This presentation gives an overview of the psychiatric and physical co-morbidities in bipolar disorder and different approaches to prevent them.

1. CO-MORBIDITIES IN
BIPOLAR DISORDER
Presenter: Dr Ashok J
Junior Resident
Kasturba Medical College, Manipal
Manipal Academy of Higher Education

2. Outline
• Demographics of bipolar disorder
• Psychiatric co-morbidities
• Physical co-morbidities
• Possible causes for elevated co-morbidities
• Preventive measures
• Conclusion
Bipolar
Disorder
Psychiatric
PhysicalCognitive

3. Co-morbidity or Co-occurrence?
Co-morbidity
• Occurrence of two or more
medical conditions
concurrently.
• Conditions are independent of
the primary illness.
• Unrelated conditions occurs at
essentially the base population
rates.
Co-occurrence
• Occurrence of two or more
medical conditions
concurrently.
• Conditions shares risk factors
with the primary illness.
• Conditions occurs at a rate
higher than population base
rates.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

4. Demographics of bipolar disorder
• All-​cause mortality rate is twofold higher than the general population
• 1.64 fold increase in mortality rates secondary to ‘natural’ causes
• Reduction in life expectancy is about 8.5–​19.8 years
• Significant increase in relative risk for both men and women
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

5. Psychiatric co-morbidities in bipolar disorder
Bipolar
Disorder
AUD
38-48% NUD
46-80%
Suicide
1%
Anxiety
42-77%PD
38-48%
ADHD
28-90%
OCD
12-18%
CI
40-60%
• Psychiatric co-morbidities can
confound illness management
• Lifetime psychiatric
co-morbidity rates in bipolar I
samples range from 50-70%
• Psychiatric co-morbidities can
typically, worsen illness course
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

6. Psychiatric co-morbidities in bipolar disorder
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

7. Alcohol use disorder
• Individuals with BD exhibit high rates of alcohol abuse,
affecting up to half of people at some point in their life.
• The prevalence of AUD in BD is 38-48%.
• The rate is three to four times higher than in the general
population.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

8. Different hypotheses for increased AUD in BD
• The symptoms of bipolar disorder lead to increased alcohol use
• Alcohol abuse was an attempt by BD individuals to self-medicate
• Alcohol abuse causes bipolar disorder
• Alcohol use and bipolar disorders share risk factors
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

9. Alcohol use disorder
• Alcohol abuse clearly worsens the course of bipolar illness
• Alcohol use disorder is associated with
• Impaired treatment response
• Increased time in depression
• Increased risk of suicide
• Worse functional outcome
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

10. Alcohol use disorder
• Clinicians must be diligent for evidence of alcohol abuse in
individuals with BD, particularly when treatment response or
course suddenly worsens.
• Once identified, both AUD and BD must be managed
aggressively; concurrent management using best practices
for both conditions likely produces the best outcomes.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

11. Nicotine use disorder
• Smoking is common in bipolar disorder, affecting 46-80% of individuals.
• Lifetime smoking rates in BD are approximately 3.5 times increased
and patients tend to be more nicotine dependent and have lower
cessation rates.
• In the general population cigarette use is associated with increased
anxiety and suicide in addition to cancer, stroke, and heart disease.
• Given the negative health effects of cigarette use, it is imperative to
aggressively address this co-occurrence.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

12. Other drug use
• The prevalence of DUD in BD is 21-41%.
• Lifetime prevalence of drug abuse in BD is three to six times greater than in
the general population.
• Cannabis is the most commonly abused illicit drug in patients with BD.
• Drug abuse significantly worsens the course of BD, with increased affective
episodes, poor psychosocial recovery and higher rates of suicide.
• Clinicians must closely monitor for drug abuse, particularly with sudden
course changes.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

13. Suicide
• In general population of developed countries, rates of completed
suicide average 0.015%.
• In bipolar disorder, this risk is 0.9% annually.
• It is 30-60 times above the general population rate.
• It accounts for 15-20% of deaths among patients with BD.
• There is relatively low ratio of attempts to completed suicides.
Baldessarini, R. J., Pompili, M., & Tondo, L. (2006). Suicide in bipolar disorder: risks and management. CNS spectrums, 11(6), 465-471.

