Friday, June 13, 2003
"Concurrent Rapid Communications Sessions"
Session C - Chair: Giovanni de Girolamo, M.D.
Bibliography
Heterogeneity of Bipolar Disorder: Proposal for 3-spectra
Model
Video | Audio
(Length: 23 min.)
M. Alda1, P. Grof2
1Department of Psychiatry, Dalhousie University, Halifax, Canada,
2Department of Psychiatry, University of Ottawa, Canada
Bipolar disorder is typically viewed as a multifactorial
disorder of mood regulation. The aetiology of bipolar disorder is at least
partly genetic, with multiple genes involved (oligogenic transmission). Clinical
data, treatment studies, as well as biological investigations in bipolar
disorder are frequently inconsistent from one study to another. We propose that
some of these inconsistencies could be resolved by considering bipolar disorder
a syndrome consisting of three main subtypes. The first subtype is the
‘classical’ bipolar disorder characterized by episodic course, and favourable
response to lithium prophylaxis. Its phenotypic spectrum would include bipolar I
and bipolar II disorders, and recurrent major depression. The second type is a
group of conditions with a close link to psychotic disorders. These patients
often experience subtle psychotic symptoms even in absence of mood symptoms,
they have more chronic clinical course with less favourable prognosis and they
rarely stabilize without antipsychotic treatment. The third subtype is
characterized by high prevalence of comorbid conditions, including anxiety
disorders, higher proportion of bipolar II patients, and rapid cycling. These
patients appear to preferentially respond to anticonvulsants such as lamotrigine. The proposed sub-typing is supported by results of genetic and
pharmacogenetic studies. Comparing lithium responders with non-responders and
with responders to lamotrigine reveals major differences in clinical picture,
presence of co morbid conditions, long term course, or family history. The
individual groups should be viewed not as exclusive categories, but rather as
partially overlapping clusters. This is also in agreement with the concept of
oligogenic transmission in which most susceptibility alleles are common and can
be shared among different subtypes. The proposed 3 spectra model can account for
some of the discrepant findings in the literature. For instance, results of
clinical trials may depend on the proportion of subjects in each category
included. Individual groups may be differentially represented in different
clinical settings with fewer ‘classical’ patients in academic/tertiary care
centres. The proposal offers a set of testable hypotheses as well as a framework
for designing research studies and interpreting research data.
Keywords: bipolar disorder, heterogeneity, treatment response
Prevalence Rates of Medical Conditions in a Bipolar
Affective Disorder Population
Video | Audio
(Length: 22 min.)
H.H. Fenn1, W.O. Williford2,
D.R. Evans3, P. Connor4, L. Altshuler5, M.S.
Bauer6
1Stanford University and Palo Alto VA Health Care System, 2VA
Cooperative Studies Program, 3Medical College of Georgia and Augusta
VAMC, 4VA Cooperative Studies Program, 5UCLA and West LA
VAMC, 6Brown University and Providence VAMC
Introduction: Prevalence rates for medical conditions
among those with bipolar disorder have not been extensively investigated. A
literature review over the past 20 years found diabetes mellitus prevalent among
hospitalized bipolar affective patients at a rate 9.9% vs. 3.4% from national
norms. There were also two studies on head injuries, and one on cholesterol
levels.
Methods: Between 1/1/97 and 12/31/00, 330 subjects were recruited from 11
VA medical centers as part of Cooperative Study #430. Each had been admitted to
an acute psychiatric unit with a diagnosis of bipolar disorder and an acute
manic, depressive, or mixed episode. Inclusion criteria included SCID-confirmed
diagnosis and at least 3 acute psychiatric admissions over the prior 5 years.
Exclusion criteria included only MMSE < 27 or inpatient hospitalization >6
months in the prior year; no other comorbidities were excluded. Intoxicated
veterans were approached for consent after detoxification. Intake assessment
included Structured Clinical Interview for DSM-IV (SCID; First et al, 1996) and
a battery of interview and self-report instruments. A structured chart review
instrument was used to gather medical history from available VA records for the
prior 10 years.
Results: Of 233 charts reviewed, prevalence rates above 10% were found
for: current hypothyroidism 10.7% and past hypothyroidism 4.3%, current
hyperlipidemias 26.0% and past hyperlipidemias 3.0%, current obesity 16.2%,
current hepatitis C 12.0%, current osteoarthritis 11.5 % and past osteoarthritis
3.4%. History of head trauma with loss of consciousness was found in 9.0% and
current diabetes mellitus in 8.54%. Prevalence rates are compared US population
rates and VA patient rates; implications for service utilization, multi-modal
treatment, and the use of specific psychotropics (e.g. lithium, atypical
neuroleptics, valproate) are discussed.
