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Comorbidities

1. Bipolar disorder
Comorbidities

2. What is a comorbidity?

3. 3
Bipolar disorder – Comorbidities
Defining comorbidity
•The idea of comorbidity is relatively new in medicine, emerging in the latter half of the last century
1-3
•In a seminal publication from 1970, Feinstein defined comorbidity: “In a patient with a particular
index disease, the term co-morbidity refers to any additional co-existing ailment”
1,3
•Comorbidity is often considered relative to an index disease, i.e., a second condition is comorbid
with the index disease or condition: “Any distinct additional entity that has existed or may occur
during the clinical course of a patient who has the index disease under study”
2,3
•However, the term ‘comorbidity’ can and has been used to convey two distinct forms of comorbidity:
1
•Co-occurrence of a disease with another condition in a single person, e.g., a person with major
depressive disorder who goes on to develop panic disorder
•Correlation of one disease with another in a sample of patients, wherein their risk of developing
the second condition appears to be greater than that of the general population
•In one patient, co-occurrence and correlation of two medical conditions is a distinction without a
difference, but across populations and for research purposes the distinction is most important
1. Krueger & Markon. Annu Rev Clin Psychol 2006;2:111–133; 2. Valderas et al. Ann Fam Med 2009;7(4):357–363; 3. Feinstein. J Chronic Dis 1970;23(7):455–468

4. 4
Bipolar disorder – Comorbidities
Correlation versus causation
BD=bipolar disorder
Bland. An Introduction to Medical Statistics, 4
th
ed. 2015
Causation Correlation
Cause (gene)
Effect (disease)
Factor 1 (e.g., genetics)
Factor 2 (e.g., trauma)
Factor 3 (e.g., lifestyle)
Outcome (BD)
Factor 4 (e.g., medications)
Outcome (obesity)
Outcome (stroke)
One thing causes another –
e.g., a gene mutation that
causes a disease
When there are multiple influences potentially influencing a disease
course, such as is often the case with humans, determining which
combination of factors cause a disease is challenging
Correlation is necessary, but not sufficient, to suggest causality –
randomized controlled trials are often necessary to help determine causality

5. 5
Bipolar disorder – Comorbidities
Models of comorbidity in bipolar disorder
Other factors increase
the risk of another
condition and BD
Higher-order factors may
influence both conditions,
increasing independently
the risk of both
Another disease
increases the risk of BD
Here BD is partly the result
of another medical
condition, e.g., drug abuse
as a risk factor for BD
episodes
BD increases the risk of
another disease
BD forms the environment
for another condition to
develop, e.g., panic attacks
in response to depression
BD is associated with an
increased rate of prior
conditions
Many patients experience
disorders prior to BD onset,
the relevance of any
relationship is hard to
establish
BD=bipolar disorder
Adapted from: Parker. Med J Aust 2010;193(S4):S18–20; Valderas et al. Ann Fam Med 2009;7(4):357–363
BDComorbidity
Risk factors
BD Comorbidity Comorbidity BD
BDRisk factors
Comorbidity

