Tables 2 and 3.

Table 2. Cardinal features of various phobic disorders

Table 3. Cardinal features of some other common anxiety disorders

The differential diagnosis has to be borne in mind and purely anxiety disorder must be distinguished from other conditions (see Table 4) that may present with anxiety-like signs and symptoms. It is particularly important to exclude illicit drug use.

Table 4. Differential diagnosis of anxiety

Treatment
Once the diagnosis of an anxiety disorder has been established, treatment can be instituted by pharmacological means or psychotherapy. In community general practice drugs remain the mainstay of treatment. However, better results may be obtained by combining the two modalities, for which experienced psychiatric advice is essential.

Pharmacological Treatment
A brief account of individual drug groups presently used in the management of anxiety disorders, to minimize symptoms and to keep the disorder under control, is presented below. It should be noted that some of the older drugs, like meprobamate and barbiturates, are no longer recommended. They produce more side-effects than the commonly used benzodiazepines and are much more dangerous in overdose.

Benzodiazepines (BZDs): This class of drugs has been in wide use for a long time. They show a rapid onset of effect, but tolerance tends to develop on continued use, leading to dose escalation and the chance of acute withdrawal reactions on interruption of dosing. The lowest effective dose should be used. Caution needs to be exercised while driving or working near moving machinery. There is also the potential for misuse and interaction with alcohol.
The commonly used agent is diazepam, which is given as 2 - 15 mg by mouth daily in divided doses. For controlling acute attacks, 10 mg of diazepam can be used intravenously (IV) very slowly, preferably in a well equipped center to avoid disastrous side effects. Intramuscular (IM) diazepam is not recommended because of its erratic absorption. GAD and PTSD respond well to diazepam, especially if they are of recent onset. Several side-effects of this agent have been reported and caution should be exercised against dependance liability and the potential for misuse.
Alprazolam is a short-acting BZD which, in addition to anxiolytic effect, shows an antidepressant property. This drug is particularly useful in panic disorders and also in short-term treatment of agoraphobia. The dose is 0.25 - 0.50 mg two to three times daily increased where necessary up to a total dose of 3 - 4 mg per day. If interdose symptoms are anticipated, dosing of this drug should be done frequently or sustained release formulations are used. Common side-effects produced by alprazolam include drowsiness, hypotension and cognitive impairment. It is important to know that sudden withdrawal can produce intense anxiety (rebound anxiety). When used along with other antidepressive agents, it can precipitate manic episode in patients suffering from bipolar disorders.
Clonazepam is a BZD with marked antiepileptic properties. It has been used in GAD, panic disorders and PTSD, starting usually at the lower dose of 0.5 mg daily and increased upto 2 - 10 mg per day depending upon the severity of illness. The principle adverse reaction is drowsiness. Concomitant administration of phenobarbital or phenytoin, may enhance the metabolism of clonazepam.
Other anxiolytic BZDs that have been used in the short-term management of anxiety include chlordiazepoxide, clorazepate, lorazepam and oxazepam. Lorazepam and oxazepam are short-acting and for this reason may be preferred in the presence of impaired liver function.

Buspirone: This is a non-BZD anxiolytic believed to act on the serotonergic system. It is generally used in the treatment of GAD, as an alternative to BZDs. Initially dose is 5 mg two to three times daily, increased every 2 - 3 days, to the usual total daily dose of 15 - 30 mg. The maximum is 45 mg daily in divided doses. Common reactions include nausea, dizziness, nervousness, lightheadedness, and occasionally palpitations and chest pain. Buspirone probably carries little dependence potential and does not show cross-tolerance with BZDs. For this reason it is used as a BZD substitute; but it also implies that it cannot be used to alleviate symptoms in a subject experiencing BZD withdrawal. If a patient receiving BZD is to be started on buspirone, the former still needs gradual withdrawal. Another problem is the long time to onset of effect, 2 weeks or longer, which creates difficulty in patient compliance in the initial stages.

Tricyclic Antidepressants (TCADs): Imipramine, the prototype TCAD, has been used to treat panic and social phobic disorders. Usually this drug is started at the dose of 75 mg daily on a divided schedule and then gradually increased to 150 - 300 mg per day over a period of 6 - 8 months. Side-effects include dry mouth, blurring of vision, constipation, sweating, etc. In elderly patients it is started at a lower dose of 10 mg daily, gradually increased to 30 - 50 mg per day. Clomipramine, another TCAD drug, is particularly useful in the treatment of OCD. Its use in phobic disorders has also been documented. The dose is 25 mg daily at bedtime (elderly 10 mg) initially, increased over 2 weeks to 100 - 150 mg daily in divided doses. Sedative and anticholinergic side-effects may be considerable at effective doses.

Other Antidepressants: The selective serotonin reuptake inhibitor (SSRI) antidepressant, fluoxetine has been found to be as effective as clomipramine in managing OCD. It has also been tried in the treatment of panic disorders, phobias and PTSD. The dose is 20 mg once daily. A dose escalation may be considered if response is unsatisfactory after several weeks to a maximum of 60 mg daily. Although a number of side-effects have been reported, most are uncommon. Higher doses carry greater risk.

Beta-Blockers: These drugs do not improve the psychological manifestations of anxiety but they can produce subjective inprovement by controlling the physical symptoms of autonomic origin such as palpitations and tremor. Non-autonomic symptoms, such as muscle tension, are not affected. The non-selective b -antagonist, propranolol, is generally preferred in social phobias. In this condition the drug is started at a low dose of 10 mg twice a day and increased slowly, as necessary, up to 80 - 160 mg per day. Chronic obstructive pulmonary disease, diabetes mellitus, heart block and other relative contraindications for the use of this drug must be borne in mind.

Psychological Treatment
Ideally psychological intervention should be an integral part of the management of anxiety disorders. Various modalities are available. employed. The more frequently used ones are:

Insight-Oriented Psychotherapy: This aims at giving the patients an insight into the origins of their anxiety symptoms from intrapsychic conflict. It is undertaken, for instance in GAD, when anxiety has persisted despite adequate trial of drug treatment and behavioral therapy has been given. It is sometimes observed that new anxiety symptom have appeared during the course of treatment inspite of resolution of the original symptoms.

Behavioral Therapy: This aims at modifying maladaptive behavior by encouraging and establishing the acceptable behavior without going to in-depth understanding of intrapsychic conflict. This therapy is mostly used were specific maladaptive behavior is seen as in phobias. In OCD, behavior therapy is effective in correcting the compulsive thought without modifying the obsessive component. There are various techniques of behavior therapy such as exposure (in imagination or actual), flooding (extreme form of exposure), desensitization and modeling of appropriate behavior by the therapist.

Cognitive Therapy: The generation of anxiety is related to the perception of the individuals regarding themselves and also the perception of what others are feeling about them. Cognitive therapy usually modifies the defects in these perceptions, thereby making the individual's expectations more realistic. Cognitive therapy has been used in various types of anxiety disorders including GAD, panic disorders, social phobias and PTSD.

Group Psychotherapy: This can provide much-needed support to the anxious individual in developing social interaction. Groups may be heterogeneous or homogenous. This type of therapy is particularly helpful in the treatment of PTSD.

Conclusion
Anxiety imposes a considerable burden on society but often goes unrecognized and untreated. Advances in pharmacotherapy and better understanding of the origin of psychological symptoms implies that today's clinician is in a better position to successfully manage various forms of anxiety disorders than his earlier-day counterparts. These benefits should be extended to all patients regardless of whether they deliberately seek help for psychological symptoms or come with physical complaints which, unknown to them, actually stem from their anxiety.

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