14. Anxiety disorders
• Anxiety occurs throughout the course of illness in most bipolar
individuals, across all mood states, and even during periods of relative
euthymia.
• The prevalence of anxiety disorders in BD is 42-77%.
• Anxiety disorders are three to four times more common in bipolar
disorder than in the general population.
• There is excessive co-occurrence of OCD, panic disorder and PTSD.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

15. Anxiety disorders in BD 1 & 2
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

16. Anxiety disorders
• Aggressive management of the primary bipolar condition will
often alleviate anxiety symptoms, but anxiety disorders
typically require additional treatment.
• Treating these conditions can be complicated, since anxiety
disorders are typically managed with antidepressants that
are not always tolerated by bipolar individuals.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

17. Anxiety disorders
• Alternative therapies (CBT, Mindfulness, EMDR etc) may
need to be relied on more extensively.
• Individuals with bipolar disorder appear to be particularly
susceptible to PTSD, so should be carefully monitored after
traumatic events.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

18. ADHD
• The prevalence of ADHD in BD is 28-90%.
• ADHD affects up to 80% of bipolar children and adolescents and
one-third of adults with bipolar disorder.
• The decrease with aging in rates of co-occurring ADHD may be due to
ADHD symptoms resolving over time.
• This decline in rates with age may represent a complex interplay
between cognitive and brain development, genetic risks for BD and
variable expression of symptoms as the illnesses progress.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

19. Different hypotheses for increased ADHD in BD
• Common symptoms in both conditions like inattention and
impulsivity lead to overdiagnosis of ADHD in bipolar individuals,
particularly in children.
• ADHD and bipolar disorder share risk factors.
• ADHD is a prodromal expression of bipolar disorder.
• ADHD is an early expression of an evolving bipolar illness in
children, before they develop mania.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

20. Personality disorders
• The prevalence of personality disorders in BD is 38-48%.
• The dynamic symptoms of bipolar disorder can be difficult to
distinguish from the affective instability and cognitive symptoms
of personality disorders, particularly those of DSM-5 cluster B
disorders.
• Co-occurring personality disorder demands ongoing behavioural
characteristics that persist beyond mood states into euthymia.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

21. Personality disorders
• Elevated rates of borderline, narcissistic, histrionic,
obsessive-compulsive, and avoidant personality disorders
are particularly common and occur in up to half of bipolar
individuals.
• The presence of a personality disorder decreases treatment
adherence, leads to lower rates of recovery, increases the
risk of drug and alcohol abuse and increases the risk of
suicide.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

22. Personality disorders
• Personality disorders typically require long-term and
focused psychotherapies (e.g., DBT) to gain improvement, in
addition to treating the primary bipolar disorder.
Stephen M. S. (2017). Illness Comorbidity and Co-occurrence in Bipolar Disorders. In Stephen M. Strakowski. (Ed.). Bipolar Disorder (pp. 23-31). Oxford University Press.

23. Eating disorders
• About 27% of patients with BD had a current eating disorder
diagnosis by DSM-5 criteria.
• 12% had BED, 15% had BN, and 0.2% had AN.
• The presence of BD among eating disorder patients is associated
with self-injury, suicide attempts, substance abuse, and
treatment resistance of the eating disorder.
• The overlap of BD and eating disorders has been hypothesized to
be due to both conditions sharing common genetic factors as
well as to exposure to certain psychotropics.
McElroy, S. L., Crow, S., Blom, T. J., Biernacka, J. M., Winham, S. J., Geske, J., ... & Mori, N. (2016). Prevalence and correlates of DSM-5 eating disorders in patients with bipolar
disorder. Journal of affective disorders, 191, 216-221.

24. Cognitive impairment
• Most patients with BD show neurocognitive dysfunction
even during euthymia.
• Approximately 40-60% of patients with BD exhibit
neurocognitive impairment.
• Some of these neurocognitive deficits seem to be present
not only in the early course of the illness but also in
premorbid stages before illness onset.
Jensen, J. H., Knorr, U., Vinberg, M., Kessing, L. V., & Miskowiak, K. W. (2016). Discrete neurocognitive subgroups in fully or partially remitted bipolar disorder: Associations with
functional abilities. Journal of affective disorders, 205, 378-386.

25. Cognitive impairment
• The most affected domains are attention, verbal learning and memory,
and executive functions, whereas premorbid intelligence appears to be
preserved.
• Although cognitive abnormalities are present across all illness phases,
they are usually more notable during acute episodes.
• There is growing evidence for impairment in some social cognition
domains even during periods of remission.
• Evidence supports a theory of mind deficit in euthymic bipolar
patients.
Jensen, J. H., Knorr, U., Vinberg, M., Kessing, L. V., & Miskowiak, K. W. (2016). Discrete neurocognitive subgroups in fully or partially remitted bipolar disorder: Associations with
functional abilities. Journal of affective disorders, 205, 378-386.

