# 11 - 8 Anxiety and stress related disorders

# 01 - 8 Anxiety and stress related disorders

# 8 Anxiety and stress-​related disorders

361
Anxiety and stress-​related 
disorders
Introduction  362
Historical perspective  364
Hyperventilation syndrome  366
Panic disorder 1: clinical features  368
Panic disorder 2: aetiological models  370
Panic disorder 3: management guidelines  372
Agoraphobia  374
Simple or specific phobias  376
Social phobia (ICD-​10)/​social anxiety disorder (DSM-​5)  378
Generalized anxiety disorder 1—​clinical features and 
aetiology  380
Generalized anxiety disorder 2—​differential diagnosis and 
management  382
Obsessive–​compulsive disorder 1—​clinical features  384
Obsessive–​compulsive disorder 2—​management  386
Olfactory reference disorder (ORD)  388
Hoarding disorder (DSM-​5)  389
Exceptional stressors and traumatic events  390
Acute stress reaction (ICD-​10)  392
Acute stress disorder (DSM-​5)  394
Adjustment disorders  398
Normal and abnormal grief  400
Post-​traumatic stress disorder 1: diagnosis  402
Post-​traumatic stress disorder 2: management  404
Depersonalization (derealization) syndrome  406
Chapter 8

362
Chapter 8  Anxiety and stress-related disorders
Introduction
If schizophrenia is ‘the heartland of psychiatry’, then the neurotic dis­
orders surely make up much of the rest of the continent, in view of their 
prevalence in the general population (see Table 8.1) and the morbidity 
they cause.
As unpopular as the term ‘neurosis’ has become (for a historical per­
spective, see E Historical perspective, p. 364), it is still retained in the 
ICD-​10 in the rubric ‘neurotic, stress-​related, and somatoform disorders’. 
DSM-​5 has effectively carved up the neuroses into ‘anxiety disorders’, 
‘obsessive–​compulsive and related disorders’ (OCRD), ‘trauma-​ and 
stressor-​related disorders’, ‘dissociative disorders’, and ‘somatic symptom 
and related disorders’. Here, we retain the use of ‘neuroses’ as shorthand 
for all these disorders but will use the subdivisions when talking about the 
particular disorders.
We have all experienced anxiety symptoms, perhaps suffer from a par­
ticular ‘phobia’, or are a little bit obsessive about certain things, but to 
be clinically significant, these problems must be severe enough to cause 
marked distress and/​or substantially interfere with our day-​to-​day lives. 
Because of the recognizable quality of some of the symptoms of neurotic 
disorders, it may be helpful to divide them into three categories.
Table 8.1  Estimated 12-​mth prevalence of psychiatric disorders in the 
general population of the European Union (2010)*
Diagnosis (DSM-​IV) 
Best estimate (%) 
Number of persons 
affected (in millions)
Alcohol dependence
3.4
14.6
Psychotic disorders
1.2
5.0
Major depression
6.9
30.3
Bipolar disorder
0.9
3.0
Anxiety disorders
14.0
61.5
 Panic disorder
1.8
7.9
 Agoraphobia
2.0
8.8
 Social anxiety disorder
2.3
10.1
 Specific phobias
6.4
22.7
 Generalized anxiety 
disorder
2.6
8.9
 Obsessive–​compulsive 
disorder
0.7
2.9
 Post-​traumatic stress 
disorder
2.0
7.7
* Data derived from Eurostat Directorate General of European Commission (Eurostat 2010) re­
ported by Wittchen, HU, et al. (2011) The size and burden of mental disorders and other 
disorders of the brain in Europe 2010. Eur Neuropsychopharmacol. 21:655–​679.

Introduction
The common neuroses
 • Anxiety/​phobic disorders: e.g. panic disorder, agoraphobia, GAD, 
specific (understandable) phobias (e.g. snakes, spiders), hypochondriasis, 
social phobia.
 • Stress-​related disorders: e.g. acute stress reactions, adjustment 
disorder, PTSD.
 • OCD.
The unusual neuroses (i.e. outwith ‘normal’ experience)
 • Anxiety/​phobic disorders: e.g. ‘non-​understandable’ phobias (e.g. dirt, 
feathers), dysmorphophobia.
 • ‘Hysterical’ conversion disorders.
 • Dissociative/​depersonalization–​derealization disorder.
 • Somatoform disorders.
‘Culture-​specific’ disorders
Seen only in certain populations:
 • Chronic fatigue syndrome (CFS)/​eating disorders (E Anorexia nervosa 
1: overview, p. 410).
 • Other ‘culture-​bound’ disorders/​cultural concepts of distress (CCDs).
This chapter deals with anxiety, phobic, and stress-​related disorders. Other 
disorders are covered in Chapter 18 (E pp. 864–​875 conversion, somatiza­
tion, CFS, hypochondriasis, and dysmorphophobia), Chapter 9 (E pp. 410–​
419: eating disorders), and Chapter 21 (E pp. 984-​–​991: CCDs).
Points to note
 • Anxiety symptoms are common in the general population.
 • Comorbidity is frequent (other neuroses, depression, substance misuse, 
personality disorder).
 • Anxiety disorders may often present with physical symptoms.
 • Management will usually involve a combined approach (pharmacological 
and psychological).

364
Chapter 8  Anxiety and stress-related disorders
Historical perspective
The term ‘neurosis’ was coined by William Cullen in 1777, replacing ‘illness 
of the nerves’ (coined by Robert Whytt in 1764 to replace the old ‘va­
pours’) and meaning any disease of the nervous system without a known 
organic basis (which, at the time, also included epilepsy). Clinical descrip­
tions of neurotic symptoms can be found in the works of Hippocrates. 
However, the ‘illness’ later vanished under the cloak of both pagan and 
Christian beliefs, with typical symptoms attributed to the work of spirits, 
possession, or divine punishment. It did not resurface properly until the 
Renaissance (the 1500s) thanks (in part) to the witchcraft trials, when doc­
tors were called in to present diagnoses of known illnesses that could be 
mistaken for demonic possession (the first recorded ‘medical defence’!). 
Although there was much debate, the brain became the final resting place 
as the organ most likely to be involved in the aetiology of the condition.
The history of the neuroses is tightly bound to the (re)discovery of 
hypnosis (formerly the remit of faith healing). The work of Franz-​Anton 
Mesmer (1734–​1815)—​mesmerism—​and James Braid (1795–​1860)—​
braidism—​was brought to France by Azam in 1859, coming to the atten­
tion of Charcot, whose experiments with hysterics would have a profound 
influence on one particular assistant—​Sigmund Freud. Freud’s first paper, 
published in 1886, shortly after his return to Vienna, was of a case of ‘trau­
matic hysteria’ in a ♂ patient. It was his Studies on Hysteria, written with 
Josef Breuer and published in 1895, that provided the starting point of his 
subsequent major concepts of psychoanalytical theory—​including repres­
sion, psychic reality, and the subconscious.
The idea of repression of trauma (out of consciousness) and the ap­
pearance of ‘defences’ was highly influential, with the neuroses regarded as 
illnesses of the mind, needing psychotherapeutic treatment. Old arguments 
of emotional vs physical factors resurfaced in the aftermath of the World 
War I, as some authorities found it difficult to attribute the illnesses seen in 
fit, healthy young men (who had indisputably experienced traumatic events) 
to conversion hysteria or phobic neurosis. The encephalitis lethargicans epi­
demic in 1919, and the presence of numerous ‘hysterical’ symptoms (e.g. 
convulsions, mutism, feelings of passion, obsessions/​compulsions, spasms), 
argued in favour of at least some of the neuroses having an organic basis.
In the 1920s, Walter Cannon proposed the concept of the ‘emergency 
reaction’, believing this ‘fight-​or-​flight’ response was mediated by the auto­
nomic nervous system. He also noted that the physiological responses were 
too slow to account for feelings and that some other ‘neural mechanism’ 
must be at work.
The dominance of the behaviourists in psychology relegated emotion to 
just another ‘way of acting’ in a particular situation (albeit internally per­
ceived). Although an over-​simplification, this led to the development of 
the ‘conditioning theory’ of anxiety. John Watson, the father of behav­
iourism, claimed to have produced an animal phobia in an 11-​mth-​old boy 
‘little Albert’ by making a loud clanging noise whilst the boy was playing 
with a rat. Watson proposed that neuroses arose out of traumatic learning 
situations and then persist to influence behaviour throughout life. This was 
adapted by the 1930s to include the concept of ‘instrumental conditioning’

Historical perspective
(association of an emotionally arousing stimulus and a neutral response), 
and, in the 1940s, Mowrer attempted to translate Freud’s theory of anxiety 
neurosis into the language of learning theory—​responses that reduce anx­
iety are learnt—​sometimes these reinforced behaviours may be aberrant, 
unhelpful, or simply bizarre and present as neuroses. ‘Avoidance’ was pos­
tulated as the behaviour that was reinforced due to successfully removing a 
‘negative reinforcer’ (e.g. fear). These ideas led to the rational treatment of 
phobias with desensitization techniques.
In the search for Cannon’s neural mechanism, neurophysiologists used 
lesioning experiments to identify the thalamus as a critical gateway for 
stimuli, and the hypothalamus as mediating the physiological response [via 
the hypothalamic–​pituitary–​adrenal (HPA) axis]—​the Cannon–​Bard theory. 
Other theories emerged over the years (e.g. the Papez Circuit, 1937), and 
understanding the emotional life of the brain remains at the forefront of 
research (see The Emotional Brain by Joseph LeDoux, 1998).
Inviting as psychological explanations appeared, the late 1950s also her­
alded the arrival of the BDZs. ‘Tranquillizers’ (e.g. Miltown®, Librium®, 
Valium®) became the ‘housewives’ choice’, effectively treating a multitude 
of neurotic symptoms. Unfortunately, the indiscriminate use of these drugs 
led to them being demonized as causing dependence problems (despite 
evidence for their effectiveness when properly used). The advent of anti­
depressants artificially separated neurotic depression from the other neur­
oses, but nonetheless some utility was also seen in treating the anxiety 
disorders. A key study was the use of clomipramine in the treatment of 
OCD (see The Boy Who Couldn’t Stop Washing by Judith Rapoport, 1989). 
The fact that clomipramine was the most serotonergic of the TCAs paved 
the way for the second-​generation antidepressants (the SSRIs) used in neur­
oses (previously thought only to be amenable to psychological approaches).
Brain imaging demonstrated underlying functional changes in OCD pa­
tients [in the frontal cortex (left orbital gyrus) and bilateral caudate nuclei], 
which ‘normalized’ after successful treatment with medication (and inter­
estingly with CBT techniques, although this took longer). For many patients 
with panic attacks, structural and functional changes were found in the tem­
poral lobes. These findings resonated with the long-​held observation that 
neurotic symptoms (e.g. anxiety, panic, somatic symptoms, depersonaliza­
tion/​derealization) were often reported in other ‘organic’ conditions (e.g. 
temporal lobe epilepsy).
Modern views are eclectic in their approach, e.g. the biopsychosocial 
model (E Figure 6.1, p. 256). For the neuroses, early environmental influ­
ences (including social factors like maternal deprivation) can alter the sensi­
tivity of physiological stress responses in adulthood. Hence, the experience 
of stressors (psychological or physical) may lead (e.g. through the effects 
of stress hormones such as cortisol, and other neurophysiological mech­
anisms) to alterations in the structure and/​or function of the brain, which, 
in turn, manifest as clinical symptoms (i.e. behavioural and/​or emotional 
change).

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Chapter 8  Anxiety and stress-related disorders
Hyperventilation syndrome
Essence
Ventilation exceeds metabolic demands, leading to haemodynamic and 
chemical changes producing characteristic symptoms (dyspnoea, agita­
tion, dizziness, atypical chest pain, tachypnoea, hyperpnoea, paraesthe­
siae, and carpopedal spasm) usually in a young, otherwise healthy, patient.1 
Hyperventilation syndrome (HVS), a relatively common presentation; may 
be mistaken for panic disorder. Considerable overlap, hence inclusion here:
 • 50–​60% of patients with panic disorder or agoraphobia have symptoms 
of HVS.
 • 25–​35% of HVS patients have symptoms of panic disorder.
It may also be confused with other organic diseases, particularly of the car­
diorespiratory system, due to the physical symptoms manifest.
Aetiology
Unknown, but certain stressors provoke an exaggerated respiratory re­
sponse in some individuals [e.g. emotional distress, sodium lactate, caffeine, 
isoprenaline, cholecystokinin, and carbon dioxide (CO2)]. HVS patients tend 
to use accessory muscles to breathe, rather than the diaphragm, resulting in 
hyperinflated lungs and perceived effort or dyspnoea when stressors induce 
the need to take a deep breath. This leads to anxiety and triggers further 
deep breathing, setting up a vicious cycle.
Epidemiology ♂:♀ = 1:7, usually presents between 15 and 55yrs but can 
occur at any age (except infancy).
Symptoms and signs
 • Cardiac: chest pain/​angina [atypical of cardiac origin: may last hours, 
not minutes; often relieved by exercise; glyceryl trinitrate (GTN) 
ineffective], ECG changes (prolonged QT, ST depression or elevation, 
and T-​wave inversion).
 • Respiratory: hyperpnoea, tachypnoea, dyspnoea, wheeze 
[bronchospasm secondary to low partial pressure of carbon dioxide in 
arterial blood (PaCO2)]. Note: in chronic forms, hyperventilation may 
not be clinically apparent.
 • CNS [due to reduced cerebral blood flow (CBF) secondary 
to hypocapnia): dizziness, weakness, confusion, agitation, 
depersonalization, visual hallucinations, syncope or seizure (rare), 
paraesthesiae (usually upper limbs and bilateral), peri-​oral numbness.
 • GI: bloating, belching, flatus, epigastric pressure (due to aerophagia), dry 
mouth (due to mouth breathing and anxiety).
 • Metabolic (due to electrolyte disturbance secondary to respiratory 
alkalosis): acute hypocalcaemia (signs: carpopedal spasm, muscle 
twitching, +ve Chvostek and Trousseau signs, and prolonged QT interval), 
hypokalaemia (with generalized weakness), acute hypophosphataemia 
(may contribute to paraesthesiae and generalized weakness).
1  Formerly known as Da Costa syndrome. Other archaic terms include:  cardiac neurasthenia, 
cardiac neurosis, circulatory neurasthenia, disordered action of the heart (DAH), effort syn­
drome, hyperdynamic–​adrenergic circulatory state, hyperkinetic heart syndrome, irritable heart, 
neurocirculatory asthenia, soldier’s heart, and vasoregulatory asthenia.

