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Bipolar a complex disorder

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  • 1. Bipolar Disorder: A complex diagnosis E Timuçin Oral, MD Prof Psychiatry Istanbul Commerce University
 Department of Psychology
  • 2. X Galen X Soranus X Hippocrates X Aretaeus
  • 3. Aretaeus of Cappadocia (AD 81–138)
 Early description of complex conditions Named diseases: – Diabetes (“a flowing through a siphon”) – Heterocrania/hemicrania (“half skull”) – Koiliakos (“coeliac disease”) ! ! Defined phenomena: – Mania-melancholia – Bronchospasm – Asthma ! Marneros & Goodwin,Cambridge University Press, 2005. Aydemir & Malhi, Acta Neuropsychiatrica. 2007:19;62
  • 4. Aretaeus of Cappadocia (AD 81–138) ‘‘I think that melancholia is the beginning and a part of mania… 
 The development of mania is really a worsening of the disease rather than a change into another... 
 The symptoms [of melancholia] are not unclear: [the melancholics] are either quiet or dysphoric, sad or apathetic. Additionally, they could be angry without reason and suddenly awake in panic” Marneros & Goodwin,Cambridge University Press, 2005 ARETAEUS of Cappadocia (fl. ca A.D. 50). Libri septem - RUFUS of Ephesus (fl. 1st century A.D.) De corporis humani partium appellationbus libri tres. in Latin by Junius Paulus Crassus (ca 1500-75). Venice: Giunta Press, 1552.
  • 5. Problems in diagnosing BPD: 
 “Cross-sectional & longitudinal”
  • 6. Problems in diagnosing BPD: 
 “Cross-sectional evaluation” Patients more likely
 to present with symptoms of depression Unipolar/bipolar depression? Mixed Symptoms Symptom overlap
  • 7. Depressive episodes and symptoms predominate in first-episode BD-I M-type (mania, hypomania, psychosis) Judd 2002
 (n=146) D-type (depression, dysthymia,
 dysphoric mixed states) Post 2003
 (n=258) Total Morbidity from 
 D-type symptoms is approximately 
 3 times greater than from M-type symptoms Joffe 2004
 (n=138) Paykel 2004
 (n=204) Baldessarini 2010
 (n=303) Overall, 5 studies
 (n=1049) Total morbidity = 54% 0 25 50 75 100 Time ill (%) Baldessarini Bipolar Disord. 2010;12:264. .
  • 8. Reclassifying major depressive
 episodes into a bipolar spectrum 50,0 37,5 Patients (%) 33.8% bipolar spectrum 25,0 12,5 0,0 Bipolar I
 (n=25) Reclassification using Semi-structured 
 Interview for Depression (SID) Bipolar II
 (n=107) Bipolar III
 (n=5) Recurrent depressive
 (n=174) Single episode
 (n=94) SID subtype Cassano Psychopathology. 1989;22:278.
  • 9. Bipolar disorder in patients with a major depressive episode: BRIDGE study DSM-IV criteria
 16% (903 patients) met criteria for bipolar disorder Bipolar specifier 
 47% (2647 patients) met criteria for bipolar disorder 53% MDD N=5635 Bipolar I disorder Bipolar II disorder Angst Arch Gen Psychiatry. 2011;68;791.
  • 10. Independent risk factors for bipolar disorder (DSM-IV-TR): BRIDGE study ≥2 Prior mood episodes Hypomania/mania in first-degree relatives Age at first psychiatric symptoms <30 y Current depressive episode ≤1 mo Mood lability with antidepressants Current mixed state Current psychotic features History of suicide attempts Seasonality of mood episodes Current atypical depression Current anxiety disorder Borderline personality disorder Current substance use disorder Female Manic/hypomanic with antidepressants 0 0.5 1.0 1.5 2.0 2.5 3.0 3.5 4.0 4.5 Odds ratio 903 patients with bipolar disorder (BP I: 685; BP II: 218) Angst Arch Gen Psychiatry. 2011;68;791.
  • 11. Bipolar vs unipolar depression:
 differentiating characteristics Bipolar Unipolar History of mania or hypomania Yes No Temperament Cyclothymic Dysthymic Sex ratio Equal Women > men Age at onset Teens, 20s, and 30s 30s, 40s, 50s Onset of episode Often abrupt More insidious Number of episodes Numerous Fewer Postpartum episodes More common Less common Psychotic episodes Psychomotor activity More common Retardation > agitation Less common Agitation > retardation Sleep Hypersomnia > insomnia Insomnia > hypersomnia Family history of BPD High Low Family history of UPD High High Adapted by Dunner D. with permission from: Akiskal J Affect Disord. 2005;84:107.
