‘Tus Joomvus or Nunvous axo Mexray Dissase (Copyright © 1973 by The Williams & Wilkins Co. ANXIETY STATES (ANXIETY NEUROSIS): A REVIEW ISAAC MARKS, M.D.} ano MALCOLM LADER, M.D. ‘An anxiety state is a cluster of symptoms based on fear, the source of which is not recognized by the patient. ‘The anxiety may be sustained, but more often is episodic from a few minutes to hours or days. The chief symp- toms are those of anxiety and its physical concomitants in the absence of other illness and independent of specific situations; they inelude breathing and swallowing difficulties, palpitations, dizziness, irritability, and faint- ness, Depression, phobias, and obsessions are common complications. The syndrome occurs in young adults of both sexes and its course may be acute or chronic, Acute forms may present in epidemics which are culture bound, €.., Koro and epidemic hysteria. Chronic forms ean fluetuate and persist for many years without other physical or psychiatrie syndromes appearing Between attacks the patient feels fairly well. Prevalence is estimated at 2 to 5 per cent of the normal population and 6 to 27 per cent of psychiatrie outpatients. The syndrome requires differentiation irom depressive and Vol 185, No. Printed in U.S.A. phobic disorders and from physical conditions which produce anxiety. Different aspects of anxiety have ocea- sionally been reported, but. integration of the existing literature has been lacking. ‘This report has drawn together the availa- ble scientific and clinical literature from the descriptive standpoint. Btiology and treat ment will only be alluded to briefly and have been reviewed in detail in the authors’ ook Clinical Anxiety (40) In this paper “anxiety” is used synony- mously with the term “free-floating,” non- situational or general anxiety, to distinguish it from phobias or normal fear, We are eon- cerned here with anxiety which is beyond the normal response to stress and which handicaps the everyday functioning of an individual, Like other emotions, anxiety can occur in a wide range of clinica! states. It is a common feature of affective disor- ders, the agoraphobie syndrome, and obses- sive-compulsive disorders, while it can also be a symptom of schizophrenia, conversion *Department, of Psychiatry, Institute of Pey- chiatry, University of London, United Kingdom. Reprint requests should be sent_to Dr. Isaac Marks, Institute of Psychiatry, De Crespigny Park, London, $E5, United Kingdom. symptoms, organic confusional state, or epi- lepsy. Where anxiety dominates the clinical picture in the absence of other gross disor- ders the term “anxiety state” is used. An anxiety state or anxiety neurosis is a cluster of symptoms based on fear, the souree of which is not recognized by the patient (46). The anxiety may be chronic and sustained, but more characteristically is episodic from a few minutes to hours or days, The chief symptoms are fear, appre- hension, inattention, palpitations, respira- tory distress, dizziness, faintness, sweating, irritability, tremor, chest pains, feelings of impending disaster, and fears of death. ‘These occur in the absence of other illness and exist independently of specific external situations. In hetween attacks the patient feels relieved but not completely well. Some psychological writings separate “state anxiety” from “trait anxiety.” “State anxiety” refers to anxiety felt at a partieu- Jar moment: “I am feeling anxious right now.” “Trait anxiety” refers to a habitual tendency to be anxious over a long period of time: “T generally feel anxious.” This dis-4 ISAAC MARKS AND MALCOLM LADER tinction can be found in anxiety states. Pa- tients may describe anxiety symptoms as a recent change from their previous norm (state anxiety). Other patients admit to al- ways having more anxiety than their peers (high trait anxiety); many factors may bring such a person to the psychiatrist, ée., change him irom an anxious “normal” to an anxious “patient,” including a change in life situation such as promotion at work, marriage, the birth of offspring, increased availability of psychiatric services, and a sympathetic general practitioner. However, the two forms of anxiety commonly occur together, with increased life stresses, raising the anxiety of an already anxiety-prone in- dividual beyond the point of tolerance. There is disagreement about whether anxiety states are a discrete homogeneous clinical syndrome (2, 53, 66, 70), and their features undoubtedly shade in many cases into several other forms of neurosis. How- ever, until further component subgroups have been reliably demonstrated the global category will remain useful for descriptive purposes. Phobie disorders used to be sub- sumed under the heading “anxiety state” until recent work showed these to be usually sufficiently distinctive to form a separate diagnosis (44). The same may apply in time to other patients who are cur- rently included under the rubrie of anxiety states. RELATIONSHIP TO DEPRESSION Anxiety states are sometimes included under the general heading of “affective dis- orders,” along with pathologies of mood like depressive illnesses and hypomania, Al- though anxiety states often resemble certain forms of depression, the different course and ireatment require their separate classifica tion. ‘When anxiety is prominent and other de- pressive features are slight it can be difficult to know whether a given patient has a de- pressive illness or an anxiety state, Of a series of patients diagnosed as anxiety states 19 per cent were subsequently re-la- beled as depressives (12). The distinction might have some prognostic import. Walker (66) studied 111 outpatients in whom free- floating anxiety was the cardinal symptom and classified them according to outcome. They were treated by reassurance and amy- lobarbitone only. A group of 24 of these patients with good outcomes was isolated these patients were thought to be best de- seribed as depressives with episodie anxiety. Such patients had no precipitant for their illness and had minor depressive features such as gloomy forebodings, inability to plan, fears of illness and death, and self reproach. ‘The distinction between depression and anxiety state is useful as a guide to treat- ment (24). Of 126 patients admitted to psy- chiatric hospitals in Neweastle with “affec- tive disorder,” 45 were diagnosed as depres- sives and 66 as