Anxious Depression: A Reemerging Subtype of Depression
Paula J. Clayton Department of Psychiatry, University of Minnesota, Minneapolis, Minnesota 55455
Clinical investigators have long been able to distinguish between the two psychiatric syndromes originally known as manic depressive insanity and anxiety neurosis. Kraepelin (9) wrote eloquently on the mood state and symptoms seen in melancholia: The fundamental mood in the state of depression is most frequently a somber and gloomy hopelessness. . . . More rarely, anxiety is the principal feature. Sometimes it is more inward anxiety and trembling, a painful tension which can rise to mute and helpless despair. Sometimes it is an uneasy restlessness. In other cases, it is a peevish, insufferable, dissatisfied and grumbling mood. Everything torments, annoys, irritates, fills the patient with bitterness; the sunshine, people enjoying themselves, music, everything done and left undone in the surroundings. Although Kraepelin felt that anxiety and agitation were frequently the transition between mania and depression, he also recognized anxiety as part of the depressive syndrome. On the other hand, Freud (7) described the nervous symptoms of the anxiety state that led him to use the term anxiety neurosis. In the 1950s clinical researchers extended our knowledge of these two syndromes by publishing studies that required specific criteria for inclusion and exclusion, systematic inquiry into symptoms, appropriate controls, even follow-up, and family history data. Wheeler et al. (16) published a 20-year follow-up of 173 patients with neurocirculatory asthenia (anxiety neurosis, effort syndrome, neurasthenia) and delineated the more specific syndrome resembling anxiety neurosis. They did not acknowledge psychological depressive symptoms as part of the picture, but did report overlapping vegetative depressive symptoms such 3s fatigue and insomnia. In the same department, in their classic paper on clinical observations in manic depressive disease, Cassidy et al. (5) designated patients tor the study who had mood changes that included any of the following terms: blue, worried, discouraged, depressed, anxious, low, scared, fearful, angry, afraid, Bloomy, hopeless, despondent, do not care, empty, disgusted, as well as the vegetative and psychological symptoms with which we are now very familiar. They reported that 33% of these patients had classic anxiety attacks, and 62% described some sort of "spell" that included anxiety attacks, dizzy spells, confused spells, and undetermined spells. Marks and Lader (10) summarized the dilemma by writing, like other emotions anxiety can occur in a wide range of clinical states. It is a common feature of affective disorder, the agoraphobic syndrome, and obsessive-compulsive disorder. While it can be a symptom of schizophrenia, conversion syndrome, organic confusional state, or epilepsy, where anxiety dominates the clinical picture, in the absence of other gross disorders, the term anxiety state should be used. It denotes a cluster of symptoms based on fear, the source of which is not recognized by the patient. With the advent of structured interviews, research diagnostic criteria, and DSM-III (1), the common sense of clinical psychiatry sometimes seems to have been lost. By defining agoraphobia, panic disorder, and generalized anxiety disorder as separate disorders (with only the last two being excluded if attributed to major depressive disorder), the field runs the risk of losing the two specific clinical syndromes of anxiety neurosis and depressive illness. Despite an excellent review by Breier et al. (4) on the diagnostic validity of the anxiety disorders that concluded that there was strong support for the diagnostic validity of panic disorder, but few data to support a separate diagnostic classification of generalized anxiety disorder, the syndrome continues to be represented in DSM-III-R (17). Although DSM-III-R has rescued part of the anxiety syndrome by recognizing that panic attacks and agoraphobia are related, the authors of it have amplified the overlap of generalized anxiety disorder with major depressive disorder by requiring for the former that the A symptom be 6 months of "excessive worry" (a symptom that occurs in 75% of patients with pure depressive disorder) and by not making the presence of major depressive disorder an exclusion criterion. Tyrer (15) recently proposed grouping together the three anxiety disorders, which would return the syndrome to the 1950 concept of anxiety neurosis. If we remember the criteria of Marks and Lader (10) for an anxiety disorder, that anxiety must dominate the clinical picture in the absence of other gross disorders, then the situation becomes clear. In the presence of another gross disorder, depression, an anxious depression appears as a potentially interesting subtype. Given that psychiatry has difficulty distinguishing between two major disorders, it is not surprising that it also has difficulty in subtyping depression. Many authors have used the terms anxious depression, agitated depression, and involutional melancholia interchangeably. The majority of data on involutional melancholia has not supported the continuation of the subtype, and thus it was deleted from DSM-III and ICD-9. How and if anxious depression, however, overlaps with agitated depression has not been well considered. In first reporting on his rating scale for depression in 1960, Hamilton (8) found that the primary factor resembled a retarded depression, but a second factor emerged that