Bipolar Disorder

Focus On Men

Juan J Fumero MD Psiquiatra

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Famous Bipolar Men

Pablo Picasso

EPIDEMIOLOGY OF BIPOLAR DISORDER

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National Comorbidity Survey

12 Month Prevalence (Kessler, 2005)
Lay interviewers, AUDADIS (DSM-IV)
N = 14,093 over 18 years of age, representative households Any disorder
2 or more disorders (11.8%)

26.2% 6.7% 2.6%

? BPII M<F

Major Depression Bipolar I and II

Serious (82.9 %)

Kessler RC, et al. Arch Gen Psychiatry. 2005;62:617-627.

SPECTRUM OF BIPOLAR DISORDER

Bipolar Spectrum
Mm-

dD-

M=Mania m=hipomania d=hipodepresion D=depresion

Adaptado de F.K.Goodwin-- K.R.Jamison 1990

Mixtures of Manic and Depressed Symptoms Are Commonly Seen

Mixed Mania Dysphoric Mania Depressive Mixed States1

Mania
MDE

Full Mania

Full Mania

2+ Mania Symptoms Full MDE

Full MDE

2+ Depressive Symptoms

MDE = Major Depressive Episode

Agitated depressions? 2,3

1. Benazzi F. Psychiatry Res. 2004;127:247-257.] 2. Maj M, et al. Am J Psychiatry. 2003;160:2134-2140. 3. Akiskal HS, et al. J Affect Disord. 2005;85:245-258.

Lifetime and 12-Month Prevalence of Bipolar Spectrum Disorder: National Comorbidity Survey Replication
Nationally representative sample of 9,282 adults ( 20 years) Direct interviews, Version 3.0 World Health Organization Composite International Diagnostic Interview for assessment of DSM-IV lifetime and 12-month Axis I disorders. February 2001April 2003
Prevalence, Mean (SD) Any BPD Lifetime 12-Month 4.4 (24.3) 2.8 (18.9) BP-I 1.0 (13.2) 0.6 (9.2) BP-II 1.1 (10.6) 0.8 (9.9) Subthreshold BPD 2.4 (23.3) 1.4 (15.1)

Subthreshold BPD is common, clinically significant, and underdetected 75% of subthreshold BPD lifetime cases received no medication
Merikangas K, et al. Arch Gen Psychiatry. 2007;64:543-552.

2.6-7.8 % Angst J. 1999

Clasificaciones Diagnosticas:
Espectros propuestos
Klerman, 1981

Bipolar I Bipolar II Bipolar III Bipolar IV Bipolar V Bipolar VI

Mana con o sin Depresin Hipomana con Depresin Mana Farmacgena Ciclotimia Dep. en Pt. Con FHx de Mana. Mana unipolar

DSM IV-TR
Bipolar I: Mana con o sin Depresin Bipolar II: Hipomana con Depresin Ciclotimia: Sntomas Hipomanacos con "Hipo" depresivos Bipolar NOS: Atpico

Akiskal & Pinto

Bipolar I Bipolar I1/2 Bipolar II Bipolar II1/2 Bipolar III Bipolar III1/2 estimulantes Bipolar IV

Depresion con Mana Depresion con Hipomana prolongada Depresion con Hipomana Depresion ciclotimica Hipomania asociada a antidepresivos Bipolaridad enmascarada-y no enmascarada por Depresion hipertimica

Famous Bipolar Men

Michaelangelo

National Trends in Increased Outpatient Diagnosis of Bipolar Disorder

Based on the National Ambulatory Medical Care Survey (NAMCS) Youth: 019 years; Adults: 20 years

Bipolar Disorder Visit Rate, %

0.6 0.5 0.4 0.3 0.2 0.1 0.0

Adults Youth

32% visits by males

19941995

19961997

19981999

20002001

20022003

Years
Diagnosis of bipolar disorder for ADULTS increased ~2X in the 10-year study period Diagnosis of bipolar disorder for YOUTH increased ~40X in the 10-year study period
Moreno C, et al. Arch Gen Psychiatry. 2007;64(9):1032-1039.

Changes in US Rates for Psychiatric Disorders (Primary Diagnoses) for Acute Care Inpatients, 19962004
% Change 19962004

Children
Substance Depression Bipolar Anxiety Conduct Psychosis 0 16.5 438.6* -20.8 6.2 0

Adolescents
-4.3 106.6 296.4* -1.7 12 -0.8

Adults
-10.1 25.9 56* -27.2 0 7.2

Developmental
Cognitive Psychophysiological Other Total

0
0 0 66.3 53.2

-39.5
0 161.3 0 58.5*

0
-29.5 -36.7 -0.8 3.3

*P < 0.01, significance of the linear trend, Pearson correlation Blader J, Carlson G. Biol Psychiatry. 2007;62(2):107-114.