Hyperventilation syndrome
Differential diagnosis
Extensive. Diagnosis of exclusion—​acute respiratory distress syndrome 
(ARDS), (venous) air embolism, asthma, atrial fibrillation (AF), atrial 
flutter, cardiomyopathy, chronic obstructive pulmonary disease (COPD), 
costochondritis, diabetic ketoacidosis (DKA), hyperthyroidism, meta­
bolic acidosis, methaemoglobinaemia, MI, nasopharyngeal stenosis, panic 
(and other anxiety) disorder, pleural effusion, pneumonia, pneumothorax, 
pulmonary embolism (PE), smoke inhalation, CO poisoning, withdrawal 
syndromes.
Investigations
 • Unless there is a clear history of HVS, any first presentations of 
hyperventilation should be referred for exclusion of serious underlying 
medical problems (E Differential diagnosis, see above).
 • These investigations may include full physical, FBC, U&Es, TFTs, 
glucose, Ca2+, phosphate (PO4), pulse oximetry, arterial blood gas 
(ABG) [in HVS: pH normal, PaCO2 and bicarbonate (HCO3) low], 
toxicology, ELISA, D-​dimer (PE), ECG, CXR, and possibly 
ventilation/​perfusion (V/​Q) scan.
 • Repeating these investigations at later presentations should only be 
done if there are new clinical findings.
Management
Acute management
If serious underlying pathology excluded, management includes:
 • Reassuring the patient.
 • Alleviating severe anxiety (e.g. use of BDZs).
 • Establishment of normal breathing pattern (instructing the patient to 
breathe more abdominally using the diaphragm; physically compressing 
the upper chest and instructing the patient to exhale maximally to 
reduce hyperinflation).
2 Note: use of rebreathing techniques (e.g. into a paper bag) is no longer 
recommended due to reports of significant hypoxia and death. This form 
of rebreathing may be unsuccessful anyway because very distressed patients 
have difficulty complying with the technique and because CO2 itself may be 
a chemical trigger for anxiety.
Further management
 • Education, e.g. hyperventilation, relaxation, and breathing techniques 
(‘provocation’ should only be performed in this setting).
 • Formal breathing retraining (usually provided by physiotherapists) is 
available in some centres.
 • β-​blockers and BDZs may be of some use. Some success reported for 
use of antidepressants in preventing further episodes.
 • If there is clear psychiatric morbidity (e.g. anxiety or depression), this 
should also be specifically addressed.

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Chapter 8  Anxiety and stress-related disorders
Panic disorder 1: clinical features
Essence
 • Panic attack: period of intense fear characterized by a constellation of 
symptoms (see Box 8.1) that develop rapidly, reach a peak intensity in 
about 10min, and generally do not last longer than 20–​30min (rarely 
over 1hr). Attacks may be either spontaneous (‘out of the blue’) or 
situational (usually where attacks have occurred previously). Sometimes 
attacks may occur during sleep (nocturnal panic attacks; E Nocturnal 
panic attacks, p. 470), and rarely physiological symptoms of anxiety 
may occur without the psychological component (non-​fearful panic 
attacks).2
 • Panic disorder:3 recurrent panic attacks, which are not secondary to 
substance misuse, medical conditions, or another psychiatric disorder. 
Frequency of occurrence may vary from many attacks a day to only a 
few a year. Usually a persistent worry about having another attack or 
consequences of the attack (which may lead to phobic avoidance of 
places or situations; E Agoraphobia, p. 374) and significant behavioural 
changes related to the attack.
Symptoms/​signs
(See Box 8.1.)
 • Physical symptoms/​signs related to autonomic arousal (e.g. tremor, 
tachycardia, tachypnoea, hypertension, sweating, GI upset), often 
compounded by HVS (in 50–​60% of cases; E Hyperventilation 
syndrome (HVS), p. 366).
Box 8.1  Symptoms associated with panic attacks
In order of frequency of occurrence:
 • Palpitations, pounding heart, or accelerated heart rate.
 • Sweating.
 • Trembling or shaking.
 • Sense of shortness of breath or smothering.
 • Feeling of choking or difficulties swallowing (globus hystericus).
 • Chest pain or discomfort.
 • Nausea or abdominal distress.
 • Feeling dizzy, unsteady, light-​headed, or faint.
 • Derealization or depersonalization (feeling detached from oneself or 
one’s surroundings).
 • Fear of losing control or going crazy.
 • Fear of dying (angor animus).
 • Numbness or tingling sensations (paraesthesiae).
 • Chills or hot flashes.
2  ‘Panic’ derives from the Greek god Pan, who was in the habit of frightening humans and animals 
‘out of the blue’.
3  ICD-​10 and DSM-​5 specify that panic attacks in panic disorder are unexpected, and not situational. 
DSM-​5 now includes ‘Panic attack specifier’ for the presence of panic symptoms associated with any 
other mental disorder (not just the anxiety disorders).

Panic disorder 1: clinical features
 • Concerns of death from cardiac or respiratory problems may be 
a major focus, leading to patients presenting (often repeatedly) to 
emergency medical services.
 • Panic disorder may be undiagnosed in patients with ‘unexplained’ 
medical symptoms (chest pain, back pain, GI symptoms including IBS, 
fatigue, headache, dizziness, or multiple symptoms).
 • Thoughts of suicide (or homicide) should be elicited; acute anxiety 
(particularly when recurrent) can lead to impulsive acts (usually directed 
towards self). Note: risk of attempted suicide substantially raised where 
comorbid depression or alcohol or substance misuse.
Epidemiology4
Lifetime prevalence [National Comorbidity Survey–​Replication 2001–​2002 
(NCS-​R)]: 1.5–​3.7% for panic disorder, 7–​9% for panic attacks. Rates much 
higher in medical clinic samples, e.g. dizziness clinics (15%), cardiac clinics 
(16–​65%), HVS clinics (25–​35%). Women are 2–​3 times more likely to be 
affected than men. Age of onset has a bimodal distribution, with highest 
peak incidence at 15–​24yrs and a second peak at 45–​54yrs. Rare after age 
65 (0.1%). Other risk factors include: being widowed, divorced, or separ­
ated; living in a city; limited education; early parental loss; and physical or 
sexual abuse.
Comorbidity
Agoraphobia (community surveys:  30–​50%; psychiatric clinics:  75%), de­
pressive disorder (up to 68%), other anxiety and related disorders (up to 
50%, e.g. social phobia, OCD), alcohol (up to 30%) and substance misuse, 
bipolar affective disorder (20%), medical conditions (e.g. mitral valve pro­
lapse, hypertension, cardiomyopathy, COPD, HVS, IBS, migraine).
Differential diagnosis
Other anxiety or related disorder (panic attacks may be part of the dis­
order), substance or alcohol misuse/​withdrawal (e.g. amphetamines, caf­
feine, cannabis, cocaine, theophylline, sedative hypnotics, steroids), mood 
disorders, psychiatric disorders secondary to medical conditions, medical 
conditions presenting with similar symptoms (e.g. endocrine: carcinoid syn­
drome, Cushing’s disease/​syndrome, hyperthyroidism, hypoglycaemia, 
hypoparathyroidism, phaeochromocytoma; haematological:  anaemia; 
cardiac:  arrhythmias (supraventricular), atypical chest pain, mitral valve 
prolapse, MI; respiratory:  COPD, asthma, HVS; neurological:  epilepsy—​
especially TLE, vestibular dysfunction).
Investigations
No specific tests for panic disorder; basic investigations should be per­
formed to exclude physical causes [e.g. FBC, U&Es, glucose, TFTs, ECG; if 
supported by history/​physical examination: toxicology, Ca2+, urinary vanillyl 
mandelic acid (VMA)/​plasma homovanillic acid (pHVA), echo, and EEG].
4  Kessler RC, Chiu WT, Jim R, et al. (2006) The epidemiology of panic attacks, panic disorder, and 
agoraphobia in the national comorbidity survey replication. Arch Gen Psychiatry 63:415–​24.

370
Chapter 8  Anxiety and stress-related disorders
Panic disorder 2: aetiological models
A number of theories, based primarily on successful pharmacological treat­
ment, explain the biological basis of panic disorder.
 • The serotonergic model: exaggerated post-​synaptic receptor response 
to synaptic serotonin, possibly secondary to subsensitivity (reduced 
binding) at 5-​HT1A receptors and 5-​HT transporters, perhaps secondary 
to disturbances in serotonin transporter (5-​HTTLPR) and promoter 
(SLC6A4) genes.
 • The noradrenergic model: i adrenergic activity, with hypersensitivity of 
presynaptic α2 receptors. (Locus caeruleus activity affects the HPA axis, 
and the firing rate is i in panic.)
 • The GABA model: d inhibitory receptor sensitivity (impaired GABA 
neuronal response to BDZs), with resultant excitatory effect.
 • The cholecystokinin–​pentagastrin model: pentagastrin induces panic 
in a dose-​dependent fashion in patients with panic disorder. Gene 
studies also implicate CCK gene polymorphisms in panic disorder (see 
Box 8.2).
 • The lactate model: postulated aberrant metabolic activity induced by 
lactate, from studies involving exercise-​induced panic attacks (replicated 
by IV lactate infusion).
 • The false suffocation CO2 hypothesis: explains panic phenomena 
by hypersensitive brainstem receptors. Panic disorder occurs more 
frequently in individuals with a raised pCO2, e.g. during sleep, during the 
premenstrual period, and due to respiratory disorders.
 • The cognitive theory postulates that panic disorder is due to a 
heightened sensitivity to internal autonomic cues such as tachycardia.
 • The neuroanatomical model: suggests that panic attacks are mediated 
by an overactive ‘fear network’ in the brain that involves the amygdala, 
hippocampus, periaqueductal grey, locus caeruleus, thalamus, 
cingulate, and orbitofrontal areas. ‘Fear’ is thought to occur through 
reciprocal activity that originates in the amygdala and is projected 
to the anterior cingulate cortex and/​or orbitofrontal cortex. Other 
projections from the amygdala to the hypothalamus mediate endocrine 
responses.

Panic disorder 2: aetiological models
Box 8.2  The genetic hypothesis
Panic disorder has moderate heritability of around 25–​50% (from 
family and twin studies). Most studies to date suggest that vulnerability 
is genetically determined and most likely multifactorial, but critical 
stressors are required to develop clinical symptoms (e.g. separation/​
loss event, adjusting to a new role, relationship problems, physiological 
stress—​childbirth, surgery, hyperthyroidism). Replicated linkages have 
been found with chromosomes 13q, 22q, 7p, and 9q31. Candidate 
genes include ADOR2A, 10832/​T, CCK, and those coding for 5-​HT1A, 
5-​HT2A, COMT, NPY1R, MAOA, HCRT (hypocretin), and linked to 
the CRH gene. Recent large GWAS have identified the neuropeptide 
S gene, the amiloride-​sensitive cation channel gene, and the adenosine 
A(2A) genes as candidate genes, with 4q21 and 7p being considered 
the strongest candidate regions for panic-​ and fear-​associated anxiety 
disorder loci.1
1 Logue MW, Bauver SR, Knowles JA, et al. (2012) Multivariate analysis of anxiety disorders 
yields further evidence of linkage to chromosomes 4q21 and 7p in panic disorder families. Am J 
Med Genet B Neuropsychiatr Genet 159B:274–​80.

