Original Research

Course and Outcome After the First Manic Episode in

Patients With Bipolar Disorder: Prospective 12-Month
Data From the Systematic Treatment Optimization
Program for Early Mania Project

Lakshmi N Yatham, MBBS, FRCPC, MRCPsych(UK)1; Marcia Kauer-Sant’Anna, MD, PhD2;

David J Bond, MD, FRCPC3; Raymond W Lam, MD, FRCPC1; Ivan Torres, PhD3

Objective: To describe clinical characteristics, course, and outcome during a 1-year period
after the first manic episode in patients with bipolar disorder (BD).
Methods: This paper describes the project design, demographics, clinical outcomes, and
predictors at 6 months to 1 year of follow-up of the first 53 recruited subjects with
first-episode mania from the Systematic Treatment Optimization Program for Early Mania.
Results: Survival analysis for recurrence of mood episodes showed that 46.7% of patients
survived without a mood episode during 1-year of follow-up, and the mean time-to-mood
event was 7.9 months. Earlier age of onset was the only variable that significantly
predicted recurrence of mood episodes. When examined separately, the survival rates were
76% for a manic episode and 58.7% for a depressive episode.
Conclusion: These results suggest that recurrences are common after the first manic
episode with more than one-half of the patients experiencing a mood event within 12
months. Aggressive treatment strategies aimed at preventing depressive episodes are
needed in the management of early course BD.
Can J Psychiatry. 2009;54(2):105–112.

Clinical Implications

· Depressive recurrences are common after the first manic episode and deserve special clinical
attention.
· Younger age at onset of mood episodes was significantly associated with worse outcome,
reinforcing the need for preventive strategies.
· As these patients received comprehensive treatments, the data suggests that currently available
treatments are not adequate in preventing depression for a significant proportion of patients.

Limitations

· The sample size may have restricted the ability to detect smaller effect sizes of other
predictors of recurrence.
· This study design does not allow an assessment of the impact of different treatments on
outcome.
· The relatively shorter period of follow-up limits the conclusions about outcome to the early
recovery phase of BD.

