Oxford Handbook of Psychiatry Panic1 disorder (1)clinical features Essence Panic attack A period of intense fear characterised by a constellation

of symptoms (see opposite) that develop rapidly, reach a peak of intensity in about 10 mins, and generally do not last longer than 2030 mins (rarely over 1 hr). 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), and rarely, physiological symptoms of anxiety may occur without the psychological component (non-fearful panic attacks). Panic disorder2 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 attacks a year. There is usually the persistent worry about having another attack or the consequences of the attack (which may lead to phobic avoidance of places or situationssee Agoraphobia), and significant behavioural changes related to the attack. Symptoms/signs (see opposite)

Physical symptoms/signs are related to autonomic arousal (e.g. tremor, tachycardia, tachypnoea, hypertension, sweating, GI upset) which are often compounded by HVS (in 5060% of cases see pp. 342, 343). 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 symptoms3 (chest pain, back pain, GI symptomsincluding IBS, fatigue, headache, dizziness, or multiple symptoms4). Thoughts of suicide (or homicide) should be elicited as acute anxiety (particularly when recurrent) can lead to impulsive acts (usually directed towards self). N.B. Risk of attempted suicide is substantially raised where there is comorbid depression, alcohol misuse, or substance misuse.

Epidemiology Lifetime prevalence: 4.2% for panic disorder, 8% for panic attacks (mean value derived from American ECAS4 and NCS5); 1.55% for panic disorder, 35.6% for panic attacks (ECA). Women are 23 times more likely to be affected than men. Age of onset has a bimodal distribution with highest peak incidence at 1524 yrs and a second peak at 4554 yrs. Rare after age 65. Comorbidity Agoraphobia (community surveys: 3050%; psychiatric clinics: 75%), depressive 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 prolapse, hypertension, cardiomyopathy, COPD, IBS, migraine).

Differential diagnosis Other anxiety or related disorder (panic attacks may be part of the disorder), substance or alcohol misuse/withdrawal P.345 (e.g. amphetamines, caffeine, cocaine, theophylline, sedative-hypnotics, steroida), mood disorders, psychiatric disorders secondary to medical conditions, medical conditions presenting with similar symptoms (e.g. endocrine: carcinoid syndrome, Cushing's disease/syndrome, hyperthyroidism, hypoglycemia, hypoparathyroidism, phaeochromocytoma; haematological: anaemia, cardiac: arrhythmias, mitral valve prolapse, MI; respiratory: COPD/asthma, HVS; neurological: epilepsyesp. TLE, vestibular dysfunction). Investigations There are no specific tests for panic disorder, however basic investigations should be performed to exclude physical causes (e.g. FBC, U&Es, glucose, TFTs, ECG, and if supported by history/physical examination: toxicology, Ca2+, urinary VMA/pHVA, ECHO, and EEG). 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. Derealisation or depersonalisation (feeling detached from oneself or one's surroundings). Fear of losing control or going crazy. Fear of dying (angor animus). Numbness or tingling sensations (paraesthesia). Chills or hot flashes.

References 1 Panic derives from the Greek god Pan who was in the habit of frightening humans and animals out of the blue. 2 ICD-10 and DSM-IV disagree on the nature of panic disorder. ICD-10 regards true panic attacks as not being situational, and DSM-IV allows for both spontaneous and situational. Hence DSM-IV includes agoraphobia within panic disorder, seeing it as a special case of situational panic disorder (panic disorder with agoraphobia), whereas ICD-10 separates agoraphobia (under the rubric phobic anxiety disorders) from panic disorder (under the rubric other anxiety disorders). Agoraphobia with panic disorder is allowed in ICD-10 when there is avoidance of places or situations where to have a spontaneous panic attack would be difficult or embarrassing.