6. 6
This observational study
compared demographic and
comorbidity data between
316,025 people with BD and
27,250,255 control
individuals
Bipolar disorder – Comorbidities
Comorbidities of bipolar disorder in a study of 27 million people
ADHD=attention–deficit/hyperactivity disorder; BD=bipolar disorder; CI=confidence interval; MDD=major depressive disorder; PTSD=post-traumatic stress disorder
Hossain et al. Cureus 2019;11(9):e5636
Diabetes 19.1 11.2 0.96 0.95–0.97 <0.001
Hypertension 50.5 31.1 0.86 0.85–0.87 <0.001
Obesity 13.4 11.1 0.82 0.81–0.83 <0.001
Asthma 6.6 11.7 1.37 1.35–1.38 <0.001
Rheumatoid arthritis 2.9 1.4 0.64 0.63–0.66 <0.001
Hypothyroidism 12 11 1.59 1.58–1.62 <0.001
Migraine 2.6 5.5 1.23 1.21–1.25 <0.001
Multiple sclerosis 0.4 0.4 0.82 0.77–0.87 <0.001
Control group
(% prevalence)
People with BD
(% prevalence)
Odds ratio 95% CI P-value
MDD 1.2 1.6 0.51 0.49–0.52 <0.001
Anxiety 10.3 31.8 2.1 2.08–2.12 <0.001
ADHD 0.5 5.2 3.06 2.99–3.11 <0.001
Borderline personality 0.2 6.9 6.93 6.81–7.07 <0.001
PTSD 0.8 10.1 2.44 2.39–2.47 <0.001
Alcohol abuse 4.7 18.3 1.94 1.92–1.96 <0.001
Drug abuse 4.7 33.5 4.33 4.29–4.37 <0.001
P
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This work is adapted from ‘Medical and psychiatric comorbidities in bipolar disorder: insights from national inpatient population-based study’
by Hossain et al., used under CC-BY. This work is licensed under Creative Commons license CC-BY-SA by The Lundbeck Foundation

7. 7
Many conditions are
associated with BD, and
appear to be more prevalent
in populations of people with
BD than in the general
population
1,2
Bipolar disorder – Comorbidities
Comorbidities of bipolar disorder
BD=bipolar disorder; OCD=obsessive–compulsive disorder; PTSD=post-traumatic stress disorder
1. Krishnan. Psychosom Med 2005;67(1):1–8; 2. Sinha et al. Curr Psychiatry Rep 2018;20(5):36
Any axis I disorder
Substance-use disorder
Alcohol abuse
Other drug abuse
Anxiety disorder
Social phobia
PTSD
Panic disorder
OCD
Binge-eating disorder
Personality disorder
Migraine
Overweight
Obesity
Type 2 diabetes
Hypothyroidism
0 10 20 30 40 50 60 70 80
65%
56%
49%
44%
71%
47%
39%
11%
10%
13%
36%
28%
58%
21%
10%
9%
Mean rate of comorbidity (%)
Average rates of comorbid conditions with BD across several studies included in a review
1

8. Psychiatric comorbidities

9. 9
Bipolar disorder – Comorbidities
Anxiety disorders
This meta-analysis
(including 135 studies)
found that the lifetime
prevalence of any anxiety
disorder in a person with
BD was more than a third
BD=bipolar disorder; CI=confidence interval
Yapici Eser et al. Front Psychiatry 2018;9:229
Prevalence (95% CI)
Feske et al., 2000
McElroy et al., 2001
Tamam et al., 2002
Keck et al., 2003
Judd et al., 2003
Perlis et al., 2005
Gaudiano et al., 2005
Altindag et al., 2006
Gao et al., 2008
Grabski et al., 2008
Albert et al., 2008
Azorin et al., 2009
Fridberg et al., 2009
Andrade-Nascimento et al., 2011
Tsai et al., 2012
Chang et al., 2013
Carmiol et al., 2013
Das, 2013
Fassassi et al., 2014
Buturak et al., 2015
McDermid et al., 2015
Total: 37.5%
0% 50% 100%
Prevalence (95% CI)
McElroy et al., 2001
Dittmann et al., 2002
Judd et al., 2003
Simon et al., 2004
Gao et al., 2008
Albert et al., 2008
Grabski et al., 2008
Chang et al., 2013
Lee et al., 2013
Fassassi et al., 2014
McDermid et al., 2015
Total: 34.4%
Prevalence of anxiety disorders in people with BD-I
0% 50% 100%
Prevalence of anxiety disorders in people with BD-II
This work is adapted from ‘Prevalence and associated features of anxiety disorder comorbidity in bipolar disorder: a meta-analysis and meta-
regression study’ by Yapici et al., used under CC-BY. This work is licensed under Creative Commons license CC-BY-SA by The Lundbeck Foundation

