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CANMAT/ISBD Guidelines for Bipolar Disorder: 
A Constant Evolution 
2013 Update 
International Society 
for Bipolar Disord...
Disclosures 
Honoraria, consultants fees or research grants received 
from: 
• AstraZeneca 
• BMS 
• Otsuka 
• Merck 
• Li...
Guidelines for the Management of Patients 
with Bipolar Disorder: Previous Versions 
2005 2007 Update 2009 Update 2013 Upd...
Contributing Authors 
• Lakshmi N Yatham 
• Sidney H Kennedy 
• Sagar V Parikh 
• Ayal Schaffer 
• Serge Beaulieu 
• Marti...
Clinical Focus Areas: 2013 Guidelines 
Section 1 Introduction 
Foundations of 
management 
Section 2 
Section 3 Acute mana...
Levels of Evidence & Treatment Recommendations 
Meta-analysis or replicated 
double-blind (DB), 
randomized controlled tri...
Acute Management of Bipolar Mania 
2013 Update 
International Society 
for Bipolar Disorders 
Canadian Network for Mood an...
Management of Acute Mania: 
What’s New in 2013 
• Remains largely unchanged 
• Lithium, valproate, and several AAPs contin...
Pharmacological Treatment of Manic Episodes 
Assess safety/functioning 
Establish treatment setting 
D/C antidepressants 
...
Pharmacological Treatment of Acute Mania 
1st Line 2nd Line 3rd Line 
• Carbamazepine 
• Carbamazepine ER 
• ECT 
• Halope...
Acute Management of Bipolar Depression 
2013 Update 
International Society 
for Bipolar Disorders 
Canadian Network for Mo...
Management of Bipolar Depression 
What’s New in 2013 
• Lithium, lamotrigine, and quetiapine monotherapy, and 
olanzapine ...
Algorithm for the Management of Bipolar I Depression 
Assess safety/functioning 
Behavioural strategies/rhythms 
Psychoedu...
Pharmacological Treatment of Acute Bipolar I Depression 
1st Line 2nd Line 3rd Line 
• Lithium 
• Lamotrigine 
• Quetiapin...
Clinical Questions and Controversies 
What is the role of 
antidepressants in patients 
with bipolar depression?
What is the role of antidepressants in 
patients with bipolar depression? 
• Role remains one of most controversial areas ...
Conclusions & Recommendations 
Role of Antidepressants in Patients With Bipolar Depression 
1. SSRIs (other than paroxetin...
Maintenance Therapy for Bipolar 
2013 Update 
International Society 
for Bipolar Disorders 
Canadian Network for Mood and ...
Maintenance Treatment of Bipolar Disorder 
What’s New in 2013 
• Lithium, lamotrigine, valproate, olanzapine, quetiapine, ...
Maintenance Therapy for Bipolar Disorder: 
Adherence 
Positively associated with: 
• Higher satisfaction with 
medication ...
Maintenance Therapy for Bipolar Disorder: 
Adherence 
Non-adherence linked to: 
–  episode frequency (particularly depres...
Predictors of Remission & Recurrence 
Predictors of symptomatic remission & recovery1,2 
• Caucasian ethnicity 
• Previous...
Maintenance Pharmacotherapy of Bipolar Disorder 
1st Line 2nd Line 3rd Line 
• Carbamazepine 
• Paliperidone ER 
• Lithium...
Special Populations 
2013 Update 
International Society 
for Bipolar Disorders 
Canadian Network for Mood and Anxiety Trea...
Special Populations: Women 
PMS/PMDD 
• Premenstrual exacerbation may predict 
more symptomatic and relapse-prone 
phenoty...
Special Populations: Women 
Postpartum 
• Distinguishing bipolar depression from MDD challenging due 
to lack of specific ...
Special Populations: Older Patients 
• EMBLEM study: Older patients with acute bipolar 
mania ⁄ mixed had history of more ...
Special Populations: 
Patients with Comorbid Conditions 
• CANMAT Comorbidity Task Force Report published in 2012 
– Provi...