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Chapter 8  Anxiety and stress-related disorders
Panic disorder 3: management guidelines
Combination of pharmacological and psychological treatments may be 
superior to single approach. Choice of initial approach will depend upon 
patient preference, past history of previous benefit, costs, availability, 
and local guidelines.5,6 For emergency treatment of a panic attack, see 
Box 8.3.
Pharmacological
Current evidence does not suggest any superior efficacy between SSRIs, 
SNRIs, BDZs, TCAs, and monoamine oxidase inhibitors (MAOIs). Other 
factors will determine the choice of medication (E Antidepressants, 
p. 276).
 • SSRIs: in the UK, citalopram (20–​30mg), escitalopram (5–​10mg), 
paroxetine (10–​40mg), and sertraline (50–​200mg) are all licensed 
for panic disorder (and recommended as first line by NICE). In view 
of possibly initially increasing panic symptoms, start with the lowest 
possible dose and gradually increase. Beneficial effect may take up to 
12wks and require high doses.
 • Alternative antidepressants (unlicensed in the UK): SNRIs (e.g. 
venlafaxine), TCAs (e.g. imipramine, clomipramine), MAOIs (e.g. 
phenelzine)—​thought by some clinicians to be superior to TCAs (for 
severe, chronic symptoms), RIMAs (e.g. moclobemide).
 • BDZs (e.g. alprazolam or clonazepam): not recommended by NICE. 
Should be used with caution (due to potential for abuse or dependence 
and cognitive impairment) but may be effective for severe, frequent, 
incapacitating symptoms. Use for 1–​2wks in combination with an 
antidepressant may ‘cover’ symptomatic relief until the antidepressant 
becomes effective. Note: ‘anti-​panic’ effects do not show tolerance, 
although sedative effects do.
 • Limited benefit: little evidence to support use of buspirone, bupropion, 
mirtazapine, inositol, reboxetine, antipsychotics, anticonvulsants, and, 
perhaps surprisingly, propranolol.
 • Second-​line treatment: consider changing to a different class agent (i.e. 
TCA, SNRI, SSRI, MAOI), addition of BDZ (or a different BDZ), trial of 
bupropion, or for severe symptoms, an SGA (e.g. olanzapine).
 • If successful: continue treatment for 12–​18mths before trial 
discontinuation (gradually tapering of dose over 2–​4mths). Do not 
confuse ‘withdrawal’ effects (10–​20% of patients) with re-​emergence of 
symptoms (50–​70% of patients). If symptoms recur, continue for 71yr 
before considering second trial discontinuation. (Note: patient may wish 
to continue treatment, rather than risk return of symptoms.)
5  National Institute for Health and Care Excellence (2011) Generalized anxiety disorder and panic dis­
order in adults: management. NICE guidance [CG113]. M https://​www.nice.org.uk/​guidance/​cg113 
[accessed 20 June 2018].
6  Baldwin DS, Anderson IM, Nutt DJ, et al. (2014) Evidence-​based pharmacological treatment of 
anxiety disorders, post-​traumatic stress disorder and obsessive-​compulsive disorder:  a revision 
of the 2005 guidelines from the British Association for Psychopharmacology. J Psychopharmacol 
28:403–​39.

Panic disorder 3: management guidelines
Box 8.3  Emergency treatment of an acute panic attack
 • Maintain a reassuring and calm attitude (most panic attacks resolve 
spontaneously within 30min).
 • If symptoms are severe and distressing, consider prompt use of 
BDZs (immediate relief of anxiety may help reassure the patient, 
provide confidence that treatment is possible, and reduce subsequent 
‘emergency’ presentations).
 • If first presentation, exclude medical causes (may require admission to 
hospital for specific tests).
 • If panic attacks are recurrent, consider differential diagnosis for panic 
disorder and address underlying disorder (may require psychiatric 
referral).
Psychological
 • CBT—​behavioural methods: to treat phobic avoidance by exposure, 
use of relaxation, and control of hyperventilation. Cognitive methods: 
teaching about bodily responses associated with anxiety/​education 
about panic attacks, modification of thinking errors.
 • Psychodynamic psychotherapy: there is some evidence for brief dynamic 
psychotherapy, particularly ‘emotion-​focused’ treatment (e.g. ‘panic-​
focused psychodynamic psychotherapy’) where typical fears of being 
abandoned or trapped are explored.
Issues of comorbidity
 • In view of high levels of comorbidity, treatment of these conditions 
should not be neglected.
 • For the other anxiety disorders and depression, this issue is somewhat 
simplified by the fact that SSRIs and other antidepressants have been 
shown to be effective for these conditions too. However, behavioural 
interventions (e.g. for OCD, social phobia) should also be considered.
 • Alcohol/​substance abuse may need to be addressed first, but 
specific treatment for persistent symptoms of panic ought not to be 
overlooked.
Course
 • Most patients seeking treatment have already experienced chronic 
symptoms for 10–​15yrs.
 • Untreated, the disorder runs a chronic course.
 • With treatment, functional recovery is seen in 25–​75% after the first 
1–​2yrs, falling to 10–​30% after 5yrs. Long-​term, around 50% will 
experience only mild symptoms.
 • Poor responses associated with: very severe initial symptoms, marked 
agoraphobia, low socio-​economic status, less education, long duration 
of untreated symptoms, restricted social networks (including loss of 
a parent, divorce, remaining unmarried), and presence of personality 
disorder.

374
Chapter 8  Anxiety and stress-related disorders
Agoraphobia
Essence
Anxiety and panic symptoms associated with places or situations where es­
cape may be difficult or embarrassing (e.g. crowds, public places, travelling 
alone or away from home), leading to avoidance.7
 • In DSM-​5, agoraphobia is diagnosed irrespective of panic disorder. If 
both criteria are met, then both diagnoses should be applied.
 • In ICD-​10, the presence or absence of panic disorder when in the 
agoraphobic situation may be specified, i.e. agoraphobia with(out) 
panic disorder. If panic disorder occurs in other situations, then both 
diagnoses should be applied. (Proposals for ICD-​11 are similar.)
Whether or not agoraphobia differs from panic disorder neurobiologically 
or simply represents a more severe form of panic disorder remains con­
troversial. The similarities of epidemiology, genetics, environmental pre­
cipitants, and effective treatments are hard to ignore. NCS-​R data (2006) 
suggest that pure agoraphobia does occur, but it is rarer than earlier epi­
demiological studies would suggest (e.g. the ECS), with a lifetime prevalence 
of 1.3% and ♂:♀ = 2:3.
Epidemiology
Prevalence (6mths) 2.8–​5.8% (ECA); ♂:♀ =1:3; as for panic disorder, 
there is a bimodal distribution, with the first being somewhat broader 
(15–​35yrs). In later life, agoraphobic symptoms may develop secondary to 
physical frailty, with an associated fear of exacerbating medical problems or 
having an accident.
Aetiology
 • Genetic: both genetic and environmental factors appear to play a role. 
The predisposition towards overly interpreting situations as dangerous 
may be genetic, and some commentators suggest an ethological factor 
involving an evolutionarily determined vulnerability to an unfamiliar 
territory. First-​degree relatives also have an i prevalence of other 
anxiety and related disorders (e.g. panic disorder, social phobia), alcohol 
misuse, and depressive disorders.
 • Psychoanalytical: unconscious conflicts are repressed and may be 
transformed by displacement into phobic symptoms.
 • Learning theory: conditioned fear responses lead to learned avoidance.
Comorbidity
Panic disorder, depressive disorder, other anxiety and related disorders 
(e.g. 55% also have social phobia), alcohol and substance misuse.
Differential diagnosis
Other anxiety and related disorders (especially GAD, social phobia, OCD), 
depressive disorders, secondary avoidance due to delusional ideas in psych­
otic disorders.
7  Literally ‘fear of the marketplace’ (Greek).

Agoraphobia
Management
 • Pharmacological Antidepressants: as for panic disorder. In the UK, 
citalopram, escitalopram, and paroxetine are licensed for the symptoms 
of panic disorder, with or without agoraphobia. Unlicensed: some 
evidence for clomipramine (high dose). BDZs: Short-​term use only (may 
reinforce avoidance)—​most evidence for alprazolam/​clonazepam/​
diazepam.
 • Psychological Behavioural methods: exposure techniques (focused 
on particular situations or places), relaxation training, and anxiety 
management. Cognitive methods: teaching about bodily responses 
associated with anxiety/​education about panic attacks, modification of 
thinking errors.

376
Chapter 8  Anxiety and stress-related disorders
Simple or specific phobias
Essence
Recurring, excessive, and unreasonable psychological or autonomic symp­
toms of anxiety, in the (anticipated) presence of a specific feared object or 
situation (see Box 8.4 for glossary) leading, whenever possible, to avoid­
ance. DSM-​5 distinguishes the subtypes:  animals, natural environment, 
blood, injection, injury, situational, and ‘other’.
Epidemiology
Prevalence: (NCS-​R) lifetime 12.5%, 12mths 8.7%, 6mths (ECA) 4.5–​11.9%; 
♂:♀ (all) = 1:3; animal/​situational phobias may be more common in ♀; 
mean age of occurrence is 15yrs: onset for animal phobias 77yrs, blood/​
injection/​injury 78yrs, situational phobias 720yrs.
Aetiology
 • Genetic: both genetic and environmental factors play a role. 
MZ:DZ = 25.9%:11.0%8 for animal phobia, situational phobia roughly 
equal suggesting a stronger role for the environment.
 • Psychoanalytical: manifest fear is the symbolic representation of an 
unconscious conflict, which has been repressed and displaced into 
phobic symptoms.
Box 8.4  Specific phobias—​the top 20
 1. Arachnophobia—​The fear of spiders
 2. Ophidiophobia—​The fear of snakes.
 3. Acrophobia—​The fear of heights.
 4. Agoraphobia—​The fear of open or crowded spaces.
 5. Cynophobia—​The fear of dogs.
 6. Astraphobia—​The fear of thunder/​lightning
 7. Claustrophobia—​The fear of enclosed spaces.
 8. Mysophobia—​The fear of germs.
 9. Aerophobia—​The fear of flying.
 10. Trypophobia—​The fear of holes.
 11. Carcinophobia—​The fear of cancer.
 12. Thanatophobia—​The fear of death.
 13. Glossophobia—​The fear of public speaking.
 14. Monophobia—​The fear of being alone.
 15. Atychiphobia—​The fear of failure.
 16. Ornithophobia—​The fear of birds.
 17. Alektorophobia—​The fear of chickens.
 18. Enochlophobia—​The fear of crowds.
 19. Aphenphosmphobia—​The fear of intimacy.
 20. Trypanophobia—​The fear of needles.
Source: data from M http://​www.fearof.net [accessed: 20 June 2018].
8  Kendler KS, Neale MC, Kessler RC, et al. (1992) The genetic epidemiology of phobias in women. 
The interrelationship of agoraphobia, social phobia, situational phobia, and simple phobia. Arch Gen 
Psychiatry 49:273–​81.

Simple or specific phobias
 • Learning theory: conditioned fear response related to a traumatic 
situation, with learned avoidance (trigger to the conditioned 
response may be a reminder of the original situation). Observational 
and informational learning also appear to be important, and the 
‘preparedness’ theory (Marks)9 suggests that fear of certain objects 
may be evolutionarily adaptive (related to survival of the individual or 
species), selectively acquired, and difficult to extinguish.
Comorbidity
The lifetime risk for patients with specific phobias experiencing at least one 
other lifetime psychiatric disorder is reportedly over 80% (NCS), particu­
larly other anxiety disorders (panic, social phobia) and mood disorders 
(mania, depression, dysthymia). However, rates of substance misuse are 
considerably less than in other anxiety disorders.
Differential diagnosis
Panic disorder (fear of having a further panic attack), agoraphobia, social 
phobia, hypochondriasis (fear of having a specific serious illness), OCD 
(avoidance/​fear of an object or situation due to obsessional thoughts, 
ideas, or ruminations), psychosis (avoidance due to a delusional idea of 
threat—​fears tend to be overly excessive).
Management
Psychological
 • Behavioural therapy: exposure is the treatment of choice—​methods aim 
to reduce the fear response, e.g. Wolpe’s systematic desensitization10 
with relaxation and graded exposure (either imaginary or in vivo—​best 
evidence for in vivo techniques). Recent studies have utilized virtual 
environments [virtual reality exposure (VRE)].
 • Other techniques: reciprocal inhibition, flooding (not better than graded 
exposure), and modelling.
 • Cognitive methods: education/​anxiety management, coping skills/​
strategies, and cognitive restructuring—​may enhance long-​term 
outcomes.
 • Pharmacological: generally not used, except in severe cases to reduce 
fear/​avoidance (with BDZs, e.g. diazepam) and allow the patient to 
engage in exposure. May reduce the efficacy of behaviour therapy by 
inhibiting anxiety during exposure. β-​blockers may be helpful but reduce 
sympathetic arousal, not subjective fear. There is limited evidence for 
SSRIs (e.g. escitalopram, paroxetine), but clear secondary depression 
may require antidepressant treatment.
Course
Without treatment, tends to run a chronic, recurrent course. However, 
individuals may not present unless life changes force them to confront the 
feared object or situation.
9  Marks IM (1969) Fears and Phobias. New York, NY: Academic Press.
10  Wolpe J (1973) The Practice of Behaviour Therapy, 2nd edn. New York, NY: Pergamon.

