Steven Bander, DO, FACOFP Bander Family Medical Center Wylie, Texas

Transcription

1 Bipolar Disorder: Lessons for Rural Physicians: Adjunctive Interventions for Maintaining Remission Steven Bander, DO, FACOFP Bander Family Medical Center Wylie, Texas

2 Disclosure Nothing to disclose

3 Objectives Recognize the importance of utilizing guideline recommendations during maintenance treatment of patients with bipolar disorder Develop a maintenance treatment plan for patients with bipolar disorder based on guidelines Systematically monitor effectiveness and safety of maintenance treatment

4 Epidemiology of Bipolar Disorder Lifetime prevalence rate is 0.7 to 1.6% Gender prevalence is equal for Bipolar I disorder Bipolar II and rapid cycling more common in women First degree relatives 24 times more likely to develop bipolar disorder Concordance rate 79% in MZ twins and 19% in DZ twins Average onset age 21

5 Bill J Bill J. is sent by his employer for a fitness-for-duty exam. He has been talking almost continuously for days, sexually propositioning his supervisees, and bursting into his boss office repeatedly with a plan to save the company. He has worked there for 12 years and generally been a good employee. There is no history of psychiatric illness. He talks non-stop during his interview with you and seems grandiose but not psychotic. States he really does not need sleep. His physical exam is essentially normal.

6 Patients With Bipolar Disorder Are Symptomatic for Almost Half of Their Lives Weeks asymptomatic Weeks manic/hypomanic Weeks depressed Weeks cycling/mixed 9% 6% 32% 53% N = years follow-up Judd LL, et al. Arch Gen Psychiatry. 2002;59:

7 Bipolar I Disorder: Diagnosis Single manic episode One manic or mixed episode (in patient s history) Recurrent Current Manic, Major Depressive, Mixed, or Hypomanic episode Previous Manic, Major Depressive, or Mixed episode Relapsing and remitting course Major Depressive Episodes have usually occurred but are not required for the diagnosis The mood symptoms are not better accounted for by a Psychotic Disorder including Schizoaffective Disorder Clear distinction between episodes and inter-episodic functioning Often well or at least much better between episodes

8 Clinical Features of Mania Hypomania Dysthymia Mania Euthymia Depression Behavioral Symptoms Grandiosity, Diminished need for sleep, Pressured Speech, Excessive Libido, Recklessness, Impulsivity, Hostility, Violence Affective Symptoms Depression, Anxiety, Euphoria, Irritability Psychotic Symptoms (Psychosis occurs in over 50% of manic episodes) Hallucinations, Delusions, Sensory Hyperactivity Cognitive Symptoms Racing Thoughts, Distractibility, Poor Insight, Disorganization, Confusion, Inattentiveness, Suicidal Thoughts Suicide and Bipolar disorder (More likely in depressive or mixed episode) 10-15% will complete suicide

9 Manic Episode Elevated, expansive, or irritable mood for 1 week 3 or more of the following, 4 if irritable mood: (DTRHIGH) Distractible Talkative or pressured speech Racing thoughts or flight of ideas Hyper-alert = decreased need for sleep Increased activity or psychomotor agitation Grandiose Hypersexual = risky acts Severe enough to cause: Marked impairment in functioning or Hospitalization (any duration of symptoms) or Psychotic features Symptoms are not due to: Substance or General medical condition

10 Differential Diagnosis: Mania General medical conditions Head trauma, Mass lesions, Post-CVA, MS, Hyperthyroidism, Cushing s, Huntington s disease, complex partial seizures Substance induced Corticosteroids, levodopa, Stimulants: amphetamine, cocaine, ephedrine, Drug or Alcohol withdrawal syndromes, Antidepressants, ECT, light therapy Schizophrenia, schizoaffective disorder Psychotic symptoms occur in absence of mood symptoms Borderline Personality Disorder Similarities: impulsivity, suicidal behavior, irritability, paranoid ideation Differences: enduring pattern, fear of abandonment, idealization/devaluation, identity disturbance, emptiness