26. Physical co-morbidities in bipolar disorder
• Co-occurrence of physical morbidity is
in the range of 32.4–​100% in clinical
surveys with a mean of 70.62% for at
least one co-​morbid general medical
condition.
• Physical co-​morbidity significantly
contributes not only to the excess
mortality but also to its premature
manifestation.
Bipolar
Disorder
Cancer
4%
Circulatory
16%
CNS
19%
GIT
21%
Respiratory
22%
Thyroid
10%
Infectious
8%
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

27. Factors for higher rates of physical co-morbidities
• Female sex
• Childhood onset
• Higher duration of untreated illness
• Longer and more severe depressive episodes
• Ten or more recurrences during the course of illness
• Presence of co-​morbid anxiety and substance misuse disorders
• History of attempted suicide and physical abuse
• Low income
• Advancing age
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

28. Consequences of physical co-morbidities
• Greater levels of disability and dependency
• Low levels of employment suitability
• Higher psychiatric consultation and hospitalization rates
• Increased refractoriness for the treatment of depressive mood states
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

29. Circulatory and related precursor diseases
Co-morbid condition Mean Prevalence
Any circulatory diseases 16%
Ischaemic heart diseases 7%
Stroke 2%
Hypertension 22%
Diabetes mellitus type II 9%
Dyslipidaemia 19%
Obesity 36%
Overweight 36%
Metabolic syndrome 37%
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

30. Circulatory diseases
• Higher rates are mainly associated with accelerated atherosclerosis
• The NESARC study showed that ischaemic heart diseases are approximately five
times higher in BD patients and they were at a 2–​3-​fold increased risk of
developing any cardiovascular disease and were diagnosed 14–​17 years earlier.
• The occurrence of ischaemic strokes was also reported to be higher in BD with a
1.74-​ fold increased risk.
• BD was proposed as one of the moderate-​risk conditions for atherosclerosis and
early diagnosis of cardiovascular diseases among youth.
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

31. Circulatory diseases
• Factors associated with greater occurrence of cardiovascular diseases
• Female sex
• Type I BD
• Longer duration of depressive episodes
• Increased manic/​hypomanic symptom burden
• Factors associated with greater occurrence of ischaemic stroke
• Male sex
• Lower socio-​economic status
• Co-​occurring physical illness
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

32. Obesity
• The prevalence of obesity in BD is 36%.
• Factors associated with greater occurrence of obesity in BD
• Pharmacological treatment
• Advancing age
• Obesity is associated with a range of negative outcomes in BD like
• Early onset of BD symptoms
• Presence of psychiatric and physical co-​morbidity
• Increased duration and hospitalization rates in depressive episodes
• Increased disability
• Decreased global and cognitive functioning
• Decreased life satisfaction
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

33. Hypertension, Dyslipidaemia & DM type 2
• There is a twofold increased hypertension risk in patients with BD with an earlier
onset than expected with a prevalence of 22%.
• The prevalence of dyslipidaemia in BD is 19% and is 1.5 times higher in patients
with BD and tend to be more frequent with advancing age and in men.
• BD patients have double the risk of DM type 2 with a prevalence of 9% and it is
more frequent with
• Lower level of education
• Later age of disease onset
• Chronic course with higher rates of rapid cycling
• Non-​response to lithium treatment
• Advancing age
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

34. Metabolic syndrome
• Metabolic syndrome has been reported to be twofold higher in BD
patients with a prevalence of 37%.
• Factors associated with greater occurrence of metabolic syndrome
• Pharmacological treatment
• Advancing age
• Metabolic syndrome is associated with a range of negative outcomes
in BD like
• Higher number of hospitalizations
• History of suicide attempts
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

35. Neurological disorders
• Higher rates of migraine are seen in type 2 BD and migraine is associated with
lower economic status, earlier age at onset, more severe and frequent depressive
episodes, co-​morbid anxiety disorders and suicidal behaviour.
• Four-​times higher risk for epilepsy.
• Two-​times higher risk for multiple sclerosis.
Co-morbid condition Mean Prevalence
Any neurological diseases 19%
Migraine 35%
Epilepsy 3%
Multiple sclerosis 0.4%
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