378
Chapter 8  Anxiety and stress-related disorders
Social phobia (ICD-​10)/​social anxiety 
disorder (DSM-​5)
Essence
Symptoms of incapacitating anxiety (psychological and/​or autonomic), not 
secondary to delusional or obsessive thoughts and restricted to particular 
social situations, e.g. having a conversation, meeting strangers, eating or 
drinking in public, or public speaking, leading to a desire for escape or avoid­
ance (which may reinforce the strongly held belief of social inadequacy).
Epidemiology
Lifetime rates vary: 2.4% (ECA), 12.1% (NCS-​R), 12-​mth prevalence 6.8% 
(NCS-​R); ♂:♀ for those seeking treatment (however, community surveys 
suggest ♂ > ♀ ); bimodal distribution with peaks at 5yrs and 11–​15yrs 
(ECA)—​often patients do not present until they are in their 30s.
Aetiology
Both genetic and environmental factors play a role. MZ:DZ = 24%:15%. 
The predisposition towards overly interpreting situations as dangerous 
may be genetic, whereas individual interpretations of social cues may be 
environmentally determined (i.e. the particular trigger for the conditioned 
fear response depends on the social situation in which the first episode 
of anxiety was experienced). Responses may be learnt from observing 
parents. Imaging studies show i activity in individuals with social anx­
iety in fear networks (prefrontal cortex, amygdala, hippocampus) during 
anxiety-​provoking tasks. Response to antidepressants suggests there may 
be dysregulation of 5-​HT, NA, or DA systems.
Symptoms/​signs
Somatic symptoms include blushing, trembling, dry mouth, and perspiration 
when exposed to the feared situation, with excessive fear (which is recognized 
as such by the patient) of humiliation, embarrassment, or others noticing how 
anxious they are. Individuals are often characteristically self-​critical and perfec­
tionistic. Avoidance of situations may lead to difficulty in maintaining social/​
sexual relationships, educational problems (difficulties in interactions with other 
students/​oral presentations), or vocational problems (work in less demanding 
jobs, well below their abilities). Thoughts of suicide are relatively common.
Comorbidity
There is a high level of psychiatric comorbidity with the most common dis­
orders, including simple phobia, agoraphobia, panic disorder, GAD, PTSD, 
depression/​dysthymia, and substance misuse.
Differential diagnosis
Other anxiety and related disorders (especially GAD, agoraphobia, OCD), 
poor social skills, anxious/​avoidant personality traits, depressive disorders, 
secondary avoidance due to delusional ideas in psychotic disorders, and 
substance misuse.
Management
 • Psychological: CBT, in either an individual or a group setting, should 
be considered as a first-​line therapy (with SSRIs/​MAOIs) and may be

Social phobia (ICD-10)/social anxiety disorder (DSM-5)
better at preventing relapse. Components of this approach include 
relaxation training/​anxiety management (for autonomic arousal), social 
skills training, integrated exposure methods (modelling and graded 
exposure), and cognitive restructuring. NICE guidelines recommend 
either the Clark and Wells model or the Heimberg model of individual 
CBT weekly over 4mths. Alternatively, supported use of a CBT-​based 
self-​help book either face-​to-​face or by telephone.
 • Pharmacological: β-​blockers (e.g. atenolol) may reduce autonomic 
arousal, particularly for ‘specific social phobia’ (e.g. performance 
anxiety). For more generalized social anxiety, SSRIs [e.g. escitalopram 
(licensed: 10mg/​day initially; range 5–​20mg/​day), fluoxetine 
(unlicensed), fluvoxamine (unlicensed), paroxetine (unlicensed), 
sertraline (licensed: 25mg/​day, i to 50mg/​day after 1wk; max 
200mg/​day)], SNRIs [e.g. venlafaxine (licensed: 75mg/​day)], and 
MAOIs [e.g. phenelzine (unlicensed)] are significantly more effective. 
Other treatment possibilities include RIMAs [e.g. moclobemide 
(licensed: 300mg/​day for 3 days, then 600mg/​day in two divided 
doses)] or the addition of a BDZ (e.g. clonazepam, alprazolam) 
or olanzapine. There is limited evidence for anticonvulsants [e.g. 
gabapentin, pregabalin, levetiracetam, valproate (all unlicensed)], and 
buspirone appears clinically ineffective for generalized social phobia. 
NICE recommends first line: trial of SSRI; second line: alternative SSRI 
or venlafaxine; third line: phenelzine or moclobemide.11,12
 • Psychotherapy: if the patient declines CBT and pharmacological 
interventions or they have proved ineffectual, short-​term 
psychodynamic psychotherapy may be offered over 6–​8mths, with 
a focus on education, establishing a secure positive therapeutic 
alliance to modify insecure attachments, core conflictual relationships, 
shame, exposure to feared social situations outside therapy sessions, 
establishing a self-​affirming inner dialogue, and improving social skills.
Course
 • Without treatment, social phobia may be a chronic, lifelong condition.
 • Course does not appear to be related to gender, age of onset, duration 
of illness, level of premorbid functioning, lifetime history of anxiety, or 
depressive disorders.
 • Extreme childhood shyness and behavioural inhibition may be early 
manifestations of social phobia.
 • With treatment, response rates may be up to 90%, especially with 
combined approaches.
 • Medication best regarded as long-​term, as relapse rates are high on 
discontinuation.
11  National Institute for Health and Care Excellence (2013) Social anxiety disorder: recognition, as­
sessment and treatment. Clinical guideline [CG159]. M https://​www.nice.org.uk/​guidance/​cg159 
[accessed 20 June 2018].
12  British Association for Psychopharmacology Guidelines (2014) Evidence-​based pharmacological 
treatment of anxiety disorders, post-​traumatic stress disorder and obsessive-​compulsive disorder: A revision 
of the 2005 guidelines from the British Association for Psychopharmacology. M https://​www.bap.org.
uk/​pdfs/​BAP_​Guidelines-​Anxiety.pdf [accessed 20 June 2018].

380
Chapter 8  Anxiety and stress-related disorders
Generalized anxiety disorder 1—​clinical 
features and aetiology
Essence
‘Excessive worry’ (generalized, free-​floating, persistent anxiety) and feel­
ings of apprehension about everyday events/​problems, with symptoms 
of muscle and psychic tension, causing significant distress/​functional 
impairment.
Symptoms/​signs
(See Box 8.5.)
Epidemiology
Prevalence: 6mths (ECA) 2.5–​6.4%, 12mths (NCS-​R) 3.1%, lifetime (NCS-​
R) 5.7%; lowest in 18–​29yrs (4.1%) and 60+ yrs (3.7%); highest 45–​59yrs 
(7.7%); ♀ > ♂, especially early onset (associated with childhood fears and 
marital/​sexual disturbance); later onset often after a stressful event; single 
(730% never marry); unemployed.
Aetiology (triple vulnerability model)13
 • Generalized biological vulnerability:
 •
​ Genetic—​modest role, shared heritability with depression.
 •
​ Neurobiological—​human studies limited. Animal work implicates the 
NA system: diminished autonomic nervous system responsiveness (? 
down-​regulation of α2 receptors); HPA axis: loss of regulatory control 
of cortisol [71/​3 of GAD patients show reduced cortisol suppression 
using the dexamethasone suppression test (DMST)]; amygdala 
and stria terminalis—​possible sustained or repeated activation by 
corticotropin-​releasing factor (CRF) due to stress; septohippocampal 
(‘behavioural inhibition’) system: sustained activation moderated 
by ascending 5-​HT and NA systems; BDZ-​GABA system: reduced 
expression of peripheral BDZ receptors due to high cortisol levels; 
other neurotransmitter systems: dysregulation of 5-​HT systems, 
cholecystokinin (CCK-​4 and CCK-​8S).
 • Generalized psychological vulnerability:
 •
​ Diminished sense of control—​trauma or insecure attachment to 
primary caregivers, leading to intolerance of uncertainty.
 •
​ Parenting—​overprotective or lacking warmth, leading to low 
perceived control over events.
 • Specific psychological vulnerability: stressful life events—​trauma (e.g. early 
parental death, rape, war) and dysfunctional marital/​family relationships.
Comorbidity
Other anxiety disorders (simple phobias, social phobia, panic disorder), de­
pression/​dysthymia, alcohol and drug problems, other ‘physical’ conditions 
(e.g. IBS, HVS, atypical chest pain).
13  Suarez L, Bennett SM, Goldstein CM, et al. (2008) Understanding anxiety disorders from a ‘triple 
vulnerability’ framework. In: Antony MM, Stein MB (eds). Handbook of Anxiety and Anxiety Disorders, 
pp. 153–​72. New York, NY: Oxford University Press.

381
GAD 1—CLINICAL FEATURES AND AETIOLOGY
Box 8.5  Symptoms of GAD (present most days)
 • At least 6 months’ history of excessive anxiety and worry, with 
marked tension and apprehension about everyday events and 
problems (e.g. work or school performance).
 • DSM-​5: at least three (or one in children) out of:
 • Restlessness or feeling keyed up or on edge.
 • Easy fatiguability.
 • Concentration difficulties or ‘mind going blank’.
 • Irritability.
 • Muscle tension.
 • Sleep disturbance.
 • ICD-​10: at least four (with at least one from ‘autonomic arousal’) 
out of:
 • Symptoms of autonomic arousal—​palpitations/​tachycardia; sweating; 
trembling/​shaking; dry mouth.
 • ‘Physical’ symptoms—​breathing difficulties; choking sensation; chest 
pain/​discomfort; nausea/​abdominal distress.
 • Mental state symptoms—​feeling dizzy, unsteady, faint or light-​headed; 
derealization/​depersonalization; fear of losing control, ‘going crazy’, 
passing out, dying.
 • General symptoms—​hot flushes/​cold chills; numbness or tingling.
 • Symptoms of tension—​muscle tension/​aches and pains; 
restlessness/​inability to relax; feeling keyed up, on edge, or mentally 
tense; a sensation of a lump in the throat or difficulty swallowing.
 • Other—​exaggerated responses to minor surprises/​being startled.
 •
​ Concentration difficulties/​’mind going blank’—​due to worry or 
anxiety; persistent irritability; difficulty getting to sleep due to 
worrying.

382
Chapter 8  Anxiety and stress-related disorders
Generalized anxiety disorder 
2—differential diagnosis 
and management
Differential diagnosis
‘Normal worries’, depression, mixed anxiety/​depression, other anxiety 
disorders (the anxiety is more focused), drug and alcohol problems, med­
ical conditions (see Box 8.6), side effects of prescribed medications (see 
Box 8.7).
Management
 • Psychological: generally less effective than in the other anxiety disorders 
(lack of situational triggers); some evidence for CBT14 combining 
behavioural methods (treat avoidance by exposure, use of relaxation, 
and control of hyperventilation) and cognitive methods (teaching about 
bodily responses related to anxiety/​education about panic attacks, 
modification of thinking errors).
 • Pharmacological: directed towards predominant anxiety symptoms:
 •
​ Somatic symptoms—​BDZs14 (e.g. lorazepam, diazepam, alprazolam).
 •
​ Psychic symptoms—​buspirone15 (beneficial effects may take 2–​4wks).
 •
​ Depressive symptoms—​ SSRIs14 (licensed—​escitalopram 10–​20mg/​day, 
paroxetine 20–​50mg/​day), SNRIs (licensed—​duloxetine 60–​120mg/​
day, venlafaxine 75–​225mg/​day), TCAs (unlicensed—​imipramine, 
clomipramine), trazodone (licensed 75–​300mg/​day), mirtazapine 
(unlicensed—​30mg/​day).
 •
​ Cardiovascular symptoms or autonomic symptoms—​β-​blockers (e.g. 
atenolol).
 •
​ Other treatments—​pregabalin (licensed—​start 150mg/​day; max 
600mg/​day; in divided doses—​alone or as an adjunct to SSRI/​SNRI), 
agomelatine (unlicensed—​25–​50mg/​day), quetiapine16 (unlicensed—​
150mg/​day—​alone or as an adjunct to SSRI/​SNRI), trifluoperazine 
(unlicensed—​2–​6mg/​day).
 • Physical: psychosurgery (very rare)—​for severe/​intractable anxiety.
Course
Chronic and disabling, prognosis generally poor, remission rates low (730% 
after 3yrs, with treatment); 6-​yr outcome—​68% mild residual symptoms, 
9% severe persistent impairment. Often comorbidity becomes more signifi­
cant (esp. alcohol misuse), and this worsens the prognosis.
14  NICE recommends SSRIs as first-​line treatment (+ CBT) and does not recommend BDZs for 
>2–​4wks. See: National Institute for Health and Care Excellence (2011) Generalised anxiety disorder 
and panic disorder in adults: management. Clinical guideline [CG113]. M https://​www.nice.org.uk/​
guidance/​cg113 [accessed 20 June 2018].
15  Buspirone should be considered as an alternative to BDZs when sedative effects are unwanted 
(e.g. drivers of vehicles, pilots, machine operators), in patients with a personal/​family history of drug 
misuse, or for those already taking other CNS depressants.
16  National Institute for Health and Care Excellence (2013) Generalised anxiety disorder: quetiapine. 
Evidence summary [ESUOM12]. M https://​www.nice.org.uk/​advice/​esuom12/​chapter/​Key-​
points-​from-​the-​evidence [accessed 20 June 2018].

383
GAD 2—DIFFERENTIAL DIAGNOSIS AND MANAGEMENT
Box 8.6  Medical conditions associated with anxiety-​like 
symptoms
 • Cardiovascular system (CVS): arrhythmias, ischaemic heart disease 
(IHD), mitral valve disease, cardiac failure.
 • Respiratory: asthma, COPD, HVS, PE, hypoxia.
 • Neurological: TLE, vestibular nerve disease.
 • Endocrine: hyperthyroidism, hypoparathyroidism, hypoglycaemia, 
phaeochromocytoma.
 • Miscellaneous: anaemia, porphyria, SLE, carcinoid tumour, pellagra.
Box 8.7  Prescribed medications causing anxiety-​like 
symptoms
 • CVS: antihypertensives, anti-​arrhythmics.
 • Respiratory: bronchodilators, α1/​β-​adrenergic agonists.
 • CNS: anaesthetics (pre-​med and post-​general anaesthetic syndrome), 
anticholinergics, anticonvulsants, anti-​Parkinsonian agents, 
antidepressants, antipsychotics (akathisia), disulfiram reactions, 
withdrawal from BDZs and other sedatives and hypnotics.
 • Miscellaneous: levothyroxine, NSAIDs, antibiotics, chemotherapy.

