© 2001 The Royal College of Psychiatrists
EDITORIAL |
The case for cothymia: mixed anxiety and depression as a single diagnosis
Department of Public Mental Health, Division of Neuroscience and Psychological Medicine, Imperial College School of Medicine, London W2 IPD, UK
Every psychiatrist and general practitioner diagnoses mixed anxiety and depression readily. The combination of typical depressive symptoms, such as low mood, lassitude and pessimism about the future, and anxious ones, such as tension, insomnia and irritability, is so common that about one in seven of the population is suffering from them at any one time in the UK (Meltzer et al, 1994). Yet the diagnosis is not allowed in either DSM—IV (American Psychiatric Association, 1994) or ICD-10 (World Health Organization, 1992) classifications except as what is curiously called a ‘sub-syndromal’ disorder, one that is allowed only if "neither the anxiety nor depressive symptoms reach the threshold for diagnosis of another psychiatric disorder" (World Health Organization, 1992). For such a common and important diagnosis this restriction might seem to be a little odd and may explain the acronym that is given to the condition: MADD — mixed anxiety and depressive disorder. Although the mixed diagnosis is not permitted except in this diluted form, general practitioners are invited to use it because ostensibly these disorders are very common in primary care and are seen most frequently in this setting. Oddly enough, mixed anxiety and depression is also formally permitted in the unduly neglected diagnostic grouping of adjustment disorders (Casey, 2001), where mixed anxiety and depression (code 43.22) is allowed as a category of diagnosis and also in combination with other symptoms. Why is the syndromal diagnosis of mixed anxiety and depression — a diagnosis that can be called cothymia, a term suggested some years ago (Tyrer, 1989) because it represents two moods of equal significance occurring together — not used in routine diagnostic practice? It is worth reviewing the evidence, both in favour of the status quo and the reasons for change.
REASONS FOR MAINTAINING THE SEPARATION OF ANXIETY AND DEPRESSION EXCEPT IN SUB-SYNDROMAL FORM
Anxiety and depression are different moods
There is no doubt that despite the frequency with which anxiety and
depression coexist they are different mood states and common sense tells us
that they should be classified in different parts of the psychiatric
classification. Indeed, a great deal of work has established that their
symptoms are generally separate. The evidence of this distinction has led to
anxiety and depression being placed in different sections of both ICD—10
and DSM—IV, with depression in all its aspects being classified under
mood disorders and anxiety being placed among neurotic and stress-related
disorders. Once this decision was reached, however, it is difficult to justify
joining two diagnoses across a major boundary of classification. No other
example exists and even mixed anxiety and depression in its sub-syndromal form
(in ICD—10) is uncomfortably classified together with the mood
disorders. Allowing a syndromal equivalent into the classification would
undermine the validity of the main classification system.
Comorbidity is an accepted part of classification in mental
disorder
After DSM—III (American
Psychiatric Association, 1980) had attempted to impose a
hierarchical system for depressive and anxiety disorders but demonstrably
failed to do this satisfactorily, many diagnoses were allowed together and the
comorbidity industry was born. If major depressive disorder can coexist with
social phobia, simple phobia, obsessive—compulsive disorder and
post-traumatic stress disorder as comorbid conditions, why should not anxiety
and depression do likewise? The fact that there is a high degree of
association between them does not invalidate their descriptions as comorbid
disorders. Similar degrees of association are found in, for example, social
anxiety disorder and avoidant personality disorder
(Herbert et al, 1992),
but this does not mean that they should be diagnosed together.
Combined diagnoses would greatly increase the classification system
and make it unworkable
This is an understandable argument. There are already nearly 500 diagnostic
groups in ICD—10 (excluding the second digit after the point in the F
codes) and many more in DSM—IV. Allowing common comorbid conditions to
exist as separate diagnoses would more than double this number and, if
multiple comorbidity also became similarly classified, the system would become
so large and cumbersome that it would cease to be of any value and collapse
under its own weight. Like the Victorian passion for classifying phobias by
their situational components, there would be regular new additions to the
classification as nosologists demonstrated more and more recondite
associations.
REASONS FOR INCLUDING COTHYMIA (OR A SIMILAR TERM) AS A SYNDROMAL DIAGNOSIS OF MIXED ANXIETY AND DEPRESSION
Evidence from genetics
Although none of the common mental disorders is inherited by a single
genetic mechanism, work on individual genes can help to determine the
vulnerability to disorder and establish a set of risk factors, each of which
is subject to a degree of genetic influence on the developmental
psychopathology. Twin studies provide no evidence that the genes responsible
for generalised anxiety disorder and major depressive disorder are different,
and at least one study suggests that they are actually the same
(Kendler et al, 1992).
Other studies in which anxiety and depression are studied together show
support for the notion of at least a partly inherited general neurotic
syndrome (Tyrer, 1985; Andrews et al, 1990)
in which personality features in the anxious/fearful group (cluster C in DSM)
are important accompaniments.