Bipolar II Disorder 
2013 Update 
International Society 
for Bipolar Disorders 
Canadian Network for Mood and Anxiety Trea...
Pharmacological Treatment of 
Acute Bipolar II Depression 
1st Line 2nd Line 3rd Line 
• Quetiapine 
• Quetiapine XR 
• Li...
Maintenance Treatment of 
1st Line 2nd Line 3rd Line 
Not recommended 
Gabapentin 
• Lithium 
• Lamotrigine 
• Quetiapine ...
Clinical Questions and Controversies 
Is cognitive dysfunction an 
issue in patients with BD II?
Is cognitive dysfunction an issue in 
patients with BD II? 
• Persistent cognitive dysfunction is common and 
debilitating...
Clinical Questions and Controversies 
Do clinical features of 
depressive episodes inform 
treatment decisions in BD II?
Do clinical features of depressive episodes 
inform treatment decisions in BD II? 
• Mixed hypomanic symptoms are common d...
What’s New in the Treatment of Bipolar Disorder? 
2013 Update 
International Society 
for Bipolar Disorders 
Canadian Netw...
What’s New in the 2013 Update? 
Acute Treatment Recommendations 
New recommendations 
Phase of illness New 1st Line Option...
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CANMAT/ISBD Guidelines for Bipolar Disorder: A Constant Evolution

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CANMAT/ISBD Guidelines for Bipolar Disorder: A Constant Evolution, presented by Dr. Roumen Milev

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CANMAT/ISBD Guidelines for Bipolar Disorder: A Constant Evolution

  1. 1. CANMAT/ISBD Guidelines for Bipolar Disorder: A Constant Evolution 2013 Update International Society for Bipolar Disorders Dr. Roumen Milev, MD, PhD, FRCPsych, FRCPC, Professor of Psychiatry and Psychology, Head, Department of Psychiatry, Queens University, Kingston, On, Canada Seoul, 19 March 2014
  2. 2. Disclosures Honoraria, consultants fees or research grants received from: • AstraZeneca • BMS • Otsuka • Merck • Lilly • Pfizer • Lundbeck • Sunovion • Valeant
  3. 3. Guidelines for the Management of Patients with Bipolar Disorder: Previous Versions 2005 2007 Update 2009 Update 2013 Update Yatham et al. Bipolar Disord 2005;7:5–69 Yatham et al. Bipolar Disord 2006;8:721–739 Purpose of 2013 update Yatham et al. Bipolar Disord 2009;11:225–255 Yatham et al. Bipolar Disord 2013;15:1-44 • Review new evidence and add previously unpublished material to the guidelines (in conjunction with the previous publications) • Ensure that the CANMAT guidelines for treatment of bipolar disorder remain current and useful for the practicing clinician
  4. 4. Contributing Authors • Lakshmi N Yatham • Sidney H Kennedy • Sagar V Parikh • Ayal Schaffer • Serge Beaulieu • Martin Alda • Claire O’Donovan • Glenda MacQueen • Roger S McIntyre • Verinder Sharma • Arun Ravindran • L Trevor Young • Roumen Milev • David J Bond • Benicio N Frey • Benjamin I Goldstein • Beny Lafer • Boris Birmaher • Kyooseob Ha • Willem A Nolen • Michael Berk
