Association of exercise with quality of life and mood symptoms
in a comparative effectiveness study of bipolar disorder
Louisa G. Sylviaa,n, Edward S. Friedmanb, James H. Kocsisc, Emily E. Bernsteina,
Benjamin D. Brodyc, Gustavo Kinrysa, David E. Kempd, Richard C. Sheltone,
Susan L. McElroyf, William V. Bobog, Masoud Kamalih, Melvin G. McInnish,
Mauricio Toheni, Charles L. Bowdenj, Terence A. Ketterk, Thilo Deckersbacha,
Joseph R. Calabresed, Michael E. Thasel, Noreen A. Reilly-Harringtona, Vivek Singhj,
Dustin J. Rabideaua, Andrew A. Nierenberga
aThe Massachusetts General Hospital, USA
bUniversity of Pittsburgh Medical Center, USA
cWeill Cornell Medical College of Cornell University, USA
dCase Western Reserve University, USA
eUniversity of Alabama at Birmingham, USA
fLindner Center for Hope, University of Cincinnati, USA
gMayo Clinic, USA
hUniversity of Michigan, USA
iUniversity of New Mexico, USA
jUniversity of Texas Health Science Center at San Antonio, USA
kStanford University School of Medicine, USA
lPerelman School of Medicine at the University of Pennsylvania, USA
a r t i c l e i n f o
Received 24 June 2013
Accepted 31 July 2013
Available online 16 August 2013
Quality of life
a b s t r a c t
Background: Individuals with bipolar disorder lead a sedentary lifestyle associated with worse course of
illness and recurrence of symptoms. Identifying potentially modifiable predictors of exercise frequency could
lead to interventions with powerful consequences on the course of illness and overall health.
Methods: The present study examines baseline reports of exercise frequency of bipolar patients in a multi-site
comparative effectiveness study of a second generation antipsychotic (quetiapine) versus a classic mood
stabilizer (lithium). Demographics, quality of life, functioning, and mood symptoms were assessed.
Results: Approximately 40% of participants reported not exercising regularly (at least once per week). Less
frequent weekly exercise was associated with higher BMI, more time depressed, more depressive symptoms,
and lower quality of life and functioning. In contrast, more frequent exercise was associated with experiencing
more mania in the past year and more current manic symptoms.
Limitations: Exercise frequency was measured by self-report and details of the exercise were not collected.
Analyses rely on baseline data, allowing only for association analyses. Directionality and predictive validity
cannot be determined. Data were collected in the context of a clinical trial and thus, it is possible that the
generalizability of the findings could be limited.
Conclusion: There appears to be a mood-specific relationship between exercise frequency and polarity such
that depression is associated with less exercise and mania with more exercise in individuals with bipolar
disorder. This suggests that increasing or decreasing exercise could be a targeted intervention for patients with
depressive or mood elevation symptoms, respectively.
& 2013 Elsevier B.V. All rights reserved.
Bipolar disorder is a severe, chronic, recurrent mental illness
characterized by depressive and manic/hypomanic mood episodes
that are associated with deficits in quality of life and psychosocial
functioning (Coryell et al., 1993; Salvatore et al., 2007; Sanchez-
Moreno et al., 2009; Tohen et al., 1990; Young and Grunze, 2013).
Pharmacotherapy is associated with the persistence of symptoms in
Contents lists available at ScienceDirect
journal homepage: www.elsevier.com/locate/jad
Journal of Affective Disorders
0165-0327/$-see front matter & 2013 Elsevier B.V. All rights reserved.
nCorrespondence to: Bipolar Clinic and Research Program, Massachusetts General Hospital, 50 Staniford Street, Suite 580, Boston, MA 02138, USA.
Tel.: þ617 643 4804; fax: þ617 726 6768.
E-mail address: email@example.com (L.G. Sylvia).
Journal of Affective Disorders 151 (2013) 722–727
54–68% of the patients (Culver et al., 2007; Keitner et al., 1996) and
is burdened by significant side effects, such as contributing to one′s
risk of cardiovascular disease (De Almeida et al., 2012; Ketter, 2010;
Serretti et al., 2013). This is particularly concerning as individuals
with bipolar disorder are already at a higher risk for cardiovascular
disease (Khot et al., 2003; Krishnan, 2005; McIntyre et al., 2005;
Soreca et al., 2008) compared to the general population, which leads
to comparatively higher rates of morbidity and mortality (Angst
et al., 2002; Hennekens, 2007; Osby et al., 2001). Thus, there is a
need to not only improve the treatment of bipolar symptoms but
also to reduce their disproportionate medical burden.