384
Chapter 8  Anxiety and stress-related disorders
Obsessive–​compulsive disorder 
1—clinical features
Essence
A common, chronic condition, often associated with marked anxiety and 
depression, characterized by ‘obsessions’ (E Dictionary of psychiatric 
symptoms, p. 115) and ‘compulsions’ (E Dictionary of psychiatric symp­
toms, p. 104). Obsessions/​compulsions (see Box 8.8) must cause distress 
or interfere with the person’s social or individual functioning (usually by 
wasting time) and should not be the result of another psychiatric disorder. 
At some point in the disorder, the person recognizes the symptoms to be 
excessive or unreasonable.
In DSM-​5, OCD is now within a separate category ‘Obsessive–​
compulsive and related disorders’, which includes body dysmorphic 
disorder (E Body dysmorphic disorder, p.  872), hoarding disorder 
(E  Hoarding disorder (DSM-​5), p.  389), trichotillomania (hair-​pulling 
disorder) (E Trichotillomania (ICD-​10/​11; DSM-​5), p. 425), excoriation 
(skin-​picking) disorder (E Excoriation (skin-​picking) disorder (DSM-​5; 
ICD-​11), p.  425), substance/​medication-​induced obsessive–​compulsive 
and related disorder, and obsessive–​compulsive and related disorder due 
to another medical condition.
ICD-​11 is likely to take a similar view with the proposed ‘Obsessive–​
compulsive and related disorders’, including OCD, body dysmorphic dis­
order, olfactory reference disorder (E Olfactory reference disorder 
(ORD), p. 388), hypochondriasis, hoarding disorder, body-​focused repeti­
tive behaviour disorders (trichotillomania, excoriation disorder), and other 
specified obsessive–​compulsive and related disorder.
Box 8.8  Common obsessions and compulsions
Obsessions
 • Contamination.
 • Order or symmetry.
 • Safety.
 • Doubt (of memory for events or perceptions).
 • Unwanted, intrusive sexual or aggressive thoughts.
 • Scrupulosity (the need to do the right thing or fear of committing an 
error, breaking the law, or religious transgression).
Compulsions
 • Checking (e.g. doors, windows, electric sockets, appliances, safety of 
children).
 • Cleaning or washing excessively.
 • Counting or repeating actions a specific number of times.
 • Arranging objects in a specific way.
 • Touching or tapping objects.
 • Hoarding (E Hoarding disorder (DSM-​5), p. 389).
 • Confessing or constantly seeking reassurance.
 • Continual list-​making.

Obsessive–compulsive disorder 1—clinical features
Epidemiology
Mean age: 20yrs, 70% onset before age 25yrs, 15% after age 35yrs, ♂ = ♀, 
prevalence: 0.5–​3% of general population.
Aetiology
 • Neurochemical: dysregulation of the 5-​HT system (possibly involving 5-​
HT1B or 5-​HT/​DA interaction).
 • Immunological: cell-​mediated autoimmune factors may be associated, e.g. 
against basal ganglia peptides—​as in Sydenham’s chorea.
 • Imaging: CT and MRI: bilateral reduction in caudate size. PET/​SPECT: 
hypermetabolism in orbitofrontal gyrus, basal ganglia (caudate nuclei), 
and cingulum that ‘normalizes’, following successful treatment (either 
pharmacological or psychological).
 • Genetic: suggested by family and twin studies (3–​7% of first-​degree 
relatives affected; MZ: 50–​80%, DZ: 25%), no candidate genes as yet 
identified, but polymorphisms of 5-​HT1B have been replicated.
 • Psychological: defective arousal system and/​or inability to control 
unpleasant internal states. Obsessions are conditioned (neutral) stimuli, 
associated with an anxiety-​provoking event. Compulsions are learnt 
(and reinforced), as they are a form of anxiety-​reducing avoidance.
 • Psychoanalytical: Freud coined the term ‘obsessional neurosis’, thought 
to be the result of regression from oedipal stage to pre-​genital anal–​
erotic stage of development as a defence against aggressive or sexual 
(unconscious) impulses. Associated defences: isolation, undoing, and 
reaction formation. Symptoms occur when these defences fail to contain 
the anxiety.
Associations
Avoidant, dependent, histrionic traits (740% of cases), anankastic/​
obsessive–​compulsive traits (5–​15%) prior to disorder. In schizophrenia, 5–​
45% of patients may present with symptoms of OCD (schizo-​obsessives—​
poorer prognosis). Sydenham’s chorea (up to 70% of cases) and other 
basal ganglia disorders (e.g. Tourette’s syndrome, post-​encephalitic 
Parkinsonism).
Comorbidity
Depressive disorder (50–​70%), alcohol-​ and drug-​related disorders, social 
phobia, specific phobia, panic disorder, somatoform disorders, eating dis­
orders, impulse-​control disorders (trichotillomania, kleptomania), PTSD, tic 
disorder (740% in juvenile OCD), Tourette’s syndrome, suicidal thoughts 
or behaviours.
Differential diagnosis
‘Normal’ (but recurrent) thoughts, worries, or habits (do not cause distress 
or functional impairment); anankastic personality disorder/​OCD; schizo­
phrenia; phobias; depressive disorder; hypochondriasis; body dysmorphic 
disorder; trichotillomania.

386
Chapter 8  Anxiety and stress-related disorders
Obsessive–​compulsive disorder 
2—​management
Management
 • Psychological:
 •
​ CBT—​recommended by NICE,17,18 but essentially takes a behavioural 
approach, including exposure and response prevention (ERP).
 •
​ Behavioural therapy—​response prevention useful in ritualistic 
behaviour; thought stopping may help in ruminations; exposure 
techniques for obsessions.
 •
​ Cognitive therapy—​so far not proven effective.
 •
​ Psychotherapy—​supportive: valuable (including family members, use of 
groups); psychoanalytical: no unequivocal evidence of effectiveness 
(insight-​orientated psychotherapy may be useful in some patients).
 • Pharmacological:
 •
​ Antidepressants SSRIs (licensed): escitalopram (10–​20mg/​day), 
fluoxetine (20–​60mg/​day), fluvoxamine (100–​300mg/​day), sertraline 
(150mg/​day), or paroxetine (40–​60mg/​day) should be considered 
first line (no clear superiority of any one agent, high doses usually 
needed, at least 12wks for treatment response, long-​term therapy). 
Clomipramine (e.g. 250–​300mg) has specific anti-​obsessional 
action (NICE second-​line choice). Other (unlicensed) agents 
include citalopram (20–​60mg/​day; NICE recommended alone or in 
combination with clomipramine), venlafaxine (225–​300mg).
 •
​ Augmentative strategies: antipsychotic (risperidone, haloperidol, 
pimozide)—​esp. if psychotic features, tics, or schizotypal traits (less 
evidence for olanzapine, quetiapine, aripiprazole, paliperidone); 
buspirone/​short-​term clonazepam (not NICE recommended)—​if 
marked anxiety; other possible adjunctive agents include mirtazapine 
(15–​30mg), lamotrigine (100mg/​day), topiramate (100–​200mg/​day), 
memantine (20mg/​day), celecoxib (400mg/​day), and dexamfetamine 
(30mg/​day) or caffeine (300mg/​day).19
 • Physical:
 •
​ ECT—​consider if patient suicidal or severely incapacitated.
 •
​ Psychosurgery—​may be considered for severe, incapacitating, 
intractable cases (i.e. treatment-​resistant: two antidepressants, three 
combination treatments, ECT, and behavioural therapy) where the 
patient can give informed consent, e.g. stereotactic cingulotomy 
(reported up to 65% success). In theory, disrupts the neuronal loop 
between the orbitofrontal cortex and basal ganglia.
 •
​ DBS—​efficacy remains to be established (severe refractory cases).
17  National Institute for Health and Care Excellence (2005) Obsessive-​compulsive disorder and body 
dysmorphic disorder:  treatment. Clinical guideline [CG31]. M https://​www.nice.org.uk/​guidance/​
CG31/​chapter/​1-​Guidance [accessed 20 June 2018].
18  British Association for Psychopharmacology Guidelines (2014) M https://​www.bap.org.uk/​
pdfs/​BAP_​Guidelines-​Anxiety.pdf [accessed 20 June 2018].
19  That is roughly the equivalent of five cups of instant coffee, three cups of freshly brewed coffee, 
six cups of tea, seven cans of Diet Coke, or six plain chocolate bars, i.e. some patients may already 
be augmenting themselves!

Obsessive–compulsive disorder 2—management
Course
Often sudden onset (after stressful event, e.g. loss, pregnancy, sexual 
problem); presentation may be delayed by 5–​10yrs due to secrecy; 
symptom intensity may fluctuate (contact-​related/​phasic) or be chronic.
Outcome
Twenty to 30% significantly improve; 40–​50% show moderate improve­
ment, but 20–​40% have chronic or worsening symptoms. Relapse rates are 
high after stopping medication. Suicide rates i, esp. if there is secondary 
depression.
Prognostic factors
 • Poor prognosis: giving in to compulsions, longer duration, early onset, ♂, 
presence of tics, bizarre compulsions, hoarding, symmetry, comorbid 
depression, delusional beliefs or over-​valued ideas, personality disorder 
(esp. schizotypal).
 • Better prognosis: good premorbid social and occupational adjustment, a 
precipitating event, episodic symptoms, less avoidance.

388
Chapter 8  Anxiety and stress-related disorders
Olfactory reference disorder
Essence
Also known as olfactory reference syndrome (ORS), characterized by 
the erroneous belief that one emits a foul or unpleasant body odour, re­
sulting in significant distress and impairment, including avoidance of social 
situations.20 Often accompanied by referential thinking and repetitive be­
haviours (showering, use of excessive deodorants or perfumes). Level of 
insight varies, and concerns may amount to having a delusional quality.
Differential diagnosis
General medical conditions—​with verifiable body odour [e.g. hyperhidrosis, 
halitosis, dental (abscess), trimethylaminuria, rectal abscess/​fistulae], (rare) 
causes of olfactory hallucinations [head injury, migraine, substance use, or 
seizure disorders—​TLE associated with medial temporal lobe tumours and 
mesial temporal sclerosis (smells: ‘rotting’, ‘bad’, ‘burning rubber’, ‘rotting 
food’)]. Psychiatric conditions—​social anxiety disorder, OCD, body dys­
morphic disorder, delusional disorder, schizophrenia, schizoaffective dis­
order, avoidant personality disorder, depression, culture-​bound variants 
[e.g. ‘jikoshu-​kyofu’ (Japan); E Culture-​bound syndromes?, p. 988].
Comorbidity
Depression (usually secondary and may be severe), social anxiety, OCD, 
body dysmorphic disorder.
Epidemiology
Prevalence 0.5–​2% (estimated) but may be higher as under-​reported.
Course
Onset usually mid-​20s but can present earlier at puberty/​adolescence, and 
runs a chronic course. Up to two-​thirds may respond to treatments.
Treatment
Combined approach best. Actively treat any comorbidity.
 • Pharmacological—​no RCTs; case reports support use of SSRIs 
(fluoxetine, paroxetine, citalopram, sertraline) or antipsychotics 
(sulpiride, amisulpride, risperidone, aripiprazole, olanzapine), alone or 
combined.
 • Psychological—​no RCTs; sparse evidence supports: CBT focusing on 
compulsive behaviours, low mood, and social avoidance; eye movement 
desensitization and reprocessing (EMDR) aimed at processing the life 
events theorized to have been causal in either triggering or maintaining 
the pathology.
20  The first published descriptions of olfactory reference disorder (ORD) date back to the late 
1800s. Also known as autodysomophobia and bromosis, the term ORD was first used in 1971 by 
Pryse-​Phillips to describe the consistent phenomenology observed in a large patient case series of 
137 patients (Acta Psychiatr Scand 47:484–​509). The world literature has been comprehensively re­
viewed by Begum and McKenna in 2011 (Psychol Med 41:453–​61). Not included in the DSM-​5, ORD 
is being considered for inclusion in ICD-​11 as an OCRD.

Hoarding disorder (DSM-5)
Hoarding disorder (DSM-​5)
Essence
Persistent difficulties discarding or parting with possessions (including pets), 
regardless of their actual value, which leads to distress associated with 
discarding them and results in the accumulation of possessions that clutter 
active living areas.21 There is significant impairment of social, occupational, 
and other areas of functioning. Associated with or without excessive acqui­
sition and varying degrees of insight.
Differential diagnosis
OCD (obsessions), depressive disorder (poor motivation), psychosis (de­
lusions), autism (restricted interests), cognitive deficits (dementia, brain in­
jury, cerebrovascular disease, Prader–​Willi syndrome).
Comorbidity
75% comorbid mood or anxiety disorder (50% depression, 20% OCD, so­
cial phobia, and GAD).
Epidemiology
Prevalence 2–​6% in the USA and Europe. More ♂ than ♀ in general popu­
lation, vice versa in clinical populations. Almost three times more prevalent 
in older adults (aged 55–​94yrs) than younger adults (aged 34–​44yrs). Risk 
factors include:  indecisiveness in individuals with the disorder and first-​
degree relatives; stressful or traumatic life events. Genetic studies suggest 
750% of the variability in hoarding disorder is heritable.
Course
Symptoms may first emerge around ages of 11–​15yrs, start interfering with 
everyday functioning by mid-​20s, and cause clinically significant impairment 
by mid-​30s. Usually runs a chronic course.
Treatment
CBT has some utility, including relaxation, and helps with decision-​making 
and coping skills. Individual, group, or family approaches have been used. 
Psychotherapy may be augmented with a trial of an SSRI. Actively treat any 
comorbidity.
21  Also known as Diogenes syndrome (E Personality problems, p. 555)—​coined by Clark et al. 
(1975) but first described by MacMillan and Shaw (1966), the name derives from Diogenes of Sinope, 
an ancient Greek philosopher, a Cynic who allegedly lived in a large jar in Athens. It is a misnomer as 
Diogenes was not a hoarder and was known to venture out each day to the Agora. Other suggested 
synonyms include ‘senile breakdown’, ‘Plyushkin’s syndrome’ (after a character from Gogol’s Dead 
Souls), ‘social breakdown’, and ‘senile squalor syndrome’.