Key Words: bipolar disorder, first-episode, mania, outcome

The Canadian Journal of Psychiatry, Vol 54, No 2, February 2009 W 105

Original Research
D is a serious psychiatric condition characterized by high
B rates of relapse, persistent subsyndromal morbidity, sig-
nificant psychosocial dysfunction, elevated mortality owing
to suicide, and increases incidence of serious medical disor-
ders. Given this, an understanding of the course of BD from
the disease onset is critical as it may contribute to the develop-
ment of timely interventions with a potential reduction in mor-
bidity and mortality. Interestingly, most of the information to
date about the longitudinal course of BD primarily comes
from tracking outcomes in people who have had multiple
mood episodes with the inevitable confounding of the results
by variables such as duration of illness, number of episodes,
and medication effects. Nonetheless, these studies support the
common clinical observation that the course of BD is not as
benign as was once supposed. Even with access to modern
medications, most patients with BD experience high levels of
morbidity, spending almost one-half of the follow-up periods
with mood symptoms, most of which are depressive.1,2 Fur-
ther, BD is associated with persistent cognitive deficits,3
changes in brain morphology,4 and reduced quality of life.5
While research has been increasingly directed toward defin-
ing the extent of these deficits, little is understood about the
interactions between them and the course of the illness.
Relapses, switches, and recurrence of mood episodes are
common in BD, with reported rates as high as 57% in mainte-
nance studies.6,7 These findings, though, cannot exclude the
confounding effect of multiple previous episodes, type of
treatment, and adherence to treatment. More recently, a few
studies that have examined course and outcome of BD in
patients who have recently had their first manic episode
showed that, like first-episode schizophrenia, first-episode
mania carries with it a high risk of poor functional outcome.8,9
These studies also reported a high risk of suicide, high preva-
lence of comorbid diagnoses, and worse outcome with earlier
age at onset.10–12 A large retrospective study, which included
Abbreviations used in this article
BD bipolar disorder
BPRS Brief Psychiatric Rating Scale
CGI-BP Clinical Global Impression Scale for
Bipolar Disorder
DSM Diagnostic and Statistical Manual of Mental
Disorders
HDRS Hamilton Depression Rating Scale
MADRS Montgomery-Asberg Depression Rating Scale
STOP-EM Systematic Treatment Optimization Program
for Early Mania
UBC University of British Columbia
YMRS Young Mania Rating Scale
106
20 350 patients with affective disorders after their first hospi-
tal admission, showed that bipolar patients had a higher risk
of recurrence than those with major depressive disorder. In
the same sample, the long-term prognosis of BD remained
poor in a significant proportion of patients as they experi-
enced decreasing lengths of interepisode intervals with an
increasing number of episodes.13 More recent prospective
studies of first episode bipolar patients reported recurrence
rates of 40% in an adult sample9,14 and 54% in an adolescent
sample.11 However, these studies recruited patients after their
first psychotic episode, from inpatient units or from early
psychosis intervention programs. The selection of the most
severe cases of BD with psychosis and with hospitalization
restricts the generalizability of the findings to all patients
with bipolar I disorder.
To overcome limitations from a research perspective of pre-
vious first-episode cohorts, STOP-EM was started at UBC
and Vancouver General Hospitals. This project recruited
patients with and without psychosis, with bipolar I disorder,
hospitalized or not, after their first manic episode. The objec-
tive of this project was to gather more information concern-
ing the clinical course and neurobiological changes in people
with bipolar I disorder, in particular in the early phase. The
study of first-episode manic patients provides an opportunity
to determine outcome on a prospective basis and to ascertain
whether cognitive and structural brain changes are present at
disease onset, develop over the course of the illness, or are
due to treatment variables. Additionally, the study of
first-episode patients allows the interaction of these changes
to be more reliably assessed.
In this report, we describe the project design and the charac-
teristics of the first 53 patients enrolled, and we also examine
the pattern of recurrence of mood episodes within 1 year of
follow-up and clinical correlates. Data from neurocognitive
testing, morphometric assessment, and functional outcomes
will be presented in separate reports.
Methods
STOP-EM is a prospective study of clinical outcomes, health
status, brain morphology, neurochemistry, cognitive func-
tioning, quality of life, and functional outcomes in patients
who have recently experienced their first bipolar manic epi-
sode, according to DSM-IV-TR criteria. This project started
in July 2004 and has been recruiting actively since then. In
our study, we will present the data on the first 53 patients
enrolled until July 2007 and their outcomes over a 6- to
12-month follow-up period. Patients were recruited from
UBC and Vancouver General Hospitals and affiliated sites as
well as through referrals from physicians and psychiatrists.
People aged between 14 and 35 years who were currently
experiencing or had experienced a first manic episode within
W La Revue canadienne de psychiatrie, vol 54, no 2, février 2009
 Course and Outcome After the First Manic Episode in Patients With Bipolar Disorder