Regular physical activity is associated with lower risk for pre-
mature mortality and improves risk factors for cardiovascular disease
(Church et al., 2007; Cornelissen and Fagard, 2005). Evidence also
suggests that exercise may improve course of bipolar illness and life
functioning (Sylvia et al., 2011; Ng et al., 2007). In other psychiatric
and non-psychiatric populations, better exercise habits have been
associated with lower levels of depression (De Moor et al., 2006;
Mead et al., 2008; Otto et al., 2007; Palomo et al., 2008; Trivedi et al.,
2011; Tsang et al., 2008), less stress (Vancamfort et al., 2011), less
neuroticism (De Moor et al., 2006), better sleep quality (Palomo et al.,
2008), social contact (Carless and Douglas, 2008; Wright et al., 2012),
energy (Crone and Guy, 2008), and better overall mental health
(Crone and Guy, 2008; Ellis et al., 2007; Stathopoulou et al., 2006;
Tordeurs et al., 2011; Vancamfort et al., 2011). Positive effects of
physical activity for major depression have proven particularly robust
(Harris et al., 2006; Tordeurs et al., 2011), for example associating
with higher remission rates (Blumenthal et al., 2007; Trivedi et al.,
2011), even controlling for gender, age, medical problems, and
negative life events (Harris et al., 2006). Despite these promising
data on the benefits for exercise in severe mental illness, little is
known about predictors of exercise within the bipolar population
and how physical activity may affect bipolar specific mood symptoms
and quality of life.
One recent, small study (N¼66) found that individuals with
serious mental illness who preferred exercising tended to have a
higher level of education, employment rates and to be Caucasian
(Sylvia et al., 2009). In the present study, we seek to replicate these
data in bipolar disorder as well as extend these findings by examining
the association of exercise and course of illness. Thus, we predict that
a higher frequency of exercise will be associated with individuals who
are younger, educated, married, have higher incomes, as well as have
better course of illness and life functioning (Sylvia et al., 2009).
The Comparative Effectiveness of a Second Generation Antipsy-
chotic Mood Stabilizer and a Classic Mood Stabilizer for Bipolar
Disorder (CHOICE) study (Nierenberg et al., under editorial review)
was a six-month multi-site, randomized comparative effectiveness
trial. CHOICE participants were randomized to receive either que-
tiapine or lithium. Regardless of treatment group, all participants
received adjunctive personalized treatment (APT), whereby study
physicians prescribed additional medications at their discretion.
Details of the rationale, design, and methods of CHOICE are reported
elsewhere (Nierenberg et al., under editorial review). The present
analyses examine baseline data from the CHOICE study.
The study protocol was approved by the Institutional Review
Boards of the eleven study sites and participants provided verbal
and written informed consent prior to initiation of any study
procedure. Four hundred eighty two individuals with bipolar
disorder between the ages of 18 and 68 enrolled in CHOICE
between 2011 and 2012. Limited inclusion and exclusion criteria
were designed to increase diversity and generalizability within the
sample (Nierenberg et al., under editorial review). To participate,
individuals had to meet DSM-IV TR criteria for bipolar I or II
disorders as well as be at least mildly symptomatic at study entry
Current and lifetime DSM-IV TR diagnoses were determined
using the Extended Mini-International Neuropsychiatric Interview
(Sheehan et al., 1998). Demographic information, psychiatric
history, medical history, and reported frequency of exercise were
obtained at baseline. Participants also completed the self-report
Quality-of-Life Enjoyment and Satisfaction Questionnaire (Q-LES-
Q) (Endicott et al., 1993). Blinded raters measured severity of
bipolar symptoms with the Clinical Global Impression Scale for
Bipolar Disorder (CGI-BP) (Spearing et al., 1997), as well as with
the Bipolar Inventory of Symptoms Scale (BISS) (Bowden et al.,
2007; Gonzalex et al., 2008). To measure overall functioning and
life satisfaction, raters administered the LIFE-Range of Impaired
Functioning Tool (LIFE-RIFT) (Leon et al., 2000).
2.4. Statistical analysis
All statistical analyses were completed using Statistical Analysis
Software (SAS; version 9.2, SAS Institute, Cary, NC). We used linear
regression analyses to examine associations between exercise
frequency and demographic features. Post hoc contrasts were
conducted for significant variables to determine significant pair-
wise differences. Linear regressions were conducted to determine
if exercise frequency was associated with the percentage of last
year spent depressed or manic/hypomanic, depression (CGI-BP
and BISS), mania (CGI-BP and BISS), life satisfaction/functioning
(LIFE-RIFT), and quality of life (Q-LES-Q). These analyses were
adjusted with any demographic variable(s) associated with exer-
cise. The analyses examining percentage of last year spent
depressed or manic/hypomanic were also controlled for current
mood state using the BISS. Finally, we conducted linear regressions
analyses to examine the association of exercise frequency and
number of psychiatric comorbidities, number of medical comor-
bidities, and risk factors for cardiovascular disease (i.e., triglycer-
ides, fasting plasma glucose, cholesterol, body mass index,
Given the exploratory nature of this paper, no adjustment for
multiple hypothesis testing was made.
Demographics and clinical features of the total sample are
reported in Table 1.
Two patients did not report exercise frequency at baseline and
thus, were excluded from the analysis. Forty percent of partici-
pants did not report exercising even one day per week while 287
participants (60.0%) reported exercising at least one day per week
(M¼3.7 days/week, SD¼2.0) with a range of 1 day per week
(10.1%) to 7 days per week (18.5%). Exercise frequency was not
associated with any demographic variables, except marital status
(p¼.025). Individuals who were married, or living as married,
exercised less than individuals who were divorced or separated (F
(1)¼6.31, p¼.01) and never married (F(1)¼4.90, p¼.027). Para-
meter estimates for the remaining analyses were adjusted for
L.G. Sylvia et al. / Journal of Affective Disorders 151 (2013) 722–727
We found that participants with greater severity of depression
reported exercising less often (Table 2). Specifically, for every ten
point increase on the BISS depression score participants reported
exercising about 0.2 fewer days per week (β¼ ?.018, p¼.019) and
for every two point increase on the CGI-BP depression score,
participants reported exercising 0.48 fewer days per week
(β¼ ?.024, p¼.010). Participants who reported experiencing
longer periods of depression in the past year also reported
exercising less often even when controlling for current depressed
mood (or BISS depression scale) (Table 2). For every change in time
spent depressed (e.g. increase from 0–20% to 21–40%), participants
reported exercising 37 fewer days per week (po.001).