  5. 5. Clinical Focus Areas: 2013 Guidelines Section 1 Introduction Foundations of management Section 2 Section 3 Acute management of bipolar mania Section 4 Acute management of bipolar depression Section 5 Section 6 Section 7 Section 8 Maintenance therapy for bipolar disorder Special populations Acute and maintenance management of bipolar II disorder Safety and monitoring Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  6. 6. Levels of Evidence & Treatment Recommendations Meta-analysis or replicated double-blind (DB), randomized controlled trial (RCT) that includes a placebo condition Level 1 At least one DB-RCT with placebo or active comparison condition Level 2 Prospective uncontrolled trial with 10 or more subjects Level 3 Anecdotal reports or expert opinion Level 4 Level 1 or Level 2 evidence plus clinical support for efficacy and safety 1st Line Level 3 evidence or higher plus clinical support for efficacy and safety Level 4 evidence or higher plus clinical support for efficacy and safety Level 1 or Level 2 evidence for lack of efficacy Not Recommend Evidence Criteria Treatment Recommendation 2nd Line 3rd Line Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  7. 7. Acute Management of Bipolar Mania 2013 Update International Society for Bipolar Disorders Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Bipolar Disord. 2013 Feb;15(1):1-44
  8. 8. Management of Acute Mania: What’s New in 2013 • Remains largely unchanged • Lithium, valproate, and several AAPs continue to be 1st line treatment ER = extended release Added 1st line options • Monotherapy: • asenapine, paliperidone ER, divalproex ER • Adjunctive therapy: • asenapine Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  9. 9. Pharmacological Treatment of Manic Episodes Assess safety/functioning Establish treatment setting D/C antidepressants Rule out medical causes D/C caffeine, alcohol and illicit substances Behavioural strategies/rhythms, psychoeducation Step 1 Review general principles & assess medication status Step 2 + Initiate/optimize, check compliance No Response Step 3 Add-on or switch therapy Lithium or DVP Atypical antipsychotic On 1st line agent 2-drug combination (Li or DVP + AAP) Add or switch to AAP Add or switch to Li or DVP Replace one or both agents with other 1st line agents Consider adding or switching to 2nd or 3rd line agent or ECT Replace one or both agents with other 1st line agents Step 4 Add-on or switch therapy Not on medication or 1st line agent No Response Step 5 No Response Add-on novel or experimental agents Consider adding novel or experimental agent Initiate Li, DVP, AAP or 2-drug combination D/C = discontinue; Li = lithium; DVP = divalproex; AAP = atypical antipsychotic; ECT: electroconvulsive therapy Novel/experimental agents: zotepine, levetiracetam, phenytoin, mexiletine, omega-3-fatty acids, calcitonin, rapid tryptophan depletion, allopurinol, amisulpride, folic acid, memantine Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  10. 10. Pharmacological Treatment of Acute Mania 1st Line 2nd Line 3rd Line • Carbamazepine • Carbamazepine ER • ECT • Haloperidol • Lithium + divalproex Not recommended Gabapentin, topiramate, lamotrigine, verapamil, tiagabine, risperidone + carbamazepine, olanzapine + carbamazepine • Lithium • Divalproex • Divalproex ER • Olanzapine* • Risperidone • Quetiapine • Quetiapine XR • Aripiprazole • Ziprasidone • Asenapine • Paliperidone ER • Lithium or divalproex + • Risperidone • Quetiapine • Olanzapine • Aripiprazole • Asenapine *given the metabolic side effects, use should be carefully monitored †not yet commercially available ECT = electroconvulsive therapy; XR or ER = extended release • Chlorpromazine • Clozapine • Oxcarbazepine • Tamoxifen • Cariprazine† • Lithium or divalproex + haloperidol • Lithium + carbamazepine • Adjunctive tamoxifen Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  11. 11. Acute Management of Bipolar Depression 2013 Update International Society for Bipolar Disorders Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Bipolar Disord. 2013 Feb;15(1):1-44