11 Bipolar I and II: Frequency of Depressive Symptoms Mixed 13% Mixed 4.5% Depressed 67% Manic/ hypomanic 20% Depressed 93% Manic/ hypomanic 2.5% Bipolar I Patients with bipolar I disorder (n = 146) experienced mood symptoms 47.3% of the time during a 12.8-year follow-up period Depression 3.4-fold more frequent than mania Bipolar II Patients with bipolar II disorder (n = 86) experienced mood symptoms 54% of the time during a 13.4-year follow-up period Depression 37-fold more frequent than mania Judd LL, et al. Arch Gen Psychiatry. 2002;59: Judd LL, et al. Arch Gen Psychiatry. 2003;60:

12 Major Depressive Disorder Relapsing and remitting course May eventually become chronic Minimum duration two weeks Clear distinction between episodes and interepisodic function Often well or at least much better between episodes

13 Clinical Features of Depression Hypomania Dysthymia Mania Euthymia Depression Affective Symptoms Depressed mood (sad, down, blue) Reduced interest or pleasure Cognitive Symptoms Poor concentration/easy distraction Inappropriate guilt/self reproach Thoughts of death, dying, suicide Behavioral Symptoms Change in appetite Change in sleep pattern Reduced energy level Psychomotor agitation/retardation Suicide and Bipolar disorder (More likely in depressive or mixed episode) 10-15% will complete suicide

14 Clinical Features: Major Depression 5 or more of these for 2 weeks: (SIGECAPS) Depressed mood most of the day Sleep decreased or increased Interests decreased Guilt (excessive) or worthlessness Energy decreased Concentration decreased or indecisive Appetite change or weight change Psychomotor retardation or agitation Suicidal ideation or attempt

15 Differential Diagnosis: Depression Psychiatric Adjustment D/O Bereavement General Medical Hypothyroidism, Anemia Post-CVA, Post-MI Ca of head of pancreas Substance-Related Rx meds: steroids, b-blockers, a-methyldopa Alcohol or Benzodiazepine abuse Cocaine/amphetamine withdrawal

16 Clinical Features of Mixed Episode Hypomania Dysthymia Mania Euthymia Depression Full symptoms of manic and major depressive episodes for 1 week Severe enough to cause: Marked impairment in functioning Or Hospitalization Or Psychosis Symptoms are not due to: Substance General medical condition

17 Clinical Features of Rapid Cycling Hypomania Dysthymia Mania Euthymia Depression 4 or more mood episodes in 12 months Major depressive, manic, mixed, or hypomanic episodes Separated by: Remission for 2 months or Switch to opposite polarity

18 Clinical Features of Bipolar II Hypomania Dysthymia Mania Euthymia Depression Current or past Major Depressive episode Current or past Hypomanic episode Never a Manic or Mixed episode Not a primary psychotic disorder Clinically significant distress or impairment in functioning

19 Clinical Features of Hypomania Hypomania Dysthymia Mania Euthymia Depression Different from usual mood Clear change in functioning Observable by others Does not cause: Marked impairment in functioning Hospitalization Psychotic features Symptoms are not due to: Substance General medical condition

20 Hypomanic Episode Elevated or irritable mood for 4 days 3 or more of the following: (DTRHIGH) Distractible Talkative or pressured speech Racing thoughts or flight of ideas Hyper alert = decreased need for sleep Increased activity or psychomotor agitation Grandiose Hypersexual = risky acts

21 Co-morbid Psychiatric Conditions Alcohol and drug abuse/dependence Most common co morbid condition Worse prognosis Must treat concurrently Personality disorders Anxiety disorders ADHD

22 Always ask about mania before treating depression

23 Goals of Treatment Symptomatic Remission Full return of psychosocial functioning Prevention of relapses and recurrences J Clin Psychiatry 66:7 July 2005

24 Setting the Stage for Treatment Engage the patient in the Treatment Plan Discuss the Diagnosis Discuss the treatment options Engage appropriate significant others in the Treatment Plan With the consent of the patient Encourage the patient to keep a daily mood log Encourage the patient to engage in therapy Psychoeducational Cognitive Therapy 2005 J Clin Psychiatry 66:7 July