anxiety states. At discharge and at 6 months follow-up independent, as- ors found a significantly better outcome to eleetroconvulsive therapy (ECT) and to trieyelie drugs in depressives than in pa- tients with anxiety states. Patients with anxiety states were also younger, their mean age being 35 compared to 51 for the depressives. In a further study principal components analysis of data from 145 patients suffering from a primary mood change of anxiety and/or depression revealed a bipolar factor, with anxiety symptoms at one pole and de- pressive symptoms at the other; this was interpreted as indicating that there are two syndromes corresponding to anxiety and de- pression within the category of affective disorder (54). Further statistical analyses suggested that these two syndromes were distinet entities with a line of demarcation between them (23). Prognostie studies showed that anxiety states were related to a poor outcome, depressive features to a good outcome (39, 57)ANXIETY STATES 5 ‘TERMINOLOGY Numerous names have been given to con- ditions which are indistinguishable from anxiety states. The cardiovascular symp- toms have led to several synonyms such as “muscular exhaustion of the heart” (31) “Irritable heart” was Da Costa’s (11) term for a condition he described as functional cardiac disorder, and subsequent authors spoke of Da Costa’s Syndrome (70). “Car- diac neurosis” (58) was an equally popular label and “vasomotor neurosis” another, while during World War I “neurocireu- Jatory asthenia” eame into vogue (50) and subsequently became widely adopted (10, 17, 35, 52, 67). Over the same period other writers supposed that the symptoms were brought on by exercise and so the “effort syndrome” came into being (42) to describe “that condition of ill-health in which [those] symptoms and signs which are pro- duced in normals by excessive exercise are called forth in patients by Jesser amounts and in which no definite signs of structural disease are discovered.” The chief symp- toms were dyspnea, palpitations, and fatigue, and patients were treated by graded exercise to try and inerease their effort tolerance. The incidence of cardiac disease was only 1 per cent in this group (19). The effort syndrome, irritable heart, soldier's heart, and neurocir- culatory asthenia were prominent in the medical literature of the time (42, 50, 52), as sufferers made poor soldiers and had a high rate of invalidism out of the army, so that its carly detection in recruits beeame a matter of some importance. The similarity of sol- dier’s heart to anxiety states was nob always recognized. As Wood (70, p. 767) com- mented, in civilian life “the change of sex, plus the lack of khaki uniform, seems to have proved an effective disguise. ‘Uffort syn- drome’ in the male soldier becomes cardiac, respiratory or other neurosis in the female civilian.” Wood noted further that the symp- toms and signs of the disorder closely re- sembled those of emotion, especially fear, rather than of effort. ‘The nervous symptoms of an anxiety state led to several other names. Neuras- thenia or nervous exhaustion was an early term (1, 32, 56) while Freud introduced a label which is still often used today, namely anxiety neurosis (16); French authors fol- lowed suit with “névrose d’angoisse” (30, 33). Yet another synonym not used today was “‘somatisation psychogenic reaction” When the clinieal picture comprises phobias as much as free-floating anxiety, it is commonly called a phobic anxiety state. PREVALENCE, Differing criteria of diagnosis make com- parison of various authors rather difficult. Nevertheless most authors agree that anxi- ety states are fairly common (Table 1). In a normal population prevalence has been estimated as 20 to 4.7 per cent in Britain and the United States, while anxiety states form 10 to 14 per cent of patients in cardiol- ogy practices (Table 1) in the same coun- tries. They make up a substantial propor- tion of patients who consult general practi- tioners, accounting for 27 per cent of those who saw their doctors for psyehiatrie prob- Jems in a London practice (36). Among psy- chiatric outpatients anxiety states are diag- nosed in 6 to 27 per cent of all cases, but other related conditions like phobie disor- ders swell some of these percentages. The figure of 8 per cent for Maudsley Hospital outpatients (29) excludes phobies and has remained constant over the past 9 years. In two series of patients who received psycho- therapy the incidence of anxiety states was mueh higher, presumably through special selection for that treatment (3, 43). ‘Anxiety states are one of the commonest neurotic disorders. At the Maudsley Hospi- tal they account for 8 per cent of all outpa- tients, in comparison with only 3 per cent6 ISAAC MARKS AND MALCOLM LADER for phobie disorders and 1 to 2 per cent for ‘obsessive-compulsive neuroses. ‘SEX. INCIDENCE Figures derived from general medical practice indicate two-thirds of patients with anxiety states to be women, but among psy- chiatric patients the sexes are equally dis- tributed (Table 2). This discrepancy may be due to differences in diagnostic usage or in actual ineidence but it is impossible to decide between these alternatives on the ev- idence available. In some series, ¢.g. ‘Wheeler et al. (67), it is clear that agora- phobies were included in the sample, and TABLE 1 Prevalence of Anziety States TABLE 2 Sex Incidence of Anziety States Source In general population 72 | Hagnell (25) In general medical practice 67 Wood (70) 7 Wheeler ef al. (67) m4 ‘Kedward and Cooper (36) In psychiatric practice 13 Yap (71) (Chinese) aL Tan (64) (mainly Chinese) 8 Miles ef al. (46) 50 Hare (20) 8B Bitinger (14) 83 Yep (71) (Western expatriates) a Winokur and Holeman (69) 60 Luff and Garrod (43) 88 Aces Source In total population 3.6 | British urban | Kedward and Cooper (86) 2.0 | British rural — | Gross (22) 210 | Tennessee rural | Roth and Luton (55) 4.6 | Swedish rural | Hagnell (25) (0-yr pe- riod prevalence) 4.7 | Boston Cohen et al. (10) In general medical practice Of patients with cardiovascular symptoms 10 | Boston White and Jones (68) 14 | London Wood (70) Of patients with peychiatric symplome 27 | London Kedward nd Cooper (36) In paychiatric practice 6 { Oslo Bitinger (14) 7 | Tekeran Davidian (12) 8 | London Hare (29) 15 | Kuala Lumpur | Tan (64) 16 | Hong Kong | Yap 71) 20 | Chieago Carmichael and Masser- man (7) 25 | London Garmany (18) 27 | Boston Cobb (9) Of prychiatric patients 18 | Teheran Davidian (12) 19 | New York Hamilton ef al. (26) 22 | New York Hamilton and Wall (27) 43 | Kuala Lumpur | Tan (64) Of patients in psychotherapy 40 | Plymouth Blair et al. (8) 44 | London ‘Luff and Garrod (43) sinee agoraphobia is commoner in women this may have overemphasized the incidence of women in the total group. On the other hand in the study of Kedward and Cooper (86) phobies were specifically excluded, yet the female preponderance of anxiety states remained. If the discrepancy is genuine it might suggest that women have milder forms of anxiety states as it is likely that the severer forms are more commonly re- ferred to psychiatrists. Alternatively, or in addition, men may ignore minor degrees of this disorder and come for treatment only when they are severely incapacitated. How- ever, no evidence for such a phenomenon has been described for phobie disorders (34). AGE INCIDENCE An anxiety state is mainly a disorder of young adult life; the mean age of onset of symptoms is the mid-twenties (Table 3), the great majority starting between the ages of 16 to 40. The mean duration of symptoms before treatment is about 5 years. Distribution of the age of onset closely follows that of the agoraphobic syndrome? * Marks, I. Unpublished data.ANXIETY STATES 7 Anxiety which begins for the first time after the age of 40 is commonly part of a depressive syndrome rather than of an anx- iety state. GENETIC ASPECTS ‘The literature on this topic has been sue- einctly reviewed by Slater and Shields (61) ‘There is much evidence for genetic influ- ences on phenomena related to anxiety. Selective breeding experiments with mam- mals show that emotional activity analo- gous to anxiety depends to some extent on multiple genetie factors (5, 13, 48). Studies in man (41, 65, 72) indicate that physiolog- ical responses such as habituation, number of spontancous fluctuations in skin conduct ance, pulse and respiration rate, and elec~ troencephalogram variables are more alike in monozygotic than in dizygotie pairs. The same applies to the number of neurotic complaints checked in questionnaires (60) ‘The similarity of monozygotic pairs reared apart was actually greater than those reared together, so that their environmental influences were unlikely to have been re- sponsible for this concordance. Evidence also points to a high incidence of anxiety states in the families of patients with anxiety neurosis. Three studies re- viewed by Slater and Shields (6, 10, 45, 61) revealed that 15 per cent of parents and siblings of anxiety neuroties were similarly affected, compared to only 0 to 5 per cent of relatives of control groups. Slater and Shields (61) found that about 50 per cent of monozygotic co-twins of anxiety neurotics had the same diagnosis, and 65 per cent had marked anxiety traits. In contrast, in ira- ternal twins concordance for anxiety neu- rosis was only about 4 per cent while marked anxiety traits were noted in only 13 per cent. Other twin studies reviewed by these authors also found monozygotic pairs to be more alike than dizygotic pairs with respect to neurosis. None of these studies excluded the effect of familial environment. However, Shields (60) described three pairs TABLE 3 Age Incidence of Anziely States Source veto | AL onset of symptoms Miles et al. (46) Wheeler ef al. (67) ‘Marks (unpublished) 0 | Hagnell (25) At time of treatment 23 a 29 20-4 a Miles et al. (46) 28 Wood (70) 32, Wheeler ef al. (67) 36 Garmany (18) of identical twins reared apart who were alike in that both twins showed marked tendencies to anxiety later in life. These findings were difficult to explain on purely environmental grounds. Slater and Shields argue that anxiety states can best be understood on an interac- tional model. The constitutional tendency to become anxious might be a component of personality which is variable in degree and in that respect is normally distributed throughout the population, predisposing to conditions like anxiety states if it is marked. Whether an anxiety state develops will also depend on the amount of exposure an individual has to stress in his environ- ment. Stress might precipitate an anxiety state which might continue irreversibly in some individuals after the stress has pasced of. The little evidence that is available sug- gests that patients with anxiety states come from stable backgrounds. Miles et al. (46) found that the childhood home environment was “good” or “fair” in 75 per cent of his sample, and only 26 per cent had lost one or both parents before the patient was eight, ‘Twenty-three per cent of the siblings had emotional difficulties. More than half their patients were married, and none were di- voreed. Intelligence and education covered the normal range. In their earlier history patients did not give a history of undue physical illness.8 ISAAC MARKS AND MALCOLM LADER CULTURAL ASPECTS Some evidence suggests that anxicty states may be commoner in certain cultural groups than in others. In a University Clinic in Kuala Lumpur significantly more Chinese than Malays or Indians presented with anxiety neurosis (64). In Bangkok more Chinese than Thai women were found with neuroses in which anxiety featured (63). It is not clear how much this reflects the marginal status of Chinese in those so- cieties. The sex ratio may also differ across cultural groups. Yap (71) found a great preponderance of men over women in Chinese patients with anxiety states in Hong Kong, whereas Western expatriates there who had similar problems were as often women as men, However, this might reflect referral practices rather than preva- lence. Not only the prevalence but also the elin- ieal features of anxiety states are culturally influenced. Among southern Chinese there is a strong belief that male genitals are essen- tial for the preservation of life, and sper- matic fluid is highly valued. Sexual exeess regarded as destructive of health. Thus, it is, not surprising that among male Chinese with anxiety states 60 per cent complained of sexual symptoms, notably of imagined spermatorthea (64). In contrast, few male Malay patients had sexual complaints. ‘The same beliefs help us to understand the phenomenon ealled Koro (49). This is a term of Malay origin to describe a culture- bound syndrome