<<

. 18
( 68 .)



>>

be related to the severity of depression. There were no differences in plasma
3-methoxy-4-hydroxyphenylglycol (MHPG) levels between the three groups.
Goodwin and Post (1975) had also found no difference in cerebrospinal fluid
MHPG levels between bipolar I and bipolar II. In contrast, some studies suggest
that reduced urinary MHPG levels may be present only in bipolar I but not in
bipolar II depressed patients (Muscettola et al., 1984; Schatzberg et al., 1989).
Further studies are needed to explore the biochemical distinctions and similarities
between bipolar I and bipolar II disorders.
On the other hand, Emamghoreishi et al. (1997) showed that the baseline Ca2+
concentration was significantly higher in the B lymphoblasts from patients with
bipolar I disorder, but not bipolar II disorder or major depression, than in healthy
subjects or psychiatric patients with non-mood disorders. There were higher basal
Ca2+ concentrations in T lymphocytes in male bipolar I patients, but not in men
with bipolar II patients or major depression, than in healthy male comparison
subjects. Phytohemagglutinin-stimulated Ca2+ concentrations did not differ
among groups, but the percentage differences from basal Ca2+ levels were lower
in bipolar I and depressed patients than in healthy subjects. The authors suggested
that trait-dependent factors account, at least partly, for the higher basal lympho-
cyte Ca2+ concentration in bipolar I subjects.

Neurophysiology
With respect to sleep electroencephalography, no differences between bipolar I
and unipolar depressed patients have been reported by Giles et al. (1986), but they
did find differences between unipolar patients and bipolar II patients: bipolar II
patients had longer rapid-eye-movement (REM) latencies, more non-REM time,
and hypersomnia. Ansseau et al. (1984, 1985) found that depressed bipolar II
patients had more variability in REM latency, as well as a trend toward more sleep-
onset REM periods than bipolar I patients.
99 Bipolar I and bipolar II: a dichotomy?



Treatment
There are few studies that compare bipolar I and bipolar II patients with respect to
treatment response.
Tondo et al. (1998) studied lithium maintenance treatment in bipolar I and II
patients. Their findings showed that lithium had superior benefits in type II patients,
with significantly greater reduction of episodes per year and of the percentage of
time ill. Reduction of depressive morbidity was similarly strong in both bipolar I and
bipolar II diagnoses. In a recent study, Tondo et al. (2001) found similar results and
concluded that long-term lithium maintenance treatment in compliant patients
without comorbid substance use-disorder remained effective, even in subgroups of
supposedly poor prognosis, such as patients with mixed episodes, psychotic epi-
sodes, or rapid cycling. Only about a quarter of the patients in this study experienced
complete remission during maintenance treatment, suggesting that full protection
was not commonly achieved with lithium or with alternative treatments. Some
clinical factors found early in the course of illness (age at illness onset, and a longer
interval between first and second lifetime episodes) or early in treatment with
lithium (rapidity of recovery from the index episode at the start of lithium treat-
ment, and a longer interval to the first subsequent recurrence) were significantly
associated with a better long-term treatment response as indicated by the overall
proportion of time ill during treatment.
Other studies found evidence of beneficial effects of lithium for both mania and
depression in bipolar I patients and for mainly depressive episodes in bipolar II
patients (Dunner et al., 1976; Fieve et al., 1976; Quitlin et al., 1978; Kane et al.,
1982; Peselow et al., 1982; Tondo et al., 1997). Koukopoulos et al. (1980)
found significant differences in lithium prophylaxis as a function of episode
sequence: the bipolar II patients with the hypomania“depression“euthymic
interval course were the best lithium responders. A higher incidence of axis-II
disorders among bipolar II patients could affect drug responses. Other authors have
replicated the significantly more favorable prophylactic response among the
mania“depression“euthymic interval course (Grof et al., 1987; Haag et al., 1987;
Maj et al., 1989; Faedda et al., 1991); in contrast, in the above-mentioned study of
Tondo et al. (2001), the sequence of manic and depressive episodes was not
associated with treatment response. Goodwin and Jamison (1990) suggested that
the poor results in patients with the depression“mania“euthymic interval course
might reflect the impact of tricyclics given to treat depression; the mania following
depression could be drug-induced, and such manias might be relatively resistant to
lithium treatment.
There was a suggestion for a higher prophylactic efficacy of carbamazepine
versus lithium in bipolar II patients compared to bipolar I in one study (Greil et al.,
100 E. Vieta et al.