Keywords: medical comorbidity, head trauma, hyperlipidaemia.
Validation of the Palm Life Chart: An Electronic Diary for
Long-term Monitoring of Bipolar Patients
Video | Audio
(Length: 18 min.)
L. Schärer, C. Biedermann, S. Dittmann, A. Forsthoff, M. Graf, H.
Grunze, V. Hartweg, M. Horn, G. Valerius, J. Walden, J.M. Langosch
Center for the Innovative Therapy of Bipolar Disorder, Department of
Psychiatry, University of Freiburg and University of Munich
Introduction: Originally based on Kraepelins early life charts, within
the last 20 years, the NIMH-LifeChart Method (LCM) (Post et al. 1988) has
evolved into the standard method for long-term monitoring of bipolar patients in
clinical and in scientific settings. Its reliability, in a large longitudinal
study with more than 600 patients (McElroy et al. 2002). It was also formally
assessed (Honig et al. 2001). Most patients report that the LCM is easy to do (Honig
et al. 2001, Schärer et al. 2002). This preliminary data is in line with the
general impression of clinicians. However, there are two major problems with the
LCM. First-for the scientific evaluation of LifeChart data – there is no
established method available to use the full potential of the longitudinal data.
And secondly, graphical summaries of the data, which become necessary after a
month, require a significant amount of work for data entry and processing,
exceeding the capacities of every days clinical practice (Leverich & Post 1996).
Methods: The Palm LifeChart (PLC), an electronic LifeChart, based on
small palmtop computers was introduced (Schärer et al. 2001) to overcome this
problem and to make the benefits of LifeCharting available to patients in
everyday clinical practice. 50 patients using the PLC on Palmpilot M100
computers participated in a feasibility and validation study.
Results: More than two thirds of the patients found a high or very high
benefit using the PLC. They report that the PLC is easy to use and requires less
effort than the LCM. Furthermore, it helps patients to detect arising episodes
early and it reflects the efficacy of the treatment. Validation against
frequently used psychometric scales (YMRS, IDS-C, GAF and CGI-BP) demonstrates
external validity. The international use of the PLC will be discussed.
Keywords: life chart, Palmpilot, validation.
Non-invasive Assessment of Circadian Rhythms in Remitted
Bipolar Patient
Video | Audio
(Length: 22 min.)
S.H. Jones, D. Hare, K. Evershed
Academic Division of Clinical Psychology, University of Manchester, United
Kingdom
Introduction: Studies have shown that markers of circadian
functioning are disrupted in bipolar patients who are acutely ill. In general,
the measures used to observe circadian functioning have been invasive and
restrictive. There has therefore been a risk that the process of observation in
itself has impacted on the circadian variables being measured. More recently it
has become possible to measure activity patterns as an indicator of circadian
functioning, providing a non-invasive alternative to previous techniques.
Disruptions of circadian rhythms have been reported using this approach, but
only with bipolar inpatients. This approach has not been used in outpatient
remitted bipolar patients, even though most effective psychological
interventions (e.g. CBT/IPSRT) share a common theme of increasing the stability
of activity patterns in such patients. A recent paper by the lead author has
proposed that the impact of circadian disruption on remitted bipolar patients
may be mediated by the attributions, which the individual has made about such
disruption. This proposal implies that bipolar patients are experiencing
circadian disruptions during remission, as well as, at a higher level, during
acute phases of illness. The present study therefore investigated whether
activity patterns, and therefore circadian functioning, were disrupted in
remitted bipolar patients, and also the extent to which this was associated with
the level and severity of subsyndromal symptoms. Non-invasive measurement of
activity patterns was used as the indicator of circadian functioning.
Methods: Remitted adult bipolar patients, who met SCID lifetime criteria
for bipolar disorder, completed self report measures of sleep, activity and
symptomatology. They also wore an actiwatch, which recorded patterns of activity
over a period of a week. The actiwatch is a small wrist-watch sized device which
contains a digital acceleration sensor. This allowed participants to engage in
their normal range of daily activities. A comparison group of age and gender
matched participants with no psychiatric history, provided control data for this
study.
Results: Analyses will be reported comparing data from 20 bipolar
patients and 20 age and gender matched controls. Key variables obtained were
intradaily variability, interdaily stability, relative amplitude and
periodicity. These results are discussed in relation to symptom and sleep data.
The significance of these findings with respect to ‘instability’ models of
bipolar disorder is also discussed.
Keywords: circadian rhythms, activity patterns, noninvasive
assessment.
Session D - Chair: Holly Swartz, M.D.
Bibliography
Video | Audio
(Length: 1 min.)