10. 10
Bipolar disorder – Comorbidities
ADHD
Meta-analysis of the comorbidity
of ADHD and BD
2
•About 1 in 13 people with ADHD had BD
(7.95%; 95% CI: 5.31, 11.06)
•About 1 in 6 people with BD had ADHD
(17.11%; 95% CI: 13.02, 21.63)
•Interestingly, the average age of onset of BD was
earlier in people with comorbid ADHD
ADHD=attention–deficit/hyperactivity disorder; BD=bipolar disorder; CI=confidence interval
1. APA. DSM-5-TR. 2022; 2. Schiweck et al. Neurosci Biobehav Rev 2021;124:100–123; 3. Salvi et al. Medicina (Kaunas) 2021;57(5):466
•ADHD describes a persistent pattern of inattention and/or
hyperactivity/impulsivity that interferes with functioning or
development
1
•ADHD is commonly comorbid with BD – with reported
rates of comorbidity as high as 20%
2,3
•In patients with BD and comorbid ADHD, the first goal of
treatment should be mood stabilization, although there
is a poor evidence base to guide treatment decisions
3
•Clinicians and healthcare workers should be aware of this
highly comorbid condition, to avoid possible misdiagnosis
and provide the best care for both disorders
1
18
countries
646,766
participants
71
studies

11. Bipolar disorder – Comorbidities
Alcohol-use disorders
•People with BD very commonly use and abuse substances and alcohol – in some studies more
than half of patients with BD have a comorbid alcohol- or substance-use disorder
1-5
•Depending on when the comorbidity develops, one can cloud the diagnosis of the other:
4,5
•Alcohol-use disorder is often accompanied by mood swings
•Intoxication can produce a state similar to mania, characterized by euphoria, increased energy,
and grandiosity
•Alcohol withdrawal can produce symptoms of depression
•The presence of alcohol-use disorder substantially complicates the treatment of BD, and can worsen
the prognosis – increasing the chance of a rapid cycling presentation, and increasing the severity of
BD symptoms and the risk of hospitalization
4,5
•Talking therapies such as motivational interviewing, CBT, and therapies incorporating the family and
social environment can be useful tools for helping patients with comorbid alcohol- or substance-use
disorders, as are pharmacotherapies that can reduce cravings and help to stabilize mood
4
BD=bipolar disorder; CBT=cognitive–behavioural therapy
1. Hunt et al. J Affect Disord 2016;206:331–349; 2. Hunt et al. J Affect Disord 2016;206:321–330; 3. Di Florio et al. Eur Psychiatry 2014;29(3):117–124;
4. Grunze et al. Front Psychiatry 2021;12:660432; 5. Sonne & Brady. Alcohol Res Health 2002;26(2):103–108
11

12. 12
Bipolar disorder – Comorbidities
Substance-use disorders
•A meta-analysis of BD with comorbid substance-use disorders in clinical settings found high rates of
comorbidity of many disorders
1
•Alcohol-use disorder – 42%
•Cannabis-use disorder – 20%
•Illicit drug use – 17%
•Patients with BD who had a comorbid substance-use disorder had an earlier age of onset of BD, and
were at greater risk of hospitalization than people without comorbid substance-use disorders
1
•A companion meta-analysis of the comorbidity outside of clinical settings found similarly high rates,
compared with the general population:
2
•Illicit drug-use increased the rate of BD by 5 times
•Alcohol-use disorder increased the rate of BD by 4 times
BD=bipolar disorder
1. Hunt et al. J Affect Disord 2016;206:331–349; 2. Hunt et al. J Affect Disord 2016;206:321–330