Hospitalizations By Gender
2

retrospective studies suggest more hospitalizations for mania in men and depression in women.
Angst, 1978. Roy-Byrne, 1985.

studies found no gender difference.

Winokur et al, 1994. 10 year prospective study, n=131. Hendrick et al, 2000. Retrospective study, n=131.

COURSE OF BIPOLAR DISORDER

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Onset Age in Bipolar Disorder: NDMDA Survey

30 25 % of Members 20 15 10
5% 12% 14% 15% 9% 16% 28%

5
0

<5

5-9

10-14

15-19 20-24 Age (years)

25-29

> 29

Initial illness manifestations in childhood or adolescent onset were associated with positive family history, depressive or mixed initial symptoms, and frequent recurrence with predominantly depressive symptoms.
Lish JD, et al. J Affect Disord. 1994;31:281-294.

Poor Prognosis of Childhood Onset Bipolar Disorder

Duration From Disease Onset to First Pharmacologic Treatment
20 Years Delay to First Treatment

16.8 years
15 11.5 years 10

N = 420

4.6 years 5 2.6 years 0 12 13-18 19-29 30 +

Childhood (n = 66)

Adolescence (n = 157)

Adult (Early) Adult (Late) (n = 133) (n = 75)

Age of Onset of Bipolar Symptoms

Leverich G, et al. J Pediatr. 2007;150(5):485-490.

Age at Onset
STEP-BD, N = 983, early onset predicts
More lifetime manias and depressions More episodes past year More likely to present depressed or mixed Similar frequency of psychosis More comorbid conditions Increased suicide attempts (onset < 13, OR 2.85) Lower QOL, but not functioning

Perlis RH, et al. Biol Psychiatry. 2004;55:875-881.

Outcome of First-episode Manic Adolescents

Syndromic recovery = 0.86 Poor predictors: ADHD, DBD, anxiety disorders, nonadherence, low socioeconomic status

M>F

Symptomatic recovery = 0.43

Functional recovery = 0.41 Syndromic recurrence = 0.54 Predictors: Alcohol use, no psychotherapy, antidepressants

DelBello M, et al. Am J Psychiatry. 2007;164(4):582-590.

Adherence to Pharmacotherapy in First-episode Bipolar Adolescents

50 45 40 35 30 25 20 15 10 5 0 Full adherence (> 75%) Partial (2575%) Nonadherence (< 25%)

DelBello M, et al. Am J Psychiatry. 2007;164(4):582-590.

Percent

The average patient with bipolar disorder does not receive a proper diagnosis for nearly a decade after the onset of his or her first episode

Lish J, et al. J Affect Disord. 1994;31(4):281-294. Hirschfeld R, et al. J Clin Psychiatry. 2003;64(2):161-174.

Famous Bipolar Men

Claude Van Damme

Conceptos Generales
Bipolar-Caracteristicas generales

Mujeres: Episodios de mania~14% (H~35%)1 60% episodios depresivos Mayor incidencia de (2,3,4) :
Episodios mixtos Rapid cicling Mania disforica

1.Angst et al Archv Fur Psychiatrie und Nerverkrankheiten 1978: 226:65-73. 2.Coryell W et al Arch Gen Psychiatry 1992; 49:126-131. 3. Bauer MS Arch Gen Psychiatry 1990;47:427-432. 4.McElroy SL et al Am J Psychiatry 1992:149:1633-1644

Misdiagnosis of Bipolar Disorder

2000 NDMDA initial diagnosis (69%)

60 60 50

Depression Anxiety Schizophrenia

Percent

40 30 20 10 0 26 18 17 14

Cluster B
Alcohol abuse

NDMDA = National Depressive and Manic-Depressive Association; N = 400

Hirschfeld RM, et al. J Clin Psychiatry. 2004;65(suppl 15):5-9.

Time Spent in Specific Bipolar Disorder Affective Symptoms

Bipolar I Patients
146 bipolar I patients followed 12.8 years

Bipolar II Patients
86 bipolar II patients followed 13.4 years

1% 2% 6% 9% 53% 32%
% of Weeks Asymptomatic Depressed Manic/hypomanic Cycling/mixed

50%

46%*

Ratio of 3:1 Depressed vs Manic/hypomanic

*%s do not add to 100 due to rounding
Judd LL et al. Arch Gen Psychiatry. 2002;59:530537. Judd LL et al. Arch Gen Psychiatry. 2003;60:261269.