the past 3 months were recruited. Inclusion criteria were
deliberately broad to capture the full range of bipolar patients
routinely encountered in clinical practice. Patients may be
enrolled as in- or outpatients and may be diagnosed with pure
or mixed mania, with or without psychotic features, and with
or without comorbidity, including substance use comorbidity.
Exclusion criteria included inability to give informed
consent and having a previous manic episode diagnosed
retrospectively on structured interview or via collateral
information.
At the baseline assessment, all subjects had a comprehensive
clinical interview by a board-certified psychiatrist. The diag-
nosis of BD-recent manic episode was established based on all
the available clinical information and a Mini International
Neuropsychiatric Interview.15 Subjects who had previously
undiagnosed or untreated manic symptoms were excluded.
Subjects who had previous hypomanic episodes were
included. The comorbidities were diagnosed according to
DSM-IV-TR criteria based on all the available information.16
Subjects enrolled in the program received open label mainte-
nance treatment for BD from clinicians with expertise in man-
agement of mood disorders and familiar with the most recent
clinical guidelines.17,18 Any new mood episodes were treated
using best evidence-based practices. In addition to regular
assessment of psychiatric status, medication monitoring, and
supportive therapy, subjects were offered the opportunity to
participate in a standardized 8-week group psychoeducation
program. Subjects enrolled in the program were assessed as
clinically indicated, and at a minimum of every 6 months for
research purposes, during a 5-year follow-up period.
Psychiatric status was assessed using clinical rating scales,
including the YMRS,19 HDRS 29-item version,20 MADRS,21
BPRS,22 and CGI-BP.23, 24
The criteria for full symptomatic remission were YMRS and
HDRS score of 8 or less.25 The remission criteria only
accounted for the previous 2 weeks of symptoms. Relapse and
recurrence, defined as mood symptoms occurring within 8
weeks of syndromal recovery and occurring after remission,
respectively, will be named recurrence from here on. Recur-
rence was considered if manic or depressive symptoms ful-
filled DSM-IV-TR for a mood episode. 16 Syndromic
remission from first manic episode was considered the start-
ing point for the survival curves. Psychiatric and medical his-
tories, and information about current and past medication use,
were obtained using all available sources of information,
including patient interview, completion of the Patient Health
Survey27 and, when available, collateral information from
family members and health records. National Instititue of
Mental Health Life Charts28 were constructed, retrospectively
detailing the subject’s course of illness. Adherence was
assessed through clinical interview and for analysis purposes;
The Canadian Jourmal of Psychiatry, Vol 54, No 2, February 2009 W
one event of discontinuing medication against medical
advice within the follow-up period was considered
nonadherence.
The STOP-EM program and all of the procedures described
in this report have received approval from the UBC Clinical
Research Ethics Board. Written informed consent was
obtained from all patients prior to any study procedures tak-
ing place.
Statistics
Statistical analyses were performed using SPSS software,
version 13.0 (SPSS Inc, Chicago, IL). Descriptive statistics
were used to report sociodemographic and clinical character-
istics of the sample. Association between dichotomous vari-
ables was assessed with chi-square test or Fisher exact test
when appropriate. Changes in mood symptoms over time, as
per mood scales scores, were assessed with repeated mea-
sures ANOVA. The cumulative probability of recurrence of a
mood episode during the 12 months following the recovery
of a first manic episode was estimated using the
Kaplan-Meier method (survival curve). In addition, the
effect of potential predictors (based on existing literature) of
recurrence and time to outcome event (any new mood epi-
sode) from entry into the program were calculated using Cox
proportional hazards modelling. Predictors were entered by
stepwise selection if associated with the event at a signifi-
cance level of P < 0.10. Sex, age, education, overall age of
onset (age at onset of first lifetime mood episode), psychosis
within manic episode, length of illness, number of previous
episodes, presence of any psychiatric comorbidity, were
entered as predictors of outcome. As exploratory analyses,
we estimated the survival function for manic and depressive
episodes separately, where the time-to-event is the time to
first recurrent manic episode or the time to first depressive
episode, respectively. Multiple episodes were not taken into
account in the survival modelling. These were exploratory
analyses as the sample size restricted the power to detect
smaller effect sizes and precluded meaningful stratifications.
All statistical tests were 2-tailed and were carried out using a
significance level of á = 0.05. Data are presented as means
plus or minus standard deviation.
Results
Fifty-three patients were recruited to date. Among the 41 due
for the 6-month follow-up, 35 completed the visit; of these,
all 27 that were due for 1-year follow-up completed the visit.
There were 6 dropouts; 2 moved out of commutable distance,
2 withdrew consent, and 2 were lost to follow-up. Descriptive
demographics are shown in Table 1. The mean age of the
sample was 22.1 years, ranging from 17 to 32 years of age.
Proportionally to their age, they were well educated, with 14
107
Original Research