25 Evidence Based Treatment These recommendations for treating Bipolar Disorder are based on: TIMA Algorithm for Bipolar Texas Implementation of Medication Algorithms (TIMA) APA Treatment Guidelines for Bipolar American Psychiatric Association 32

26 Slide Please confirm this information is correct , 8/19/2011

27 Algorithm Mania Symptoms Treating Acute Hypomanic/Manic/Mixed Episodes of Bipolar I Disorder Monotherapy (Euphoric) Lithium, valproate, aripiprazole, quetiapine, risperdone, ziprazidone No response: olanzapine, carbamazepine Monotherapy (mixed) valproate, aripiprazole, risperdal, ziprazidone No response: olanzapine, carbamazepine

28 Algorithm If monotherapy fails (two drug combinations) lithium, valproate, or atypical antipsychotic Note: not two atypical antipsychotics and not aripiprazole or clozapine If partial or no response lithium, valproate, atypical antipsychotic, carbamazepine, oxcarbazepine, typical antipsychotic Note: not two atypical antipsychotics and not clozapine

29 Algorithm Depressive Symptoms Treating Acute Depressive Episodes in Patients with Bipolar I Disorder To begin this algorithm we must establish some key facts: A patient taking lithium (increase to 0.8 meq/l), or A patient is taking another antimanic medication, or Patient is not taking any antimanic medication and has a history of severe and/or recent mania The treatment step would be to provide the patient with an antimanic medication and lamotrigine

30 Algorithm Depressive Symptoms You may have a patient without a history of severe and/or recent mania and is not taking any antimanic medication The treatment step would be to provide the patient with lamotrigine

31 Algorithm Depressive Symptoms The previous 2 slides outlined Stage 1 of the TIMA algorithm for Treating Acute Depressive Episodes in Patients with Bipolar I Disorder If there was only partial or non-response to stage 1 interventions taper off any medications that need tapering and start a monotherapy of quetiapine or an olanzapine-fluoxetine combination

32 Algorithm Depressive Symptoms If there was only partial or non-response to stage 2 interventions and start a combination therapy of any two of the following medications lithium, lamotragine, quetiapine or an olanzapine-fluoxetine combination Consider consultation if this fails

33 FDA Approved Drugs FDA Approved Drugs for Mania Aripiprazole Carbamazepine Chlorpromazine Divalproex Lithium Olanzapine Quetiapine Risperidone Ziprasidone FDA Approved Drugs for Bipolar Depression Olanzapine-Fluoxetine Combination Quetiapine

34 Definition of a Mood Stabilizer Treats acute depression and/or mania Reduces risk of relapse of mania and/or depression Does not increase risk of mania Does not increase risk of depression

35 Rationale for lithium salts as the Mood Stabilizer of First Choice Track record (dating to 1960s) Evidence of efficacy Well-characterized tolerability and safety profiles Low cost Evidence of reduction of suicidal behavior

36 Lithium Carbonate FDA approved for acute mania and maintenance Workup Beta-HCG, BUN, creatinine, thyroid profile, EKG Serum levels Acute mania= meq/l Maintenance= meq/l Toxicity at above 1.5 meq/l

37 Lithium Carbonate Pregnancy First trimester: cardiac defects Toxicity Narrow therapeutic index Nausea, vomiting, blurred vision, vertigo, confusion, seizures, coma Lithium level increased by: Low serum sodium, Diuretics, ACE inhibitors, NSAID s Excreted by kidneys

38 Lithium: Adverse Effects Diuretics (e.g., thiazides) can reduce lithium clearance by as much as 25% -Preferentially eliminate Na+ NSAIDs can reduce lithium clearance. Worsens extrapyramidal syndromes produced by older antipsychotic drugs. Side Effects and their management Begin with dose decrease Tremor - propranolol Polyuria - amiloride Hypothyroidism levothyroxine -TSH every 6-12 months G.I. Distress - take with food, change to lithium citrate Cardiac: T-wave & conduction changes Mild cognitive impairment Transient acneiform eruptions Leukocytosis

