Download Mood disorders: pearls of wisdom from a lifetime of observation

Keynote Lecture
Latest Advances in Psychiatry
LATEST ADVANCES
IN PSYCHIATRY
A
At 83 years of age, Professor Angst
still takes more than a keen interest
in research into mood disorders
and in particular is actively engaged
in analysing the data collected from
an epidemiological cohort he began
to observe more than 30 years ago.1
Furthermore, he still does not shy
away from questioning perceived
wisdom when data he and his colleagues have collected point to a different conclusion.
Prospective trials show that
there is a high lifetime prevalence
of psychiatric disorders – of the
order of 40-50 per cent 1-5 – and
prevalence rates for mood disorders, anxiety disorders and substance abuse/dependence of 20-30
per cent. Professor Angst personally felt that in reality the prevalence rates for psychiatric disorders
may be higher because the figures
are based on retrospective data and
not lifelong prospective studies.
However, the lifetime prevalence rates of major depressive disorder (MDD) compared with
bipolar disorder (BD) have been
generally
overestimated
in
Professor Angst’s view. The discrepancy may be due to trial selection criteria largely based on the
classification systems, DSM-IV and
ICD-10. So, instead of the 1:1 ratio
of MDD to BP Professor Angst and
colleagues have obser ved in the
Zurich study, 1 others have
recorded much higher ratios of
MDD to BP of around 4:1.2-5
If broader diagnostic criteria that
reflect more closely the real-life
experience of those with mood disorders are applied to patient populations, then a higher proportion of
bipolar disorders would emerge.
For example, when Professor
Angst’s diagnostic specifier for bipolarity6 criteria were applied to stud-
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Mood disorders: pearls of wisdom
from a lifetime of observation
Professor Jules Angst provided a fascinating account of some of the work that has led him
to challenge fundamental thinking about bipolar disorder in his Keynote Lecture on the
classification, course and treatment of mood disorders, at the ninth Latest Advances in
Psychiatry Symposium in London in March 2010. Steve Titmarsh had the privilege of
listening and here provides a brief overview.
ies where the ratio of MDD to BP is
much higher than 1:1, then overdiagnosis of major depressive disorder was reduced, revealing a higher
proportion of patients with bipolar
disorders; this was the case in a
patient study across 18 countries7
and in two well-known prospective
epidemiological studies (EDSP
Munich,8 NCS-R USA9). Identifying
such ‘hidden’ or subthreshold bipolar patients might make it possible
to make an earlier diagnosis of bipolar disorder, for which there is an
average delay of 10 years from onset
of depressive symptoms, and perhaps specific treatment could be
employed earlier.
In any case, Professor Angst
explained, the risk of someone with
depression becoming bipolar is
about 1.25 per cent per year – and
the risk of becoming bipolar remains
the same no matter how many
episodes of depression have been
experienced before a hypomanic or
manic episode manifests. So that, he
argued, if people with depression
lived to be more than a 100 years old,
they would all become bipolar. The
risk of switching from mania to
depression is 3 per cent per year.
Continuum of mood disorders
Professor Angst explained that his
obser vations, in particular of the
male conscripts and female subjects on the electoral role in the
canton of Zurich in his native
Switzerland, whom he has followed
from age 19 and 20 years to age 49
and 50 years, have led him to the
conclusion that mood disorders
exist on a continuum from depression via bipolar disorders to mania.
He felt that there are no distinct
classes between the different disorders. The divisions between the
disorders defined by classification
systems are arbitrar y, but they
make sense clinically because they
help with treatment decisions.
In reality, almost ever yone
exhibits at least mild ‘symptoms’ of
mood disorders; it is part of normal
human experience. For example,
people in love have traits similar to
hypomania. The difference between
those who are in love and people
who are pathologically hypomanic is
that people in love do not exhibit the
kind of dangerous risky behaviours
– gambling, driving too fast, etc. –
that people who are ill are prone to.
Other clues to the hidden bipolar pathology are family history and
comorbid disorders such as anxiety and substance abuse. Mania is
significantly associated with family
history of mania, Professor Angst
explained. Bipolar disorder is significantly associated with anxiety
disorders and substance abuse,
such as alcoholism, in contrast to
major depressive disorder, which
is significantly associated with suicide. Around 30 per cent of bipolar
patients, as defined by DSM-IV cri-
Progress in Neurology and Psychiatry 27
Keynote Lecture
Latest Advances in Psychiatry
Jules Angst, MD, is Emeritus Professor of Psychiatry at the
University of Zurich and Honorary Doctor of Heidelberg
University, Germany. He trained under Manfred Bleuler
and was Professor of Clinical Psychiatry and Head of the
Research Department of Zurich University Psychiatric
Hospital (the Burghölzli) from 1969 to 1994. He continues
to work full-time in epidemiological and clinical research.
His 1966 monograph established and validated the distinction between bipolar disorders, depression and
schizoaffective disorders on the basis of genetics, course
and personality. He was the first to show the unfavourable
long-term course of mood disorders.
His recent main research has been in epidemiology covering the classification, comorbidity and course of mood and
anxiety disorders including subdiagnostic syndromes (recurrent brief depression, bipolar-II disorders, hypomania, minor
bipolar disorder and anxiety), obsessive-compulsive disorder, neurasthenia, perimenstrual syndromes and migraine.