13. 13
Bipolar disorder – Comorbidities
Eating disorders
•Eating disorders include several disorders characterized
by persistent disturbance of eating behaviour resulting in
significantly impaired functioning
1
•Eating disorders are commonly comorbid with BD, and
can worsen the prognosis of BD
2
•Furthermore, the comorbidity can complicate treatment,
because some treatments for BD or eating disorders can
worsen the symptoms of the other
2
•e.g., mood episodes as a result of a medication for an eating
disorder, or pharmacotherapies for BD that can cause weight
changes
•Ideally, therapies will be chosen that do not worsen the
symptoms of either BD or the comorbid eating disorder
2
Comorbidity of BD and eating disorders
in a large meta-analysis
a,4
•Occurrence of eating disorders in people with BD:
•Binge-eating disorder: 12.5%
•Bulimia nervosa: 7.4%
•Anorexia nervosa: 3.8%
•Occurrence of BD in people with an eating disorder:
•Binge-eating disorder: 9.1%
•Bulimia nervosa: 6.7%
•Anorexia nervosa: 2.0%
•Generally, the comorbidity was higher in females
a
n=15,084 people with BD, and n=15,146 people with eating disorders
BD=bipolar disorder
1. APA. DSM-5-TR. 2022; 2. Yakovleva et al. Consort Psychiatr 2023;4(2):91–106;
3. Craba et al. Emerg Trends Drugs Addict Health 2021;1:100023; 4. Fornaro et al. J Affect Disord 2021;280(Pt A):409–431

14. 14
Bipolar disorder – Comorbidities
Borderline personality disorder
•BPD represents a pervasive pattern of instable interpersonal
relationships, self-image, and affect, with marked impulsivity
1
•Although differential diagnosis of BD and BPD is challenging –
because of the overlap in symptoms – there is a high rate of
comorbidity between the two
2,3
BD=bipolar disorder; BPD=borderline personality disorder; CI=confidence interval
1. APA. DSM-5-TR. 2022; 2. Fornaro et al. J Affect Disord 2016;195:105–118; 3. Durdurak et al. Psychol Med 2022;52(16):3769–3782
Overlap between BD and BPD
3
Prevalence of BD in people with BPD
2
BD BPD Shared elements
Childhood
adversity
Risk factor Risk factor A shared risk factor
Sleep
disturbances
Various
disturbances to
sleep patterns
Chronic
nightmares
A shared factor in both
disorders
Depression Bipolar depressionUnipolar
depression
Depression is shared but
differentiated by the
polarity
Suicidality Recurrent
thoughts of death
and planning for
suicide
Risk of self-harmSuicidality is a shared
factor
Family Family history of
BD
Family histories of
various
psychopathologies
Family history is a shared
risk factor
Comorbidity Various
comorbidities
Various
comorbidities
Substance-use disorders,
affective instability, and
anxiety disorders are
common in both
Prevalence (95% CI)
Meta-analysis of 14 studies
0% 100%
In this meta-analysis, the prevalence of BD in a pooled
sample of 1,814 people with BPD was 16.58%
2
This work is adapted from ‘Understanding the development of bipolar disorder and borderline personality
disorder in young people: a meta-review of systematic reviews’ by Durdurak et al., used under CC-BY.
This work is licensed under Creative Commons license CC-BY-SA by The Lundbeck Foundation

15. 15
Bipolar disorder – Comorbidities
Smoking
•Generally speaking, people with BD are more likely to
smoke than those without BD, and are less likely to
successfully stop smoking
1-3
•Alongside the well-known health risks of smoking,
smoking behaviour in people with BD can have a
detrimental effect on the course and prognosis of BD
1
•Given the increased likelihood of people with BD to
smoke, and their decreased cessation rate, the treatment
of tobacco-use disorder or nicotine dependence is
important to consider in people with BD
1
•Helping people with BD to stop smoking involves an
integrated approach treating BD and the smoking at the
same time, although data on which to base treatment
decisions is scarse
1
BD=bipolar disorder
1. Grunze et al. Front Psychiatry 2023;13:1114432; 2. Heffner et al. Bipolar Disord 2011;13(5–6):439–453; 3. Jackson et al. Bipolar Disord 2015; 17(6):575–597
Current smoking Smoking cessation
0.0
1.0
2.0
3.0
4.0
3.50
0.34
3.20
0.32
3.30
0.34
All BD
Men
Women
O
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d
s

r
a
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Risk of smoking behaviour in people with BD
compared with the general population
3
This meta-analysis found that BD increased the chance of
smoking and decreased the odds of smoking cessation
3