We found that having more manic symptoms was associated
with exercising more frequently such that with every ten point
increase on the BISS mania score, participants reported exercising
3 more days per week (β¼.027, p¼.003) (Table 2). For every two
point increase on the CGI-BP mania score, participants reported
exercising 36 more days per week (β¼.178, p¼.036). Participants
who reported being manic or hypomanic more often during the
last year also reported exercising more often (even when
Association of exercise frequency and bipolar symptoms and life functioning.
Note: BISS: Bipolar Inventory of Symptoms Scale; CGI-BP: Clinical Global Impres-
sions for Bipolar Disorder scale; LIFE-RIFT: Longitudinal Interval Follow-up Evalua-
tion-Range Impaired Functioning Tool; Q-LES-Q: Quality of Life, Enjoyment, and
Satisfaction Questionnaire. All parameter estimates are adjusted for marital status
which is associated with exercise frequency.
aPercentage of the past year spent depressed and manic were treated as continuous
variables with rank scores for each ordinal category of the variable (e.g. 0–20%¼1, 20–
40%¼2, etc.). These analyses were also controlled for current mood state using the BISS.
Baseline demographic and clinical features of CHOICE participants.
Randomized treatment group
Overall (N¼482) LiþAPT (N¼240) QTPþAPT (N¼242)P
Ethnicity: hispanic or latino
Less than high school
High school or GED
Tech school or associates degree
Graduate or professional degree
History of psychiatric hospitalizations
History of suicide attemptsa
Any substance use disorder (lifetime)b
Any anxiety disorder (current)c
Age of first depressive episode
Age of first manic episode
Age of first mood episode
Duration of depression (years)
Duration of mania (years)
Illness duration (years)
BISS total: overall
BISS total: depression
BISS total: mania
CGI severity score
Statistics reported are % (n/N) for categorical variables and mean7SD (N) for continuous variables. P-values reported are based on chi square test for categorical variables and
t-test for continuous variables. BISS: Bipolar Inventory of Symptoms Scale; CGI: Clinical Global Impressions scale; MADRS: Montgomery-Asberg Depression Rating Scale; CGI:
Clinical Global Impressions Scale; YMRS: Young Mania Rating.
aBased on psychiatric history interview.
bIncludes patients with any current alcohol/drug abuse/dependence (based on MINI).
cIncludes patients with any one of the following current diagnoses (based on MINI): panic disorder, agoraphobia, social phobia, and generalized anxiety disorder.
L.G. Sylvia et al. / Journal of Affective Disorders 151 (2013) 722–727
controlling for current manic symptoms, or BISS mania subscale
score), such that for every increase in category choice, participants
reported exercising .28 more days per week (p¼.012). We also
found that more frequent exercise was associated with better life
functioning (LIFE-RIFT) and quality of life (QLESQ overall quality of
life item) (Table 2). Similar to the association of exercise with
mania, patients experiencing mixed episodes at study entry
(N¼82, M¼2.7972.68) tended to exercise more frequently than
individuals who entered the study in a major depressive episode
(N¼269, M¼1.7772.12). Specifically, patients entering the study
in a major depressive episode exercised significantly less than both
those patients who entered the study in a manic or hypomanic
episode (N¼56, M¼2.9972.57) (difference between the mean-
s¼ ?1.22, 95% CI: ?2.10 to ?.35, po.05) or mixed episode
(difference between the means¼ ?1.03, 95% CI: ?1.78 to ?0.27,
po.05). There was no significant difference between the manic/
hypomanic or mixed groups.
In regards to medical comorbidity, a higher frequency of
exercise was associated with lower BMI such that there was a
5 point increase in BMI associated with each 0.2 days per week of
less exercise (F(1)¼7.05, p¼.008). Exercise frequency was not
associated with other cardiovascular risk factors assessed in this
study (p4.05). In regards to psychological comorbidity, partici-
pants without any comorbid anxiety disorder (defined as not
having Panic Disorder, Agoraphobia, Social Phobia, or Generalized
Anxiety Disorder) reported exercising marginally more often than
those with a comorbid anxiety disorder, although this effect did
not reach significance (Odds ratio¼.94, p¼.105).
This study found that approximately 40% of participants
reported not exercising at least once per week. Being married,
higher BMI, more time depressed in the past year, more depressive
symptoms, lower quality of life and life functioning were asso-
ciated with less frequent weekly exercise whereas spending a
greater number of days being manic in the past year, having more
manic symptoms, and being in a mixed episode were associated
with more frequent exercise.