Is Adjunctive CBT Superior to Psychoeducation in the Maintenance Treatment
of Bipolar Disorder?
Video | Audio
(Length: 17 min.)
A.E. Zaretsky, W. Lancee, S.V. Parikh, C. Miller
Department of Psychiatry, University of Toronto, Toronto, Canada
Introduction: Although mood-stabilizing medication is the mainstay of
treatment for bipolar disorder, many patients still experience residual
affective symptoms, high non-adherence, high relapse and significant
psychosocial functional impairment. Only 10% of published articles on
psychosocial interventions in bipolar disorder are randomized trials and
psychoeducation is currently the most scientifically validated treatment. There
is no evidence that more labor-intensive interventions such as CBT are superior
to psychoeducation. We analyzed preliminary 6 month follow-up data from a
randomized controlled trial comparing adjunctive CBT to psychoeducation in the
maintenance treatment of bipolar disorder, in order to determine if adding CBT
to psychoeducation would yield better overall mood stability.
Methods: This was a randomized controlled trial. Male and female bipolar
patients 18 to 75 years old with bipolar I or II were entered after they were no
longer in a full episode of mania or depression and were on an unchanged regimen
of mood-stabilizing medication for 4 weeks prior to entry. All patients received
7 weekly sessions of individual psychoeducation. Patients randomized to CBT
received 13 additional weekly sessions of individual CBT based on the Basco &
Rush (1996) manual. Medication treatment was monitored naturalistically. The
Personal Calendar, a daily mood chart based on the NIMH Life Chart Method was
the primary instrument used in determining efficacy. Bad outcome was defined as
at least 1 week per month with at least low moderate depressive or low moderate
hypomanic symptoms.
Results: Of 87 bipolar patients enrolled, 57 completed 6-month follow-up.
Only 3.2% of patients who received 13 additional sessions of adjunctive CBT had
poor outcomes whereas 30.8% of patients who received psychoeducation alone had
poor outcomes [X2(1)=8.07, p<0.005].
Conclusions: A longer course of adjunctive CBT appears to enhance mood
stability more than a short course of psychoeducation alone.
Keywords: CBT, bipolar disorder, psychoeducation.
Why are Some Depressions Worsened by Antidepressant?
Video | Audio
(Length: 10 min.)
C. Henry, D. Van den Bulke, N. Demazeau, J. Demotes-Mainard
Hôpital Charles Perrens, Bordeaux, France
Background: Extensive use of antidepressant drugs in the treatment of
all forms of depression raises the issue of the real nature of agitated
depression. These agitated patients are often worsened by antidepressants (Koukopoulos
and Koukopoulos, 1999) and the failure to recognize agitated depression as a
mixed state may be responsible for some of these disappointing outcomes. The aim
of this study was i) to assess the frequency of mild to moderate manic dysphoric
episodes masked by depressive manifestations, ii) to look for the more relevant
symptoms helping to differentiate dysphoric from genuine depressive episodes.
Methods: Fifty consecutive patients referred by psychiatrists for a major
depressive episode were enrolled in this study. Patients were assessed using the
French version of the Mini International Neuropsychiatric Interview 5.0 (MINI
5.0) assessing the suicidal risk and providing DSM-IV diagnosis. Intensity of
mood episodes were evaluated using the MADRS and Beck and Rafaelsen Mania scale,
as well as the modified hypomania Checklist of Angst.
Results: 21 patients (42%) had typical depression with anhedonia,
psychomotor and cognitive retardation (“major depressive episode” (MDE) group) ;
21 patients (42%) had manic (22%), hypomanic (14%) or mixed states (6%)
(referred to as the “exalted dysphoric mood” (EDM) group), and 8 patients (16%)
had others diagnoses. The treatment leading to recovery was very different
between the two affective groups, with a good response for antidepressants
(76.9%) in MDE patients (among which 38% had an association with mood
stabilizer), whereas the EDM group had a good response to neuroleptics (80.9%)
(in association with a mood stabilizer in 85.7%). Five patients (23.8%) in the
MDE group and one patient in the EDM group required electroconvulsant therapy.
The risk of suicide was not different between the two groups (p=0.7). In order
to improve the differential diagnosis between both groups, we have assessed the
occurrence of a series of symptoms in these patients. The most frequently
encountered (in more than 75%) in the EDM group were: insomnia, decreased
shyness, an increased restlessness and irritability, distractibility, subjective
experience that thoughts are racing, and the feeling that intensity of emotions
is increased.
Conclusions: Some mood episodes with depressive symptoms are worsened by
antidepressant treatment because they turn out to correspond to dysphoric manic,
hypomanic or mixed states rather than to genuine depressive episodes. This
concept is supported by the positive response to antimanic treatment in this
latter group. This study provides a set of symptoms (particularly emotional
hyperreactivity) that may help to distinguish between these two groups.