  12. 12. Management of Bipolar Depression What’s New in 2013 • Lithium, lamotrigine, and quetiapine monotherapy, and olanzapine + SSRI, and lithium or divalproex + SSRI/bupropion remain 1st line options • New treatment algorithm devised Added 2nd line options • Luradisone monotherapy • Lurasidone or lamotrigine + lithium or divalproex Not recommended • Monotherapy: ziprasidone • Adjunctive therapy: ziprasidone, levetiracetam SSRI = selective serotonin reuptake inhibitor Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  13. 13. Algorithm for the Management of Bipolar I Depression Assess safety/functioning Behavioural strategies/rhythms Psychoeducation Step 1 Review general principles & assess medication status Step 2 + Initiate/optimize, check compliance Li OLZ No Response On OLZ, RIS, ARI or ZIP DVP = divalproex; OLZ = olanzapine; RIS = risperidone; ARI = aripiprazole; ZIP = ziprasidone; SSRI = selective serotonin reuptake inhibitor; BUP = bupropion; Li = lithium; LAM = lamotrigine; QUE = quetiapine; ECT = electroconvulsive therapy +SSRI* Li+DVP Add SSRI*/BUP or add/switch to Li , LAM or QUE Add SSRI*/BUP or switch Li or DVP to LAM or QUE Replace one or both agents with alternate 1st or 2nd line agents Step 3 Add-on or switch therapy Li or DVP +SSRI*/BUP Add SSRI*/BUP or add/switch to LAM or QUE Switch to QUE, QUE+SSRI*, Li, Li+SSRI*/BUP or LAMa LAM Add/switch to Li or QUE No Response Step 4 Add-on or switch therapy Switch Li or DVP to QUE or OLZ or switch SSRI*/BUP to LAMb On 1st line agent Step 5 Add-on or switch therapy Consider ECT, 3rd line agents and novel or experimental options No Response On DVP QUE Add SSRI, Li or LAM or switch to Li, LAM or OLZ+SSRI* Add SSRI*, Li or LAM or switch to Li, LAM or QUE Not on medication *Except paroxetine aOr switch the SSRI to another SSRI bOr switch the SSRI or BUP to another SSRI or BUP Novel/experimental agents: adjunctive pramipexole, eicosapentaenoic acid (EPA), riluzole, topiramate, N-acetyl cysteine (NAC), ketamine, armodafinil, chronotherapy Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  14. 14. Pharmacological Treatment of Acute Bipolar I Depression 1st Line 2nd Line 3rd Line • Lithium • Lamotrigine • Quetiapine • Quetiapine XR • Lithium or divalproex + SSRI† • Olanzapine + SSRI† • Lithium + divalproex • Lithium or divalproex + bupropion • Divalproex • Lurasidone • Quetiapine + SSRI† • Adjunctive modafinil • Lithium or divalproex + lamotrigine • Lithium or divalproex + lurasidone *Could be used 1st or 2nd line in certain situations; †except paroxetine SSRI = selective serotonin reuptake inhibitor; MAOI = monoamine oxidase inhibitor; ECT = electroconvulsive therapy; AAP = atypical antipsychotic; TCA = tricyclic antidepressant • Carbamazepine • Olanzapine • ECT* • Lithium + carbamazepine • Lithium + pramipexole • Lithium or divalproex + venlafaxine • Lithium + MAOI • Lithium or divalproex or AAP + TCA • Lithium or divalproex or carbamazepine + SSRI† + lamotrigine • Quetiapine + lamotrigine Not recommended Gabapentin, aripiprazole, ziprasidone, adjunctive ziprasidone, adjunctive levetiracetam Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  15. 15. Clinical Questions and Controversies What is the role of antidepressants in patients with bipolar depression?