Our findings are consistent with previous studies that found
less exercise to be associated with more depressive symptoms,
poorer quality of life and functioning, and higher BMI (Carless and
Douglas, 2008; Crone and Guy, 2008; De Moor et al., 2006; Mead
et al., 2008; Otto et al., 2007; Palomo et al., 2008; Trivedi et al.,
2011; Tsang et al., 2008; Vancamfort et al., 2011). Interestingly,
individuals in a manic, hypomanic, or mixed state at study entry
tended to be exercising at greater frequency than individuals
currently depressed suggesting a complex relationship between
bipolar disorder and physical activity. This dynamic has been
noted anecdotally by Wright et al. who described exercise as a
“double-edged sword” for bipolar disorder, or that exercise could
help them to regulate their emotions and bring structure to their
chaotic lives and illness, but it may also stimulate them with
consequent affective dysregulation (Murray et al., 2011; NIH, 2006;
Wright et al., 2012). In short, more research is needed to under-
stand the relationship between exercise and bipolar disorder. We
did not find significant relationships between anxiety, medical
comorbidity, and exercise frequency, despite strong extant find-
ings that relate better exercise habits with less anxiety and fewer
psychological disorders (Stephens, 1988; Strohle et al., 2006) as
well as better cardiorespiratory fitness, weight, high-density
lipoprotein cholesterol level, and fasting insulin level (Church
et al., 2007; Cornelissen and Fagard, 2005). The null findings could
be because participants were not asked when they began to
exercise as well as information about the type or intensity of their
exercise. Limitations of this study include it being a cross-sectional
analysis, only relying on self-report of exercise frequency, not
assessing type or intensity of exercise as well as whether it was
compulsive exercise. We also did not examine whether exercise
may be associated with elevated mood due to individuals becom-
ing addicted with exercise; however, preliminary evidence sug-
gests that exercise may not be addictive for bipolar patients (Di
Nicole et al., 2010).
Given the mood-specific association of exercise in bipolar
disorder, further research is merited to better understand the
relationship between exercise and affective states in this illness,
particularly the direction of causality. Overall, the present study
illustrates that exercise regimes may not be a “one size fits all”
intervention, but rather an intervention that requires personaliza-
tion to meet the specific needs of bipolar patients.
Role of funding source
The Agency for Healthcare Research and Quality′s (AHRQ) provided funding for
the design, execution, and analysis of the 11-site Bipolar CHOICE study. This
included assessments, participant remuneration, biostatistics support, and study
staff salary support.
Conflict of interest
Dr. Sylvia was a shareholder in Concordant Rater Systems and serves as a
consultant for Bracket Global, Inc and Clintara. She also receives royalties from New
Dr. Friedman receives grant support from Repligen, Astra-Zeneca, Roche,
Takeda, Neosync. He has been a consultant for Pamlab. He receives royalties from
Springer. He has served as an expert forensic consultant for Thomson Rhodes &
Cowie P.C. and Berger and Zavesky Co. L.P.A.
Dr. Kocsis has received research grants and contracts from AHRQ, NIMH, NIDA,
Burroughs Wellcome Trust, Pritzker Consortium, Takeda, Forest, Astra Zeneca,
Roche. He is on the speaker′s bureau at Pfizer and Merck and on the advisory
board at Corcept.
Ms. Bernstein reports no competing interests in the past three years.
Dr. Brody has received salary support over the past 3 years from grants funded
by Forrest, Agency for Healthcare Quality and Research, and Pritzker neuropsychia-
tric disorders research consortium.
Dr. Kinrys has received research support from Astra-Zeneca, Bristol-Myers
Squibb Company, Cephalon, Elan Pharmaceuticals, Eli Lilly & Company, Forest
Pharmaceuticals Inc., GlaxoSmithkline, Sanofi/Synthelabo, Sepracor Inc., Pfizer Inc,
UCB Pharma, and Wyeth-Ayerst Laboratories. He has been an advisor or consultant
for Astra-Zeneca, Cephalon, Eli Lilly & Company, Forest Pharmaceuticals Inc.,
GlaxoSmithkline, Janssen Pharmaceutica, Pfizer Inc, Sepracor Inc., UCB Pharma, and
Wyeth-Ayerst Laboratories. Dr. Kinrys has been a speaker for Astra-Zeneca, Forest
Pharmaceuticals Inc., GlaxoSmithkline, Sepracor Inc., and Wyeth-Ayerst Laboratories.
Dr. Kemp serves on the speakers bureau for Pfizer and AstraZeneca, is a
consultant for Bristol-Myers Squibb, Teva, Corcept, Janssen. His spouse is a minor
stockholder for Sanofi and Abbott.
Dr. Shelton has served as a consultant to Bristol-Myers Squibb, Cyberonics, Inc.,
Elan, Corp., Eli Lilly and Company, Euthymics Bioscience, Forest Pharmaceuticals,
Janssen Pharmaceutica, Medtronic, Inc., Otsuka Pharmaceuticals, Pamlab, Inc., Pfizer,
Inc., Ridge Diagnostics, Takeda Pharmaceuticals. Dr. Shelton has received research grant
support from Appian Labs, Bristol-Myers Squibb, Elan, Corp., Eli Lilly and Company,
Euthymics Bioscience, Forest Pharmaceuticals, Janssen Pharmaceutica, Naurex, Inc.,
Novartis Pharmaceuticals, Otsuka Pharmaceuticals, Pamlab, Inc., Repligen, Corp., Ridge
Diagnostics, St. Jude Medical, Inc., Takeda Pharmaceuticals.