Moreover, these patients with dysphoric episodes seem to more easily report
negative symptoms during consultation, and this may partly account for the high
rate of misdiagnoses.
Keywords: bipolar depression, mixed state, emotional
hyperreactivity.
Pharmacological Treatment of Bipolar Disorder: Psychotropic Medication Use
in the First 500 Patients in the Systematic Treatment Enhancement Program for
Bipolar Disorders
Video | Audio
(Length: 19 min.)
D.J. Hsu1,2, S.N. Ghaemi1,2,
M.E. Thase3,
S.R. Wisniewski3,
G.S. Sachs3,4
1Cambridge Hospital, Cambridge, MA, 2Harvard Medical
School, Boston, MA, 3University of Pittsburgh School of Medicine,
Pittsburgh, PA, 4Massachusetts General Hospital, Boston, MA, USA
Objective: To evaluate medication use in bipolar disorder, including
frequency of polypharmacy and the roles of bipolar subtype, history of
rapid-cycling, and history of psychosis.
Method: Cross-sectional medication use of the first 500 patients in the
Systematic Treatment Enhancement Program for Bipolar Disorders (STEP-BD).
Results: 72% received mood stabilizers, most commonly lithium (38%) and
valproate (37%). 41% received antidepressants, most commonly bupropion (15%).
30% received neuroleptics, mainly atypical agents (most commonly olanzapine,
14%). Only 11% received mood stabilizer monotherapy. Type I patients were more
likely than type II patients to receive mood stabilizers (RR=1.19, 95% CI
[1.045-1.36], p=0.005) and neuroleptics (RR=1.25, CI [1.145-1.37], p < 0.001),
but less likely to receive antidepressants (RR=0.89, CI [0.80-0.99], p=0.04).
Patients with a history of psychosis were more likely to receive mood
stabilizers (RR=1.17, CI [1.05-1.30], p=0.01) and neuroleptics (RR=2.20, CI
[1.65-2.93], p < 0.001) than patients with no history of psychosis. Notably,
antidepressants were used similarly in rapid-cycling and non-rapid cycling
patients.
Conclusions: Nearly three quarters of patients received mood stabilizers
in treating bipolar disorder, with valproate and lithium equally used. Almost
one half received antidepressants, and one third received atypical neuroleptics.
Polypharmacy occurred in 89% of patients. Type II patients received less mood
stabilizing and neuroleptic, but more antidepressant, treatment. Presence of
psychosis predicted more mood stabilizing and neuroleptic treatment.
Antidepressants were not used cautiously in rapid-cycling patients.
Keywords: prescribing patterns, pharmacotherapy, polypharmacy.
Clinical Experience with Topiramate in a Psychiatric-Based
Weight Management Program
Video | Audio
(Length: 18 min.)
S.L. McElroy, R. Kotwal, S. Malhotra, K. King, A. Guerdjikova, S. Wu, K.
Harding, J. Capece, N. Rosenthal
University of Cincinnati, College of Medicine, Cincinnati, OH, USA
Objective: Assess long-term effectiveness of topiramate (TPM) in a
psychiatric-based weight management program.
Methods: Naturalistic data review of all patients seen for weight
management between 2000-2002 who were assessed by structured clinical interview
for eating and/or mood (depressive and bipolar) disorders and treated with TPM
as primary/adjunctive therapy. Topiramate was titrated by 25 mg/wk to median
daily dose of 200 mg. Efficacy was assessed by mean weekly binge episodes,
CGI-Severity, and weight/BMI.
Results: 148 patients (100% eating + mood disorders; 56%
adjunctive therapy), mean age 45 + 10 years and mean baseline weight/BMI
110 + 28 kg/40 kg/m2, were followed for a median treatment duration of
110 days (range 1–688). Patients experienced significant reductions in mean
weekly binge frequency to 1.2 binges/week, a 49% change from baseline. Shift
analysis of CGI-Severity showed 37% of patients at final visit improved to a
normal or borderline-normal rating compared to baseline 0.7%. Patients lost an
average of 4.7 kg and BMI fell 1.7 kg/m2. Correlations with associated mood
(depressive and bipolar) disorders will be shown. Most common adverse events
included paresthesia, fatigue, dry mouth, and taste perversion.
Conclusions: Topiramate appeared effective for weight management in
outpatients with obesity associated with eating/mood disorders.
Keywords: topiramate, eating disorder, bipolar disorder.
Questions for all Panel Members After 4 Presenters
Audio
(Length: 33 min.)
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