3 Katon W (1984) Panic disorder and somatization. Review of 55 cases. American Journal of Medicine 77, 1018. 4 Simon GE and Van Korff M (1991) Somatization and psychiatric disorder in the NIMH Epidemiologic Catchment Area study. AJP 148, 1494500. 5 Eaton WW, Kessler RC, Wittchen HU, Magee WJ(1994) Panic and panic disorder in the United States. AJP 151, 41320. P.346 Panic disorder (2)aetiological models There are a number of theories, based primarily on successful pharmacological treatment, to explain the biological basis of panic disorder: The serotonergic model Exaggerated post-synaptic receptor response to synaptic serotonin, possibly secondary to subsensitivity of 5HT1A receptors. The noradrenergic model Increased adrenergic activity, with hypersensitivity of presynaptic alpha2 receptors. (Locus coeruleus activity affects the hypothalamic-pituitary-adrenal axis and the firing rate is increased in panic.) The GABA model Decreased inhibitory receptor sensitivity, with resultant excitatory effect. Cholecystokinin-pentagastrin model Pentagastrin induces panic in a dose-dependent fashion in patients with panic disorder. 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 carbon dioxide hypothesis Explains panic phenomena by hypersensitive brainstem receptors. The neuroanatomical model Suggests that panic attacks are mediated by a fear network in the brain that involves the amygdala, the hypothalamus, and the brainstem centres. The genetic hypothesis Panic disorder has moderate heritability of around 3040% (from family and twin studies). Most studies to date suggest that vulnerability is genetically determined, but critical stressors are required to develop clinical symptoms. The recently discovered genomic duplication (DUP25) on chromosome 15 (found in 7% of the population, but -95% of patients with panic disorder) is perhaps the best evidence yet for genetic susceptibility1. References 1 Gratacos M, Nadal M, Martin-Santos R, et al. (2001) A polymorphic genomic duplication on human chromosome 15 is a susceptibility factor for panic and phobic disorders. Cell 106, 36779. P.347

P.348 Panic disorder (3)management guidelines Combination of pharmacological and psychological treatments may be superior to single approach. Pharmacological

SSRIs (e.g. paroxetine [at least 40 mg], fluoxetine, fluvoxamine, citalopram, sertraline) are recommended as the drug of choice (unless contraindicatedsee p. 280). In view of the possibility of initially increasing panic symptoms, start with low dose and gradually increase. Beneficial effect may take 38 weeks. Alternative antidepressant TCAs (e.g. imipramine or clomipramine) although not specifically licensed in the UK have been shown to be 7080% effective (possible alternatives include: desipramine, doxepin, nortryptiline, or amitriptyline.) MAOIs (e.g. phenelzine) again not licensed, but may be superior to TCAs (for severe, chronic symptoms). There is also some favourable evidence for RIMAs (e.g. moclobemide). BDZs (e.g. alprazolam or clonazepam) should be used with caution (due to potential for abuse/dependence/cognitive impairment) but may be effective for severe, frequent, incapacitating symptoms. Use for 12 weeks in combination with an antidepressant may cover symptomatic relief until the antidepressant becomes effective. N.B. Anti-panic effects do not show tolerance, although sedative effects do. If initial management is ineffective Consider change to a different class agent (i.e. TCA, SSRI, MAOI) or combination (e.g. TCA+Lithium, SSRI+TCA). If treatment-resistant consider alternative agent (e.g. carbamazepine, valproate, gabapentin, low-potency BDZ [diazepammay need high dose], venlafaxine, inositol, verapamil). If successful Continue treatment for -1yr before trial discontinuation (gradual tapering of dose). Do not confuse withdrawal effects (1020% of patients) with re-emergence of symptoms (5070% of patients). If symptoms recur, continue for -1yr before considering second trial discontinuation. (N.B. Patient may wish to continue treatment, rather than risk return of symptoms).

Psychological

Behavioural methods: to treat phobic avoidance by exposure, use of relaxation, and control of hyperventilation (have been shown to be 5883% effective1). Cognitive methods: teaching about bodily responses associated with anxiety/education about panic attacks, modification of thinking errors2. Psychodynamic methods: 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. P.349

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.

Emergency treatment of an acute panic attack

Maintain a reassuring and calm attitude (most panic attacks spontaneously resolve within 30 mins). 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).

References 1 Ballenger JC et al. (1997) Panic disorder and agoraphobia. In Treatments of psychiatric disorders (2nd ed.) Vol.2. American Psychiatric Press, Washington DC, pp 142152. 2 Barlow DH and Craske MG (1988) Mastery of your anxiety and panic. Center for Stress and Anxiety Disorders, State University for New York at Albany.