Dr. McElroy is a consultant to or member of the scientific advisory boards of
Alkermes, Bracket, Corcept, MedAvante, Shire, Sunovian, and Teva. She is a principal
or co-investigator on studies sponsored by the Agency for Healthcare Research &
Quality (AHRQ), Alkermes, AstraZeneca, Cephalon, Eli Lilly and Company, Forest,
Marriott Foundation, National Institute of Mental Health, Orexigen Therapeutics,
Inc., Pfizer, Shire, Takeda Pharmaceutical Company Ltd., and Transcept Pharmaceu-
tical, Inc. She is also an inventor on United States Patent no. 6,323,236 B2, Use of
Sulfamate Derivatives for Treating Impulse Control Disorders, and along with the
patent′s assignee, University of Cincinnati, Cincinnati, Ohio, has received payments
from Johnson & Johnson, which has exclusive rights under the patent.
Dr. Bobo reports no competing interests in the past three years.
Dr. Kamali reports no competing interests in the past three years.
Dr. McInnis has received grants for research support from NIMH, the Heinz C
Prechter Research Fund, and the Michigan Institute for Clinical Health Research
(MICHR). MM has received consulting income from the Qatar National Research
Foundation and Merck Pharmaceuticals.
Dr. Tohen was an employee of Lilly (1997 to 2008) and has received honoraria
from or consulted for AstraZeneca, Bristol Myers Squibb, GlaxoSmithKline, Lilly,
L.G. Sylvia et al. / Journal of Affective Disorders 151 (2013) 722–727
Johnson & Johnson, Otsuka, Merck, Sunovion, Forest, Roche, Elan, Lundbeck, Teva,
Pamlab, Wyeth and Wiley Publishing; his spouse is a full time employee and minor
stockholder at Lilly.
Dr. Bowden is a research collaborator with Elan and a consultant with Teva, he
has no participation with speaker bureaus, nor does he or his wife hold any equity
position in any biomedical or pharmaceutical corporation.
Dr. Ketter, between May 14, 2010 and May 14, 2013, had the following financial
interests/arrangements or affiliations that could be perceived as real or apparent
conflicts of interest: Grant/Research Support from the AstraZeneca Pharmaceuticals
LP, Cephalon Inc., Eli Lilly and Company, Pfizer Inc., and Sunovion Pharmaceuticals;
Consultant Fees from Allergan, Inc., Avanir Pharmaceuticals, Bristol-Myers Squibb
Company, Cephalon Inc., Forest Pharmaceuticals, Janssen Pharmaceutica Products,
LP, Merck & Co., Inc., Sunovion Pharmaceuticals, Teva Pharmaceuticals; Lecture
Honoraria from Abbott Laboratories, Inc., AstraZeneca Pharmaceuticals LP, Glax-
oSmithKline, and Otsuka Pharmaceuticals; and Publication Royalties from Amer-
ican Psychiatric Publishing, Inc. In addition, Dr. Ketter′s spouse is an employee of
and holds stock in Janssen Pharmaceuticals.
Dr. Deckersbach has received research support from NIMH, NARSAD, TSA, OCF,
Tufts University, NIH, NIA, Janssen Pharmaceuticals, the Forest Research Institute,
Shire Development Inc., Medtronic, Cyberonics, Northstar. He has received honor-
aria, consultation fees and/or royalties from the following: Medacorp, MGH
Psychiatry Academy, BrainCells Inc., Systems Research and Applications Corpora-
tion, Boston University, Tufts University, the Catalan Agency for Health Technology
Assessment and Research, the National Association of Social Workers Massachu-
setts, the Massachusetts Medical Society, and Oxford University Press.
Dr. Calabrese receives federal funding from the Department of Defense, Health
Resources Services Administration, and NIMH; he receives research funding or
grants from the following private industries or nonprofit funds: Cleveland Founda-
tion, NARSAD, and Stanley Medical Research Institute; he receives research grants
from Abbott, AstraZeneca, Cephalon, GlaxoSmithKline, Janssen, Eli Lilly, and
Lundbeck; he serves on the advisory boards of Abbott, AstraZeneca, Bristol-Myers
Squibb, Dainippon Sumitomo Pharma, Forest, France Foundation, GlaxoSmithKline,
Janssen, NeuroSearch, OrthoMcNeil, Repligen, Schering-Plough, Servier, Solvay/
Wyeth, Takeda, and Supernus Pharmaceuticals; and he reports CME activities with
AstraZeneca, Bristol-Myers Squibb, France Foundation, GlaxoSmithKline, Janssen,
Johnson & Johnson, Schering-Plough, and Solvay/Wyeth.
Dr. Thase has been an advisor/consultant: to Alkermes, AstraZeneca, Bristol-
Myers Squibb, Eli Lilly, Forest Laboratories, GlaxoSmithKline, Janssen Pharmaceu-
ticals, Lundbeck, MedAvante, Merck, Mylan, Neuronetics, Otsuka, Pamlab, Pharma-
Neuroboost, Pfizer, Rexahn, Roche, Shire, Sunovion, Supernus, Takeda, and Teva, as
well as the US Food and Drug Administration and the National Institute of Mental
Health. During the same time frame, Dr. Thase has received honoraria for talks from
AstraZeneca, Bristol-Myers Squibb, Eli Lilly, Merck, and Pfizer and he has received
research grants from Alkermes, AstraZeneca, Eli Lilly, Forest, GlaxoSmithKline,
Otsuka, PharmaNeuroboost, and Roche, as well as the National Institute of Mental
Health and the Agency for Healthcare Research and Quality.