16. Medical comorbidities

17. 17
•In total, 36,984 people in
Canada completed the
CCHS survey, which
included 938 people with
a lifetime manic episode
(i.e., 2.5% of the sample)
•Many conditions were
found to be present at a
higher rate in people with
BD than in the general
population
Bipolar disorder – Comorbidities
Prevalence of comorbid general medical conditions
*p<0.05 versus no manic episode group
BD=bipolar disorder; CCHS=Canadian Community Health Survey
McIntyre et al. Psychiatr Serv 2006;57(8):1140–1144
≥
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18. 18
Bipolar disorder – Comorbidities
Sleep disorders
•Sleep disorders are relatively common among the general
population – with as many as half the population
estimated to experience some form of sleep disorder
1
•Sleep disorders are commonly comorbid with BD,
including conditions such as:
1,2
•Insomnia
•Excessive daytime sleepiness
•Nightmares
•Difficulty falling asleep or maintaining sleep
•Poor sleep quality
•Sleep talking
•Sleep walking
•Obstructive sleep apnea
•Sleep disturbance in people with BD can add to the
already heavy burden of disease, increasing the chance
of poorer disease outcomes and of other comorbidities
2
BD=bipolar disorder
1. Steardo et al. Front Psychiatry 2019;10:501; 2. Morton & Murray. Curr Opin Psychol 2020;34:1–6
How sleep disruptions might influence mood stability
1
Social rhythm
disruption events
Circadian pacemaker
abnormality
Disruption to
social rhythm
Mood episodes/
symptoms
External trigger
Internal trigger
Disruption to
circadian rhythm
This work is adapted from ‘Sleep disturbance in bipolar disorder: neuroglia and circadian rhythms’
by Steardo et al., used under CC-BY. This work is licensed under Creative Commons license
CC-BY-SA by The Lundbeck Foundation

19. 19
Bipolar disorder – Comorbidities
Obesity, type 2 diabetes, and metabolic comorbidities
•Mental disorders, including BD, are associated with premature mortality:
•A meta-analysis of 21 studies found bipolar disorder to be associated with a 12.5 year shorter life expectancy
1
•A Swedish national cohort study, including 6.5 million adults, found that people with BD died on average ~9 years earlier than
those without BD – a burden partly explained by increased mortality from various cardiovascular diseases, and diabetes
2
•A meta-analysis of 32 systematic reviews found that the prevalence of type 2 diabetes was elevated in several
psychiatric disorders compared with the control populations without psychiatric disorders – BD increased the risk of
type 2 diabetes by 1.6–3.2 times
3
•Among people with BD, obesity is roughly twice as prevalent as in the general population
4

•A naturalistic study followed 129 people with BD
5
•There was a high prevalence of obesity – 39% of the sample
•People medicated with lithium appeared to have a lower risk of type 2 diabetes, although the difference in this study was not
significant
•To complicate the picture further, obesity and metabolic dysfunction are thought to be risk factors for the
development of mood disorders, including BD
4
BD=bipolar disorder
1. Chan et al. EClinicalMedicine 2023;65:102294; 2. Crump et al. JAMA Psychiatry 2013;70(9):931–939;
3. Lindekilde et al. Diabetologia 2022;65(3):440–456; 4. Mansur & McIntyre. FOCUS 2015;13(1):12–18; 5. Prillo et al. BMC Psychiatry 2021;21(1):558