of acute anxiety which predominantly affects emigré southern Chinese, It was described as early as 1834. ‘The Chinese phrase for this condition is “shook yang’—literally “shrinking penis.” ‘The syndrome normally occurs sporadically but can be epidemic. It takes the form of an acute panic in which the patient fears his penis is shrinking into the abdomen with potentially lethal consequences. To prevent this the penis is grasped manually by the patient or his relatives and friends. Occa- sionally chopsticks or string are tied to the penis to prevent its retraction, Together with this acute fear come palpitations, breathlessness, bodily pain, visual blurring, fainting, vomiting or nausea, and paresthe- sia. In the rare female cases there are com- plaints of retraction of the nipples of the breasts, and even of the vulva. ‘The response to anxiety and pain takes place within an elaborate cultural context in which the patient, his family, and the community respond in socially patterned ways. Zhorowski (73) found that Jewish and Italian Americans respond emotionally and tend to exaggerate their pain experi- ence, while Irish and “old Americans” in contrast are more stoical. Worry is clearly not solely the preroga- tive of modern man. Anxiety about being bewitched was commonplace in medieval Europe and a detailed guide to recognize witchoraft was widely published (62). One chapter of this book is devoted to demon- strating how witches deprive men of their “virile members,” which suggests that even Koro-like syndromes may have occurred. ‘The terror of being under a spell has been described by anthropologists observing many other pre-industrial societies. Austra- lian aborigines who lived in primitive con- ditions in Northern Queensland completed @ Cornell Medical Index translated into the vernacular. They had many complaints about fatigue, anger, insomnia, backache, and respiratory trouble (8) EPIDEMICS OF ACUTE ANXIETY From time to time epidemics of acute anxiety affect various communities. These epidemics are short-lived and the affected are not left with any sequelae. Preeipitating factors can usually be discerned in the background, and the form of the anxiety is culturally determined. In Singapore one such epidemie took the form of Koro and was described by Ngui (49). In July 1967 there was an outbreak of wine fever in Singapore and amid much publicity pigs were inoculated to control theANXIBTY STATES 9 outbreak. In October a few cases of Koro presented, and rumors spread that Koro could be caused by eating pork from in- fected or inoculated pigs. Over the next few days up to 100 cases of Koro a day pre- sented at general hospitals and many more patients consulted their general practition- ers. On the 7th day, at the height of the epidemic, a panel of experts appeared on television and radio explaining to the public the psychological nature of Koro and the impossibility of penile retraction occurring. ‘The incidence of Koro dropped sharply the next day and the epidemic ended shortly after. Of 232 cases which were interviewed, 94 per cent were southern Chinese, the re- mainder being from several groups. Only 3 per cent of the eases were females. Forty- nine per cent of patients were age 21 to 40 and 81 per cent age 16 to 20. Seventy-seven per cent of the patients were single. Only 1 in 5 of the patients had more than one epi- sode of Koro, The condition appeared to be benign, with the majority recovering fully without serious consequences. Koro is reminiscent of other forms of acute anxiety in different cultures. In West- ern societies occasional cases of panic are described in young men who suddenly think they are homosexual. This, however, does not become epidemic. Epidemics of anxiety symptoms such as overbreathing and faint- ness sometimes occur in young women, es~ pecially those like schoolgirls or nurses who are associated together in institutions. Two such epidemics were studied in de- tail in Britain, Both oceurred in schools and lasted only a few days. The first epidemic (47) affected girls in a secondary modern school in Blackburn. Two-thirds of the total of 500 girls were affected, and one- third of the affected girls required inpatient care, Many had repeated episodes. The pre~ cipitating circumstances were clear. Earlier in the year the town had received wide- spread adverse publicity during an epidemic of polio. Immediately before the epidemic of anxiety the schoolgirls went to a cathe- dral to attend a ceremony under Royal pa- tronage. The ceremony was delayed by 3 hours because of late arrivals, and the girls waited in parade mainly outside the build- ing. Twenty of them felt faint and had to. break ranks to lie down. The next morning there was much chatter about fainting. At assembly in school there was one faint, fol- lowed shortly after by three girls saying they felt dizzy. When a fourth girl was asked to get a glass of water for the original fainters, she too said she felt faint. Over the next two school periods more girls felt faint and were sat on chairs in a main corridor. A mistress thought that to prevent their fall- ing from the chairs in a second faint they should lie on the floor. They lay thus in the corridor in full view at mid-morning break. ‘The phenomenon now became epidemic. The chief symptoms were excitement and fear leading to overbreathing and its conse- quences—faintness, dizziness, paresthesia, and tetany. The appearance of many girls was quite alarming. Each time school as- sembled more cases appeared. By day 12, however, the nature of the epidemie was realized and firm management prevented the problem from spreading again. ‘The opidemie began among the 14-year- olds and spread to younger children. On the first day 25 per cent of the girls were af- fected, and on day 5, 16 per cent developed symptoms. The cases occurred during break two times more frequently than at any other time. The symptoms slowly subsided over 2 few days in the affected subjects. Affected girls had higher neuroticism and extroversion scores on the Eysenck Person- ality Inventory, and the highest scores were found in those girls who were the only members of their class to develop symp- toms. A similar pattern was noted in an epi- demic of faintness in a Portmouth girls’ sehool. This again lasted but a few days. ‘The symptoms occurred exclusively during school hours, Onee again