Dr. Reilly-Harrington receives royalties from Oxford University Press, the American
Psychological Association, and New Harbinger. She serves as a consultant for United
Biosource Corporation and was a shareholder in Concordant Rater Systems.
Dr. Singh has been a speaker for Merck and Sunovion. He has received research
support from Novartis and Astra Zeneca.
Mr. Rabideau reports no competing interests in the past three years.
Dr. Nierenberg is a consultant for Abbott Laboratories, Astra Zeneca, Basilea,
BrainCells Inc., Brandeis University, Bristol-Myers Squibb, Cephalon, Corcept, Eli Lilly &
Co., Forest, Genaissance, GlaxoSmithKline, Innapharma, Janssen Pharmaceutica, Jazz
Pharmaceuticals, Lundbeck, Merck, Novartis, PamLabs, PGx Health, Pfizer, Ridge
Diagnostics, Roche, Sepracor, Schering-Plough, Shire, Somerset, Sunovion, Takeda,
Targacept, and Teva. He is a stakeholder in Appliance Computing, Inc. (MindSite); Brain
Cells, Inc., InfoMed (potential share of income). He receives research support from
AHRQ, Bristol-Myers Squibb, Cederroth, Cyberonics, Elan, Forest Pharmaceuticals,
GlaxoSmithKline, Janssen Pharmaceutica, Lichtwer Pharma, Eli Lilly, Mylin (formerly
Dey Pharmaceuticals), NARSAD, NIMH, Pamlabs, Pfizer, Shire, Stanley Foundation, and
Wyeth-Ayerst. Honoraria include MGH Psychiatry Academy in the past 3 years (Prior to
3 years ago, honoraria from Bristol-Myers Squibb, Cyberonics, Forest Pharmaceuticals,
GlaxoSmithKline, Eli Lilly, Shire, Wyeth-Ayerst). Dr. Nierenberg receives other income
from legal case reviews for CRICO, MBL Publishing for past services as Editor-in-chief of
CNS Spectrums, Slack Inc. for services as Associate Editor of Psychiatric Annals, and
Editorial Board, Mind Mood Memory, Belvior Publications. He has copyright joint
ownership with MGH for Structured Clinical Interview for MADRS and Clinical Positive
Affect Scale and additional honoraria from ADURS, American Society for Clinical
Psychopharmacology and Zucker Hillside Hospital and Forest and Janssen, Biomedical
Development, Boston Center for the Arts, University of Pisa, University of Wisconsin at
Madison, University Texas Southwest at Dallas, Health New England and Harold
Grinspoon Charitable Foundation and Eli Lilly and AstraZeneca, Brandeis University,
International Society for Bipolar Disorder, 2nd East Asian Bipolar Forum, Mid-Atlantic
Permanente Research Institute, Up-to-Date.
This study was funded by AHRQ Grant R01 HS019371-01.
Angst, F., Stassen, H.H., Clayton, P.J., Angst, J., 2002. Mortality of patients with mood
disorders: follow-up over 34–38 years. Journal of Affective Disorders 68,
Blumenthal, J.A., Babyak, M.A., Doraiswamy, P.M., Watkins, L., Hoffman, B.M.,
Barbour, K.A., Herman, S., Craighead, W.E., Brosse, A.L., Waugh, R., Hinderliter,
A., Sherwood, A., 2007. Exercise and pharmacotherapy in the treatment of
major depressive disorder. Psychosomatic Medicine 69, 587–596.
Bowden, C.L., Singh, V., Thompson, P., Gonzalez, J.M., Katz, M.M., Dahl, M., Prihoda,
T.J., Chang, X., 2007. Development of the bipolar inventory of symptoms scale.
Acta Psychiatrica Scandinavica 116, 189–194.
Carless, D., Douglas, K., 2008. Social support for and through exercise and sport in a
sample of men with serious mental illness. Issues in Mental Health Nursing 29,
Church, T.S., Earnest, C.P., Skinner, J.S., Blair, S.N., 2007. Effects of different doses of
physical activity on cardiorespiratory fitness among sedentary, overweight or
obese postmenopausal women with elevated blood pressure: a randomized
controlled trial. JAMA 297, 2081–2091.
Cornelissen, V.A., Fagard, R.H., 2005. Effects of endurance training on blood
pressure, blood pressure-regulating mechanisms, and cardiovascular risk
factors. Hypertension 46, 667–675.
Coryell, W., Scheftner, W., Keller, M., Endicott, J., Maser, J., Klerman, G.L., 1993. The
enduring psychosocial consequences of mania and depression. American
Journal of Psychiatry 150, 720–727.
Crone, D., Guy, H., 2008. 'I know it is only exercise, but to me it is something that
keeps me going’: a qualitative approach to understanding mental health service
users′ experiences of sports therapy. International Journal of Mental Health
Nursing 17, 197–207.
Culver, J.L., Arnow, B.A., Ketter, T.A., 2007. Bipolar disorder: improving diagnosis
and optimizing integrated care. Journal of Clinical Psychology 63, 73–92.
