The term ‘anxiety disorder’ encompasses a variety of complaints which can either exist on their own or in conjunction with another psychiatric or physical illness. Symptoms of anxiety vary but generally present with a combination of psychological, physical and behavioural symptoms (Fig. 28.2). Some of these symptoms are common to many anxiety disorders while others are distinctive to a particular disorder. Anxiety disorders are broadly divided into generalised anxiety disorder (GAD), panic disorder, social phobia, specific phobias, post-traumatic stress disorder (PTSD) and obsessive-compulsive disorder (OCD), see Table 28.1. Patient testimonials are presented in Box 28.1. Approximately two-thirds of sufferers of an anxiety disorder will have another psychiatric illness. This is most commonly depression and often successful treatment of an underlying depression will significantly improve the symptoms of anxiety. Many patients will also present with more than one anxiety disorder at the same time which can further complicate treatment. Anxiety disorders are the most commonly reported mental illness and as a whole have a lifetime prevalence of 21% (Baldwin et al., 2005) with specific phobias the most commonly reported.

Fig. 28.2 The symptoms of anxiety.

Table 28.1 A brief description of the common anxiety disorders

Symptoms common to all anxiety disorders	Fear or worry, sleep disturbances, concentration problems, dry mouth, sweating, palpitations, GI discomfort, restlessness, shortness of breath, avoidance behaviour
Generalised anxiety disorder (GAD)	Persistent (free floating), excessive and inappropriate anxiety on most days for at least 6 months. The anxiety is not restricted to a specific situation
Panic disorder (with or without agoraphobia)	Recurrent, unexplained surges of severe anxiety (panic attack). Most patients develop a fear of repeat attacks or the implications of an attack. Often seen in agoraphobia (fear in places or situations from which escape might be difficult)
Social phobia (or social anxiety disorder)	A marked, persistent and unreasonable fear of being observed, embarrassed or humiliated in a social or performance situation (e.g. public speaking or eating in front of others)
Specific phobia	Marked and persistent fear that is excessive or unrealistic, precipitated by the presence (or anticipation) of a specific object or situation (e.g. flying, spiders). Sufferers avoid the feared object/subject or endure it with intense anxiety
Post-traumatic stress disorder (PTSD)	Can occur after an exposure to a traumatic event which involved actual or threatened death, or serious injury or threats to the physical integrity of self or others. The person responds with intense fear, helplessness or horror. Sufferers can re-experience symptoms (flashbacks) and avoid situations associated with the trauma. Usually occurs within 6 months of the traumatic event
Obsessive-compulsive disorder (OCD)	Persistent thoughts, impulses or images (obsessions) that are intrusive and cause distress. The person attempts to get rid of these obsessions by completing repetitive time-consuming purposeful behaviours or actions (compulsions). Common obsessions include contamination while the compulsion may be repetitive washing or cleaning

Box 28.1 Patient testimonies (NICE, 2005a,b)

Symptoms described by a sufferer of post-traumatic stress disorder:

I would feel angry at the way the crash happened and that there was nothing I could do to stop it or help. I was physically exhausted, but was finding it hard to sleep. As soon as the bedroom light went out at night a light would come on in my head and all I could do was lie there and think. When I would eventually fall asleep, I would wake up with nightmares of the crash. I could not get away from it. It was all I could think about in the day and all I would dream about at night.

Thoughts from a sufferer of obsessive-compulsive disorder:

I’ve just arrived home from work. Tired and tense, I’m convinced my hands are contaminated with some hazardous substance and my primary concern now is to ensure that I don’t spread that contamination to anything that I, or others, may subsequently touch. I will wash my hands, but first I will need to put a hand in my pocket to get my door keys, contaminating these, the pocket’s other contents, and everything else I touch on my way to the sink. It will be late evening before I will have completed the whole decontamination ritual.

A slow recovery described by a post-traumatic stress disorder and panic attack sufferer:

Slowly I gained ground and as each new insight came I was able to see my symptoms diminish. The panic attacks tapered off, the intensity of the flashbacks dwindled, and my irritable bowel began to loosen some of its hold on me. I was able to breathe again.