  16. 16. What is the role of antidepressants in patients with bipolar depression? • Role remains one of most controversial areas in psychiatry • Antidepressants (ADs) are the most common treatments for bipolar depression1,2 – Clinicians believe ADs are effective based on clinical experience • However, growing body of clinical trial data not consistent in supporting role3-6 – Meta-analysis (n= 15 RCTs) evaluating ADs (primarily adjunctive therapy) for acute bipolar depression7 • Strong trend for superiority of ADs vs. placebo (p=0.06) • ADs not associated with significant risk of manic switch – Most negative studies of ADs for bipolar depression to date used paroxetine6,8,9 AD= antidepressant; RCT = randomized controlled trial 1. Baldessarini et al. Psychiatr Serv 2007;58:85-91; 2. Schaffer et al. J Clin Psychiatry 2007;68:1785-92; 3. Brown et al. J Clin Psychiatry 2006;67:1025-33; 4. Tohen et al. Arch Gen Psychiatry 2003;60:1079-88; 5. Sachs et al. N Engl J Med 2007;356:1711-22; 6. Shelton et al. J Clin Psychiatry 2004;65:1715-9; 7. Sidor et al. J Clin Psychiatry 2011;72:156-67; 8. McElroy et al. J Clin Psychiatry 2010;71:163-74; 9. Nemeroff et al. Am J Psychiatry 2001;158:906-12
  17. 17. Conclusions & Recommendations Role of Antidepressants in Patients With Bipolar Depression 1. SSRIs (other than paroxetine) and bupropion could be used as 1st line treatments in conjunction with mood stabilizer for acute short-term treatment 2. Avoid use of TCAs and venlafaxine as they are associated with increased risk of manic switch 3. Antidepressants should not be used for current mixed episode or in patients with history of rapid cycling 4. Monotherapy with antidepressants NOT recommended SSRI = selective serotonin reuptake inhibitor; TCA: tricyclic antidepressant Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  18. 18. Maintenance Therapy for Bipolar 2013 Update International Society for Bipolar Disorders Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Bipolar Disord. 2013 Feb;15(1):1-44
  19. 19. Maintenance Treatment of Bipolar Disorder What’s New in 2013 • Lithium, lamotrigine, valproate, olanzapine, quetiapine, aripiprazole, and risperidone long-acting injection (LAI), and ziprasidone continue to be 1st line options Added 3rd line options • Monotherapy: asenapine • Adjunctive therapy: asenapine Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  20. 20. Maintenance Therapy for Bipolar Disorder: Adherence Positively associated with: • Higher satisfaction with medication • Monotherapy • College degree • Fear of relapse Negatively associated with: • Illness factors • Substance use • Previous hospitalization • Psychotic symptoms • Reduced insight into illness • Medication factors • Side effects • No perceived daily benefit • Difficulties with medication routines • Patient attitudes • Belief that medications are unnecessary • Negative attitudes toward medications • Perceived change in appearance • Perceived interference with life goals 1. Devulapalli et al. Psychopharmacol Bull 2010;43:5-14; 2. Sajatovic et al. Compr Psychiatry 2009;50:100-7; 3. Gonzalez-Pinto et al. Pharmacopsychiatry 2010;43:263-70; 4. Hou et al. European psychiatry 2010;25:216-9; 5. Lang et al. J Med Econ 2011;14:217-26; 6. Bates et al. PCC J Clin Psychiatry 2010;12; 7. Gianfrancesco et al. Annals Clin Psychiatry 2009;21:3-16
  21. 21. Maintenance Therapy for Bipolar Disorder: Adherence Non-adherence linked to: –  episode frequency (particularly depressive episodes) –  risk of hospitalization –  risk of emergency room visits –  absenteeism –  short-term disability –  workers’ compensation 1. Lang et al. J Med Econ 2011;14:217-26; 2. Gutierrez-Rojas L et al. J Affect Disord 2010;127:77-83; 3. Bagalman E et al. J Occup Environ Med 2010;52:478-85; 4. Lage et al. Ann Gen Psychiatry 2009;8:7; 5. Hassan et al. AJHP 2009;66:358-65