390
Chapter 8  Anxiety and stress-related disorders
Exceptional stressors 
and traumatic events
ICD-​10 definition
‘Common sense’ approach: ‘a stressful event or situation . . . of an excep­
tionally threatening or catastrophic nature, which is likely to cause pervasive 
distress in almost anyone’. Includes traumatic events (e.g. rape, bombing, 
criminal assault, natural catastrophe) and unusual sudden changes in the so­
cial position and/​or network of the individual (e.g. domestic fire, multiple 
bereavement).
DSM-​5 definition
Exposure to actual or threatened death, serious injury, or sexual violence 
in one (or more) of the following ways: directly experienced, witnessed 
in person, learning that the traumatic event(s) occurred to a close family 
member or close friend, or repeated or extreme exposure to aversive de­
tails of the traumatic event(s) (e.g. first responders collecting human re­
mains, police officers repeatedly exposed to details of child abuse).
Types I and II trauma
(See Box 8.9.)
 • Type I trauma: single, dangerous, and overwhelming events, comprising 
isolated (often rare) traumatic experiences of a sudden, surprising, 
devastating nature, with limited duration (i.e. ICD-​10/​DSM-​5 
definitions).
 • Type II trauma: due to sustained and repeated ordeal stressors (series of 
traumatic events or exposure to prolonged trauma); may be variable, 
multiple, chronic, repeated, and anticipated, usually of intentional human 
design (e.g. ongoing physical or sexual abuse, combat). May lead to 
‘complex PTSD’ or ‘complex trauma’. Symptoms include: somatization, 
dissociation, detachment from others, restricted range or dysregulation 
of affect, emotional lability (poor impulse-​control, self-​destructive 
behaviour, pathological patterns of relationships), and emotional 
numbing. ICD-​10 acknowledges this type of reaction with the diagnosis 
‘enduring personality changes after catastrophic experience’, whereas DSM-​
5 allows for coding under ‘other specified trauma-​ and stressor-​related 
disorder’ or ‘other specified personality disorder’.
How common are these events?
Community studies have found that up to 80% of men and 75% of women22 
experience at least one traumatic event in their lifetime (but see cautionary 
notes in Box 8.10). Common events include sudden death of a loved one, 
accidents, fire, flood, natural disasters, or being a witness to severe injury 
(or murder).
22  Stein MB, Walker JR, Hazen AL, et al. (1997) Full and partial posttraumatic stress disorder: find­
ings from a community survey. Am J Psychol 154:1114–​19.

Exceptional stressors and traumatic events
Box 8.9  Continued debate
 • Both of the ICD-​10 and DSM-​5 definitions fail to address ‘low-​
magnitude stressors’ (e.g. divorce, job loss, failing exams), even 
though 0.4% of the population may develop ‘PTSD-​like’ symptoms.1
 • Equally, ‘common’ events (e.g. RTAs, sexual assault) quite often lead 
to PTSD-​like symptoms.
 • Even perpetrators (albeit ‘unwilling’) of traumatic events (e.g. 
war-​related crimes, torture) may experience PTSD-​like symptoms 
(associated with feelings of shame or guilt).
 • Emphasis on life-​threatening events/​threats to physical integrity 
may also be too restrictive. The perception of threat to, or loss of, 
autonomy and mental defeat may actually be more significant than 
physical assault—​seen in studies of victims of sexual/​physical assault 
and political prisoners.
 • Whether diagnosis should be made on the basis of symptom clusters, 
rather than any definition of what constitutes a ‘valid’ traumatic event, 
becomes academic when a patient presents with clinically significant 
problems (although it may generate much heat when issues of 
compensation are involved).
1 McNally RJ (2000) Post traumatic stress disorder. In: Millon T, Blaney PH, David RD (eds). 
Oxford Textbook of Psychopathology, pp. 144–​65. Oxford: Oxford University Press.
 Box 8.10  Recovered and false memories
 • Survivors of traumatic events, esp. child abuse, sometimes claim to 
have recovered memories after a long period of time.
 • Organizations such as the False Memory Syndrome Foundation 
(USA) and the False Memory Society (UK) suggest that many, if not 
all, of these recovered memories are the product of inappropriate 
therapeutic suggestion.
 • The possibility of false accusations of supposed perpetrators, 
disruption of families, and accusations of malpractice against therapists 
have meant that debate is polarized, and subsequently, the literature is 
very difficult to interpret.
 • Few would disagree with Lindsay and Read’s summary (1995):1 ‘In our 
reading, the scientific evidence has clear implications . . . memories 
recovered via suggestive memory work by people who initially denied 
any such history should be viewed with skepticism, but there are few 
grounds to doubt spontaneously recovered memories of common 
forms of child sexual abuse or recovered memories of details of 
never-​forgotten abuse. Between these extremes lies a grey area within 
which the implications of existing scientific evidence are less clear and 
experts are likely to disagree.’
1 Lindsay DS, Read JD (1995) ‘Memory work’ and recovered memories of childhood sexual 
abuse: scientific evidence and public, professional and personal issues. Psychol Publ Policy Law 
1:846–​908.

392
Chapter 8  Anxiety and stress-related disorders
Acute stress reaction (ICD-​10)
Essence
A transient disorder (lasting hours or days) that may occur in an individual 
as an immediate (within 1hr) response to exceptional stress (e.g. natural ca­
tastrophe, major accident, serious assault, warfare, rape, multiple bereave­
ment, fire). The stressor usually involves severe threat to the security or 
physical integrity of the individual or of a loved person(s).
Symptoms/​signs
Symptoms tend to be mixed/​changeable, with an initial state of daze, fol­
lowed by depression, anxiety (as for GAD; E Generalized anxiety disorder 
1—​clinical features and aetiology, p. 380), anger, or despair. Presence of 
social withdrawal, narrowed attention, disorientation, aggression, hopeless­
ness, over-​activity, or excessive grief defines mild (none of these symptoms 
present), moderate (two present), or severe (four present, or dissociative 
stupor) forms.
Epidemiology
Incidence variable across studies, but estimated around 15–​20% of individ­
uals, following exceptional stress.
Aetiology
No specific theories, as it is a transient disorder.
Risk factors
Physical exhaustion, presence of other organic factors, elderly.
Differential diagnosis
PTSD (‘exceptional trauma’, delayed or persistent symptoms, re-​
experiencing of the traumatic event), adjustment disorder (not necessarily 
exceptional stressor, wider range of symptoms), concussion/​mild brain in­
jury (neuropsychological testing cannot always distinguish), brief psychotic 
disorder, dissociative disorders (no clear stressor), substance misuse.
Management
By definition, no specific treatment needed. Ensure other needs are ad­
dressed, i.e. safety, security, practical assistance, social supports.
Outcome
 • Once the stressor is removed, symptoms resolve (usually) within a 
few hours.
 • If the stress continues, the symptoms tend to diminish after 24–​48hrs 
and are minimal within about 3 days.

Acute stress reaction (ICD-10)
393

394
Chapter 8  Anxiety and stress-related disorders
Acute stress disorder (DSM-​5)
Essence
Clear overlap with ‘acute stress reaction’ (symptoms of dissociation, anx­
iety, hyperarousal), but greater emphasis on dissociative symptoms; onset 
within 4wks, lasting 3 days to 4wks (after which diagnosis changes to PTSD).
Symptoms/​signs
Similar to PTSD with symptoms in the categories of: re-​experiencing of 
events (intrusion), avoidance, negative mood, and hyperarousal (but lasting 
no more than 4wks). Also it must be specified whether qualifying traumatic 
events were experienced directly, witnessed, or indirectly.
Epidemiology
Incidence depends on trauma, e.g. 13–​14% in road traffic accident (RTA) 
survivors, 19% in victims of assault, 33% in victims of mass shooting.
Aetiology
Similar to PTSD.
 • Psychological: ‘re-​experiencing symptoms’. Fear response to harmless 
situations associated with original trauma, perhaps due to emotional 
memories (i.e. having personal significance). Remodelling underlying 
schemas requires holding trauma experiences in ‘active’ memory until 
the process is complete (working through). Dissociation—​a mechanism 
of avoiding overwhelming emotion (i.e. ‘thinking without feeling’), 
which, if persistent, delays the process of integration.
 • Biological: neurophysiological changes leading to permanent neuronal 
changes as a result of the effects of chronic stress or persistent re-​
experiencing of the stressful event. Neurotransmitters implicated—​
cathecholamines, 5-​HT, GABA, opioids, and glucocorticoids.
Risk factors
Previous history of psychiatric disorder, previous traumatic event(s), pre­
morbid depression, or dissociative symptoms.
Comorbidity
Similar to PTSD (i.e. depression, substance misuse).
Differential diagnosis
(See Box 8.11.)
PTSD (time frame >4wks’ duration), adjustment disorder (does not meet 
criteria for ‘traumatic’ event; E Exceptional stressors and traumatic events, 
p. 390; wider range of symptoms), concussion/​mild brain injury (neuro­
psychological testing cannot always distinguish), brief psychotic disorder, 
dissociative disorders (no clear stressor), substance misuse.

Acute stress disorder (DSM-5)
Management
 • Simple practical measures: e.g. support, advice regarding police 
procedures, insurance claims, dealing with the media, course and 
prognosis, may be all that is required.
 • Psychological:
 •
​ Debriefing—​may be useful for certain individuals (needing supportive 
therapy), but reviews suggest there is little positive benefit of single 
session debriefing alone and may worsen outcome!23 (See also 
Box 8.12.)
 •
​ CBT—​brief interventions (education, relaxation, graded in vivo 
exposure, and cognitive restructuring) may reduce the development 
of chronic problems/​PTSD (not immediate, but ∼2wks after the 
event appears best).
 • Pharmacological: TCAs, SSRIs, and BDZs may be useful for clinically 
significant symptoms (evidence lacking).
Box 8.11  DSM-​5 ‘Trauma-​ and stressor-​related disorders’ 
and ICD-​11 ‘Disorders specifically associated with stress’
This new chapter in DSM-​5 (and ICD-​11 proposals) attempts to accom­
modate childhood and adult-​onset trauma-​ and stressor-​related disorders 
together. This means that ‘reactive attachment disorder’ and ‘disinhib­
ited social engagement’ are included. While these disorders may share 
aetiological pathways (the result of social neglect), the lack of attach­
ments seen in reactive attachment disorder is not necessarily found in 
disinhibited social engagement, which may present very much like ADHD 
(E Attachment, p. 658).
The other disorders included in this category are ‘Acute stress dis­
order’, ‘Adjustment disorders’, ‘PTSD’, and ‘Other/​unspecified trauma-​ 
and stressor-​related disorders’. Like acute stress disorder, PTSD has four 
symptom clusters:  avoidance, persistent negative alterations in cogni­
tions and mood, re-​experiencing, and alterations in arousal and reactivity 
(which includes irritable or aggressive behaviour and reckless or self-​
destructive behaviour). Diagnostic thresholds are lowered to allow the 
diagnosis in children and adolescents, with separate criteria for children 
aged 6 or younger.
ICD-​11 proposes a narrowing of PTSD to three core symptoms: re-​
experiencing, avoidance, and heightened threat perception. Complex PTSD 
is added—​characterized by severe and pervasive problems in affect regula­
tion; persistent beliefs about oneself as diminished, defeated, or worthless, 
accompanied by deep and pervasive feelings of shame, guilt, or failure re­
lated to the traumatic event; and persistent difficulties in sustaining relation­
ships and in feeling close to others (with a clear relationship with emotionally 
unstable personality disorder; E Table 12.1, p. 523). A new category of 
prolonged grief disorder, with symptoms lasting for at least 6mths, clearly 
exceeding social, cultural, or religious norms for the individual.
23  Rose SC, Bisson J, Churchill R, Wessely S (2002) Psychological debriefing for preventing post 
traumatic stress disorder (PTSD). Cochrane Database Syst Rev 2:CD000560.