39 Efficacy of Lithium: All Relapse Geddes JR, et al. Am J Psychiatry. 2004;161(2):

40 Valproic Acid Formulations Valproic acid Sodium valproate Divalproex sodium=combination of both Compared to lithium Faster onset of anti-manic effects Better for mixed episodes & rapid cycling Wide therapeutic window

41 Valproic Acid Side Effects and their management Elevated hepatic transaminases - monitor LFT s Rare hepatotoxicity Leukopenia - monitor WBC G.I. Distress - decrease dose, try divalproex Sedation - give more at bedtime Weight gain - diet & exercise Hair loss - zinc, selenium

42 Valproic Acid Pregnancy First trimester - neural tube defects, craniofacial abnormalities Therapeutic serum level mcg/ml Workup Beta-HCG, CBC + differential, liver function tests (LFT s)

43 Rationale for status of Divalproex Efficacy comparable to lithium Useful in patients who do not respond to or don t tolerate lithium More useful than lithium for patients with mixed affective states and significant substance abuse histories Vigorously marketed, without opposition, from

44 33 Shifts in Prescription of Lithium and Divalproex Market Share Total N: 20,638 Goodwin, et al. JAMA 2003;290:

45 Slide Will work on this graph to make it more appealing , 8/19/2011

46 Carbamazepine Side Effects Sedation, weight gain Dermatitis, rashes G.I. Distress Dizziness, ataxia, diplopia Leukopenia, LFT elevations Rare, but serious Agranulocytosis, aplastic anemia Exfoliative dermatitis (Stevens-Johnson syndrome) Hepatic failure

47 Carbamazepine Pregnancy First trimester - neural tube defects Drug-drug interactions Induces metabolism and decreases levels of: Carbamazepine (auto-induction), valproic acid, lamotrigine, oral contraceptives Therapeutic serum level 4-12 mcg/ml Workup CBC + differential, platelets, liver function tests

48 Lithium, Divalproex or Carbamazepine, Risk of Suicidal Behaviors 34 Advantage for Lithium vs. DVPX vs. CARB Suicide attempts: ER 1.8 ( ) * 1.4 ( ) Suicide attempts: Admission 1.7 ( ) * 2.9 ( ) * Suicide attempts: Death 2.7 ( ) * 1.5 ( ) Goodwin, et al. JAMA 2003;290:

49 Slide Is there a way to clarify this graph? Does it need to be clarified? Dr. Hall had confusion at first, but when explained it was clear , 8/19/2011

50 Lamotrigine Not effective in acute mania Lamotrigine is especially effective against depression (Bowden et al 2003) Effective for bipolar depression Serious side effect Stevens-Johnson syndrome Discontinue if rash occurs Use slow titration Drug-drug interactions Valproic acid inhibits metabolism & doubles serum concentration Carbamazepine induces metabolism and halves serum concentration

51 Second Generation Antipsychotic Safety and Tolerability Concerns Weight gain Sedation Diabetes Cardiac ± Akathisia ± Hyperprolactinemia Cerebrovascular (elders)

52 Olanzapine FDA approved for acute mania Side effects Sedation Weight gain Elevated hepatic transaminases

53 Quetiapine FDA approved for acute mania Side effects Sedation Orthostasis (during titration)

54 Risperidone FDA approved for acute mania Side effects: at higher doses Extrapyramidal symptoms Elevated serum prolactin

55 Antidepressants Use in bipolar depression Concurrent with mood stabilizer Some cause switch to mania Tricyclic antidepressants & venlafaxine Bupropion and paroxetine have low rate of switch to mania

56 Adjunctive medications Antipsychotics Use when psychosis is present Taper and discontinue when psychosis resolves Benzodiazepines Lorazepam, clonazepam Use in severe mania as a short term sedative

57 Electroconvulsive therapy Highly effective treatment Acute illness and maintenance treatment Indications Severe or refractory mania or depression Psychosis with depression or mania Patient cannot tolerate medication

58 Other Mood Stabilizers: Antipsychotics or Benzodiazepines Antipsychotics Including: olanzapine, haloperidol, risperidone, quetiapine, ziprasidone, and aripiprazole Primarily used for controlling acute mania. Clonazepam or Lorazepam Benzodiazepines may be given to control acute mania (often as an adjunct to treatment with an antipsychotic drug or other mood stabilizing drug, be cautious of disinhibition).