36. Gastrointestinal disorders
Co-morbid condition Mean Prevalence
Any gastrointestinal diseases 21%
Peptic ulcer 8%
Irritable bowel disease 4%
Co-morbid condition Mean Prevalence
Any respiratory diseases 22%
Asthma 11%
COPD 9%
Respiratory disorders
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

37. Thyroid disorders
Co-morbid condition Mean Prevalence
Any thyroid diseases 10%
Hypothyroidism 8%
Hyperthyroidism 0.3%
• The prevalence of thyroid diseases in BD is related with poorer response to
standard treatments and more frequent with advancing age and in women.
• In particular, hypothyroidism is associated with negative clinical outcomes in BD
including rapid cycling and cognitive decline.
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

38. Co-morbid condition Mean Prevalence
Any infectious diseases 8%
HIV 1.3%
HCV 7%
Infectious diseases
• HIV infection in BD is associated with
• Escalation in clinically significant cognitive decline
• Enhanced impairment in daily functioning
• Decreased adherence to treatment for both HIV and BD
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

39. Neoplastic disorders
• The mean prevalence of cancer co-morbidity in patients with
BD is about 4%.
• Significant increase of female-​hormone-​regulated cancers
• Breast
• Cervix
• Uterus
• Significant increase of tobacco and alcohol related cancers.
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

40. Comorbid medical illness in BD in a study in UK
• Participants were recruited at three UK sites (Birmingham, Cardiff and
London) as part of ongoing molecular genetic and clinical studies of affective
disorders.
• Individuals meeting DSM-IV and ICD-10 criteria for bipolar disorder (n= 1720)
were included in the study.
• All participants were aged 18 years or older and of White European ethnicity
• Individuals were excluded if they
• Had a lifetime diagnosis of intravenous drug dependency
• Had only experienced affective illness as a result of alcohol or substance dependence
• Had only experienced affective illness secondary to medical illness or medication
• Were biologically related to another study participant
Forty, L., Ulanova, A., Jones, L., Jones, I., Gordon-Smith, K., Fraser, C., ... & Rivera, M. (2014). Comorbid medical illness in bipolar disorder. The British Journal of Psychiatry, 205(6), 465-472.

41. Lifetime rates of physical co-morbidities
Forty, L., Ulanova, A., Jones, L., Jones, I., Gordon-Smith, K., Fraser, C., ... & Rivera, M. (2014). Comorbid medical illness in bipolar disorder. The British Journal of Psychiatry, 205(6), 465-472.

42. Rates of physical co-morbidities in bipolar 1 and 2
Forty, L., Ulanova, A., Jones, L., Jones, I., Gordon-Smith, K., Fraser, C., ... & Rivera, M. (2014). Comorbid medical illness in bipolar disorder. The British Journal of Psychiatry, 205(6), 465-472.

43. Co-morbidities in BD in a study at our centre
• Observational study involving retrospective file review to ascertain the
prevalence of physical and psychiatric co-morbidities in bipolar disorder
patients.
• Case record files of patients evaluated in detail in the year 2010 and
diagnosed as having bipolar disorder according to ICD-10 DCR were included.
• 140 patients received a diagnosis of bipolar disorder. Of these, 15 files had
insufficient data or could not be traced. The remaining 125 files were
included.
• Operational criteria checklist (OPCRIT) was used to generate lifetime
diagnosis of bipolar disorder.
• 120 patients fulfilled the diagnosis of bipolar disorder on evaluation in OPCRIT
Munoli, R. N., Praharaj, S. K., & Sharma, P. S. V. N. (2014). Co-morbidity in bipolar disorder: a retrospective study. Indian journal of psychological medicine, 36(3), 270.

44. Psychiatric co-morbidity in BD at our centre
Munoli, R. N., Praharaj, S. K., & Sharma, P. S. V. N. (2014). Co-morbidity in bipolar disorder: a retrospective study. Indian journal of psychological medicine, 36(3), 270.

45. Physical co-morbidity in BD at our centre
Munoli, R. N., Praharaj, S. K., & Sharma, P. S. V. N. (2014). Co-morbidity in bipolar disorder: a retrospective study. Indian journal of psychological medicine, 36(3), 270.