  • 12. Melancholia, by Dürer Melancholia, by Cranach
  • 13. Problems in diagnosing BPD: “Longitudinal evaluation” Delayed diagnosis Initial diagnosis can take ≥10 years Hirschfeld J Clin Psychiatry. 2003;64:161.
  • 14. Bipolar disorder: 
 age at onset predicts initial polarity 80 Depression 72% Mania Frequency (%) 70 P=0.001* 60 55.5% 50 40 30 20 10 Early AAO Intermediate AAO (< 20 years) (20-39 years) *Type of first episode (early AAO vs intermediate AAO) AAO, age at onset
 Biffin Acta Neuropsych. 2009;21:191.
  • 15. Problems in diagnosing BPD: 
 “Cross-sectional evaluation” “Missed” diagnosis 1/3 of patients are misdiagnosed Hirschfeld J Clin Psychiatry. 2003;64:161.
  • 16. Why is it important to get the
 diagnosis right? ! Misdiagnosis associated with ineffective treatment – worse outcome ! Potential risk of antidepressant switching ! Treatment approaches are different Perlis Am J Manag Care. 2005;11:S271; Singh Psychiatry. 2006;3:57; 
 Marcus Psychiatr Serv. 2009;60:617; Awad Prim Care Comp J Clin Psychiatry. 2007;9:195. !
  • 17. Costs associated with potential misdiagnosis of bipolar disorder Pharmacy Outpatient Emergency room Inpatient Annual direct costs per patient (US$ 2004) 10000 7500 5000 2500 54% P<0.01 30% 0 Potentially misdiagnosed (n=94) Correctly diagnosed (n=2398) Kamat AMCP. 2007.
  • 18. Problems in diagnosing BPD: 
 “Cross-sectional evaluation” Psychotic symptoms Mixed symptoms
  • 19. Proposed three-dimensional model of mood-psychotic disorders Lifetime Mania Bipolar II Bipolar I Schizoaffective disorder, Bipolar Cyclothymia Schizophrenia Subclinical BP Lifetime Psychosis Minor depression Schizophrenia Lifetime Depression Major depression Schizoaffective disorder, Depressive Altınbaş Nöropsikiyatri Arşivi. 2011;48:167.
  • 20. Painting “Mania" Florencio Yllana Rybakowski J Affect Disord. 2011;128:319.
  • 21. Mixed states vs pure mania in the EMBLEM study: outcome at 24 months Pure mania Mixed episodes Patients (%) 70 53 * 35 18 0 Relapse Recurrence Remission Based on 771 French patients followed for 24 months; *P=0.006 Recovery Azorin BMC Psychiatry. 2009;9:33.
  • 22. Problems in diagnosing BPD: 
 “Cross-sectional evaluation” Residual 
 symptoms
  • 23. Subthreshold depressive symptoms in bipolar, unipolar and healthy subjects in remission 50 Healthy control Bipolar disorder MDD *** Patients (%) 40 * 30 20 * 10 0 d le te ilt es tion tion iety iety tom ms ms asis ight ight de arly oo dd ia la iviti gu uici x x to i e a to p ri Ins ta m we m of n act tard ia S gi c an c an sym ymp ymp ond d n e s A hi ia om d of ti s s l h ss ling Re om mn Ins an ss re yc oma tina atic ital poc o e ns s S p Lo s I e k n s P F In m Ge Hy De or te W in So tro as G 17-Item Hamilton Depression Rating Scale *P<0.05; ***P<0.000 Vieta J Affect Disord. 2008;107:169.