Table 1 Demographic characteristics of patients with BD after their first manic episode
Entry 6-month follow-up 1-year follow-up
Variable n = 53 n = 35 n = 27

Sex, %
Male 50.9 54.3 59.3
Female 49.1 45.7 40.7
Age, years, mean (SD) 22.2 (3.7) 22.4 (3.4) 23.3 (3.4)
Education, years, mean (SD) 14.0 (2.3) 13.8 (2.2) 13.5 (2.1)
Marital status, %
Single 92.5 94.3 96.3
Married 5.7 2.9 3.7
Separated 1.9 2.9 0.0
Ethnicity, %
Caucasian 77.4 77.1 77.8
Asian 17.0 20.0 22.2
Other 5.7 2.9 0.0

mean years of education. The ratio for males and females was
close to the unity.
Clinical characteristics of patients at entry showed that mean
length of illness (from the first mood episode to the study
entry) was 2.9 years (SD 3.3), and the age at onset of any mood
episode was 19.3 years (SD 4.3). Eighty-eight percent of
patients were hospitalized for their first manic episode. The
polarity of first mood episode was depressive in 52.9% of
patients, manic in 35.3%, and hypomanic in 11.8% of sample.
A total of 58.49% of patients had a previous depressive epi-
sode prior to their first manic episode. Psychosis was present
within the first manic episode in 67.9% of patients. As
expected for BD samples, comorbidities were highly preva-
lent, including 54% with substance abuse, 20% with alcohol
abuse, 10% with anxiety disorder, and 26% with medical
comorbidity. Family history (in first-degree relatives) of
depression was reported by 30.2% of patients, of BD by 10%
of patients, and of other psychiatric diagnosis by 5.7%. Only
9.4% of patients reported a previous suicide attempt. At entry
into the first-episode mania program, 86.8% (46/53) of
patients were taking a mood stabilizer, 77.4% (41/53) of
patients were taking an antipsychotic, and only 3 patients
were taking antidepressants. Seventy-two percent of patients
(38/53) were on a combination of one mood stabilizer and one
antipsychotic. All patients were referred for psychoeducation
but only 43.4% completed the full 8-week psychoeducation
program. During 1 year of follow-up, 63% (17/27) of patients
reported consistent adherence with treatment, while 37%
(10/27) had at least one event of discontinuation of medica-
tions against medical advice. There was a significant
association between nonadherence to treatment and sub-
stance abuse disorder (÷2 = 5.2, df = 1, P = 0.02).
Clinical outcome and mood changes over follow-up period
are shown in Table 2. The repeated measures ANOVA
showed an improvement of mood symptoms and functioning
over the one-year follow-up period, according to clinical rat-
ing scale scores. Significant improvements were seen in
Global Assessment of Functioning Scale, CGI-BP, BPRS,
YMRS, HDRS, and MADRS scores from entry into the pro-
gram to 6-month and 1-year follow-up. Recurrence of
depressive episodes was more common (32.4%) in compari-
son with recurrence of manic episode (5.9%) within the first 6
months of follow-up. Despite high rates of recurrence, most
patients had only one recurrent episode. For instance, during
1 year of follow-up, no patient had more than one depressive
or hypomanic episode, and only one patient had 2 recurrent
manic episodes. Even considering all types of mood episodes
together, only 3 patients had more than one recurrent episode.
There was no association between type of first episode and
polarity of first recurrent episode (÷2 = 1.2, df = 4, P = 0.84).
Clinical recovery, here defined by remission of symptoms,
was achieved by 62.3% (33/53) of patients both for manic
and depressive symptoms at entry into the program. By 6
months, all of the patients (35/35) had remitted from the first
manic episode, but only 80% (28/35) achieved remission for
depressive symptoms. By 1-year follow-up, 96.3% (26/27)
and 88.9% (24/27) achieved remission for manic and
depressive symptoms, respectively.
Survival analysis for recurrence of mood episodes showed
that 53.3% of patients experienced a recurrent mood episode
during a 1-year follow-up period, and the mean time-to-event

108 W La Revue canadienne de psychiatrie, vol 54, no 2, février 2009

 Course and Outcome After the First Manic Episode in Patients With Bipolar Disorder

Table 2 Outcome characteristics of patients with BD after their first manic episode
Entry 6-month follow-up 1-year follow-up
Variable n = 53 n = 35 n = 27