For all anxiety disorders together the overall female to male ratio is 2:1. The age of onset of most anxiety disorders is in young adulthood (20s and 30s), although the maximum prevalence of generalised anxiety and agoraphobia in the general population is in the 50–64 year age group.

Pathophysiology

Anxiety occurs when there is a disturbance of the arousal systems in the brain. Arousal is maintained by at least three interconnected systems: a general arousal system, an ‘emotional’ arousal system and an endocrine/autonomic arousal system (Fig. 28.3). The general arousal system, mediated by the brainstem reticular formation, thalamic nuclei and basal forebrain bundle, serves to link the cerebral cortex with incoming sensory stimuli and provides a tonic influence on cortical reactivity or alertness. Excessive activity in this system, due to internal or external stresses, can lead to a state of hyperarousal as seen in anxiety. Emotional aspects of arousal, such as fear and anxiety, are contributed by the limbic system which also serves to focus attention on selected aspects of the environment. There is evidence that increased activity in certain limbic pathways is associated with anxiety and panic attacks.

Fig. 28.3 Diagram of arousal and sleep systems. Arousal systems receive environmental and internal stimuli, cause cortical activation and mediate motor, autonomic and endocrine responses to arousal. Reciprocally connected sleep systems generate slow-wave sleep (SWS) and rapid eye movement sleep (REMS). Either system can be excited or inhibited by cognitive activity generated in the cortex.

These arousal systems activate somatic responses to arousal, such as increased muscle tone, increased sympathetic activity and increased output of anterior and posterior pituitary hormones. Inappropriate increases in autonomic activity are often associated with anxiety states; the resulting symptoms (palpitations, sweating, tremor, etc.) may initiate a vicious circle that increases the anxiety.

Several neurotransmitters have been implicated in the arousal systems. Acetylcholine is the main transmitter maintaining general arousal but there is evidence that heightened emotional arousal is particularly associated with noradrenergic and serotonergic activity. Drugs which antagonise such activity have anxiolytic effects. In addition, the inhibitory neurotransmitter γ-aminobutyric acid (GABA) exerts an inhibitory control on other transmitter pathways and increased GABA activity may have a protective effect against excessive stress reactions. Many drugs which increase GABA activity, such as the benzodiazepines, are potent anxiolytics.

Aetiology and clinical manifestations

Anxiety is commonly precipitated by stress but vulnerability to stress appears to be linked to genetic factors such as trait anxiety. Many patients presenting for the first time with anxiety symptoms have a long history of high anxiety levels going back to childhood. Anxiety may also be induced by central stimulant drugs (caffeine, amphetamines), withdrawal from chronic use of central nervous system depressant drugs (alcohol, hypnotics, anxiolytics) and metabolic disturbances (hyperventilation, hypoglycaemia, thyrotoxicosis). It may form part of a depressive disorder and may occur in temporal lobe lesions and in rare hormone-secreting tumours such as phaeochromocytoma or carcinoid syndrome.

Apart from the psychological symptoms of apprehension and fear, somatic symptoms may be prominent in anxiety and include palpitations, chest pain, shortness of breath, dizziness, dysphagia, gastro-intestinal disturbances, loss of libido, headaches and tremor. Panic attacks are experienced as storms of increased autonomic activity combined with a fear of imminent death or loss of control. If panic becomes associated with a particular environment, commonly a crowded place with no easy escape route, the patient may actively avoid similar situations and eventually become agoraphobic. When anxiety is precipitated by a specific cause then behaviour can become altered to ensure the sufferer avoids the cause. This avoidance behaviour can maintain the often irrational fear and strengthen the desire to avoid the threat.

Investigations and differential diagnosis

In patients presenting with symptoms and clinical signs of anxiety, it is important to exclude organic causes such as thyrotoxicosis, excessive use of stimulant drugs such as caffeine and the possibility of alcoholism or withdrawal effects from benzodiazepines. However, unnecessary investigations should generally be avoided if possible. Extensive gastroenterological, cardiological and neurological tests may increase anxiety by reinforcing the patient’s fear of a serious underlying physical disease.