396
Chapter 8  Anxiety and stress-related disorders
Outcome
By definition, either self-​limiting or continues into PTSD.
Box 8.12  Debriefing—​more harm than good?
Surely it is better to get your emotions out than leave them bottled up? 
Debriefing, a technique that evolved from military psychiatry, where 
groups discussed their shared experiences, was used with first re­
sponders, and then to help victims of trauma. The idea was to prevent 
PTSD and other psychological problems with an efficient and affordable 
intervention that often comprised a cathartic retelling of events. In the 
1980s and 1990s, counsellors were often among the first to arrive at the 
scene of a crisis.
This vogue for debriefing was challenged when a number of trials of 
single-​session debriefing appeared to show a negative effect. In 1997, 
Bisson and colleagues conducted a study on burn victims and found that 
those who received debriefing were more likely to score highly for symp­
toms of PTSD, anxiety, and depression 13mths later. Similarly, in 2000, 
a study by Hobbs and colleagues showed that vehicle accident survivors 
who received debriefing, when compared to those who were simply 
assessed, had worse PTSD symptoms at 4mths and when followed up 
3yrs later.
In 2002, a Cochrane systematic review and meta-​analysis con­
cluded: ‘There is no evidence that single session individual psychological 
debriefing is a useful treatment for the prevention of post traumatic stress 
disorder after traumatic incidents. Compulsory debriefing of victims of 
trauma should cease.’
The controversy that ensued is well summarized in a debate article in 
the British Journal of Psychiatry in 20031 and highlighted the problems with 
reliance on evidence-​based medicine—​that ‘by satisfying the rigorous 
methodological criteria demanded of level I evidence, many RCTs lose 
validity and become so divorced from clinical reality that their findings 
are clinically meaningless.’ (E Trust me, I’m an epidemiologist, p. 30). 
However, rather than throw the baby out with the bath water, it is now 
generally agreed that debriefing should be part of a comprehensive, prag­
matic ‘screen and treat’ package that appropriately assesses psychological 
and practical support needs, allowing early detection and prompt treat­
ment of stress-​ or trauma-​related disorders.
1 Wessley S, Deahl M (2003) Psychological debriefing is a waste of time. Br J Psychiatry 
183:12–​14.

Acute stress disorder (DSM-5)
397

398
Chapter 8  Anxiety and stress-related disorders
Adjustment disorders
Adjustment disorders sit uneasily between what are regarded as normal or 
just ‘problematic’ difficulties and the major psychiatric diagnoses. They must 
occur within 1 (ICD-​10) or 3mths (DSM-​5) of a particular psychosocial 
stressor and should not persist for longer than 6mths after the stressor (or 
its consequences) is removed (except in the case of ‘prolonged depressive 
reaction’ in ICD-​10). Symptoms are ‘clinically significant’ due to marked 
distress or impairment of normal functioning, and may be ‘subthreshold’ 
(due to symptom or duration criteria) manifestations of mood disorders, 
anxiety disorders, stress-​related disorders, somatoform disorders, or con­
duct disorders.
Subclassification
 • ICD-​10: brief depressive reaction (>1mth), prolonged depressive 
reaction (>6mths, but <2yrs), mixed anxiety and depressive reaction, 
predominant disturbance of other emotions, predominant disturbance 
of conduct, mixed disturbance of emotion and conduct, and other 
specified predominant symptoms. Allows inclusion of bereavement/​
grief reactions.
 • DSM-​5: specifiers: with depressed mood, anxiety, mixed anxiety 
and depressed mood, disturbance of conduct, mixed disturbance 
of emotions and conduct, and unspecified. Specifically excludes 
bereavement reactions (E Normal and abnormal grief, p. 400). 
‘Acute’ disorders <6mths; ‘chronic’ disorders >6mths.
Epidemiology
Prevalence in inpatient/​outpatient psychiatric populations is conservatively 
estimated at around 5%. In general hospital settings, it may be as high as 20% 
(physical illness being the primary stressor for up to 70% of these cases).
Aetiology
By definition, the problems are caused by an identifiable stressor. Individual 
predisposition plays a greater role than in other conditions, but symptoms 
would not have arisen without the stressor.
Comorbidity
Possibly higher incidence of alcohol-​related problems than the general 
population, but no different from other psychiatric disorders.
Differential diagnosis
Diagnostic uncertainty may arise if debate surrounds whether the stressor 
is sufficiently severe to be labelled ‘exceptional’ or ‘traumatic’ (acute stress 
reaction/​disorder or PTSD may be considered). Equally, it may be difficult 
to determine whether symptoms (e.g. low mood, anxiety, sleep disturb­
ance, anorexia, lack of energy) are attributable to a medical disorder or 
are primarily psychiatric in nature. Use of alcohol and drugs (illicit and pre­
scribed) may complicate the picture.

Adjustment disorders
Management
 • Psychological: the mainstay of management is essentially supportive 
psychotherapy to enhance the capacity to cope with a stressor that 
cannot be reduced or removed, and to establish sufficient support 
(esp. practical help, e.g. provision of carers/​childcare, financial support 
and benefits, OT assessment, contact with specific support groups) to 
maximize adaption. Ventilation/​verbalization of feelings may be useful 
in preventing maladaptive behaviours (e.g. social isolation, destructive 
behaviours, suicidal acts), and understanding the ‘meaning’ of the 
stressor to the individual may help correct cognitive distortions.
 • Pharmacological: the use of antidepressants or anxiolytics/​hypnotics 
may be appropriate where symptoms are persistent and distressing (e.g. 
prolonged depression/​dysphoria) or where psychological interventions 
have proved unsuccessful.
Outcome
 • 5-​yr follow-​up suggests recovery in 770% (adolescents: 740%), 
intervening problems in 710% (adolescents: 715%), and development of 
major psychiatric problems in 720% (adolescents: 745%).
 • In adults, further psychiatric problems are usually depression/​anxiety or 
alcohol-​related problems.
0 There is a very real risk of suicide and self-​harm (esp. in younger popu­
lations). Additional risk factors include poor psychosocial functioning, pre­
vious psychiatric problems, personality disorder, substance misuse, and 
mixed mood/​behavioural symptoms. Do not ignore.

400
Chapter 8  Anxiety and stress-related disorders
Normal and abnormal grief
Controversy surrounds how we should regard normal/​abnormal grief, 
and whether they are distinct from depression or other stress-​related 
disorders.24 It is very common for those suffering bereavement to have 
depressive symptoms. However, it is less common for people to experi­
ence a clear depressive episode that requires treatment.25 Normal grief 
is variable in its intensity and duration. Some commentators regard be­
reavement as just another stressor and argue that, depending on the phe­
nomenology, grief may be regarded as an acute stress reaction/​disorder, 
an adjustment disorder, or even a form of PTSD (‘traumatic grief ’). Just 
as the former reactive/​endogenous debate surrounding depression has 
led to recommendations that ‘clinical’ symptoms should be treated, a be­
reaved person should not be denied effective treatment on the basis of 
‘understandability’, nor should arbitrary time frames [e.g. <4wks (ICD-​
10), <2mths (DSM-​5)] become more important than assessment of 
clinical need.
Definitions
 • Bereavement: any loss event, usually the death of someone.
 • Grief: feelings, thoughts, and behaviour associated with bereavement.
 •
​ ‘Normal’—​typical symptoms experienced after bereavement 
include: disbelief, shock, numbness, and feelings of unreality; anger; 
feelings of guilt; sadness and tearfulness; preoccupation with the 
deceased; disturbed sleep and appetite and, occasionally, weight 
loss; and seeing or hearing the voice of the deceased. Usually these 
symptoms gradually reduce in intensity, with acceptance of the 
loss and readjustment. A typical ‘grief reaction’ lasts up to 12mths 
(mean 6mths), but cultural differences exist. Intensity of grief is 
usually greatest for the loss of a child, then spouse or partner, then 
parent.
 •
​ ‘Abnormal (pathological/​morbid/​complicated)’—​grief reaction that is 
very intense, prolonged, or delayed (or absent), or where symptoms 
outside the normal range are seen, e.g. preoccupation with feelings 
of worthlessness, thoughts of death, excessive guilt, marked slowing 
of thoughts and movements, a prolonged period of not being able to 
function normally, hallucinatory experiences (other than the image or 
voice of the deceased) (see Box 8.13).
Risk factors for depression after bereavement
History of depression, intense early grief/​depressive symptoms, lack of so­
cial support, little experience of death, ‘traumatic’/​unexpected death.
24  Stroebe MS, Hanson RO, Stroebe W, et al. (eds) (2007) Handbook of Bereavement Research 
and Practice: 21st Century Perspectives. Washington, DC: American Psychological Association Press.
25  Results vary, e.g. in one study 16% of late-​life widows had depression 13mths after bereavement. 
Zisook S, Paulus M, Shuchter SR, Judd LL (1997) The many faces of depression following spousal 
bereavement. J Affect Disord 45:85–​95.

Normal and abnormal grief
Management
Generally ‘normal’ grief does not require specific treatment, although BDZs 
may be used to reduce severe autonomic arousal or treat problematic sleep 
disturbance in the short term. Where there are features of ‘abnormal’ grief, 
or where there are clinical symptoms of depression/​anxiety, treatment 
with antidepressants ought to be considered, along with culturally appro­
priate supportive counselling (e.g. through organizations such as CRUSE).
‘Near the end of his life Sigmund Freud was consulted by a woman 
who had become depressed following the death of her husband. After 
listening to her, Freud quietly stated, “Madam, you do not have a 
neurosis, you have a misfortune”.’
Wahl CW (1970) Arch Found Thanatol 1: 137.
‘I know of only one functional psychiatric disorder, whose cause is 
known, whose features are distinctive, and whose course is usually 
predictable, and this is grief, the reaction to loss. Yet this condition 
has been so neglected by psychiatrists that until recently it was not 
even mentioned in the indexes of most of the best-​known general 
textbooks of psychiatry.’
Parkes CM (1986) Bereavement studies of grief in adult life. 
2nd edn. Tavistock Publications, London and New York.
Box 8.13  Prolonged grief disorder (PGD) [also known 
as persistent complex bereavement disorder (DSM-​5), 
complicated grief disorder, and traumatic grief]
Prigerson et al.,1 a group of international researchers, have attempted to 
refine this syndrome for inclusion in DSM-​5 (only made it into ‘Other spe­
cified trauma-​ and stressor-​related disorder’—​as a condition for future 
study) and ICD-​11 proposals (successfully as ‘Prolonged grief disorder’), 
with criteria to identify bereaved persons at heightened risk for enduring 
distress and dysfunction. Criteria require reactions to a significant loss 
that involve the experience of yearning (e.g. physical or emotional suf­
fering as a result of the desired, but unfulfilled, reunion with the deceased) 
and at least five of the following nine symptoms experienced at least daily 
or to a disabling degree:
 • Feeling emotionally numb, stunned, or that life is meaningless.
 • Experiencing mistrust.
 • Bitterness over the loss.
 • Difficulty accepting the loss.
 • Identity confusion.
 • Avoidance of the reality of the loss.
 • Difficulty moving on with life.
Symptoms must be present at sufficiently high levels for at least 6mths 
from the death and be associated with functional impairment.
1 Prigerson HG, Horowitz MJ, Jacobs SC, et al. (2009) Prolonged grief disorder: psychometric 
validation of criteria proposed for DSM-​V and ICD-​11. PLoS Med 6:e1000121.

402
Chapter 8  Anxiety and stress-related disorders
Post-​traumatic stress disorder 1: 
diagnosis
Essence
Severe psychological disturbance following a traumatic event (E Excessive 
stressors and traumatic events, p. 390), characterized by involuntary re-​
experiencing of elements of the event, with symptoms of hyperarousal, 
avoidance, and emotional numbing.
Symptoms/​signs
Symptoms arise within 6mths (ICD-​10) of the traumatic event (delayed 
onset in 710% of cases) or are present for at least 1mth, with clinically sig­
nificant distress or impairment in social, occupational, or other important 
areas of functioning (DSM-​5).
Both ICD-​10 and DSM-​5 include:
 • Two or more ‘persistent symptoms of increased psychological sensitivity 
and arousal’ (not present before exposure to the stressor): difficulty 
falling or staying asleep; irritability or outbursts of anger; reckless 
or self-​destructive behaviour (DSM-​5); difficulty in concentrating; 
hypervigilance; exaggerated startle response.
Other ICD-​10 criteria
 • Persistent remembering/​‘reliving’ of the stressor in intrusive flashbacks, 
vivid memories, or recurring dreams; and distress when exposed to 
circumstances resembling or associated with the stressor.
 • Actual/​preferred avoidance of circumstances resembling/​associated 
with the stressor (not present before exposure to the stressor).
 • Inability to recall, either partially or completely, some important aspects 
or the period of exposure to the stressor.
Other DSM-​5 criteria
(More specific; see Boxes 8.12 and 8.14.)
Epidemiology
Risk of developing PTSD after a traumatic event: 8–​13% for men, 20–​30% 
for women. Lifetime prevalence: around 7.8% (♂:♀ = 1:2). Cultural differ­
ences exist. Some types of stressor are associated with higher rates (e.g. 
rape, torture, being a prisoner of war).
Aetiology
 • Psychological/​biological (E Acute stress disorder (DSM-​5), p. 394).
 • Neuroimaging: reduced hippocampal volume (may relate to appreciation 
of safe contexts and explicit memory deficits). Dysfunction of the 
amygdala, hippocampus, septum, and prefrontal cortex may lead to 
enhanced fear response. High arousal appears to be mediated by the 
anterior cingulate, medial prefrontal cortex, and thalamus; dissociation 
by the parietal, occipital, and temporal cortex.
 • Genetic: higher concordance rates seen in MZ than DZ twins.
Risk factors
 • Vulnerability factors: low education, lower social class, Afro-​Caribbean/​
Hispanic, ♀ gender, low self-​esteem/​neurotic traits, previous (or family)

Post-traumatic stress disorder 1: diagnosis
history of psychiatric problems (esp. mood/​anxiety disorders), previous 
traumatic events (including adverse childhood experiences and abuse).
 • Peri-​traumatic factors: trauma severity, perceived life threat, peri-​
traumatic emotions, peri-​traumatic dissociation.
 • Protective factors: high IQ, higher social class, Caucasian, ♂ gender, 
psychopathic traits, chance to view the body of a dead person.
Comorbidity (may be primary or secondary)
Depressive/​mood disorders, other anxiety disorders, alcohol and drug 
misuse disorders, somatization disorders.
Differential diagnosis
Acute stress reaction/​disorder, enduring personality change after a cata­
strophic event (duration at least 2yrs; E Exceptional stressors and 
traumatic events, p.  390), adjustment disorder (less severe stressor/​dif­
ferent symptom pattern), other anxiety disorder, depressive/​mood dis­
order, OCD, schizophrenia (or associated psychosis), substance-​induced 
disorders.
Box 8.14  Other DSM-​5 criteria
The traumatic event is persistently re-​experienced in one (or more) of 
the following ways:
 • Recurrent and intrusive distressing recollections of the event, including 
images, thoughts, or perceptions (or repetitive play in which themes 
or aspects of the trauma are expressed in children).
 • Recurrent distressing dreams of the event (or frightening dreams 
without recognizable content in children).
 • Dissociative reactions (e.g. flashbacks)—​acting or feeling as if the 
traumatic event were recurring (or re-​enactment in play in children).
 • Intense psychological distress at exposure to internal or external cues 
that symbolize or resemble an aspect of the traumatic event.
 • Marked physiological reactions at exposure to internal or external 
cues that symbolize or resemble an aspect of the traumatic event.
Persistent avoidance of stimuli associated with the trauma (not present 
before the trauma), as evidenced by:
 • Efforts to avoid thoughts, feelings, or memories associated with the 
trauma.
 • Efforts to avoid external reminders (activities, places, or people) that 
arouse recollections of the trauma.
Negative alterations in cognition and mood associated with the traumatic 
event(s), as evidenced by two (or more) of:
 • Inability to recall an important aspect of the trauma.
 • Persistent exaggerated negative beliefs or expectations about self, 
others, and the world.
 • Persistent distorted cognitions.
 • Persistent negative emotional state.
 • Markedly diminished interest or participation in significant activities.
 • Feeling of detachment or estrangement from others.
 • Persistent inability to experience positive emotions.