Comorbidity, %
Any new diagnosis n/a 25.0 0.0
Scales scores, mean (SD)
CGI-BP-S 2.1 (1.2) 1.4 (0.8) 1.3 (0.7)a
YMRS 3.9 (5.8) 0.6 (1.2) 0.8 (4.2)b
HDRS 6.9 (8.9) 4.1 (5.3) 2.0 (4.3)b
MDRS 6.3 (7.9) 4.1 (5.8) 1.4 (4.3)b
BPRS 22.4 (5.5) 19.6 (2.4) 19.2 (3.8)a
GAF 64.5 (13.0) 76.4 (9.5) 77.6 (11.4)c
Recurrence (new episode), %
Mania n/a 5.9 11.1
Depression n/a 32.4 14.8
Hypomania n/a 5.7 3.7
Full remission, %
Mania 86.8 100.0 96.3
Depression 66.0 80.0 88.9
Both 62.3 80.0 88.9

a
P < 0.01; b P < 0.05; c P < 0.001; ANOVA repeated measures
CGI-BP-S = Clinical Global Impression Scale for Bipolar Disorder—Severity; GAF = Global Assessment of Functioning;
n/a = not applicable at baseline

was 7.9 months. Among predictors of survival, earlier age of
onset was the only variable that significantly predicted recur-
rence of mood episodes. However, the hazard ratio showed
only a small (â = 1.119; P = 0.02) increase in survival time
with later age of onset. When examined separately, the 1-year
survival rates were 76% for a manic episode and 58.7% for a
depressive episode. The mean time-to-event was 11 months
for manic and 8.3 months for depressive episode.
Discussion
The data from the STOP-EM program showed that of the 53
patients with a first manic episode, 52.9% of the patients had
experienced a depressive episode before their first manic epi-
sode. The mean length of illness was close to 3 years, when
previous depressive and hypomanic episodes were included.
Further, our data suggest that more patients achieve remission
of manic symptoms than of depressive symptoms. Despite the
low threshold criteria, nonadherence rates were only 37% and
were consistent with data from previous studies.26 Interest-
ingly, rates of substance abuse in our sample were as high as
54% and were significantly associated with nonadherence to
treatment. The findings also indicate a high relapse rate over a
1-year period, despite comprehensive clinical care that
in c lu d e d ev id e n c e - b a s e d p h a r ma c o th e r a p y an d
psychoeducation, with only 46.7% of patients surviving
without a mood episode. Among patients who had recurrence
of symptoms, depression was responsible for most episodes.
Among predictors of recurrence, age of onset was the only
variable with significant association with the outcome.
Recurrence rates of 53% observed in this sample are consis-
tent with survival rates reported in previous studies of
first-episode patients.11,14 For instance, in a sample of adoles-
cents who were hospitalized for a first-episode mania, of
those who achieved syndromal recovery, 54% had a recur-
rence of a mood episode within a 12-month period.11 Simi-
larly, in the McLean first-episode cohort of hospitalized
manic or mixed-episode patients, of those that attained
syndromal recovery from the first manic episode, 40% had a
recurrence, while 20% of the initial cohort switched into a
depressive episode without recovery from mania.14 Interest-
ingly, the mean time to recurrence of a mood episode of 7.9
months was slightly longer in our sample, compared with the
populations in previous reports. Tohen et al14 reported a mean
time to any mood episode of 6.5 months, to a manic episode
of 8.1 months, and to a depressive episode of 7.9 months,14
while De Bello et al11 reported a mean time to any mood
episode of 4.2 months in an adolescent sample. 11 Poorer