20. 20
Bipolar disorder – Comorbidities
Migraine
•There appears to be an association between BD and migraine
1-3
•One early small-scale analysis studied patients with affective disorders who were consecutively
admitted to a hospital in Norway, and found that the patients with unipolar depression or bipolar
depression had high rates of migraine comorbidity
2
•Interestingly, there was a stark and significant difference between patients with BD-I and BD-II –
migraine was found in 77% of patients with BD-II, compared with only 14% of those with BD-I
2
•A systematic literature review identified several studies investigating the comorbidity of BD with
migraine, or vice versa of migraine with BD:
3
•Prevalence of migraine in people with BD: 16–58%
•Prevalence of BD in people with migraine: 4–13%
•There was a higher prevalence of comorbidity among women, and people with BD-II
•As with other comorbidities of BD, clinicians should be aware of the potential for comorbid migraine,
and plan treatment approaches that account for both conditions
3
BD=bipolar disorder
1. APA. DSM-5-TR. 2022; 2. Fasmer. Cephalalgia 2001;21(9):894–899; 3. Leo & Singh. Scand J Pain 2016;11:136–145

21. 21
Bipolar disorder – Comorbidities
Dementia
•BD has been linked to an increased risk of developing
dementia
1,2
•A groundbreaking meta-analysis published in 2017
identified 6 studies evaluating the risk of developing
dementia in people with BD (n=3,026)
1
•Although there was bias and heterogeneity in the data,
BD increased the risk of dementia by 2.36 times
1
•A subsequent meta-analysis published in 2020 identified
10 studies, including 6,859 people with BD
2
•This meta-analysis found that BD increased the risk of
dementia by 2.96 times
2
•Interestingly, the increased risk of dementia was
attenuated with lithium treatment
2

BD=bipolar disorder; CI=confidence interval
1. Diniz et al. Am J Geriatr Psychiatry 2017;25(4):357–362; 2. Velosa et al. Acta Psychiatr Scand 2020;141(6):510–521
In this meta-analysis there were 5 studies that included
data on dementia and lithium in people with BD
The neuroprotective effect of lithium
2
6,483 people with BD taking lithium,
of whom 197 developed dementia
…compared with 43,496 people who were
not taking lithium, of whom 2,982
developed dementia
Odds ratio: 0.51 (95% CI: 0.36, 0.72)

22. Management of patients
with comorbidities

23. 23
BD can have a substantial
impact on the patient and
their families, including
placing a greater financial
strain and increasing the
risk of hospitalization
Bipolar disorder – Comorbidities
The impact of medical comorbidities on patients
*p<0.05 versus group without comorbidity
ADL=activity of daily living; BD=bipolar disorder
McIntyre et al. Psychiatr Serv 2006;57(8):1140–1144
0
10
20
30
40
50
60
With comorbidity (n=622)Without comorbidity (n=316)
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Employment, personal, and healthcare-related impact of comorbidity in people with lifetime manic episode
*
*
*
*
* *
*

24. 24
Bipolar disorder – Comorbidities
The impact of comorbidity on treatment outcomes
•Compared with people with BD without a psychiatric or medical comorbidity, the presence of a
psychiatric or medical comorbidity is associated with:
•Earlier age of onset
•Worse or intensified symptomatology
•Increased suicidality
•Poorer symptomatic and functional recovery
•Diminished acute response to treatment
(pharmacologic or psychosocial)
•Decreased quality of life
•A more complex presentation of affective disorder
•A lower rate of recovery
•Unfavorable course and outcome
BD=bipolar disorder
McIntyre et al. Ann Clin Psychiatry 2012;24(2):163–169

25. 25
Bipolar disorder – Comorbidities
The impact of cognitive dysfunction on patients
•A cross-sectional analysis of 60 stable, euthymic, patients with BD compared with 30
control individuals assessed cognitive functioning between episodes
•People with BD had a significantly lower IQ score than controls: 97.3 versus 112.5
(p<0.001)
•People with BD had significantly poorer scores on scales measuring intelligence and
memory functioning
•People with BD showed lower performance on the WCST executive functioning test
•Scores on executive functioning were correlated with previous hospitalizations for BD –
a greater number of hospitalizations predicted worse executive functioning
•Therefore, cognitive dysfunction – whether strictly a comorbidity or a symptom of the
condition – places an additional burden on people with BD
People with BD can
experience cognitive
dysfunctions, which can
have an additional impact
on the patient
BD=bipolar disorder; IQ=intelligence quotient; WCST=Wisconsin Card Sorting Test
Okasha et al. J Affect Disord 2014;166:14–21