Ratio of 39:1 Depressed vs Hypomanic

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Famous Bipolar Men

Mark Twain

Initial Treatment of Bipolar Disorders in the United States 20022003

Antidepressant monotherapy twice as common as mood stabilizers

First prescribed drug class 40 (%) 30 20 10 0

70 60 50

50

17

15

11

N = 7,760 patients with bipolar disorder; 69% BP I, 16% BP II, 14% BP NOS Data from US national MarketScan research databases
Baldessarini R, et al. Psychiatr Serv. 2007;58(1):85-91.

Ciclaje Rapido:
Induccion por AD?
Koukopulos (N=109)1

Comienzo de ciclaje associado a AD- 73% Continuar AD continua ciclaje

1 ao en 30% 2 aos en 13% > 2 aos en 4.5%

Wehr et al2 (N=51):

Asociado a uso de AD
TCA y acortamiento de duracion del ciclo
1.Koukopulos et al, Comprehensive Psychiatry 24:249-258, 1983 2.Wehr et al, Am J Psychiatry 145:179-184,1988

Si D/C ADs 1/3 se detuvo ciclaje

Gender Distribution of Rapid Cycling Bipolar Disorder

Leibenluft E . Am J Psychiatry 1996;153:163-173.

Tondo and Baldessarini, Am J Psychiatry,1998

VIRAJE FARMACOLOGICO. BROWDEN (2005)

ATC IMAO VENLAFAXINA LAMOTRIGINA PLACEBO ISRS SIN TRATAMIENTO

11-70 % 35-50 % 13 % 5% 4% 3% 41 %

Bipolar Depression and Antidepressants General Guidelines and Risks

Always use mood stabilizer in bipolar I patients, even while depressed Promptly wean the antidepressant if evidence of hypomania or mania

emerges

Antidepressants may trigger mania (mood destabilization) or accelerate

mood cycle

Up to 33% of patients with bipolar disorder may be susceptible to

antidepressant-induced manias

Possibly less efficacious in BP than UP depression Few standard antidepressants have been studied in bipolar depression

Dantzler A, Osser DN. Psychiatr Ann. 1999;29:270-284. Frances AJ, et al. J Clin Psychiatry. 1998;59(suppl 4):73-79. Goldberg JF, Ernst CL. J Clin Psychiatry. 2002;63:985-991. Goldberg JF, Truman CJ. Bipolar Disord. 2003;5:407-420. Mller HJ, et al. J Affect Disord. 2001;67:141-146.

Bipolar Disorder in Men

Increased Mortality Rates in Bipolar Disorder Due to Suicide or Violence

Patients with bipolar disorder have an 80% increased risk of death due to suicide/violence Patients with bipolar disorder have higher SMRs from suicide
15.0 males/22.4 females in bipolar disorder
The SMR for suicide was especially high for younger patients during the first years after initial diagnosis

SMR = standardized mortality ratio (observed/expected deaths) Harris EC, et al. Br J Psychiatry. 1998;173:11-53.

Famous Bipolar Men

Ben Stiller

Mortality and Severe Mental Illness

Osby et al studied > 15,000 patients with bipolar disorder diagnosis (Sweden)1
Standardized mortality ratios (SMRs) (all causes) in the bipolar patients was 2.5 for males, 2.7 for females (values greater than 1.0 indicate greater risk than general population) Most frequent cause of death for bipolar patients Cardiovascular disease 31% Suicide 19% Cancer 14%

Patients with severe schizophrenia, bipolar disorder, and depression lose 25 or more years of life expectancy, with most of the premature deaths due to cardiovascular disease3
1. Osby U, et al. Arch Gen Psychiatry. 2001;58(9):844-850. 2. Angst F, et al. J Affect Disord. 2002;68(2-3):167-181. 3. Newcomer J, Hennekens C. JAMA. 2007;298(15):1794-1796.

Increased Mortality in Patients With Bipolar Disorder

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Standardized Mortality Ratio*
12.7

12 10

Males (n=6578) Females (n=8808)

8.6

8 6 4
2.5 2.7 2.6 1.9 1.1 1.2 1.9 2 2 1.9

0
All Causes CVD

Cancer

Cerebrovascular

GI

Unnatural

*SMR = standardized mortality ratio: observed events expected events; Unnatural = accidents, suicide, homicide, undetermined deaths. GI = gastrointestinal.
Osby U et al. Arch Gen Psychiatry. 2001;58:884-850.