46. Causes of elevated physical co-morbidities in BD
Co-morbidity
Lifestyle choices
Allostatic load
Treatment effects

47. Lifestyle choices
• Increased tobacco consumption
• Sedentary lifestyle
• Substance misuse
• Unhealthy diet habits

48. Allostatic load
• It is "the wear and tear on the body" which accumulates as
an individual is exposed to repeated or chronic stress.
• It results in DNA damage, endothelial dysfunction, decrease
in inflammatory response, and telomere shortening.
• It contributes to the onset or to the accelerated evolution
of the wide range of medical conditions observed in BD with
a higher frequency.
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

49. Allostatic load

50. Pharmacological treatment
• The excess of general medical conditions and mortality
associated with BD antecede modern psychopharmacology.
• However, some treatments have the potential to increase the
risk of developing or worsening general medical conditions in
view of their association with metabolic and endocrine effects.
• Contributory factors include dose of the psychotropic drugs,
concurrent medications and their side effects and potential
interactions, diet, lifestyle, and physical activity levels.

51. Lithium
• Associated with impaired nephrogenic function,
hypothyroidism, hyperparathyroidism and weight gain.
• Clinical hypothyroidism is nearly six times higher.
• Lithium-​induced hypothyroidism is more prevalent in women
• Progress to nephrogenic diabetes insipidus and chronic
interstitial nephropathy are seen in some cases.
• Weight gain is present in more than 70% of treated
individuals with 30% reaching obesity.
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

52. Valproate
• It is associated with weight gain in 3–​20%.
• Weight gain may continue without plateau for months or years
throughout treatment
• Levels above 125 μ/​ml have been associated with more
frequently occurring weight gain
• It is also associated with higher plasma insulin levels indicating
possible development of insulin resistance, higher triglyceride
and lower HDL levels as dyslipidaemia disturbances distinct from
weight gain effects.
Nefize Yalin, Danilo Arnone, and Allan Y. Young. (2017). Bidirectional relationships between general medical conditions and bipolar disorder: treatment considerations. In Carvalho, A.
F., & Vieta, E. (Eds.). The treatment of bipolar disorder: integrative clinical strategies and future directions (pp. 271-289). Oxford University Press.

53. SGA with mood stabilizing properties
• Associated with weight gain, insulin resistance, diabetes mellitus, and
hyperlipidaemia.
• Clozapine and olanzapine are the greatest contributors for weight gain,
lipid abnormalities and diabetes mellitus.
• Metabolic effects of ziprasidone and aripiprazole have been shown to
be minimal.
• All antipsychotics have the potential to reduce the seizure threshold
and increase the risk of sudden cardiac death in a dose-​related fashion.

54. Antidepressants
• SSRIs have been associated with weight loss in the acute
treatment phase and weight gain in maintenance phase.
• Mirtazapine and TCAs are known to induce weight gain.
• Venlafaxine is associated with dose-​dependent hypertension
• TCAs and bupropion are known for epileptogenic potential.

55. Preventive measures
• Minimizing health risks
• Assessment and monitoring of physical health
• Minimum frequency of follow-​ups at six weeks, three months, and six
months after baseline assessment and on yearly basis subsequently.
• Psychopharmacological optimization and psychotherapy
• Pharmacological management of general medical conditions

56. Conclusion
• BD is associated with an excess of psychiatric/physical conditions and
increased premature mortality compared with the general population.
• Comorbidity is usually associated with poorer prognosis and also may
present a challenge for the treating psychiatrist.
• Awareness of co-​morbidities and a systematic approach to the needs of
patients are important components of the treatment provided.
• Attention to modifiable risk factors and pharmacological optimization can
help improving clinical outcome and quality of life of patients.

57. Conclusion
• Theoretically, co-morbidity may advance
our knowledge by shedding some light on
a possible common psychopathological
pathway, therefore providing an
important lead for innovative research
and therapeutic approaches.
• Comorbidity in bipolar disorder is the rule
rather than the exception and more than
60% of bipolar patients have a comorbid
diagnosis.
Sasson, Y., Chopra, M., Harrari, E., Amitai, K., & Zohar, J. (2003). Bipolar comorbidity: from diagnostic dilemmas to therapeutic challenge. International Journal of
Neuropsychopharmacology, 6(2), 139-144.

58. References
• Baldessarini, R. J., Pompili, M., & Tondo, L. (2006). Suicide in bipolar disorder: risks and management. CNS
spectrums, 11(6), 465-471.
• Forty, L., Ulanova, A., Jones, L., Jones, I., Gordon-Smith, K., Fraser, C., ... & Rivera, M. (2014). Comorbid medical
illness in bipolar disorder. The British Journal of Psychiatry, 205(6), 465-472.
• Jensen, J. H., Knorr, U., Vinberg, M., Kessing, L. V., & Miskowiak, K. W. (2016). Discrete neurocognitive subgroups in
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