affected girls had higher neuroticism seores than unaffected10 ISAAC MARKS AND MALCOLM LADER girls, but their extroversion scores were not high. CLINICAL FEATURES Anxiety states are characterized by the appearance of many symptoms and but few signs. The chief complaints may be of epi- sodie anxiety or attacks of panic, spells of choking, smothering or difficulty in breath- ing, palpitations with rapid heartbeat, pain in the chest, nervousness, dizziness, faint- ness, “get tired easily,” “irritable with the children,” or “believe I have heart trouble.” The chief type of complaint may determine which kind of specialist the patient will see. Diserete episodes of anxiety are charac teristic of the disorder. The patient sud- denly feels ill, anxious, weak, has palpita- tions, lightness and dizainess in the head (as opposed to true vertigo), feels a lump in the throat and weakness of the legs, and has an illusion of walking on shifting ground. He feels as though he can’t breathe, or he may breathe rapidly to the point of hyper- ventilation which leads to paresthesia. He fears he may faint, or die, or seream out loud, or “lose contro!” or “go mad.” His nervous panie may become s0 intense that he may be rooted to the same spot for some minutes until the intensity diminishes. ‘The seizure may last a few minutes or several hours. It may pass off leaving the patient feeling as fit as before until the next attack occurs the same day or weeks or even months later, or he may feel apprehen- sive and tremulous throughout the day (with the panic attacks being periodie exac- exbations of this feeling). The attacks may occur only once in a few days or come in successive waves every few minutes to be- ‘come so troublesome that the patient is eon- fined to bed. In more chronic forms the course is typically punctuated by remis- sions and relapses of varying duration, ‘The intensity of the nervousness varies from paralyzing terror to mild tension, or the patient may not even be aware of subjective anxiety as such, but simply com- plain of autonomic symptoms, Anxiety may be continuous without punctuation by dis- erete attacks of panic. It may be mixed with mild feelings of depression, desires to cry, and even transient suicidal ideas, but serious suicidal urges are not a feature, Breathing difficulties are common. The complaint may be “I can’t take deep breaths,” “I can’t get enough air,” “my breath keeps catching,” and the patient may in fact show repeated catches in his breathing. The opposite problem of hyper- ventilation may also be found. Choking and swallowing feelings are prominent and may be intensified in crowds so that patients will have to open a window in crowded places. Chest discomfort may inelude precordial pain or aching, palpitations, epigastrie pres- sure or feelings, of gas around the heart, Desires to micturate or defecate can reflect intense anxiety, and the patient may need to be constantly in reach of a toilet. Severe tension may also produce nausea and vom- iting, and this can lead to secondary fears of vomiting when the patient is in public places, with avoidanee of such situations. Anorexia and loss of weight are nob rare. Oceasionally slight mucous diarrhea can occur. ‘Troublesome faintness and dizziness may be triggered by walking or standing. The patient may feel so insecure as to hold on to ‘a nearby chair or walk elose to the walls of nearby buildings. Acute feelings of choking, palpitations, and chest discomfort can ac- company these and lead to fears of fainting, falling, having a heart attack, or dying. These feelings may be intensified in certain situations and may lead to their avoidance, thus giving rise to agoraphobic symptoms. Patients may tend to avoid hot crowded rooms or stores, and will stay clear of a cinema, theater, hairdresser, or church, or if they go there will sit near the end of the aisle to ensure that exit is possible with speed and dignity. Crowded streets, buses, and trains ean become unendurable ordeals which evoke repeated attacks of panie, soANXIETY STATES i that the patient may progressively restrict his activities until he is virtully confined to his home. Travel by automobile is often possible, however, even when all other forms of transport are avoided and the pa- tient is unable to walk alone in the streets, Phobie symptoms are often alleviated by the presence of reassuring adults, so that the patient may be able to accomplish ac- companied what he cannot by himself. Sometimes he may need to be with someone even at home, and spouses may need to give up work and remain at home with the pa- tient. When phobic avoidance is marked its clinical features become indistinguishable from severe agoraphobia. Hypochondriacal fears are frequent. The patient may believe that heart disease or cancer is responsible for his symptoms and may entreat the doctor for repeated rea: surance on this score, yet multiple investi- gations will not allay his fears. General irritability is common. Patients have a low tolerance of irustration, lose their tempers easily, and snap at their spouses and children. Fatigue develops readily, and the patient finds it hard to get through the day’s work. Depersonalization and derealization com- monly occur in anxiety states. Patients complain of feeling unreal, strange, and de- tached or faraway from their surroundings or may attribute the same quality to their environment. The feeling may come at the height of a panic, or at other times when there is no sensation of anxiety. It is more common than is generally appreciated as many patients find it difficult to deseribe their feelings of pereeptual strangeness and may not volunteer these symptoms sponta- neously. The following patient illustrates many of the typical features found in anxiety states, In this case the anxiety began in a normal well-adjusted personality. A 36-year-old mathematician gave a history of episodic palpitations and faintness over the previous 15 years, There had been periods of re- mission of up to 5 years, but in the past year the symptoms had increased, and in the last few days the patient had stopped working because of his distress. His chief complaints were that at any time and without warning, he might sud- denly feel he was about to faint and fall down, or tremble and experience palpitations, and if standing would cringe and clutch at the nearest wall or