59 Combination Therapy Average Number of Medications in 258 Bipolar Outpatients Followed Up Prospectively for 1 Year % Number of Patients % 0 6.6% % 17.1% 12.0% 12.0% 6.6% 3.1% Total Number of Medications % 9 0.8% 10 Post RM, et al. J Clin Psychiatry. 2003;64(6):

60 Pros and Cons of Combination Therapy FOR 40% of patients do not respond to monotherapy Lower doses improved tolerability AGAINST Drug interactions Suboptimal dosing of both agents More complex treatment regimen Decreased adherence Increased side effects Cost Bowden 2004; Goodwin & Vieta 2005

61 Goal of Treatment: Mood Stabilization Hypomania Dysthymia Mania Euthymia Depression Mood stabilizers Effective in the acute treatment or stabilization of manic/mixed, hypomanic, and depressive episodes Do not induce alternate mood symptoms (ie, switch) Prevent against future relapse or recurrence of manic/mixed, hypomanic, or depressive symptoms or episodes

62 Visit Timelines First Week Third Week Monthly for at least 3 months Then Every 2-3 months thereafter When the patient has been stable for 4 to 6 months (engage the patient via phone or contact with non-physician clinicians)

63 Therapeutic Challenges No cure for bipolar disorder Noncompliance rate is high Symptom overlap among comorbid diagnoses Longer Term Efficacy Across symptom domains Definition of a mood stablizer Safety and tolerability

64 Managing Complex Medication Regimens Try to ensure that at least 1 medication is a mood stabilizer Understand that side effect burden is additive Periodically review the need for all medications

65 Recommended Options for Acute Treatment of Breakthrough Bipolar Depression Optimization of mood stabilizer (MS) Addition of second MS or SGA Addition of antidepressant to MS Addition of focused Psychotherapy to MS

66 How long should antidepressants be continued? 36 What do we do when there s no consensus? Expert recommendations for duration of antidepressant therapy range between 8 12 weeks and indefinite-lifetime

67 Slide Should the information be added that was discussed such as: 1 epidose = 6 weeks 2 episodes =2 years 3 episodes = Lifetime 32528, 8/19/2011

68 Role of Psychotherapy in Bipolar Disorder If effective for depression, avoids pharmacologic risk of TEAS Only 1 controlled study of acute phase therapy (conducted as part of STEP-BD) Preferred option for many patients Relapse prevention and adherence-enhancing effects demonstrated for CBT, FFT, and IPSRT TEAS=treatment emergent affective switch. CBT=cognitive behavioral therapy. FFT= functional family therapy. IPSRT= Interpersonal and Social Rhythm Therapy. STEP-BD=Systematic Treatment Enhancement Program for Bipolar Disorder. Miklowitz DJ, et al. Arch Gen Psychiatry. 2007;64(4):

69 Importance of Treatment Adherence Most people with bipolar disorder will have periods of non-adherence to therapy Abrupt discontinuation of medications hastens relapse Ask about adherence at each visit! Keep track of prescription refills

70 Factors Frequently Associated With Noncompliance in Bipolar Patients Young age Male gender Being unmarried Multiple medication regimens Fewer episodes First year of lithium treatment History of manic episodes Comorbid psychiatric illness Substance abuse

71 The Fundamental Factor in Long-Term Outcome in Bipolar Disorder Being in a treatment relationship Inadequate treatment associated with adverse outcomes (e.g., use of antidepressants alone) Treatment per se, even with placebo, improves outcomes, including reduced suicidality Not being in treatment increases costs, principally by higher rates of hospitalization, emergency care Begley CE et al. (2001), Pharmacoeconomics 19(5 pt 1): , Angst F et al. (2002), J Affect Disord 68(2-3): ; Yerevanian BI et al. (2003), J Affect Disord 73(3):

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