De Almeida, K.M., Moreira, C.L., Lafer, B., 2012. Metabolic syndrome and bipolar
disorder: what should psychiatrists know? CNS Neuroscience and Therapeutics
De Moor, M.H., Beem, A.L., Stubbe, J.H., Boomsma, D.I., De Geus, E.J., 2006. Regular
exercise, anxiety, depression and personality: a population-based study. Pre-
ventive Medicine 42, 273–279.
Di Nicole, M., Tedeschi, D., Mazza, M., Martinotti, G., Harnic, D., Catalano, V.,
Bruschi, A., Pozzi, G., Bria, P., Janiri, L., 2010. Behavioural addictions in bipolar
disorder patients: Role of impulsivity and personality dimensions. Journal of
Affective Disorders 125, 82–88.
Ellis, N., Crone, D., Davey, R., Grogan, S., 2007. Exercise interventions as an adjunct
therapy for psychosis: a critical review. British Journal of Clinical Psychology 46,
Endicott, J., Nee, J., Harrison, W., Blumenthal, R., 1993. Quality-of-life enjoyment
and satisfaction questionnaire—a new scale. Psychopharmacology Bulletin 29,
Gonzalex, J.M., Bowden, C.L., Katz, M.M., Thompson, P., Singh, V., Prihoda, T.J., Dahl,
M., 2008. Development of the Bipolar Inventory of Symptoms Scale: concurrent
validity, discriminant validity and retest reliability. International Journal of
Methods in Psychiatric Research 17, 198–209.
Harris, A.H., Cronkite, R., Moos, R., 2006. Physical activity, exercise coping, and
depression in a 10-year cohort study of depressed patients. Journal of Affective
Disorders 93, 79–85.
Hennekens, C., 2007. Increasing global burden of cardiovascular disease in general
populations and patients with schizophrenia. Journal of Clinical Psychiatry 68,
Keitner, G.I., Solomon, D.A., Ryan, C.E., Miller, I.W., Mallinger, A., Kupfer, D.J., Frank,
E., 1996. Prodromal and residual symptoms in bipolar I disorder. Comprehen-
sive Psychiatry 37, 362–367.
Ketter, T.A., 2010. Strategies for monitoring outcomes in patients with bipolar
disorder. Primary Care Companion to the Journal of Clinical Psychiatry 12,
Khot, U.N., Khot, M.B., Bajzer, C.T., Sapp, S.K., Ohman, E.M., Brener, S.J., Ellis, S.G.,
Lincoff, A.M., Topol, E.J., 2003. Prevalence of conventional risk factors in
patients with coronary heart disease. JAMA 290, 898–904.
Krishnan, K.R., 2005. Psychiatric and medical comorbidity of bipolar disorder.
Psychosomatic Medicine 67, 1–8.
Leon, A.C., Solomon, D.A., Mueller, T.I., Endicott, J., Posternak, M., Judd, L.L.,
Schettler, P.J., Akiskal, H.S., Keller, M.B., 2000. A brief assessment of psychoso-
cial functioning of subjects with bipolar I disorder: the LIFE-RIFT. Longitudinal
interval follow-up evaluation-range impaired functioning tool. Journal of
Nervous and Mental Disease 188, 805–812.
McIntyre, R.S., Konarski, J.Z., Misener, V.L., Kennedy, S.H., 2005. Bipolar disorder and
diabetes mellitus: epidemiology, etiology, and treatment implications. Annals
of Clinical Psychiatry 17, 83–93.
Mead, G.E., Morley, W., Campbell, P., Greig, C.A., McMurdo, M., Lawlor, D.A., 2008.
Exercise for depression. Cochrane Database of Systematic Reviews, CD004366.
Murray, G., Suto, M., Hole, R., Hale, S., Amari, E., Michalak, E.E., 2011. Self-
management strategies used by ‘high functioning’ individuals with bipolar
disorder: from research to clinical practice. Clinical Psychology and Psychother-
apy 18, 95–109.
Ng, F., Dodd, S., Berk, M., 2007. The effects of physical activity in the acute
treatment of bipolar disorder: a pilot study. Journal of Affective Disorders
L.G. Sylvia et al. / Journal of Affective Disorders 151 (2013) 722–727
Nierenberg, A.N., Sylvia, L.G., Leon, A., Reilly-Harrington, N., Shesler, L., McElroy, S.L., Download full-text
Friedman, E.S., Thase, M., Shelton, R.C., Bowden, C.L., Tohen, M., Singh, V.,
Deckersbach, T., Ketter, T.A., Kocsis, J.H., McInnis, M.G., Schoenfeld, D.A., Bobo,
W.V., Calabrese, J.R., Group, T.B.C.S., in preparation. Clinical Health Outcomes
Initiative in Comparative Effectiveness for Bipolar Disorder (Bipolar CHOICE): A
Pragmatic Trial of Complex Treatment for a Complex Disorder.
NIH, 2006. Bipolar Disorder Clinical Guideline. National Institute for Health and
Clinical Excellence, London.
Osby, U., Brandt, L., Correia, N., Ekbom, A., Sparen, P., 2001. Excess mortality in
bipolar and unipolar disorder in Sweden. Archives of General Psychiatry 58,
Otto, M.W., Church, T.S., Craft, L.L., Greer, T.L., Smits, J.A., Trivedi, M.H., 2007.