Common Medical Conditions & BP

Migraine Thyroid disease Lithium Type 2 diabetes Antipsychotics Obesity Mood stabilizers Antipsychotics Polycystic Ovarian Syndrome Valproate and other anticonvulsants Multiple sclerosis Multiple episodes may increase risk of dementia

Obesity and Bipolar Disorder in the General Population

30 Percent Obese Class I-III 25 20 15 No Mood Disorder Mood Disorder

10
5 0

*P < 0.05

Total

Males

Females

McIntyre R, et al. Can J Psychiatry. 2006;51(5):274-280.

Obesity Is Correlated With Important Clinical Features in Bipolar I Disorder

Obese BP I patients
Experience greater number of lifetime depressive and manic episodes Present with more severe and difficult-to-treat index affective episodes Are more likely to develop an affective recurrence, in particular, depressive recurrence

Fagiolini A et al. Am J Psychiatry. 2003;160:112-117.

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Obesity and Bipolar Disorder: More Severe Disease

Obesity
Negative impact on general physical well-being and functioning Quality of life Self-esteem Psychological well-being Sleep apnea
Disrupts sleep Causes or contributes to mood destabilization

Bipolar disorder
Increased risk of obesity due to medication exposure Disease-specific symptoms occur during depressive episodes
Increased appetite Reduced energy expenditure

Fagiolini A et al. Am J Psychiatry. 2003;160:112-117.

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Substance Use Disorders and Overweight/Obesity in Bipolar I Disorder: Preliminary Evidence for Competing Addictions
Data from 36,984 individuals (> 15 years old) in the 2002 Canadian Community Health Survey Overweight and obesity were defined as BMI of 25.029.9 and 30.0 kg/m2, respectively.
60 Rate of Substance Dependent (%) 50 40 Comorbid Conditions in Bipolar I Disorder 60 Rate of Overweight/Obesity (%) 50 39 40 30 20 10 0 Substance Dependent

54

30
21 20

The results demonstrate that individuals with bipolar I disorder exhibit an inverse relationship between comorbid overweight/obesity and substance use disorders Comorbid addictive disorders may compete for identical brain reward systems
Nondependent

13
10 0

Overweight/ Nonoverweight/ Obese Obese P < 0.01

McIntyre R, et al. J Clin Psychiatry. 2007;68(9):1352-1357.

Gender-specific lipid profiles in patients with bipolar disorder

Mytilee Vemuri, a, , Heather A. Kennaa, Po W. Wanga, Terence A. Kettera and Natalie L. Rasgona
a

Department of Psychiatry and Behavioral Sciences, Stanford University, 401 Quarry Road, Stanford, CA 94305-5723, United States
M> F

Available online 4 March 2011

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Potential Health Disturbances With Prolactin-Elevating Antipsychotic Agents

Women
Short-Term Menstrual disturbances Galactorrhea Breast engorgement Sexual dysfunction Infertility Long-Term Decreased bone density Mediated by relative or absolute deficiency of estrogen Cardiovascular disease? Cancer (breast, endometrial)? Depression?
? = few data available Maguire GA. J Clin Psychiatry. 2002;63(suppl 4):56-62.

Men
Short-Term Loss of libido Erectile dysfunction Ejaculatory dysfunction Reduced spermatogenesis Gynecomastia Long-Term Decreased bone density Mediated by relative or absolute deficiency of testosterone Cardiovascular disease? Depression?

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Famous Bipolar Men

Ted Turner

Comorbid Conditions in Bipolar Disorder Patients

Condition
Substance abuse Anxiety disorders Obsessive compulsive disorder Attention deficit hyperactivity disorder Non-psychiatric disorders*
*Allergies, asthma, migraine, and chronic fatigue
1. Hilty DM, et al. Psychiatr Serv. 1999;50:201-213. 2. Regier DA, et al. JAMA. 1990;264:2511-2518. 3. Strober M, et al. J Affect Disord. 1988;15:255-268. 4. Calabrese JR, et al. J Clin Psychiatry. 2003;64:425-432.

Percentage Comorbidity
33%70%1,2 12%37%1 13%25%1 24%3 3%13%4

Anxiety Disorder Comorbidity in Bipolar Disorder

% Range
Generalized Anxiety Disorder Agoraphobia Simple Phobia Social Phobia Panic Disorder Posttraumatic Stress Disorder Obsessive Compulsive Disorder 243 662 267 447 438 540 239

McIntyre RS, et al. Bipolar Disord. In press.