26. 26
The CANMAT guidance for
managing medical and
psychiatric comorbidity in
individuals with MDD or BD
stress the importance of
screening patients for
comorbid conditions
Bipolar disorder – Comorbidities
Principles of treating patients with BD and comorbidities
1.Establish the diagnosis – treating a patient with comorbidities begins with accurate
diagnosis of mood disorders
2.Do a risk assessment – people with mood disorders should be risk-assessed to
establish whether they are at risk of self-harm or suicide
3.Establish the appropriate treatment setting – ideally, the most appropriate
treatment setting is the least restrictive setting
4.Manage chronic diseases – components of good chronic disease management
should be integrated into the treatment plan (e.g., patient education)
5.Plan concurrent or sequential treatment – some evidence suggests integrated
treatment of both conditions is preferred, however, in some circumstances a
sequential approach favouring mood stabilization first is superior
6.Undertake measurement-based care – ongoing assessment of treatment efficacy,
patient functioning, and adverse drug effects is important, and can improve treatment
outcomes
BD=bipolar disorder; CANMAT=Canadian Network for Mood and Anxiety Treatments; MDD=major depressive disorder
McIntyre et al. Ann Clin Psychiatry 2012;24(2):163–169

27. 27
Bipolar disorder – Comorbidities
Assessment of comorbidities
•Ongoing assessment of patients with BD is critical, and this includes assessment of comorbid
psychiatric and medical conditions
1
•Indeed, the symptoms of a depressive or manic episode in a person with BD may mask the
symptoms of the comorbid condition, which means it can be important to monitor and assess the
patient between mood episodes
1
•Sometimes, assessment and diagnosis of a comorbidity may involve screening blood or urine
samples – for instance where substance-use disorder is suspected, and the patient has not
responded fully with adequate information when questioned
1
•Depending on the treatment setting and its feasibility, standardized rating scales can be useful for
documenting the severity of accompanying symptoms
1
•The primary goal of BD treatment should be stabilization of mood, after this is considered,
treatment options for the comorbid conditions should be explored
2
BD=bipolar disorder
1. Shah et al. Indian J Psychiatry 2017;59(Suppl 1):S51–S66; 2. Altinbaş. Noro Psikiyatr Ars 2021;58(Suppl 1):S41–S46

28. 28
Bipolar disorder – Comorbidities
General principles of caring for physical health – NICE
1.Develop and use practice case
registers to monitor the physical and
mental health of people with BD in
primary care
2.Monitor the physical health of people
with BD when responsibility for
monitoring is transferred from
secondary care, and then at least
annually. The health check should be
comprehensive, focusing on physical
health problems such as
cardiovascular disease, diabetes,
obesity and respiratory disease.
A copy of the results should be sent
to the care coordinator and
psychiatrist, and put in the secondary
care records
3.Ensure that the physical health
check for people with BD is
performed at least annually, including:
•Weight or BMI, diet, nutritional
status and level of physical activity
•Cardiovascular status, including
pulse and blood pressure
•Metabolic status, including fasting
blood glucose or glycosylated
haemoglobin (HbA1c), and blood
lipid profile
•Liver function
•Renal and thyroid function, and
calcium levels, for people taking
long-term lithium
4.Identify people with BD who have
hypertension, have abnormal lipid
levels, are obese or at risk of obesity,
have diabetes or are at risk of
diabetes (as indicated by abnormal
blood glucose levels), or are
physically inactive, at the earliest
opportunity, and follow appropriate
guidelines on treatment
5.Offer treatment to people with BD
who have diabetes and/or
cardiovascular disease in primary
care in line with treatment guidelines
BD=bipolar disorder; BMI=body mass index;
HbA1c=glycated haemoglobin (a measure of long-term glucose control);
NICE=National Institute for Health and Care Excellence
NICE CG185 https://www.nice.org.uk/guidance/cg185/resources/bipolar-disorder-assessment-and-management-35109814379461