Exercise for mood and anxiety disorders. Primary Care Companion to the
Journal of Clinical Psychiatry 9, 287–294.
Palomo, T., Beninger, R.J., Kostrzewa, R.M., Archer, T., 2008. Affective status in
relation to impulsive, motor and motivational symptoms: personality, devel-
opment and physical exercise. Neurotoxicity Research 14, 151–168.
Salvatore, P., Tohen, M., Khalsa, H.M., Baethge, C., Tondo, L., Baldessarini, R.J., 2007.
Longitudinal research on bipolar disorders. Epidemiologia e Psichiatria Sociale
Sanchez-Moreno, J., Martinez-Aran, A., Tabares-Seisdedos, R., Torrent, C., Vieta, E.,
Ayuso-Mateos, J.L., 2009. Functioning and disability in bipolar disorder: an
extensive review. Psychotherapy and Psychosomatics 78, 285–297.
Serretti, A., Chiesa, A., Calati, R., Fabbri, C., Sentissi, O., De Ronchi, D., Mendlewicz, J.,
Souery, D., 2013. Side effects associated with psychotropic medications in
patients with bipolar disorder: evidence from two independent samples.
Journal of Psychopharmacology.
Sheehan, D.V., Lecrubier, Y., Sheehan, K.H., Amorim, P., Janavs, J., Weiller, E.,
Hergueta, T., Baker, R., Dunbar, G.C., 1998. The Mini-International Neuropsy-
chiatric Interview (M.I.N.I.): the development and validation of a structured
diagnostic psychiatric interview for DSM-IV and ICD-10. Journal of Clinical
Psychiatry 59 (Suppl. 20), 22–33. (quiz 34–57).
Soreca, I., Fagiolini, A., Frank, E., Houck, P.R., Thompson, W.K., Kupfer, D.J., 2008.
Relationship of general medical burden, duration of illness and age in patients
with bipolar I disorder. Journal of Psychiatric Research 42, 956–961.
Spearing, M.K., Post, R.M., Leverich, G.S., Brandt, D., Nolen, W., 1997. Modification of
the clinical global impressions (CGI) Scale for use in bipolar illness (BP): the
CGI-BP. Psychiatry Research 73, 159–171.
Stathopoulou, G., Powers, M.B., Berry, A.C., Smits, J.A., Otto, M.W., 2006. Exercise
interventions for mental health: a quantitative and qualitative review. Clinical
Psychology 13, 179–193.
Stephens, T., 1988. Physical activity and mental health in the United States and
Canada: evidence from four population surveys. Preventive Medicine 17, 35–47.
Strohle, A., Feller, C., Strasburger, C.J., Heinz, A., Dimeo, F., 2006. Anxiety modulation
by the heart? Aerobic exercise and atrial natriuretic peptide. Psychoneuroen-
docrinology 31, 1127–1130.
Sylvia, L.G., Kopeski, L.M., Mulrooney, C., Reid, J., Jacob, K., Neuhaus, E.C., 2009. Does
exercise impact mood?: Exercise patterns of patients in a psychiatric partial
hospital program. Journal of Psychiatric Practice 15, 70–78.
Sylvia, L.G., Nierenberg, A.A., Stange, J.P., Peckham, A., Deckersbach, T., 2011.
Development of an integrated psychosocial treatment to address the medical
burden in bipolar disorder. Journal of Psychiatric Practice 17, 224–232.
Tohen, M., Waternaux, C.M., Tsuang, M.T., 1990. Outcome in mania. A 4-year
prospective follow-up of 75 patients utilizing survival analysis. Archives of
General Psychiatry 47, 1106–1111.
Tordeurs, D., Janne, P., Appart, A., Zdanowicz, N., Reynaert, C., 2011. Effectiveness of
physical exercise in psychiatry: a therapeutic approach? Encephale 37,
Trivedi, M.H., Greer, T.L., Church, T.S., Carmody, T.J., Grannemann, B.D., Galper, D.I.,
Dunn, A.L., Earnest, C.P., Sunderajan, P., Henley, S.S., Blair, S.N., 2011. Exercise as
an augmentation treatment for nonremitted major depressive disorder: a
randomized, parallel dose comparison. Journal of Clinical Psychiatry 72,
Tsang, H.W., Chan, E.P., Cheung, W.M., 2008. Effects of mindful and non-mindful
exercises on people with depression: a systematic review. British Journal of
Clinical Psychology 47, 303–322.
Vancamfort, D., De Hert, M., Knapen, J., Wampers, M., Demunter, H., Deckx, S.,
Maurissen, K., Probst, M., 2011. State anxiety, psychological stress and positive
well-being responses to yoga and aerobic exercise in people with schizophre-
nia: a pilot study. Disability and Rehabilitation 33, 684–689.
Wright, K., Armstrong, T., Taylor, A., Dean, S., 2012. 'It′s a double edged sword’: a
qualitative analysis of the experiences of exercise amongst people with bipolar
disorder. Journal of Affective Disorder 136, 634–642.
Young, A.H., Grunze, H., 2013. Physical health of patients with bipolar disorder. Acta
Psychiatrica Scandinavica, 3–10.
L.G. Sylvia et al. / Journal of Affective Disorders 151 (2013) 722–727