<<

. 45
( 68 .)



>>

REFERENCES


Alexopoulos, G. S., Meyers, B. S., Young, R. C., et al. (1993). The course of geriatric depression
with ˜reversible dementia™: a controlled study. Am. J. Psychiatry, 150, 1693“9.
Alexopoulos, G. S., Meyers, B. S., Young, R. C., et al. (1997). Vascular depression hypothesis.
Arch. Gen. Psychiatry, 54, 915“22.
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders,
4th edn. (DSM-IV). Washington, DC: APA.
Angst, J. (1978). Verlauf endogener Psychosen. In Aktuelle Neurologie und Psychiatrie,
ed. J. Finke and R. Tolle, pp. 203“10. Berlin: Springer.
Berrios, G. E. and Bakshi, N. (1991). Manic and depressive symptoms in the elderly: their
relationships to treatment outcome, cognition and motor symptoms. Psychopathology,
24, 31“8.
Braun, C. M. J., Larocque, C., Daigneault, S., et al. (1999). Mania, pseudomania, depression,
and pseudodepression resulting from focal unilateral cortical lesions. Neuropsychiatry,
Neuropsychol. Behav. Neurol., 12, 35“51.
Broadhead, J. and Jacoby, R. (1990). Mania in old age: a first prospective study. Int. J. Geriatr.
Psychiatry, 5, 215.
Chen, S. T., Altshuler, L. L., and Spar, J. E. (1998). Bipolar disorder in late life: a review. J. Geriatr.
Psychiatry Neurol., 11, 29“35.
Dhingra, U. and Rabins, P. V (1991). Mania in the elderly: a five-to-seven-year follow-up.
J. Am. Geriatr. Soc., 39, 582“3.
Dinan, T. (2002). Lithium in bipolar mood disorder. Br. Med. J., 324, 989“90.
Fazekas, F., Niederkorn, K., Schmidt, R. et al. (1988). White matter signal abnormalities in
normal individuals: correlation with carotid ultrasonography, cerebral blood flow measure-
ment and cerebrovascular risk factors. Stroke, 19, 1285“8.
261 Atypical features of bipolarity in old age


Fujikawa, T., Yamawaki, S., and Touhouda, Y. (1995). Silent cerebral infarctions in patients with
late-onset mania. Stroke, 26, 946“9.
Goodwin, F. K. and Jamison, K. R. (1984). The natural course of manic-depressive illness.
In Neurobiology of Mood Disorders, ed. R. M. Post and J. C. Ballenger, pp. 20“37. Edinburgh:
Williams and Wilkins.
Goodwin, F. K. and Jamison, K. R. (1990). Manic-Depressive Illness. New York: Oxford
University Press.
Hardy, B. G., Shulman, K. I., and Zucchero, C. (1997). Gradual discontinuation of lithium
argumentation in elderly patients with unipolar depression. J. Clin. Psychopharmacol., 17, 22“6.
Hays, J. C., Krishnan, K. R. R., George, L. K., et al. (1998). Age of first onset of bipolar disorder:
demographic, family history, and psychosocial correlates. Depress. Anxiety, 7, 76“82.
Jeste, D. V., Lacro, J. P., Bailey, A., et al. (1999). Lower incidence of tardive dyskinesia in
risperidone compared with haloperidol in older patients. J. Am. Geriatr. Soc., 47, 716“19.
Kessler, R. C., Rubinow, D. R., Holmes, C., et al. (1997). The epidemiology of DSM-III-R bipolar
I disorder in a general population survey. Psychol. Med., 27, 1079“89.
Kobayashi, S., Okada, K., and Yamashita, K. (1991). Incidence of silent lacunar lesions in normal
adults and its relation to cerebral blood flow and risk factors. Stroke, 22, 1379“83.
Krauthammer, C. and Klerman, G. L. (1978). Secondary mania: manic syndromes associated
with antecedent physical illness or drugs. Arch. Gen. Psychiatry, 35, 1333“9.
Krishnan, K. R. R. and McDonald, W. M. (1995). Arteriosclerotic depression. Med. Hypotheses,
44, 111“15.
McDonald, W. M., Tupler, L. A., Marsteller, F. A., et al. (1999). Hyperintense lesions on
magnetic resonance images in bipolar disorder. Biol. Psychiatry, 45, 965“71.
Murray, N., Hopwood, S., Balfour, D. J. K., et al. (1983). The influence of age on lithium efficacy
and side effects in out-patients. Psychol. Med., 13, 53“60.
Petterson, U. (1977). Manic-depressive illness. A clinical, social and genetic study. Acta
Psychiatr. Scand., 269, 1“93.
Rasanan, P., Tiihonen, J., and Hakko, H. (1998). The incidence and onset-age of hospitalised
bipolar affective disorder in Finland. J. Affect. Disord., 48, 63“8.
Roose, S. P., Bone, S., Haidorfer, C., et al. (1979). Lithium treatment in older patients.
Am. J. Psychiatry, 136, 843“4.
Shulman, K. I. (1997). Disinhibition syndromes, secondary mania and bipolar disorder in old
age. J. Affect. Disord., 46, 175“82.
Shulman, K. I. and Herrmann, N. (1999). The nature and management of mania in old age.
Psychiatr. Clin. North Am., 22, 649“65.
Shulman, K. I. and Herrmann, N. (2000). Bipolar disorder in old age. In Bipolar Disorders: 100
Years after Manic-Depressive Insanity, ed. A. Marneros and J. Angst, pp. 153“74. Dordrecht:
Kluwer Academic Publishers.
Shulman, K. I. and Herrmann, N. (2002). Manic syndromes in old age. In Psychiatry in the Elderly,
3rd edn, ed. R. Jacoby and C. Oppenheimer, pp. 683“95. Oxford: Oxford University Press.
Shulman, K. and Post, F. (1980). Bipolar affective disorder in old age. Br. J. Psychiatry, 136, 26“32.
Shulman, K. I. and Singh, A. (1999). Comorbidity and bipolar disorder in old age.
In Comorbidity in Affective Disorders, ed. M. Tohen, pp. 249“61. New York: Marcel Dekker.
262 K. I. Shulman