Treatment

Treatment for anxiety disorders often requires multiple approaches. The patient may need short-term treatment with an anxiolytic, such as a benzodiazepine, to help reduce the immediate symptoms combined with psychological therapies and an antidepressant for longer term treatment and prevention of symptoms returning.

Psychotherapy

Psychological therapies (talking therapies) are generally considered first-line treatments in all anxiety disorders because they may provide a longer lasting response and lower relapse rates than pharmacotherapy. Psychotherapy, however, is less available, more demanding and takes longer time to work than pharmacotherapy. If the patient is unable to tolerate the anxiety or associated distress, then medicines are often used before psychotherapy or while awaiting psychotherapy. The ideal treatment should be tailored to the individual and may involve a combination of both psychotherapy and pharmacotherapy. The type of treatment should depend on symptoms, type of anxiety disorder, speed of response required, long-term goals and patient preference.

The specific psychotherapy with the most supporting evidence in anxiety disorders is cognitive behavioural therapy (CBT). Cognitive behaviour therapy focuses on the ‘here and now’ and explores how the individual feels about themselves and others and how behaviour is related to these thoughts. Through individual therapy or group work the patient and therapist identify and question maladaptive thoughts and help develop an alternative perspective. Individual goals and strategies are developed and evaluated with patients encouraged to practise what they have learned between sessions. Therapy usually lasts for around 60–90 minutes every week for 8–16 weeks, or longer in more resistant cases. Cognitive behavioural therapists are usually health professionals such as mental health nurses, psychologists, general practitioners, social workers, counsellors or occupational therapists who have undertaken specific training and supervision.

In PTSD, CBT is trauma focused, with the therapist helping the patient confront their traumatic memory and people or objects associated with this trauma. At the same time, patients are taught skills to help them cope with the emotional or physical response of this trauma. One such skill includes relaxation training which may involve systematically relaxing major muscle groups in a way that decreases anxiety. Another psychotherapy sometimes recommended in PTSD is eye movement desensitisation and reprocessing (EMDR). This involves briefly recounting the trauma or objects associated with the trauma to the therapist who will then simultaneously initiate another stimulus, for example, moving a finger continuously in front of the patient’s eyes or hand tapping. Over time it enables the patient to focus on alternative thoughts when associations with the trauma occur. A single session of debriefing following a traumatic event is not thought effective to prevent PTSD and, therefore, not recommended.

In OCD, CBT includes exposure and response prevention (ERP). This involves the therapist and the patient repeatedly facing the fears, beginning with the easiest situations and progressing until all the fears have been faced. At the same time the person must not perform any rituals or checks.

Specific phobias are also almost exclusively treated using exposure techniques and most patients will respond to this treatment. Only a very few will require additional drug therapy.

Other psychotherapies, although occasionally tried, have a poorer evidence base than CBT and are, therefore, not usually recommended. Self-help is one alternative technique which is recommended (NICE, 2007) for GAD and panic disorder. It involves using materials either alone or in part under professional guidance to learn skills to help cope with the anxiety. The materials such as books, tapes or computer packages can be accessed at home and in the patients’ own time. Some self-help material, however, is of poor quality, so it is probably best used in those who have mild symptoms and who do not need more intensive treatments.

Pharmacotherapy

Benzodiazepines

Benzodiazepines are commonly prescribed to provide immediate relief of the symptoms of severe anxiety. A number of different benzodiazepines are available (Table 28.2). These drugs differ considerably in potency (equivalent dosage) and in rate of elimination but only slightly in clinical effects. All benzodiazepines have sedative/hypnotic, anxiolytic, amnesic, muscular relaxant and anticonvulsant actions with minor differences in the relative potency of these effects.

Table 28.2 Profile of selected benzodiazepines (Bazire, 2009; Taylor et al., 2009)