Professor Angst has received many awards in recognition of his work, including the Anna Monika Award (1967
and 1969), Paul Martini Prize for Methodology in Medicine
(1969), Otto Naegeli Prize (1983), Eric Strömgren Medal
Professor Angst with Dr David Baldwin, Chairman
of PSIG, at the ninth Latest Advances in Psychiatry
Symposium in March 2010
after one week. If there is no
response after two weeks, it is fairly
certain the patient will not respond
to the treatment.
Combination therapy has been
shown to be more ef fective than
monotherapy in terms of reducing
the number of relapses and in
reducing suicide rates. Finally,
something perhaps a little more
surprising: lithium and clozapine
therapy may protect against
dementia: several studies show
that the drugs attenuate the development of dementia.11-14
References
(1987) and the Emil Kraepelin Medal of the Max Planck
Institute, Munich (1992). He has also received the Selo Prize
NARSAD/Depression Research, USA (1994), Mogens Schou
Award for Research in Bipolar Disorder, USA (2001), the
Burghölzli Award for Social Psychiatry (2001), the Lifetime
Achievement Award of the International Society of Psychiatric Genetics (2002) and the Wagner-Jauregg Medal (2007).
teria, have a family history of mania
compared with 14 per cent among
people with depression.
Pharmacological myths
Professor Angst was keen to dispel
a couple of myths about drug treatment. First, he contended that
there is no statistical evidence that
antidepressants induce hypomanic
episodes more frequently than
placebo. The idea is a result of
wrong statistical thinking and computations, he said. The natural history of bipolar disorder is an up and
down course, by definition, and
studies have shown that there is
around a 30 per cent spontaneous
switch rate from depression to
hypomania. As Professor Angst
explained in his autobiographical
notes published in Acta Psychiatrica
Scandinavica last year:10 ‘Switches
to hypomania can only occur in
response to treatment, non-responders, who prevail among placebotreated patients, cannot switch; the
statistics have therefore to correct
for responders; unbiased metaanalyses were negative.’
Similarly, Professor Angst contended that, contrary to the general
view, correct statistical analysis of
trial data shows that antidepressants start to induce change within
the first 12 days of their administration and do not take a number of
weeks to have an effect as has been
assumed. That has implications for
treatment.
Treatment recommendations
Professor Angst’s observations over
many years lead him to the conclusion that people with depression
should be treated with an antidepressant first – whether they are bipolar
or not. If there is a response, such as
an increase in activity signaled by
something such as the patient sleeping less in the first week or two, then
a mood stabiliser should be added.
If there is no response, then the dose
of antidepressant should be doubled
28 Progress in Neurology and Psychiatry
1. Angst J, Gamma A, Neuenschwander M, et al.
Prevalence of mental disorders in the Zurich cohort
study: a twenty year prospective study. Epidemiol
Psychiatr Soc 2005;14:68-76.
2. Zimmermann P, Wittchen U, Lieb R, et al. Early
developmental stages of psychopathology (EDSP)
Study. Arch Gen Psychiatry 2009:66:1341-52.
3. de Graaf R, Bijl RV, Smit F, et al. Psychiatric and
Sociodemographic Predictors of Attrition in a
Longitudinal Study The Netherlands Mental Health
Survey and Incidence Study (NEMESIS). Am J Epidemiol
2000;152:1039-47.
4. Kessler RC, McGonagle KA, Zhao S, et al. Lifetime
and 12-month prevalence of DSM-III-R psychiatric disorders in the United States: results from the National
Comorbidity Survey. Arch Gen Psychiatry 1994;51:8-19.
5. Kessler RC, Berglund P, Demler O, et al. Lifetime
prevalence and age-of-onset distributions of DSM-IV
disorders in the National Comorbidity Survey
Replication. Arch Gen Psychiatry 2005;62:593-602.
6. Angst J, Gamma A, Benazzi F, et al. Diagnostic specifier for bipolarity. J Affect Disord 2004;73:133-46.
7. Angst J. Diagnostic concepts of bipolar disorders: a
European perspective. Clin Psychol Sci Pract
2009;16:161-5.
8. Zimmermann P, Bruckl T, Nocon A, et al.
Heterogeneity of DSM-IV major depressive disorder
as a consequence of subthreshold bipolarity. Arch Gen
Psychiatry 2009;66:1341-52.
9. Angst J, et al. Major depressive disorder with subthreshold bipolarity in the National Comorbidity
Survey Replication. Am J Psychiatry (in press).
10. Angst J. From psychoanalysis to epidemiology:
autobiographical notes. Acta Psychiatr Scand
2009:119:87–97.
11. Gasse C, et al. Does lithium therapy protect against
dementia? (abstract). In: Fifth European Stanley Conference
on Bipolar Disorder. October 5 - 7 2006, Barcelona, Spain.
The Stanley Medical Research Institute.
12. Nuñez PV, Orestes FV, Gattaz WF. Lithium and risk
for Alzheimer’s disease in elderly patients with bipolar
disorder. Br J Psychiatry 2007;190:359-60.
13. Angst J, Gamma A, Gerber-Werder R, et al. Does
long-term medication with lithium, clozapine or antidepressants prevent or attenuate dementia in bipolar and
depressed patients? Int J Psychiatr Clin Prac 2007;11:2-8.
14. Kessing LV, Forman JL, Andersen PK. Does lithium
protect against dementia? Bipolar Disord 2010;12:87-94.
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