chair. If he was driving a car at the time he would pull up at the curbside and wait for the ieelings to pass off before he resumed his journey. If it ocourred during sexual intercourse with his wife he would immediately separate from her, If it happened while he was lecturing his thoughts became distracted, he could not concentrate and he found it difficult to continue. He was becoming afraid of walking alone in the street or of driving his car for fear that the episodes would be trig gered by it and was loathe to travel by publi transport. Although he felt safer when accom- panied, this did not abolish his symptoms. Be- tween attacks the patient did not feel completely well, and a slight tremulousness persisted. The attacks could come on at any time of day or night. The patient felt that he lacked energy but ‘was not depressed. He denied that he experienced fear, anxiety or panic during his attacks. The patient, had had a happy childhood with- out nervous symptoms, led an active social life when in remission, and had a contented marriage and vigorous professional life. There was no family history of psychiatrie disorder. During interview the patient was articulate and frank, although unduly humble, Thought content, memory, and orientation were all nor- mal. He had a persistent fine tremor of the head and hands, cold sweaty palms, and a persistent regular heart rate of 106 per minute at rest While his blood pressure was being measured the patient suddenly became extremely anxious, was restless and sweaty, and would not lie down. He cringed when he stood up and sat down crying weakly “help, help.” He tried to tear the ephyg- momanometer cuff from his arm, saying it ‘was painful. Blood pressure was 130/80 mm Hg at this time, pulse rate remaining at 116 per minute, After 3 to 4 minutes he calmed down again but wanted to remain sitting in an easy chi This patient illustrates the fluctuating nature of the disorder: that subjective feel-12 ings of anxiety need not be complained of during these episodes despite multiple phys- iological and behavioral concomitants of fear, that depression can be minimal or ab- sent, that anxiety is largely nonsituational although colored by phobie elements, and that autonomie signs of anxiety may be prominent. It shows the marked overreae- tion to mild stresses such as measurement of one’s blood pressure and it also shows that the disorder can occur in well funetion- ing personalities with stable backgrounds. Anxiety states ean also present as an ex- acerbation of life-long increased anxiety, as the following case illustrates, A 52-year-old civil servant had suffered with excessive anxiety all his life. He recalled that as a child he had been timid and had avoided situations where physical harm could occur such as schoolboy fights and rough sports. He had on ‘two occasions played truant from school when ‘the school bully had threatened him. His aca- demie record at school bad been indifferent and he did especially poorly in examinations when he became very anxious. In oral examinations he would usually stammer to a halt, ‘The patient's mother was deseribed as highly strung and both his siblings had been treated by their general practitioners for anxiety attacks precipitated by marital erises. As a young man, ‘the patient had been very shy of social oc- casions and of girls but he had fought against his shyness by making himself do public speaking. He married at age 28. His wife had always been sympathetic towards his anxiety symptoms but regretted that he had not been able to achieve his full potontial beeause of them. He was work- ing as an administrative assistant but was study- ing part-time to take a degree and to become & teacher. ‘The patient. described how any alterations in routine threw him into a panic and he would worry for days in advance over minor difficulties at work. He had visited his general practitioner many times over the previous 25 years and had used barbiturates to help him over exacerbations of his anxiety. However, he thought that the use of drugs was a weakness in him. The present episode had been precipitated 3 months earlier when he had been given additional responsibilities ISAAC MARKS AND MALCOLM LADER at work and also as examinetions became im- rminent At interview the patient gave a very good ac- count of himself. His symptoms were “all-per- vasive feelings of anxiety,” “tension in the neck,” and “palpitations, dry mouth, and sweating, On physical examination the expected signs of sympathetic overactivity were present, ‘Treatment consisted of small doses of diazepam (1 mg six times a day) and supportive and re-educative psychotherapy in which the patient learned to take a realistic view of his sapabilities and shortcomings. He attained a pre- earious equilibrium which he has maintained for 4 years. Exacerbations of anxiety are treated with sedatives for a limited period. Systematic observations of the frequency of each complaint in anxiety states have been made by Wheeler et al, (67) and by Miles et al. (46). Wheeler et al. studied 173 patients suffering from “neurocireulatory asthenia” who were identified in a cardiol- ogy practice. Their controls were 50 men and 11 women from a large industrial plant and 41 healthy postpartum women from the Boston Lying-In Hospital. The patients of Miles et al. suffered from “anxiety neu- rosis” and came from the inpatient wards of the Massachusetts General Hospital. For- ty-three were men and 33 were women. Fifty of these were selected for detailed study of symptoms. Detailed analysis of symptoms in patients from the two studies is seen in Table 4. The five commonest symptoms found by Wheeler et al. were palpitations, tires early, breathlessness, nervousness, and chest pain. The five com- monest complaints found by Miles et al. were nervousness, palpitations, acute anxi- ety at home, apprehensiveness, and fatigue. Patients with anxiety states have symp- toms similar to those of the average anxious person, but the symptoms are more intense. Hamilton (28) devised a 14-item rating scale for anxiety which differentiated 42 pa- tients with anxiety states from 53 dermato- logical patients who had anxiety. The pro- files of the two groups were parallel, sug- gesting that the patteming of the symptomsANXIETY STATES 13 was the same in each group, even though patients with anxiety states had the more