resembled agitated depression with loadings on agitation, insomnia, anxiety, hypochondriasis, gastrointestinal symptoms, and weight loss. A more recent multivariate analysis by Overall and Rhoades (13) of the Hamilton Depression Rating Scale on depressed patients entered into clinical psychopharmacology drag trials indicated that in 420 profiles, five preliminary clusters emerged: anxious, suicidal, somatizing, vegetative, and paranoid. The anxious type was identified by elevated levels of depressed mood, psychic anxiety, and initial insomnia. Other potentially important symptoms were agitation and obsessive-compulsive symptoms. The authors postulated that, because of the symptoms, the anxious subtype might be milder than the other subtypes. The authors made no attempt to correlate the subtypes with age, sex, race, outcome, or family history. Thus, whether the subtype is clinically meaningful, many studies have shown an association between anxious and agitated symptoms and included it as a subtype of depressive disorders. More recently, Fawcett and Kravitz (6) have looked at anxiety symptoms as they occur in depressive illness. Using 200 in- and outpatients diagnosed as major depressive disorder using the SADS and RDC criteria, they found that 72% of these patients reported moderate worry, 62% reported psychic anxiety, 42% reported somatic anxiety (autonomic and muscular symptomatology), 29% panic attacks, 19% reported phobic symptoms, and 1.2% obsessive-compulsive symptoms. These anxiety ratings correlated positively with also being of the endogenous subtype on the SADS. Further unpublished data on an expanded sample confirms these findings. The majority of depressed patients when interviewed systematically reported the whole spectrum of anxiety symptoms, with worry and psychic anxiety being the most common. Other anxiety symptoms such as discouragement, insomnia, lack of energy, somatic concern, depersonalization, subjective anger, distrustfulness, as well as decreased concentration and classic diurnal variation, correlate significantly with this anxious depression. How this subtype correlates with other variables such as age, sex, outcome, treatment, and family history is not yet understood. In the Fawcett and Kravitz paper (6) the authors noted that by finding that a substantial proportion of depressed patients also report
ed anxiety symptoms, clinicians were forced to consider this in planning management and predicting treatment response. They pointed out that in the future, it may be used as a guide in determining which antidepressant might be most appropriate for which patient. They also theorized that if anxiety symptoms were not controlled early in the treatment of depression, they may produce noncompliance and premature termination. More recent work with the use of anxiolytics in depressed states may also need to be reviewed in light of these findings. In contrast to the suggestion of Overall and Rhoades, based on patients’ initial symptoms only, that anxious depression may be milder, more recent studies concluded the opposite —anxious depression or mixed anxiety and depression have the worst prognosis. Stavrakaki and Vargo (14) found that when anxiety and depression coexist, function is most impaired. They reported increased chronicity of illness, reduced response to conventional therapies, and a poorer Prognosis. Two recent epidemiologic studies confirmed this. Angst and Dobler-Mikola (2), in a field sample of young men and women, reported that most of the anxiety syndromes (anxiety states, simple phobia, social phobia, agoraphobia, panic attacks) coexisted. They also found in comparing various subgroups of depressives and anxiety disordered subjects that those with diagnoses of depression and anxiety had the highest frequencies of serious depressive symptoms and, as expected, more symptoms on the SCL-90 scales of depression, anxiety, and phobias. Murphy et al. (12), in a follow-up study of the "cases" of depression and anxiety in the Sterling County study, found a poorer outcome in those who were depressed compared to those who were anxious. The worst outcome was in those with depression and anxiety, although they resembled closely the depression-only study group. An interesting result of this study is that even in a community sample like this, the number who are depressed and anxious (N = 24) was three times greater than those with pure depression (N = 8). A further morbidity study of this population (11) confirms a poorer outcome for the total group of depressives. In summary, there seems to be a sizable group of classic depressed patients who report along with depressed mood, symptoms of worry, anxiousness, tenseness, fearfulness, panic attacks, phobic, and obsessive-compulsive symptoms. These patients appear to have many other symptoms that we have previously associated with endogenicity (especially diurnal variation). Despite their high scores on anxiety, in current studies they receive no specific treatment; the symptoms go unrecognized, not verbalized, or minimized. Although early studies, probably combining a number of outpatients with inpatients, indicated that the anxious depressives were the most mild and resembled "the old neurotic depression," more recent studies have all coalesced to conclude that the overlap of anxiety and depression predicts the most serious outcome, including poorer treatment response, more chronicity, and higher mortality. This subtype of depression demands further study.
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