1998), which deserves replication. Data on the comparative efficacy of valproate
are scant.
With a sample of rapid-cycling bipolar patients, Calabrese et al. (2000) studied
the safety and efficacy of lamotrigine in a double-blind, placebo-controlled study.
The results suggested that lamotrigine might be a well-tolerated and effective
mood stabilizer with prophylactic properties when used as monotherapy in
some patients with rapid cycling. Differences favoring lamotrigine were consistently
greater for bipolar II than bipolar I patients. An open study is also supporting the
efficacy of lamotrigine in bipolar II disorder (Vieta et al., 2003), though an
unpublished double-blind trial could not separate its effects from placebo in this
particular population. Another anticonvulsant, topiramate, seemed to be more
useful for the hypomanic phase (Vieta et al., 2002b).
Regarding antidepressant treatment, its impact is positive for unipolar
patients but unclear and sometimes self-defeating for bipolar patients because
antidepressant treatment, especially tricyclic antidepressants, implies an important
risk of switch induction or cycle acceleration. In bipolar I patients the treatment
aims to prevent manic relapses; consequently, lithium is the primary treatment
in bipolar I patients because of its prophylactic effect on mania, and also because
it has greater antidepressant efficacy in bipolar I depressive disorder. On the
other hand, in bipolar II patients it is very important to control and prevent
depressive episodes; consequently, lamotrigine and antidepressant treatment
(mostly represented by the selective serotonin reuptake inhibitors), which have
less propensity for hypomania induction, may be useful (Bourgeois, 2002).
In practice, the decision to use concurrent mood stabilization during the treat-
ment of bipolar II depression must be made on a case-by-case basis, with age at
onset, cycle length, past history of rapid cycling, patient gender, and prior
frequency and severity of hypomanias important considerations (Thase and
Sachs, 2000).
Atypical antipsychotics have also been tried in bipolar II disorder, though no
randomized, double-blind trials are yet available (Crespo and Vallejo, 2002;
Vieta, 2003). A cohort of bipolar II hypomanic patients was treated with
adjunctive risperidone by Vieta et al. (2001a), with good results. Efficacy was
fully comparable to that found in bipolar I manic patients (Vieta et al., 2001b),
thus supporting the dimensionality of the (hypo)manic spectrum. Besides,
doses correlated with the intensity of symptoms, being higher for manic than
for hypomanic patients (Vieta et al., 2001b). Other atypicals have been
reported to be useful in the treatment of patients within the bipolar spectrum,
including bipolar I and II. Olanzapine (Vieta et al., 2001c) and quetiapine
(Vieta et al., 2002c) may show some promise, even in the ˜˜softer™™ range of
bipolarity.
101 Bipolar I and bipolar II: a dichotomy?



Conclusion
From a clinical and therapeutic point of view, bipolarity looks clearly dimensional.
The strongest support for the theory that bipolar II disorder ˜˜breeds true™™ comes
from genetic studies. Pathophysiological and neuroimaging studies are still incon-
clusive. The dimensionality of the bipolar spectrum runs against the existence of a
true dichotomy between bipolar I and bipolar II. In fact, as far as the molecular level,
it seems to be uncategoric. Dichotomies are useful for education, communication,
and simplification; unfortunately, simplicity is useful but untrue, whereas complex-
ity is true, but useless. In clinical practice, we may use current classifications, such as
DSM-IV, as categoric backgrounds that may help to establish the treatment and
prognosis. However, the presence of mixed symptoms in many bipolar II patients,
their not-so-rare switch into mania, and the need for vigorous treatment to deal with
the high frequency of relapse may make the apparent dichotomy less likely to shed
light on the nature of bipolarity and the needs of our patients.


Acknowledgments
This work was supported by the Stanley Research Foundation (Bethesda,
MD, USA).


REFERENCES

Akiskal, H. S. (1983). The bipolar spectrum: new concepts in classification and diagnosis.
In Psychiatry Update: The American Psychiatric Association Annual Review, ed. L. Grinspoon,
pp. 271“92. Washington, DC: American Psychiatric Press.
Akiskal, H. S. (2002a). Classification, diagnosis and boundaries of bipolar disorders: a review. In
´
Bipolar Disorder, ed. M. Maj, H. S. Akiskal, J. J. Lopez-Ibor, and N. Sartorius, pp. 1“52. New
York: John Wiley.
Akiskal, H. S. (2002b). Towards a new classification of bipolar disorders. In Bipolar Disorders.
Clinical and Therapeutic Progress. ed. E. Vieta, pp. 185“215. Madrid: Panamericana.
Akiskal, H. S., and Mallya, G. (1987). Criteria for the ˜˜soft™™ bipolar spectrum: treatment
implications. Psychopharmacol. Bull., 23, 68“73.
Akiskal, H. S., Walker, P., Puzantian, V. R., et al. (1983). Bipolar outcome in the course of
depressive illness. J. Affect. Disord., 5, 115“28.
Akiskal, H. S., Maser, J. D., Zeller, P. J., et al. (1995). Switching from ˜˜unipolar™™ to bipolar II.
An 11-year prospective study of clinical and temperamental predictors in 559 patients. Arch.
Gen. Psychiatry, 52, 114“23.
Akiskal, H. S., Bourgeois, M. L., Angst, J., et al. (2000). Re-evaluating the prevalence of and
diagnostic composition within the broad clinical spectrum of bipolar disorders. J. Affect.
Disord., 59, 5“30.
102 E. Vieta et al.