Shulman, K. I. and Tohen, M. (1994). Unipolar mania reconsidered: evidence from an elderly
cohort. Br. J. Psychiatry, 164, 547“9.
Shulman, K. I., MacKenzie, S., and Hardy, B. (1987). The clinical use of lithium carbonate in old
age. J. Progr. Neuro-Psychopharmacol. Biol. Psychiatry, 11, 159“64.
Shulman, K. I., Tohen, M., Satlin, A., Mallya, G., and Kalunian, D. (1992). Mania compared with
unipolar depression in old age. Am. J. Psychiatry, 142, 341“5.
Shulman, R. W., Singh, A., and Shulman, K. I. (1997). Treatment of elderly institutionalised
bipolar patients with clozapine. Psychopharmacol. Bull., 33, 113“18.
Sibisi, C. D. (1990). Sex differences in the age of onset of bipolar affective illness. Br. J. Psychiatry,
156, 842“5.
Smith, R. E. and Helms, P. M. (1982). Adverse effects of lithium therapy in the acutely ill elderly
patient. J. Clin. Psychiatry, 43, 94“9.
Snowdon, J. (1991). A retrospective case-note study of bipolar disorder in old age. Br.
J. Psychiatry, 158, 484“90.
Spicer, C. C., Hare, E. H., and Slater, E. (1973). Neurotic and psychotic forms of depressive
illness: evidence from age-incidence in a national sample. Br. J. Psychiatry, 123, 535“41.
Starkstein, S. E., Mayberg, H. S., Berthier, M. L., et al. (1990). Mania after brain injury: neuro-
radiological and metabolic findings. Ann. Neurol., 27, 652“9.
Steffens, D. C. and Krishnan, K. R. R. (1998). Structural neuroimaging and mood disorders. Recent
findings, implications for classification, and future directions. Biol. Psychiatry, 43, 705“12.
Stone, K. (1989). Mania in the elderly. Br. J. Psychiatry, 155, 220“4.
Strakowski, S. M., McElroy, S., Keck, P., et al. (1994). The co-occurrence of mania with medical
and other psychiatric disorders. J. Psychiatry Med., 24, 305“28.
Taragano, F. E., Allegri, R., Vicario, A., et al. (2001). A double blind, randomized clinical trial
assessing the efficacy and safety of augmenting standard antidepressant therapy with nimo-
dipine in the treatment of ˜vascular depression™. Int. J. Geriatr. Psychiatry, 16, 254“60.
Tohen, M., Waternaux, C. M., and Tsuang, M. T. (1990). Outcome in mania: a four year
prospective follow-up study utilising survival analysis. Arch. Gen. Psychiatry, 47, 1106“11.
Tohen, M., Shulman, K. I., and Satlin, A. (1994). First-episode mania in late life. Am.
J. Psychiatry, 151, 130“2.
Tohen, M., Snager, T. M., McElroy, S. L., et al. (1999). Olanzapine versus placebo in the
treatment of acute mania. Am. J. Psychiatry, 156, 702“9.
`
Verdoux, H. and Bourgeois, M. (1995). Manies secondaires a des pathologies organiques
cerebrales. Ann. Med. Psychology, 153, 161“8.
Weissman, M. M., Bruce, M. L., Leak, P. J., et al. (1991). Affective disorders. In Psychiatric
Disorders in America. The Epidemiologic Catchment Area Study, ed. L. N. Robins and
D. A. Regier, p. 53. New York: Free Press.
Wylie, M. E., Mulsant, B. H., Pollock, B. G., et al. (1999). Age at onset in geriatric bipolar
disorder. Am. J. Geriatr. Psychiatry, 7, 77“83.
Young, R. C. and Klerman, G. L. (1992). Mania in late life: focus on age at onset.
Am. J. Psychiatry, 149, 867“76.
Young, R. C., Nambudiri, D. E., Jain, H., et al. (1999). Brain computed tomography in geriatric
manic disorder. Biol. Psychiatry, 45, 1063“5.
12