404
Chapter 8  Anxiety and stress-related disorders
Post-​traumatic stress disorder 2: 
management
Psychological
Meta-​analyses support the superior efficacy of trauma-​focused treat­
ments,26,27 specifically trauma-​focused CBT and EMDR. These are recom­
mended as first-​line treatments in all recent guidelines.
 • CBT: includes elements of—​education about PTSD, self-​monitoring of 
symptoms, anxiety management, breathing techniques, imaginal reliving, 
supported exposure to anxiety-​producing stimuli, cognitive restructuring 
(esp. for complicated trauma), anger management.
 • EMDR: novel treatment using voluntary multi-​saccadic eye movements 
to reduce anxiety associated with disturbing thoughts and to help 
process the emotions associated with traumatic experiences (see 
Box 8.15).
 • Other psychological treatments:
 •
​ Psychodynamic therapy—​focus on resolving unconscious conflicts 
provoked by the stressful events, the goal being to understand the 
meaning of the event in the context of the individual.
 •
​ Stress management (stress inoculation)—​teaching skills to help 
cope with stress such as relaxation, breathing, thought stopping, 
assertiveness, positive thinking.
 •
​ Hypnotherapy—​use of focused attention to enhance control over 
hyperarousal and distress, enabling recollection of traumatic event. 
Concern over possible induction of dissociative states.
 •
​ Supportive therapy—​non-​directive, non-​advisory method of exploring 
thoughts, feelings, and behaviours to reach clearer self-​understanding.
Pharmacological
Medication may be considered when there is severe ongoing threat, if the 
patient is too distressed or unstable to engage in psychological therapy or 
fails to respond to an initial psychological approach. Where there is a good 
treatment response, medication should be continued long term, with trial 
reduction after 12mths.
 • SSRIs (e.g. paroxetine 20–​40mg/​day; sertraline 50–​200mg/​day) are 
licensed for PTSD, and their use is supported by a systematic review.28 
Other unlicensed possibilities include: venlafaxine, mirtazapine, 
fluoxetine, escitalopram, and fluvoxamine. Other antidepressants: 
although unlicensed, there is some evidence for TCAs (e.g. amitriptyline, 
imipramine); MAOIs (e.g. phenelzine) may also reduce anxiety (over-​
arousal) and intrusiveness, and improve sleep.
26  National Institute for Health and Care Excellence (2005) Post-​traumatic stress disorder: manage­
ment. Clinical guideline [CG26]. M http://​www.nice.org.uk/​CG26 [accessed 20 June 2018].
27  Bisson J, Ehlers A, Matthews R, et al. (2007) Systematic review and meta-​analysis of psychological 
treatments for post-​traumatic stress disorder. Br J Psychiatry 190:97–​104.
28  Stein DJ, Ipser JC, Seedat S (2006) Pharmacotherapy for posttraumatic stress disorder (PTSD). 
Cochrane Database Syst Rev 1:CD002795.

Post-traumatic stress disorder 2: management
It may be helpful to target specific symptoms:
 • Sleep disturbance (including nightmares): may be improved by 
mirtazapine (45mg/​day), levomepromazine, prazosin (mean dose 
9.5mg/​day), or specific hypnotics (e.g. zopiclone, zolpidem).
 • Anxiety symptoms/​hyperarousal: consider use of BDZs (e.g. clonazepam 
4–​5mg/​day), buspirone, antidepressants, propranolol.
 • Intrusive thoughts/​hostility/​impulsiveness: some evidence for use of 
carbamazepine, valproate, topiramate, or lithium.
 • Psychotic symptoms/​severe aggression or agitation: may warrant use of an 
antipsychotic (some evidence for olanzapine, risperidone, quetiapine, 
clozapine, aripiprazole).
Outcome
 • 750% will recover within first year, 730% will run a chronic course.
 • Outcome depends on initial symptom severity. Recovery will be 
helped by: good social support; lack of negative responses from 
others; absence of ‘maladaptive’ coping mechanisms (e.g. avoidance, 
denial, ‘safety behaviours’, not talking about the experience, thought 
suppression, rumination); no further traumatic life events (secondary 
problems such as physical health, acquired disability, disfigurement, 
disrupted relationships, financial worries, and litigation).
 Box 8.15  EMDR controversy
In 1987, Francine Shapiro, a California psychologist in private practice, 
while walking in the woods, preoccupied with disturbing thoughts, dis­
covered her anxiety improved during the walk. She realized that she had 
been moving her eyes back and forth, from one side of the path to the 
other, while walking. Shapiro tried out variants of this procedure with her 
clients and found that they felt better too. Her findings were published in 
1989, and EMDR was born.
Initially developed to help clients with PTSD and other anxiety dis­
orders, therapists have since extended EMDR to other conditions, 
including depression, sexual dysfunction, schizophrenia, eating disorders, 
and stress associated with illnesses such as cancer. Like other serendip­
itous discoveries, the claims for EMDR were treated with a healthy dose 
of scepticism, especially when its proponents tried to explain ‘how’ it 
worked, using erroneous theories of memory, right–​left brain imbalance, 
and REM sleep-​like processing. It became associated with alternative ther­
apies, such as Roger Callahan’s thought field therapy and Gary Craig’s 
emotional freedom therapy. These therapies have all the hallmarks of 
pseudoscience (E Psychomythology, p. 24). Although the mechanism of 
action of EMDR is not fully understood, it has been shown that the eye 
movements are not a necessary component of the therapy. In fact, well-​
established psychological principles of attention, imaginal exposure, and 
methods of relaxation are probably sufficient to explain the efficacy of 
the EMDR procedure.
Shapiro F (1995) Eye Movement Desensitization and Reprocessing: Basic Principles, Protocols, and 
Procedures. New York, NY: Guildford Press.

406
Chapter 8  Anxiety and stress-related disorders
Depersonalization (derealization) 
syndrome
Essence
A rare disorder, characterized by persistent or recurrent episodes of a 
distressing feeling of unreality or detachment in relation to the outside 
world (derealization) or the person’s own body, thoughts, feelings, or be­
haviour (depersonalization). It is viewed as an anxiety-​/​stress-​related dis­
order in ICD-​10, and as one of the ‘dissociative disorders’ in DSM-​5, along 
with dissociative amnesia, identity disorder, and fugue (E Dissociative 
(conversion) disorders, p. 868).29
Clinical features
Patients may find it difficult to describe their experiences, often reporting 
feeling ‘as if’ they are a passive observer of what is going on around them or 
their own actions. This may be accompanied by an emotional numbness (in­
ability to experience feelings) and a dream-​ or trance-​like state. There may 
also be the experience of alterations in the perception of objects or people, 
appearing unfamiliar or different in respect to the usual colour, shape, dis­
tance, or size. Insight tends to be preserved (unlike ‘passivity phenomena’ 
in psychoses)—​the patient recognizes the experiences as abnormal, un­
pleasant, distressing, and anxiety-​provoking.
Epidemiology
Up to 50% of ‘normal’ individuals may experience depersonalization in 
their lifetime (usually in the context of psychological distress), with 1–​
2% having more chronic symptoms. In psychiatric populations, it is a very 
common experience (lifetime prevalence 780%), with persistent symp­
toms (and associated functional impairment) in 712%. In clinical popu­
lations:  ♂:♀  =  1:2, whereas in the general population:  ♂  =  ♀. Age 
of onset usually adolescence/​early adulthood (may go undetected in 
children).
Aetiology
 • Psychoanalytical: ego defence against painful and conflicting memories, 
impulses, or affects; usually rooted in childhood trauma.30
 • Psychological: adaptive response to overwhelming stress, allowing 
continued function by protecting against potentially overwhelming 
anxiety. Specific precipitant(s) may not be readily identifiable.
29  ICD-​11 ‘dissociative disorders’ proposals include depersonalization–​derealization disorder, dis­
sociative neurological symptom disorder (conversion disorders), dissociative amnesia, trance dis­
order, possession trance disorder, dissociative identity disorder, and partial dissociative identity 
disorder.
30  Dangers of attributing present psychopathology to childhood events cannot be overstated, illus­
trated by high-​profile cases of alleged ‘recovered memories’ (see Box.8.10). Unsubstantiated claims 
of childhood (or other) abuse should be regarded with caution, and the significance of childhood 
trauma, even in empirical studies, finds little support. See Pope HG (1997) Psychology Astray: Fallacies 
in Studies of ‘Repressed Memory’ and Childhood Trauma. Boca Raton, FL: Upton.

Depersonalization (derealization) syndrome
 • Biological:31 altered function in systems central to integrated processing 
of information in the brain (with functional localization in the 
parietotemporal and limbic areas) where serotonergic mechanisms 
play a key role. Possible role for the effects of illicit drugs, as 10–​20% 
of patients describe symptoms first occurring when using drugs (esp. 
cannabis).
Comorbidity
Anxiety disorders (particularly phobias, panic disorder, OCD), depressive 
disorders, personality disorders [anankastic/​obsessional, borderline per­
sonality disorder (BPD)].
Differential diagnosis
Depersonalization may be experienced in the context of sleep or sensory 
deprivation, being in unfamiliar surroundings, or an acutely stressful/​trau­
matic situation. May also be a symptom in schizophrenia/​psychosis (usually 
accompanied by a delusional explanation, e.g. Cotard delusion), mood/​anx­
iety disorders, acute intoxication/​withdrawal from alcohol, illicit substances 
(particularly cannabis or hallucinogens), or medication, and in organic dis­
orders (e.g. hyperventilation, hypoglycaemia, migraine, epilepsy—​brief 
stereotyped episodes, other neurological conditions).
Management
 • Use of rating scales32 (e.g. the Cambridge Depersonalization Scale)33 
may assist the assessment of treatment response.
 • Exclude organic causes with appropriate investigations, which may 
sometimes include brain imaging (CT/​MRI) and EEG.
 • Comorbid psychiatric conditions should be identified and treated. 
Despite successful treatment, depersonalization may persist.
 • Evidence for successful management of depersonalization syndrome is 
poor. No drugs are licensed for use in the UK.
 • Some evidence supports a role for SSRIs (usually citalopram or 
escitalopram), alone or in combination with lamotrigine (up to 500mg/​
day).
 • Where there is marked anxiety, clonazepam (0.5–​4mg/​day) may be 
useful; anecdotal evidence supports clomipramine (if obsessional 
symptoms are marked), naltrexone, and bupropion.
 • CBT is the only psychological treatment shown to be beneficial in an 
open trial, particularly in tackling anxieties, ruminations, and avoidance 
behaviours relating to identifiable stressors.
 • Other psychotherapeutic approaches: acceptance and understanding 
of symptoms; identification of ‘putative’ defence functions; identifying 
underlying psychopathology; integration of traumatic experiences.
31  As early as 1935, Mayer-​Gross thought psychological explanations to be of ‘limited value’, seeing 
depersonalization as ‘an unspecific preformed functional response of the brain’. Mayer-​Gross W 
(1935) On depersonalization. Br J Med Psychol XV:103–​26.
32  Medford N, Sierra M, Baker D, et al. (2005) Understanding and treating depersonalization dis­
order. Adv Psychiat Treat 11:92–​100.
33  M https://​www.docdroid.net/​zIAJlG7/​cds-​state.pdf [accessed 20 June 2018].

408
Chapter 8  Anxiety and stress-related disorders
Course
 • Onset is usually sudden, with symptoms persisting only for a brief 
period. Gradual onset does occur, and the course is very variable—​both 
episodic and continuous. Occasionally, symptoms may persist for hours, 
days, weeks, months, or even years (rare).
 • Resolution tends to be gradual. Recurrent episodes generally occur in 
the context of recurring (perceived) stressful situations or fatigue.
 • Chronic fluctuating symptoms may be treatment-​resistant.