Altshuler, L. L., Curran, J. G., Hauser, P., et al. (1995). T2 hyperintensities in bipolar disorder:
MRI comparison and literature meta-analysis. Am. J. Psychiatry, 152, 1139“44.
American Psychiatric Association (1980). Diagnostic and Statistical Manual of Mental Disorders,
3rd edn (DSM-III). Washington, DC: American Psychiatric Association.
American Psychiatric Association (1987). Diagnostic and Statistical Manual of Mental Disorders,
3rd edn revised. Washington, DC: American Psychiatric Association.
American Psychiatric Association (1994). Diagnostic and Statistical Manual of Mental Disorders,
4th edn. Washington, DC: American Psychiatric Association.
Andreasen, N. C., Rice, J., Endicott, J., et al. (1987). Familial rates of affective disorder. Report from
the National Institute of Mental Health collaborative study. Arch. Gen. Psychiatry, 44, 461“9.
Angst, J. (1966). Zur Aetiologie und Nosologie endogener depressiver Psychosen. Berlin: Springer.
Angst, J. (1995). Epidemiology of the bipolar spectrum. Encephale, 6, 37“42.
Angst, J. (1998). The emerging epidemiology of hypomania and bipolar II disorder. J. Affect.
Disord., 50, 143“51.
Angst, J., and Marneros, A. (2001). Bipolarity from ancient to modern times: conception, birth
and rebirth. J. Affect. Disord., 67, 3“19.
Ansseau, M., Kupfer, D. J., Reynolds, C. F., and McEachran, A. B. (1984). REM latency distribu-
tion in major depression: clinical characteristics associated with sleep onset REM periods.
Biol. Psychiatry, 19, 1651“66.
Ansseau, M., Kupfer, S. J., and Reynolds, C. F. (1985). Internight variability of REM latency
in major depression: implications for the use of REM latency as a biological correlate.
Biol. Psychiatry, 20, 489“505.
´
Arato, M., Demeter, E., Rihmer, Z., and Somogy, E. (1988). Retrospective psychiatric assessment
of 200 sucides in Budapest. Acta Psychiatr. Scand., 77, 454“6.
´
Ayuso-Gutierrez, J. L., and Ramos-Brieva, J. A. (1982). The course of manic-depressive illness.
A comparative study of bipolar I and bipolar II patients. J. Affect. Disord., 4, 9“14.
` ´
Baillarger, J. (1854). De la folie a double forme. Ann. Med. Psychol., 6, 369“89.
Baldessarini, R. J., Tondo, L., Floris, G., and Hennen, J. (2000). Effects of rapid cycling on
response to lithium maintenance treatment in 360 bipolar I and II disorder patients. J. Affect.
Disord., 61, 13“22.
˜
Benabarre, A., Vieta, E., and Lomena, F. (2002). Structural and functional neuroimaging: facts,
pitfalls and challenges. In Bipolar Disorders. Clinical and Therapeutic Progress, ed. E. Vieta,
pp. 185“215. Madrid: Panamericana.
Benazzi, F. (1997). Prevalence of bipolar II disorder in outpatient depression: a 203-case study in
private practice. J. Affect. Disord., 43, 163“6.
Benazzi, F. (1999). A comparison of the age of onset of bipolar I and bipolar II outpatients.
J. Affect. Disord., 54, 249“53.
Benazzi, F. (2000). Depression with DSM-IV atypical features: a marker for bipolar II disorder.
Eur. Arch. Psychiatry Clin. Neurosci., 250, 53“5.
Berns, G. S., Martin, M., and Proper, S. W. (2002). Limbic hyperreactivity in bipolar II disorder.
Am. J. Psychiatry, 159, 304“6.
Bourgeois, M. (1996). Subtypes of bipolar disorder: EPIMAN and EPIDEP studies. Med. Express
Rep., 8, 3“4.
103 Bipolar I and bipolar II: a dichotomy?