severe anxiety. The threshold for anxiety is lowered in patients with anxiety states, ie., stimuli which produce only slight or no anxiety in a normal person lead to much anxiety in pa- tients with anxiety states, PHYSIOLOGICAL CHANGES Despite the earlier description of irritable heart for this syndrome, there is generally no sign of overreactivity to normal sympa thetic stimulation (e.g., by injection of ad- renaline) nor does the condition result from hyperadrenalism or hypersensitivity of the peripheral autonomic apparatus (70). ‘There is no characteristic electrocardiogram abnormality associated with anxiety states (35) ‘A number of abnormalities have been re- ported in patients with anxiety states in re- sponse to standard exercise or stress (re~ viewed in 10 and 51). Stimuli and stresses which produce abnormal responses or un- usual responses at lower stimulus levels in- clude pain, cold, muscular effort, earbon di- oxide, noise, flash, and anticipation. Abnor- mal responses to these situations were noted in patient’s pulse, minute respiration/vol- ume, ventilatory efficiency, increase in blood lactate concentration, work perform- ance, oxygen consumption, and wineing and withdrawal reaetions. On the other hand 24-hour urinary excretion of 17-ketosteroids does not differ from normal. It is not clear whether any of the abnormalities demon strated so far apply specifically to patients with anxiety neurosis or whether they are the general signs of poor health, chronic illness, or poor state of physical training. Recent investigations (10, 38) demon- strated that infusions of sodium lactate produced anxiety in patients with anxiety neurosis much more than they did in con- trols and that glucose and saline infusio caused no anxiety. This work confirms that TABLE 4 Percentage of Patients with Anziety Neurosis Who Showed Particular Symptome All figures refer to patients of Wheeler et al. (67) except figures in parentheses which refer to 50 patients of Miles et al. (46) Patients | Controls Palpitation 97 0) | 9 Tires easily 95 (78) | 19 Breathlessness 90 (75) | 13 Nervousness 88 (99) | 27 Chest pain | 10 Sighing 7 (0) | 16 Dizainess 78 (5) | 16 Faintness 70 @0) | 2 Apprehension a1 0) | 3 Headache 38 (65) | 28 Paresthesia i 25) | 7 Weakness 5605) | 3 Trembling 40) | 17 Breath unsatisfactory 5) | 4 Insomnia | Bas) | 4 Unhappiness | -) | 2 Shakiness 47) | 16 Fatigue 4578) | 6 Sweating 45 62) | 33 Fear of death ao] 2 Smothering 40 (8) | 4 Syneope ac) | ou Flushes, we) | — Yawning a) | Pain radiating to left arm | 30 (—) | 2 Vascular throbbing mo] 4 Dry mouth mE) | 1 Nervous chill we) | = Frequency wr) | 2 Nightmares 18 (40) | 9 Vomiting and diahoes | 14 (—) | 0 Anorexia BGs) | 3 Ponting sO | - *—, not cited. patients with anxiety neurosis react abnor- mally to many stresses of a psychological, physiological, and biochemical kind, but we remain ignorant of the basie disturbance di tinguishing anxiety states from normals which leads to this abnormal reaction. Patients with anxiety states have been shown to have increased forearm blood flow at rest (37). Their skin conductance also shows an inorease in spontaneous fluctua- tions and a decrease in rate of habituation to repeated auditory stimuli (41).4 ISAAC MARKS AND MALCOLM LADER DIFFERENTIAL DIAGNOSIS ‘The commonest and most difficult prob- lem is the differentiation of anxiety states from depressive disorders. So difficult ean this be that many suggest the two condi- tions cannot usefully be distinguished. Tn depressive disorders there may be marked anxiety with all its psychological and phys- iological concomitants. However, there are also pronounced depressive moods, hopeless- ness about the future, feelings of guilt and unworthiness, desires to ery, and suicidal ideas. In addition, there may be a past his- tory of depressive episodes, or of mania, and a family history of the same. Where the de- pressive and anxiety components appear present to equal degree in a patient, the clinical practice is justifiable whereby anti- depressive measures are resorted to firs and only after their failure are sedatives employed. Anxiety states are distinguished from phobie states by the fact that the anxiety tends to occur at any time and is not pre- cipitated by particular situations. Phobie anxiety oceurs only when the patient finds himself in specific situations, and not on other oceasions, unless the patient is antici- pating future contact with the phobic ob- ject. In phobias, free-floating (nonsitua- tional) anxiety is more prominent than sit- uational anxiety. The quality of the anxiety is the same whether or not it is generated by particular events and does not serve to distinguish phobic from anxiety states. Be- cause some anxiety states are exacerbated by specific circumstances, while some pho- bias, especially agoraphobia, are accompa- nied by free-floating anxiety, certain pa- tients do straddle the two disgnostic cate- gories and ean be said to have phobie anxi- ety states. Where possible, the distinction between anxiety states and phobias is im- portant to make, since, unlike anxiety states, phobias do respond to psychological treatments like flooding and desensitization. In patients with marked anxiety and al- coholism, doubts may arise whether the al- coholism is primary or secondary. In the latter case there is usually a clear history of alcohol being employed to alleviate pre-ex- isting anxiety or phobias and, where there are multiple phobias removal of the patient from the phobie situations should result in reduction in alcohol intake, thus clarifying the diagnosis. Primary aleoholism would be suspected where anxiety appears to follow withdrawal rather than precede it, or to fol low excessive aleohol intake, Acute anxiety states could be confused with a few physical disorders (59). Tachy- cardia can occur both in anxiety states and in paroxysmal tachycardia. During parox- ysmel tachycardia patients can experience great anxiety and extreme exhaustion. With very fast rates there may be sweating, pal- lor, and faintness. In anxiety states the rate is usually below 140 per minute, while in paroxysmal tachycardia the rate is usually between 140 and 220. Diagnosis of the lat- ter depends upon the history of repeated attacks of tachycardia of extremely abrupt onset and offset, usually without cause but sometimes related to postural changes, and