Evidence from neurobiology
There are several different experimental models of anxiety and depression
and for years attempts have been made to find those that can be used
independently to evaluate anti-anxiety and antidepressant drugs. All these
models have failed demonstrably, possibly because there has been a failure to
understand the interrelationship between cholinergic, dopaminergic and
adrenergic systems in the brain and, in particular, for the role of ascending
serotonergic pathways in opposing the effects of other symptoms
(Robbins, 1997). Newer models
that better fit the data posit a greater role for serotonin than other
monoamines and show that an interactive model involving both depression and
anxiety is the ‘best fit’ for the data. Thus, for example, the
difference between the antidepressant and anxiolytic effects of compounds such
as selective serotonin reuptake inhibitors (SSRIs) may depend only on whether
they are acting on presynaptic (anxiolytic) or post-synaptic (anti-depressant)
5-HT1A receptors (de Vry,
1995). The persistent efforts to find different mechanisms for
anxiety and depressive symptoms therefore are likely to fail and the evidence
that pharmacological treatments for depression are just as appropriate for
anxiety and depression is consistent with the neuropharmacological
evidence.
Epidemiological studies
Mixed anxiety and depression is the most common mental disorder by far in
epidemiological studies in which it has been possible to be measured
(Meltzer et al,
1994). Unfortunately, because it is not in the DSM classification,
international comparisons are not possible and this hinders interpretation.
Evidence from the data of the mixed category and of anxiety and depression
separately suggests that they possess the same factor structure and therefore
it is not surprising that mixed conditions are more common than pure ones
(Jacob et al, 1998).
There are also social class differences that support the recording of anxiety
and depressive conditions together (Lenzi
et al, 1993).
Evidence from treatment studies
There has long been an interest in diagnosis acting as a selection process
for treatment. This notion of treatment being dissected by diagnosis is
seductive because one important way of demonstrating that conditions that
appear to be similar are really different is if only a proportion responds to
a specific treatment (e.g. the dissection of iron-deficiency anaemia from
pernicious anaemia through the effect of iron supplements). The different
diagnoses within the anxiety group have largely failed to be effective
dissectors of treatment. However, both psychological therapies and drug
treatments, such as benzodiazepines, tricyclic antidepressants, SSRIs and
newer compounds (selective noradrenaline and serotonin reuptake inhibitors,
e.g. venlafaxine), show some differences between anxiety and depressive
disorders and it is important to know whether the linked
anxiety—depressive disorders respond differently as well. The possible
differences in the efficacy of these agents have been handicapped by the
Procrustean diagnostic straightjackets forcing a primary diagnosis of anxiety
or depression. Allowing the joint diagnosis would be likely to improve the
scope of treatment studies and improve recommended guidelines.
Research studies in this area should test the effect of treatments in single anxiety and depressive disorders as well as in cothymia. This would prevent the counteracting tendency of what could be described as ‘pharmacopsychiatric creep’, in which the pharmaceutical industry greets every new single diagnosis with enthusiasm in the hope that a specific therapeutic agent can be tailored to fill ‘a hole in the market’. Clinicians seldom get an opportunity to determine whether any agent found to be effective in a specific disorder (e.g. generalised anxiety disorder) is equally effective in others that are similar, because treatment studies are generally carried out only within the confines of specific diagnosis, not between them.
The use of psychological approaches, such as cognitive—behavioural therapy and other psychotherapies, also needs to be assessed in joint disorders, and may require modification in such conditions. Prospective studies of the treatment of cothymia would add much more than post hoc evaluations of comorbid anxiety and depression studies and also would help in determining whether there is real merit in combining these moods in a single diagnosis.
Evidence from outcome studies
The outcome of cothymia, or mixed anxiety—depression in which both
anxiety and depression are present at a syndromal level, is significantly
worse than the outcome of either diagnosis alone
(Emmanuel et al,
1998). The difference between the outcome of the combined
diagnosis and the individual diagnoses is much greater than the differences
between anxiety and depressive conditions compared separately, which are
generally small and not significant overall
(Emmanuel et al, 1998;
Seivewright et al,
1998), although more information is needed from less selected
populations. The outcome studies to date support the value of the cothymia
diagnosis to a greater extent than individual anxiety and depressive
diagnoses.
CONCLUSIONS
On balance, the evidence in favour of a diagnosis of syndromal combined anxiety and depressive disorder as useful in clinical practice is good. Selection of treatment and prediction of prognosis are two possible practical advantages of such a diagnosis, but more needs to be done to determine its clinical importance in prospective intervention studies. Other labels for this condition are possible, but the suggested title of cothymia (Tyrer, 1989) implies that anxiety and depression are equal partners in its presentation. Greater awareness of these important mood states in combination would automatically follow the granting of at least provisional diagnostic status, and act as a spur to improving a part of psychiatric classification that remains in some disarray.
REFERENCES
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[Abstract/Free Full Text] - Casey, P., Dowrick, C. & Wilkinson, G. (2001) Adjustment disorders: fault line in the psychiatric glossary. British Journal of Psychiatry, in press.
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