The Canadian Jourmal of Psychiatry, Vol 54, No 2, February 2009 W 109

Original Research
Figure 1 Survival curve: recurrent mood episodes
Cumulative survival
Time-to-event
outcomes in adolescent cohorts may be due to poorer adher-
ence to treatment as 65% of patients in that cohort were
reported to be nonadherent to treatment. In contrast, despite
low threshold for definition of nonadherence, the rates were
only 37% in our sample. Many patients in our cohort received
a group psychoeducation after enrolment, which may have
contributed to better outcomes in our first-episode cohort.
Nonadherence rates in BD treatment for long-term prophylac-
tic pharmacotherapy range from 18% to 52%, with a median
prevalence of 44.7%.29 Thus the 37% nonadherence rate in
our sample is consistent with these previous reports. One rea-
son for poor adherence to treatment is comorbidity with sub-
stance abuse disorder. A recent study described lifetime
adherence rates of 65.5% for patients with BD with comorbid
substance abuse disorder, compared with 82.5% for those
without comorbidity.30 Substance abuse was also a predictor
of poor adherence to treatment in a sample of patients with BD
followed after their first hospitalization,31 similar to the
results found in our cohort.
Our results also confirm findings from previous reports that
earlier age of onset is associated with a worse outcome. In our
sample, those with earlier age of onset presented a higher risk
of recurrence of a mood episode. This is consistent with
the recent perspective of BD as a developmental
psychopathology. Between 50% and 66% of adults with BD
experience illness onset before the age of 19 years, and
between 15% to 28% before the age of 13 years.32,33 Child-
hood or adolescence onset of BD is associated with a more
severe, adverse, and rapid cycling course of illness and multi-
ple comorbidities.34–37
110
Long-term prospective studies suggest that of time spent
symptomatic, patients with BDI experience depressive
symptomatology about 3 times as frequently as hypomanic or
manic symptoms.38 Our findings confirm the importance of
the depressive phase early in the course of BD, as depressive
episodes in our cohort not only preceded the first manic epi-
sode but depressive recurrence was more common than
manic recurrence. Depressive episodes preceding the first
manic episode might have been underrecognized in previous
studies that only examined episodes requiring hospitalization
and reflect a common clinical challenge in the treatment of
BD; the differential diagnosis with major depression, when
mania has not yet occurred. This is of clinical relevance, as
the deleterious impact of delay in the diagnosis of BD has
been highlighted in previous reports. For example, the num-
ber of years that patients with BD go undiagnosed and with-
out appropriate treatment is associated with worse quality of
life and higher levels of depression.39 Recent studies also
report the negative effects of cumulative mood episodes.40
Previous literature of maintenance studies suggests that
polarity of index episode predicts the polarity of subsequent
relapse.41 For example, a randomized maintenance study of
lamotrigine and lithium showed that, when the index episode
was mania, about two-thirds of patients had higher ratio of
relapse of mania, while, when the index episode was depres-
sion, all patients had a higher ratio of relapse of depression.42
Similarly, for patients recovered from a bipolar depressive
episode, the risk of relapse into depression is higher than the
risk of relapse into mania within 1 year of follow-up, even if
antidepressants were added to mood stabilizers.43 However,
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 Course and Outcome After the First Manic Episode in Patients With Bipolar Disorder
in our sample recently treated for a manic episode, the recur-
rence of depressive episodes was most commonly observed.
One reason for the discrepancy in findings may be that
patients in our cohort were treated with one or more medica-
tions plus psychoeducation as clinically indicated, in contrast
to clinical trials of maintenance treatment in which patients
are usually not allowed to receive any psychosocial treatments
or concomitant medications. That depressive recurrence was
more common in our cohort, despite comprehensive
evidence-based pharmacotherapy and psychosocial treat-
ments, suggests that currently available treatments are less
effective in preventing depression than in preventing mania.
Indeed, there are studies showing that the magnitude of pro-
phylactic efficacy is greater for preventing mania than depres-
sion for lithium42,44 and olanzapine, 45–47 and likely for many
other psychotropic medications with the exception of
lamotrigine.
While the index episode is considered the episode preced-
ing the maintenance treatment, some studies examined the
association of polarity of the first illness episode and polarity
of relapse during maintenance treatments. Studies from the
pre-lithium era suggested that if the first episode was manic,
there was an increased risk of manic relapse.41 In our sample,
more than one-half of patients had a first episode of depres-
sion. However, there was no association between polarity of
first episode and polarity of first recurrence during follow-up.
Many of the earlier studies included only episodes of recur-
rence that required hospitalization, leading to a possible
underestimation of depressive episodes.
Some limitations should be considered when interpreting
these results. The sample size may have restricted the ability
to detect smaller effect sizes of other variables in the Cox pro-
portional hazards model. As most patients were taking both
one mood stabilizer and one antipsychotic, the assessment of
impact of treatment on outcomes and comparison between
treatments was limited. The relatively short period of
follow-up dictates that our conclusions should be limited to
the early recovery phase of first manic episodes.
Conclusions
The findings suggest that depressive episodes are an impor-
tant part of the clinical course of early phase BD. This is in line
with longitudinal studies, which showed that depression con-
stitutes the most time spent with affective symptoms, outstrip-
ping mania and hypomania by a ratio of 3:1.42 The findings
point out that syndromal remission may be easy to achieve but
difficult to maintain; symptomatic remission is common in the
early course of BD, but recurrence is also common. The effect
of earlier age of onset on recurrence highlights the importance
of preventive strategies and the need for studies with at-risk
populations. The clinical features reported here reinforce the
The Canadian Jourmal of Psychiatry, Vol 54, No 2, February 2009 W
pressing need for improved understanding of the early course
of BD, with special attention to the increased risk of
depressive relapse.
Funding and Support
This study was funded by an unrestricted grant from Astrazeneca
to Dr Yatham. Dr Yatham is on speaker and advisory boards for,
or has received research grants from: AstraZeneca, Bristol Myers
Squibb, Canadian Institutes of Health Research, Canadian
Network for Mood and Anxiety Treatments, Eli Lilly,
GlaxoSmithKline, Janssen, Michael Smith Foundation for Health
Research, Pfizer, Servier, and Stanley Foundation.
Dr Kauer-Sant’Anna has been an investigator in clinical trials
sponsored by Novartis, Servier, Canadian Institutes of Health
Research, and Stanley Foundation, and has received salary
support from an American Psychiatric Association and an
AstraZeneca unrestricted educational grant. Dr Bond has been an
investigator in clinical trials sponsored by Sanofi-Aventis,
GlaxoSmithKline, and Servier, and has received speaking fees
from AstraZeneca and Canadian Network for Mood and Anxiety
Treatments. Dr Lam is on speaker and advisory boards for, or has
received research grants from: ANS Inc, AstraZeneca, Biovail,
Canadian Institutes of Health Research, Canadian Network for
Mood and Anxiety Treatments, Eli Lilly, GlaxoSmithKline,
Great-West Life, Janssen, Litebook Company Ltd, Lundbeck,
Sanofi-Aventis, Servier, Vancouver General Hospital and UBC
Hospital Foundation, and Wyeth.
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Manuscript received January 2008, revised, and accepted May 2008.
1
Professor of Psychiatry, Mood Disorders Program, Department of
Psychiatry, University of British Columbia, Vancouver, British Columbia.
2
Clinical Fellow Mood Disorders Program, Department of Psychiatry,
University of British Columbia, Vancouver, British Columbia.
3
Associate Professor of Psychiatry, Mood Disorders Program, Department
of Psychiatry, University of British Columbia, Vancouver, British
Columbia.
Address for correspondence: Dr LN Yatham, Professor of Psychiatry and
Associate Head, Research and International Affairs Department of
Psychiatry, University of British Columbia, Room 2C7–2255 Wesbrook
Mall, Vancouver, BC V6T 2A1; yatham@exchange.ubc.ca