29. 29
Bipolar disorder – Comorbidities
Treatment of comorbid alcohol-use disorder
Substance-use disorders
are common among people
with BD, and because
alcohol is available and
socially acceptable in many
parts of the world,
clinicians should be aware
of the potential of alcohol-
use disorder comorbid with
BD
BD=bipolar disorder
Grunze et al. Front Psychiatry 2021;12:660432
•Control vital signs
•For severe withdrawal, and in patients at risk,
initiate and taper medication
•Check motivation for abstinence
•Symptomatic treatment of mania,
mixed state, or depression
•Check motivation for BD therapies
Acute treatment of alcohol-use disorder
Detoxification and withdrawal
Acute treatment of BD
Control of mood
•Establish or consolidate the therapeutic alliance
•Stop medications for withdrawal symptoms
•Adjust BD treatment: initiate mood stabilizer if not already done so
•Establish with patient the therapy programme, clarifying the focus (alcohol-use
disorder versus BD), the setting, and the duration of treatment
•Consider and initiate psychotherapies or community treatments, as appropriate
Immediate/continuation treatment
•Maintain regular contact, and ensure adherence to BD therapies and medication
(consider e-health to support adherence)
•Motivate the patient to attend and participate in self-help groups for BD and alcohol-use disorder
•Consider refresher of psychotherapies, as required, and anti-craving medications if necessary
Long-term/maintenance treatment
This work is adapted from ‘Comorbid bipolar and alcohol use disorder – a therapeutic challenge’ by Grunze et al., used
under CC-BY. This work is licensed under Creative Commons license CC-BY-SA by The Lundbeck Foundation

30. 30
Bipolar disorder – Comorbidities
Treatment of medical comorbidities
•Treating people with BD and medical comorbidities can be complicated – because the patient’s only
routine contact may be with a psychiatrist, that psychiatrist should watch for the signs of medical
comorbidity, and be aware of the potential risks of psychotropic medications in this population
1
•Some treatments have been trialled that – specifically or as a secondary effect – may help treat the
comorbidities of BD, although there are few high-quality studies
2
•The use of a GLP-1 agonist has been trialled in people with mood disorders, with some preliminary
results suggesting that the weight loss resulting from the treatment was accompanied by concomitant
beneficial changes in frontal–striatal brain structures and cognitive functioning
3
•One recent pilot study investigated the use of metformin in treatment-resistant BD
4
•Metformin is a drug used in the treatment of diabetes that increases insulin sensitization
•Among the 10 patients with BD who successfully reversed insulin resistance, there were significant improvements
in depressive and anxious symptoms versus those whose insulin resistance did not improve (p<0.05)
BD=bipolar disorder; GLP-1=glucagon-like peptide 1
1. McLaren & Marangell. Ann Gen Hosp Psychiatry 2004;3(1):7; 2. McIntyre et al. Ann Clin Psychiatry 2012;24(2):163–169;
3. Mansur et al. Eur Neuropsychopharmacol 2017;27(11):1153–1162; 4. Calkin et al. J Clin Psychiatry 2022;83(2):21m14022

31. Summary

32. 32
Bipolar disorder – Comorbidities
Summary
•Various psychiatric disorders and general medical conditions are highly comorbid with BD
•The presence of both psychiatric and physical comorbidities can have a significant negative
impact on the clinical course and treatment outcomes for patients with BD
•BD is associated with a substantial, and potentially avoidable reduction in life expectancy
•The evidence-base for choosing effective treatments targeting comorbidities in BD is scarce
•Diagnosis, ongoing monitoring, and treatment of general medical conditions in individuals with
BD is an important unmet need
BD=bipolar disorder

33. Patients with affective disorders
are an at-risk group for myriad
medical disorders, which are
often undiagnosed and
subsequently left untreated
McIntyre et al. Psychiatr Serv 2006;57(8):1140–1144