Comorbidity in mixed states and rapid-cycling
forms of bipolar disorders
Peter Brieger
Martin-Luther-University Halle-Wittenberg, Halle, Germany




Relevance of comorbidity
In recent years, much has been written on the comorbidity of bipolar disorders
with other mental illnesses. Several studies have reported distinct patterns showing
how bipolar disorders and other mental disorders co-occur (Brieger, 2000;
McElroy et al., 2001). Generally, in patients with bipolar disorders, there is an
unexpected excess of co-occurring anxiety disorders and substance-abuse dis-
orders. Concerning personality disorders, there is some evidence that patients with
bipolar disorders show higher rates than the normal population, but lower rates
than patients with unipolar affective disorders (Brieger et al., 2003a). Such results
are descriptive. Therefore, one has to examine the relevance of these findings.
Some analyses have cast doubt as to whether one can simply assume that the more
disorders a patient suffers from, the more impaired he or she is (Strakowski et al.,
1992; Brieger et al., 2002a). Nevertheless, in several studies, comorbidity tended to
be a complicating factor (Zimmerman and Mattia, 2000; McDermut et al., 2001).
In addition to other elements, it may lead to an increase in the length of hospital
stay (Wancata et al., 2001).
A useful definition of comorbidity is the ˜˜joint occurrence of two or more
mental disorders occurring with each other and/or with medical conditions™™
(Klerman, 1990). Classical psychiatrists, such as Karl Jaspers (1973), postulated
that all signs of an illness should be subsumed under a single diagnosis, which
usually implies that this ˜˜main diagnosis™™ is meaningful in terms of prognosis and
outcome. Nowadays, in operational diagnostic systems, such as Diagnostic and
Statistical Manual of Mental Disorders, 4th edn (DSM-IV: American Psychiatric
Association, 1994) and Tenth Revision of International Classification of Diseases
(ICD-10: World Health Organization, 1993), comorbidity is the rule, not the
exception (Merikangas, 1990). But, nevertheless, ˜˜diagnosis and need for treatment

Cambridge University Press, 2005.
#
264 P. Brieger


are not the same™™ (Spitzer, 1998). Questions of methodology are important in
understanding comorbidity (Brieger and Marneros, 2000). The growing importance
of spectra, of subthreshold, and of the subsyndromal disorders in psychiatry, as well
as the suspension of exclusionary principles, has led to an increase in comorbidity,
which makes it complicated to appraise the potential consequences of two
co-occurring disorders.
There is some indication that mixed states and rapid-cycling forms of bipolar
disorders may have a worse prognosis than ˜˜typical™™ forms (Marneros and Brieger,
2002), although when looking at empirical data, the difference may be neither as
great nor as clear as is often assumed. One central question is whether mixed states
and rapid-cycling forms of bipolar affective disorders show patterns of comorbid-
ity that differ from those observed in other forms of bipolar affective disorders. If
that were true, it would make a case for viewing mixed states and rapid-cycling
forms of bipolar affective disorders as distinct groups. A basic problem here is the
difference between cross-sectional and longitudinal observations. Since the times
of Kahlbaum (1863) and Kraepelin (1909“1915), there has been a consensus that,
in psychiatric research, longitudinal observation is superior to cross-sectional
observation. Nevertheless, both the co-occurrence of two mental disorders and
the occurrence of mixed states and rapid-cycling forms of bipolar affective dis-
orders may be transient with potential low long-term stability. It is an overt
weakness of present diagnostic systems, such as DSM-IV and ICD-10, that they
pay little (or almost no) attention to such a long-term course. At the same time, it
becomes increasingly clear that complex interactions between long-term and
subsyndromal features of a disorder are important for its prognosis (Marneros
and Brieger, 2002).