upon the electrocardiogram. Thyrotoxicosis can mimic an anxiety state when physical signs are minimal and the complaints are mainly of palpitations, tiredness, anxiety, and tremor. However, the tremor is fine, not coarse, and the palms are warm and pink, not cold and clammy as in anxiety. Tachycardia is usually present but the pulse rate does not slow to normal Jevels during sleep. Diagnosis can be con- firmed by finding an elevated protein bound iodine, an inereased uptake of radioiodine, or a raised level of serum triiodothyronine. Rarely a pheochromocytoma might mimic an anxiety state, Here patients can have attacks of sweating, palpitations, nervousness, coldness, and pallor. However, they may also complain of angina and ab- dominal pains, and all these complaints are associated with very high blood pressure. The hypertension may be sustained, al- though it usually fluctuates or is paroxys-ANXIETY STATES mal. During hypertensive phases the urine will contain large amounts of catechola~ mines and vanilly] mandelic acid. Another uncommon mimic is “sponta- neous” hypoglycemia, especially if ib is epi- sodie. The symptoms are relieved by food, and the blood sugar level during an attack will reveal the problem. The glucose toler- ance test shows a flattened curve or even a progressive diminution and symptoms may occur during the test and be relieved by intravenous glucose. COURSE AND PROGN' Anxiety states may be acute or chronie, Acute forms ean follow extreme stress such as near fatal accident or injury and last but a few days or weeks. No referral at all to a doctor may result or the patient may only see his general practitioner or attend psy- chiatric outpatients. Short-lived anxiety states can be indistinguishable from depres sive disorders, so that it is common clinical practice to treat acute anxiety states with antidepressants on the premise that they are depressive episodes. The long term outeome of such cases is unclear, as most prognostic studies have concerned more severe chronic forms which have required inpatient treat- ment. There is no evidence that patients with anxiety states develop diseases said to be caused by anxiety any more than other peo- ple, even though they all have high anxiety. For example, in 2 20-year follow-up of 173 patients Wheeler ef al. (67) found that they ‘were not predisposed to develop hyperten- sion, heart disease, peptic ulcer, diabetes, asthma, thyrotoxicosis, ulcerative colitis, hysteria, or schizophrenia. In that study fewer deaths had occurred than were to be expected. In another study (46), a 2- to 12-year follow-up of 62 cases of anxiety neurosis found no case of previous unrecog- nized medical or surgical disease which was ater found to be associated with the symy toms, and no patient later became psy- chotie. 15 A careful review of the literature on out- come of anxiety states was made by Greer (20). He confined his account to studies which: 1) had followed up patients with anxiety states for more than 1 year from discharge from treatment; 2) had ascer- tained outcome in more than 20 patients, representing at least 75 per cent of the orig- inal sample; and 3) had obtained follow-up information at least in part from psychiat- rie interviews. Reports based entirely on evidence from mailed questionnaires were excluded. Six investigations were found which met these requirements (Table 5), all of which were retrospective. The diagnostic criteria were not always explicit. The data supplied suggested that they conformed to the clini- cal picture described earlier. ‘The proportion of neuroses diagnosed as anxiety states in these studies varied from 6 to 40 per cent. ‘Methods used to determine outeome dil fered in these studies. Some were based on verbal assessment (4, 14, 15, 67). These in- cluded an evaluation of symptoms and their incapacitating effect. Wheeler et al. (67) also assessed family and social life. Miles et al. (46) and Greer and Cawley (21) used rating seales to measure symptomatic out- come and social functioning, From Table 5 we can see that 41 to 59 per cent of cases were recovered or much improved at 1- to 20-year follow-up in the different. studies ‘Thus the outcome of anxiety states appears to be satisfactory in roughly 50 per cent of the eases in these studies. None of the stud- ies found a high incidence of serious phy: cal or other psychiatric illness at follow-up. One report nob meeting Greer’s criteria found a much poorer outcome of anxiety states in the 3 years follow-up. Kedward and Cooper (36) followed up patients who had consulted general practitioners in Lon- don and found 18 per cent to be recovered or much improved. Firm prognostic variables did not emerge from these studies, although in another re- port (2) patients who had been ill for Jess16 ISAAC MARKS AND MALCOLM LADER TABLE 5 Systemctic Follow-up Studies of Anziely Neurosis Based on Greer (20) Outcome Fotlowyo| Ba ‘Author and Souree Treatment iat) So pags PR] ne proved | proved | B25 ” %e) ele! ® Wheeler et al. (67): outpa- | Reassurance; sed: tients, Cardiac Clinic, Bos- ton 20 | co | 12 | 35 8 Miles et al. (46): inp: ‘Massachusetts General Hospital, Boston sessions Bitinger (14): inpatients Uni- versity Psychiatric Clinic, ts, | Psychotherapy, mean 2.7 212 | 62 | 8 | so | a) 2 Drugs; ECT; supportive Oslo 10 | 2% 41 35 | 24 Blair ef al. (3): Outpatients, | Psychotherapy, mean 7 Plymouth, United King- | sessions dom 16 | 8 59 a2] 9 Ernst (15); Outpatients, Uni- | Psychotherapy: 34 5 ses- versity Psychiatric Clinie,| sions, 34 5-82 sessions; Zurich rest, hypnosis, analysis | 24 | 31 | 13 | 32 | a5 | 19 Greer and Cawley (21): Inpa- | Supportive, physical, or tients, Maudsley Hospital, |” psychotherapy London 5 | av | 27 | 30 | 19 | 2 than a year showed the most short term tural change: ‘The case of the Australian improvement on placebo or barbiturates. REFERENCES 1, Beard, G. M. Neurasthenia or nervous ex- hhaustion. Boston Med. Surg. J, 3: 217-220, 1869. 2. Black, A. A, Factors predisposing to a placebo response in new outpatients with anxiety states. Brit. J. Peychiat., 118: 557-567, 1969. 3. Blair, R, Gilroy, J. M. and Pilkington, F” Some observations on out-patient. psychotherapy with @ follow up of 285 cases, Brit. Med. J., 1; 318-821, 1967. 4. Deleted in proof. 5. Broadhurst, P. L. and Bignami, G. 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