Bourgeois, M. L. (2002). The bipolar spectrum of depressions. In Bipolar Disorders. Clinical and
Therapeutic Progress, ed. E. Vieta, pp. 113“26. Madrid: Panamericana.
´
Bourgeois, M. L., Verdoux, H., Peyre. F., and Dupart, A. (1996). Indices et facteurs predictifs de
´ ´ ´ ´ ´
bipolarite dans les etats depressifs. Etude de 219 patients hospitalises pour depression. Ann.
´
Med-Psychol., 154, 577“88.
Calabrese, J. R., Suppes, T., Bowden, C. L., et al. (2000). A double-blind, placebo-controlled,
prophylaxis study of lamotrigine in rapid cycling bipolar disorder. J. Clin. Psychiatry, 61,
841“50.
Cassano, G. B., Akiskal, H. S., Musetti, L., et al. (1989). Psychopathology, temperament, and past
course in primary major depressions. Toward a redefinition of bipolarity with a new semi-
structured interview for depression. Psychopathology, 22, 278“88.
Cassano, G. B., Akiskal, H. S., Savino, M., Musetti, L., and Perugi, G. (1992). Proposed subtypes
of bipolar II and related disorders: with hypomanic episodes (or cyclothymia) and with
hyperthymic temperament. J. Affect. Disord., 26, 127“40.
Cooke, R. G., Young, T., Levitt, A. J., Pearce, M. M., and Joffe, R. T. (1995). Bipolar II: not so
different when co-morbidity excluded. Depression, 3, 154“6.
Coryell, W., Endicott, J., Reich, T., Andreasen, N., and Keller, M. (1984). A family study of
bipolar II disorder. Br. J. Psychiatry, 145, 49“54.
Coryell, W., Endicott, J., Andreasen, N., and Keller, M. (1985). Bipolar I, bipolar II,
and nonbipolar major depression among the relatives of affectively ill probands.
Am. J. Psychiatry, 142, 817“21.
Coryell, W., Andreasen, N., Endicott, J., and Keller, M. (1987). The significance of past
mania or hypomania in the course and outcome of major depression. Am. J. Psychiatry,
144, 309“15.
Coryell, W., Keller, M., Endicott, J., et al. (1989). Bipolar II illness: course and outcome over a
five-year period. Psychol. Med., 19, 129“41.
Coryell, W., Endicott, J., and Keller, M. (1992). Rapidly cycling affective disorder: demo-
graphics, diagnosis, family history and course. Arch. Gen. Psychiatry, 49, 126“31.
Coryell, W., Scheftner, W., Keller, M., et al. (1993). The enduring psychosocial consequences of
mania and depression. Am. J. Psychiatry, 150, 720“7.
Coryell, W., Endicott, J., Maser, J. D., et al. (1995). Long-term stability of polarity distinctions in
the affective disorders. Am. J. Psychiatry, 152, 385“90.
´ ´ ´
Crespo, J. M., and Vallejo, J. (2002). Tratamiento Farmacologico de la Hipoman±a. In Hipoman±a,
´
ed. E. Vieta, pp. 91“105. Madrid: Aula Medica.
Dunner, D. L. (1983). Subtypes of bipolar affective disorder with particular regard to bipolar II.
Psychiatr. Dev., 1, 75“86.
Dunner, D. L. (1998). Diagnostic revisions for DSM-IV. In Mania. Clinical and Research
Perspectives, ed. P. J. Goodnick, pp. 3“10. Washington, DC: American Psychiatry Press.
Dunner, D. L., Gershon, E. S., and Goodwin, F. K. (1976). Heritable factors in the severity of
affective illness. Biol. Psychiatry, 11, 31“42.
Egeland, J. A., Blumenthal, R. L., Nee, J., Sharpe, L., and Endicott, J. (1987). Reliability and
relationship of various ages of onset criteria for major affective disorder. J. Affect. Disord., 12,
159“65.
104 E. Vieta et al.


Emamghoreishi, M., Schlichter, L., Li, P. P., et al. (1997). High intracellular calcium concentra-
tions in transformed lymphoblasts from subjects with bipolar I disorder. Am. J. Psychiatry,
154, 976“82.
Endicott, J., Nee, J., Andreasen, N. C., et al. (1985). Bipolar II: combine or keep separate?
J. Affect. Disord., 8, 17“28.
Endicott, N. A. (1989). Psychophysiological correlates of ˜˜bipolarity™™. J. Affect. Disord., 17, 47“56.

<<

. 18
( 68 .)



>>