Medical conditions and neuropsychiatric disorders
The comorbidity of medical conditions and bipolar affective disorders is a topic
that warrants systematic research. The interaction between bipolar affective dis-
orders and disorders of thyroid axis has received more attention than most other
medical conditions. Nevertheless, no clear picture has emerged. It has been dis-
cussed that patients with mixed bipolar disorders may exhibit more thyroid
hormone deficiency than controls (Zarate et al., 1997; Chang et al., 1998;
McElroy et al., 2000), but there are also negative studies that have found no
differences between bipolar affective patients with or without mixed episodes as
regards thyroid hormones (Joffe et al., 1994), including a retrospective chart
analysis prepared in our department (Reinelt, 2003). A recent study of 443 bipolar
patients (Cassidy et al., 2002) showed no indication of ˜˜overt or subclinical thyroid
disease™™ in mixed manic episodes. In regard to rapid-cycling bipolar disorders,
265 Comorbidity in mixed states and rapid-cycling disorders


several studies have not been able to support the idea that rapid cycling is related to
thyroid dysfunction (Joffe et al., 1988; Post et al., 1989; Bartalena et al., 1990),
including a large study of almost 500 bipolar affective patients (Kupka et al., 2002).
However, there are reports in favor of this possibility (Extein et al., 1982; Cowdry
et al., 1983; Bauer et al., 1990; Oomen et al., 1996). Therefore, a higher frequency of
co-occurring thyroid dysfunction has neither been proven nor ruled out for either
mixed or rapid-cycling bipolar affective disorders, although some indications of
such a relationship may exist. Mood-stabilizing medication, especially lithium,
may affect the thyroid axis and complicate such analyses, as most bipolar affective
patients will have previously received a mood stabilizer.
A report on a series of 13 patients with epilepsy and manic episodes (Kudo et al.,
2001) showed that, compared to bipolar affective controls, the patients with
epilepsy and mania had less severe manic and depressive episodes. Interestingly,
the majority of the patients with mania and epilepsy (8 out of 13) had a rapid-
cycling course pattern with regard to mood episodes. Although there is no clear
general estimate concerning the frequency of manic episodes in epilepsy, temporal
lobe epilepsy has been reported to be among the leading causes of organic bipolar
affective disorder (Rundell and Wise, 1989). Additionally, the etiological relation-
ship between epilepsy and manic episodes is not clear. Rapid-cycling bipolar
disorder has also been reported in a series of five patients with primary idiopathic
dystonia (Lauterbach et al., 1992).
Rapid cycling has been reported in various other neuropsychiatric disorders,
such as head injury (Zwil et al., 1993), stroke (Berthier, 1992), learning disability
(Jan et al., 1994; Raghavan et al., 1995), or rarer illnesses, such as cerebral
sarcoidosis (Walbridge, 1990) or tuberous sclerosis (Hagenah et al., 1999). For
mixed bipolar affective disorders, we are only aware of one report of a mixed
bipolar affective episode following head injury (Bamrah and Johnson, 1991).
Overall, one must be careful to equate such cases of rapid cycling in organic
brain disease with ˜˜idiopathic™™ rapid cycling in bipolar affective disorder concern-
ing symptomatic presentation. Instead, in some reports, the symptomatology
seems to be ˜˜very atypical™™ and would not necessarily meet DSM-IV criteria for
bipolar affective disorder. Nevertheless, in organic brain disease, rapid-cycling-like
syndromes may be either more frequent than mixed bipolar affective episodes or
more often noticed by clinicians, as they may have a higher relevance for acute
treatment (i.e., the treatment could become longer or more complicated). In some
cases, the fluctuating course of organic brain disease might mimic rapid-cycling
forms (or even mixed states) in bipolar affective disorders.
Although it has been discussed that patients with mixed bipolar affective
disorders may show more neuropsychological impairment than other bipolar
affective patients, no such evidence was shown in a recent empirical study
266 P. Brieger


(Basso et al., 2002). As the authors of this study readily admit, this single negative
study cannot rule out the possibility that subtle differences may exist, but it seems
unlikely that they appear on a clinically meaningful level.


Substance-abuse disorders
Substance abuse is far more often found in subjects with bipolar affective disorder
than in the general population (Sonne and Brady, 1999; Brieger, 2000). In this
respect, alcohol (Winokur et al., 1995) and cocaine (Weiss et al., 1988) have
received specific attention. Nevertheless, the overall trend seems to be true for
most substances that can be abused, although it may well be that patients with
bipolar affective disorder show a certain preference for stimulant drugs (Winokur
et al., 1998; Sonne and Brady, 1999; Brieger, 2000).
Already in the 1970s, Himmelhoch et al., (1976) postulated that mixed episodes
correlated with higher rates of sedative abuse. Later reports on mixed bipolar
affective disorders referred to this observation. There are further empirical reports
of higher frequency of substance-abuse disorders in patients with mixed bipolar
affective disorders than patients with pure manic episodes (McElroy et al., 1995;
Goldberg et al., 1999) or of a higher frequency of dysphoric manic episodes in
bipolar patients with substance abuse (Sonne et al., 1994). Nevertheless, other
studies with even larger samples have failed to find such differences: Cassidy et al.

<<

. 45
( 68 .)



>>