Susan y cols., 2001 ; Zimmerman y cols 2002

Prevalence And Correlates Of Eating Disorders In 875 Patients With Bipolar Disorder.
Prevalence and correlates of eating disorders in 875 patients with bipolar disorder.
McElroy SL, Frye MA, Hellemann G, Altshuler L, Leverich GS, Suppes T, Keck PE, Nolen WA, Kupka R, Post RM. Craig and Frances Lindner Center of HOPE, Mason, OH 45040, USA. [email protected]

J Affect Disord. 2011 Feb;128(3):191-8. Epub 2010 Jul 31.

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Famous Bipolar Men

Vincent Van Gogh

Prefrontal Cortex Left inferior prefrontal gray volumes with illness duration

Structural Changes With BPD Progression: Episodes Are Associated With Brain Tissue Loss

Gray matter volume with age Striatum No difference in putamen between first- and multi-episode patients

Cerebellum Cerebellar vermis volume in multi- vs first-episode patients Amygdala M=F Amygdala volume with age in young patients Ventricles Ventricular volume in multi- vs first-episode patients Ventricular volume with number of manic episodes Ventricular volume with number of affective episodes
Reviewed in Strakowski S, et al. Molecular Psychiatry. 2005;10(1):105-116.

Gender Differences In Immediate Memory In Bipolar Disorder.

Method: 86 remitted patients with BD, type 1, (36 male and 50 female) and 46 healthy participants (21 male and 25 female) on Tasks of general intellectual ability Memory encoding, recognition and retrieval, response inhibition and executive function (abstraction and perseveration). The impact of illness severity in patients was assessed using the global assessment of functioning (GAF).
MF
D. Carrus, T. Christodoulou, M. Hadjulis, M. Haldane, A. Galea, A. Koukopoulos, V. Kumari and S. Frangou (2010). Gender differences in immediate memory in bipolar disorder. Psychological Medicine, 40, pp 1349-1355 doi:10.1017/S0033291709991644

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Immune Function
Bipolar disorder (both mania and depression) is associated with increased production of proinflammatory cytokines
IL-8 TNF- IL-6 C-reactive protein

IL-6 stimulation of the HPA axis; stimulation of cortisol

OBrien S, et al. J Affect Disord. 2006;90(2-3):263-267. Taylor V, MacQueen G. J Clin Psychiatry. 2006;67(7):1034-1014.

Sex-specific Cortisol Levels In Bipolar Disorder And Schizophrenia During Mental Challenge - Relationship To Clinical Characteristics And Medication.
Sex-specific cortisol levels in bipolar disorder and schizophrenia during mental challenge - relationship to clinical characteristics and medication. Steen NE, Lorentzen S, Barrett EA, Lagerberg TV, Hope S, Larsson S, Berg AO, Agartz I, Melle I, Berg JP, Andreassen OA. Psychosis Research Unit, Division of Mental Health and Addiction, Oslo University Hospital, Ullevl Hospital, P.O. Box 4956 Nydalen, 0424 Oslo, Norway; Acute Psychiatric Emergency Unit, Division of Mental Health and Addiction, Oslo University Hospital, Aker Hospital, P.O. Box 4959 Nydalen, 0424 Oslo, Norway.

M=M
Prog Neuropsychopharmacol Biol Psychiatry. 2011 Mar 17. [Epub ahead of print]
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The Role Of Gender In Single Vs Married Individuals With Bipolar Disorder.

The role of gender in single vs married individuals with bipolar disorder.
Lieberman DZ, Massey SH, Goodwin FK. Department of Psychiatry and Behavioral Sciences, George Washington University School of Medicine and Health Sciences, Washington, DC 20037, USA. [email protected]

Compr Psychiatry. 2010 Jul-Aug;51(4):380-5. Epub 2009 Dec 21.

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Burden of Male caregivers of patients with bipolar affective disorders.

Burden of caregivers of patients with bipolar affective disorders.
Bauer R, Gottfriedsen GU, Binder H, Dobmeier M, Cording C, Hajak G, Spiessl H.
University Medical Center Regensburg, Germany. [email protected]

Am J Orthopsychiatry. 2011 Jan;81(1):139-48. doi: 10.1111/j.19390025.2010.01081.x.

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Summary #1 Is sex important? Gender differences in bipolar disorder

No consistent gender differences have been found in a number of variables including rates of depressive episodes, Age polarity of onset, symptoms, severity of the illness, response to treatment and suicidal behaviour.

Unsurprisingly, however, perhaps the major distinction between men and women with bipolar disorder is the impact that reproductive life events, particularly childbirth, have on women with this diagnosis.
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Arianna Diflorio and Ian Jones International Review of Psychiatry 2010, Vol. 22, No. 5 : Pages 437-452

Summary #2
Bipolar Men

Bipolar Women