  22. 22. Predictors of Remission & Recurrence Predictors of symptomatic remission & recovery1,2 • Caucasian ethnicity • Previous manic episode • Good social functioning* • Outpatient treatment • Being neither satisfied nor dissatisfied with life Factors with increased risk for non-stabilization/recurrence3,4 • Recent substance use disorder history • Early life verbal abuse • Female gender • Late onset of first depressive episode • Atypical features (mood-incongruent psychotic symptoms) • Inter-episodic residual symptomatology • Rapid cycling *no work or social impairment, living independently or with family 1. Dikeos et al. World J Biol Psychiatry 2010;11:667-76; 2. Haro et al. Eur Neuropsychopharmacol 2011;21:287-93; 3. Gao et al. Psychopharmacol Bull 2010;43:23-38; 4. Pfennig et al. Bipolar Disord 2010;12:390-6
  23. 23. Maintenance Pharmacotherapy of Bipolar Disorder 1st Line 2nd Line 3rd Line • Carbamazepine • Paliperidone ER • Lithium + divalproex • Lithium + carbamazepine • Lithium or divalproex + olanzapine • Lithium + risperidone • Lithium + lamotrigine • Olanzapine + fluoxetine Not recommended Gabapentin, topiramate or antidepressants, adjunctive flupenthixol • Lithium • Lamotrigine* • Divalproex • Olanzapine† • Quetiapine • Risperidone LAI‡ • Aripiprazole ‡ • Lithium or divalproex + • Quetiapine • Risperidone LAI • Aripiprazole • Ziprasidone • Asenapine • Adjunctive • Phenytoin • Clozapine • ECT • Topiramate • Omega-3-fatty acids • Oxcarbazepine • Gabapentin • Asenapine *limited efficacy in preventing mania †given the metabolic side effects, use should be carefully monitored ‡mainly for prevention of mania LAI = long acting injection; ECT = electroconvulsive therapy Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  24. 24. Special Populations 2013 Update International Society for Bipolar Disorders Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Bipolar Disord. 2013 Feb;15(1):1-44
  25. 25. Special Populations: Women PMS/PMDD • Premenstrual exacerbation may predict more symptomatic and relapse-prone phenotype1 • Moderate-to-severe PMS⁄PMDD more frequent in women with BD II than healthy controls2 • Women with chronic pelvic pain and endometriosis more likely to have BD and poorer QoL than women with nonendometriosis pelvic pain3 PMS: premenstrual syndrome; PMDD: premenstrual dysphoric disorder; QoL: quality of life 1. Dias et al. Am J Psychiatry 2011;168:386-94; 2. Choi et al. J Affect Disord 2011;129: 313-6; 3. Kumar et al. J Obstet Gynaecol Can 2011;33:1141-5;
  26. 26. Special Populations: Women Postpartum • Distinguishing bipolar depression from MDD challenging due to lack of specific screening instruments1 • Hypomanic symptoms common in early puerperium, but often overlooked leading to misdiagnosis of MDD2 Menopause • Menopausal transition associated with significantly more visits due to depressive symptoms and fewer euthymic visits3 MDD: major depressive disorder 1. Chessick, Dimidjian. Arch Womens Ment Health 2010;13:233-48; 2. Sharma et al. Am J Psychiatry 2009;166:1217-21; 3. Marsh et al. J Psychiatr Res 2009;43:798-802
  27. 27. Special Populations: Older Patients • EMBLEM study: Older patients with acute bipolar mania ⁄ mixed had history of more rapid cycling, fewer suicide attempts, and less severe manic and psychotic symptoms, but no difference in depressive symptomatology1 • Compared to age-matched controls, older patients with bipolar disorder have higher prevalence of diabetes mellitus, atopic diseases, smoking, unfavourable social functioning, cognitive dysfunction2-6 • Data assessing pharmacotherapy specifically in older patients with bipolar disorder remain scarce 1. Oostervink et al. J Affect Disord 2009;116:176-83; 2. Tsai et al. Am J Geriatr Psychiatry 2009;17:1004-11; 3. Gildengers et al. Bipolar Disord 2009;11:744-52; 4. Shimizu et al. Psychopathology 2009;42:318-24; 5. Delaloye et al. Int J Geriatr Psychiatry 2011;26:1309–18; 6. Schouws et al. Am J Geriatr Psychiatry 2009;17:508-15
  28. 28. Special Populations: Patients with Comorbid Conditions • CANMAT Comorbidity Task Force Report published in 2012 – Provides detailed information on management of patients with mood disorders and comorbid psychiatric and medical conditions • ~⅓ of patients also have ≥1 general medical conditions1 – Many medical issues associated with worse bipolar disorder course • Rates of psychiatric comorbidity in patients with bipolar disorder: – Anxiety disorder, 46%2 – Substance use disorder, 67%2 – ADHD, 18%3 ADHD: attention deficit/hyperactivity disorder 1. Perron et al. J Clin Psychiatry 2009;70:1407-15; 2. Gao et al. Int J Clin Pract 2010;64;336-44; 3. McIntyre et al. PCC J Clin Psychiatry 2010;12:e1-7