Résumé : Évolution et résultat après le premier épisode maniaque chez des patients souffrant du
trouble bipolaire : les données prospectives de 12 mois du programme d’optimisation systématique du
traitement pour la manie précoce
Objectif : Décrire les caractéristiques cliniques, l’évolution, et le résultat sur une période d’un an après le premier épisode
maniaque chez des patients souffrant du trouble bipolaire (TB).
Méthodes : Cet article décrit la méthode du projet, les données démographiques, les résultats cliniques, et les prédicteurs de 6
mois à 1 an de suivi des 53 premiers sujets recrutés au premier épisode de manie, dans le programme d’optimisation
systématique du traitement pour la manie précoce (STOP-EM).
Résultats : L’analyse de survie de la récurrence des épisodes d’humeur a montré que 46,7 % des patients survivaient sans
épisode d’humeur durant le suivi d’un an, et que le délai moyen avant un nouvel épisode d’humeur était de
7,9 mois. L’âge plus précoce d’apparition de la maladie était la seule variable qui prédisait significativement la récurrence des
épisodes d’humeur. Examinés séparément, les taux de survie d’un épisode maniaque étaient de 76 % et ceux d’un épisode
dépressif de 58,7 %.
Conclusion : Ces résultats suggèrent que les récurrences sont fréquentes après le premier épisode maniaque, car plus de la
moitié des patients subissent un événement d’humeur dans les 12 mois. Les stratégies de traitement agressif visant à prévenir
les épisodes dépressifs sont nécessaires dans la prise en charge du début du TB.

112 W La Revue canadienne de psychiatrie, vol 54, no 2, février 2009