  • 24. Progression from unipolar depression to bipolar disorder Proportion without hypomania or mania 1.0 0.9 0.8 0.7 Time to either hypomania or mania Time to hypomania Time to mania 0.6 0.5 0 5 10 15 20 Years of Follow Up 25 30 Number of subthreshold hypomanic symptoms associated with onset of threshold mania or hypomania 550 patients with diagnosis of major depression 
 followed for mean of 17.5 years Fiedorowicz Am J Psychiatry. 2011;168:40
  • 25. Problems in diagnosing BPD: “Longitudinal evaluation” Rapid cycling Ineffective treatment = worse outcome, poor QoL
  • 26. Rapid cycling vs non-rapid cycling: course of illness Rapid Cyclers
 (n=86) Nonrapid Cyclers
 (n=872) p Mean age at onset (years) 26.31±10.24 28.21±10.30 0.04 Mean delay (years) 
 Symptom onset to current episode 
 20.38±11.88 
 15.90±10.92 
 0.0005 Illness progression, (%) 
 Episodes with free intervals 59.3 72.6 0.009 Stressors (current episode), (%) 83.7 89.6 0.09 First episode polarity, (%) 
 Depression 52.2 35.9 0.01 19±16.54 7.09±6.40 <0.0001 44.2 14 37.6 6.5 0.22 0.01 10.5 4.5 0.004 Mean previous episodes Suicide attempts, (%) Lifetime (at least 1) Past year (at least 1) 
 Previous hospitalisations, (%) 
 Multiple 
 Azorin CNS Spectrum. 2008;13:780.
  • 27. “Tree of Life”
 by Selen Şanlı
  • 28. Problems in diagnosing BPD: “Longitudinal evaluation” Comorbidities Almost the rule Severity, complications, worse outcome, poor QoL
  • 29. Comorbidities complicate diagnosis and management of bipolar disorder Complicates diagnosis and treatment Decreased QoL Impaired psychosocial functioning Comorbid condition Greater risk of depressive and mixed episodes, and suicidal behaviour Possible earlier age 
 of onset More severe disease course Poorer treatment adherence Colom J Clin Psychiatry. 2000;61:549; Pollack Subst Abus. 2000;21:193; 
 Vieta Bipolar Disord. 2001;3:253; Keller J Clin Psychiatry. 2006;67(suppl 1);5.
  • 30. Time to remissiona (weeks) Anxiety symptoms delay time to remission in patients with bipolar I disorder No anxiety Anxiety Log rank=1.45 
 df=1, P=0.29 70 Log rank=2.95
 df=1, P=0.09 53 35 Log rank=4.37
 df=1, P=0.04 18 0 n=23 n=7 Manic n=24 n=11 n=18 Depressed n=9 Mixed Polarity treated in acute phase aBased on Kaplan-Meier survival analysis; Anxiety-related correlates included history of panic attacks, diagnosis of lifetime threshold or sub-threshold anxiety disorder, baseline Hamilton Rating Scale for Depression (HAM-D) psychic and somatic anxiety Feske Am J Psychiatry. 2000;157:956.
  • 31. Problems in diagnosing BPD: “Longitudinal evaluation” Switching
  • 32. “Illusion of Rising”
 by Tamer Ertuna
  • 33. Revised DSM-5 criteria for mood disorder 
 Mixed features ! Full criteria for manic or hypomanic episode, plus 2–3 of the following symptoms nearly every day for at least
 1 week: – – – – – – Depressed/down Decreased interest or pleasure Psychomotor retardation Fatigue Worthlessness/guilt Death/suicide ! Full criteria for major depressive episode, plus 2–3 of the following nearly every day for at least 1 week – – – – – – – – Expansive or irritable Grandiose Increased/pressured speech Flight of ideas Increased/excessive involvement in activities with high potential for painful consequences Increased goal-directed activity Increased energy Decreased need for sleep American Psychiatric Association. http://www.dsm5.org/ProposedRevisions/Pages/proposedrevision.aspx?rid=428. 
 Accessed April 20, 2010.
  • 34. Bipolar disorder: a complex diagnosis
  • 35. Bipolar disorder: a complex diagnosis Psychotic symptoms ! Delusions ! Hallucinations Manic mood and behaviour ! Delusions ! Euphoria ! Grandiosity ! Pressured speech ! Impulsivity ! Excessive libido ! Recklessness ! Social intrusiveness ! Diminished need for sleep Cognitive symptoms ! Racing thoughts ! Distractability ! Disorganisation ! Inattentiveness Dysphoric or negative
 mood and behaviour ! Depression ! Anxiety ! Irritability ! Hostility ! Violence or suicide
  • 36. Summary ! Bipolar disorder is a chronic, frequent and debilitating illness ! Although it is one of the well- and first-known disorders, it is still misdiagnosed frequently ! Appropriate diagnosis is the first step in choosing the best treatment available ! Rational psychopharmacology is a sine qua non for prevention and is possible
  • 37. Questions?