  29. 29. Bipolar II Disorder 2013 Update International Society for Bipolar Disorders Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Bipolar Disord. 2013 Feb;15(1):1-44
  30. 30. Pharmacological Treatment of Acute Bipolar II Depression 1st Line 2nd Line 3rd Line • Quetiapine • Quetiapine XR • Lithium • Lamotrigine • Divalproex • Lithium or divalproex + antidepressants • Lithium + divalproex • Atypical antipsychotics + antidepressants • Antidepressant monotherapy (primarily for those with infrequent hypomanias) • Switch to alternate antidepressant • Quetiapine + lamotrigine • Adjunctive ECT • Adjunctive NAC • Adjunctive T3 ECT: electroconvulsive therapy; NAC: N-acetylcysteine; T3: triiodothyronine Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  31. 31. Maintenance Treatment of 1st Line 2nd Line 3rd Line Not recommended Gabapentin • Lithium • Lamotrigine • Quetiapine • Divalproex • Lithium or divalproex or AAP + antidepressant • Adjunctive quetiapine • Adjunctive lamotrigine Combination of two of: o Lithium, divalproex, or AAP: atypical antipsychotic; ECT = electroconvulsive therapy AAP • Carbamazepine • Oxcarbazepine • AAP • ECT • Fluoxetine Bipolar II Disorder Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  32. 32. Clinical Questions and Controversies Is cognitive dysfunction an issue in patients with BD II?
  33. 33. Is cognitive dysfunction an issue in patients with BD II? • Persistent cognitive dysfunction is common and debilitating – Lower performance scores in all cognitive domains compared to healthy controls1 – Cognitive impairment as severe as in BD I with exception of memory and semantic fluency BD: bipolar disorder 1. Bora et al. Acta Psychiatr Scand 2011;123:165-74
  34. 34. Clinical Questions and Controversies Do clinical features of depressive episodes inform treatment decisions in BD II?
  35. 35. Do clinical features of depressive episodes inform treatment decisions in BD II? • Mixed hypomanic symptoms are common during depressive episodes – Occur in 70% of patients with BD II vs. 66% of patients with BD I1 • Psychotic symptoms also common in BD II depression2 • Little information to guide treatment of psychotic depression in patients with BD II – Clinical experience and MDD studies suggest antipsychotics may be required • Either monotherapy (e.g., quetiapine) or combined with mood stabilizers BD: bipolar disorder; MDD: major depressive disorder 1. Goldberg et al. Am J Psychiatry 2009;166:173-81; 2. Mazzarini et al. J Affect Disord 2010;126:55-60
  36. 36. What’s New in the Treatment of Bipolar Disorder? 2013 Update International Society for Bipolar Disorders Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013 Yatham LN, Kennedy SH, Parikh SV, Schaffer A, Beaulieu S, Alda M, O'Donovan C, Macqueen G, McIntyre RS, Sharma V, Ravindran A, Young LT, Milev R, Bond DJ, Frey BN, Goldstein BI, Lafer B, Birmaher B, Ha K, Nolen WA, Berk M. Bipolar Disord. 2013 Feb;15(1):1-44
  37. 37. What’s New in the 2013 Update? Acute Treatment Recommendations New recommendations Phase of illness New 1st Line Options New 2nd Line Options New 3rd Line Options Acute mania asenapine monotherapy or adjunctive to lithium or divalproex, paliperidone ER, divalproex ER haloperidol cariprazine Bipolar I depression lurasidone, lamotrigine + lithium or divalproex, lurasidone + lithium or divalproex ECT: electroconvulsive therapy; NAC: N-acetylcysteine; T3: triiodothyronine; XR or ER = extended release ECT, quetiapine + lamotrigine Bipolar II depression quetiapine XR quetiapine + lamotrigine, adjunctive ECT, adjunctive NAC, adjunctive T3 Not recommended Bipolar 1 Depression: ziprasidone monotherapy or adjunctive, adjunctive levetiracetam Yatham LN, et al., Bipolar Disorder, 2013 Feb;15(1):1-44
  38. 38. Thank you!

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