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The Treatment of Bipolar Disease in the Individual with IDD Nanette R Wrobel, RPh

The Treatment of Bipolar Disease in the Individual with IDD Nanette R Wrobel, RPh Co-Director of Special Populations Enloe Drugs May, 2007. Bipolar Disease. What is it? In a national survey done in the year 2000 of 4192 individuals diagnosed with bipolar disease:

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The Treatment of Bipolar Disease in the Individual with IDD Nanette R Wrobel, RPh

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  1. The Treatment of Bipolar Disease in the Individual with IDD Nanette R Wrobel, RPh Co-Director of Special Populations Enloe Drugs May, 2007

  2. Bipolar Disease • What is it? In a national survey done in the year 2000 of 4192 individuals diagnosed with bipolar disease: 1/3 or respondents sought help within 1yr, 69% misdiagnosed, 4 different MDs prior to correct diagnosis

  3. 35% of patients waited 10 years or longer for correct diagnosis and treatment initiation!!!

  4. Most frequent misdiagnosis: • Depression (60%) • Anxiety disorder (26%) • Schizophrenia (18%) • Borderline or antisocial personality (17%)

  5. Definition of Terms • Bipolar • Bipolar I: manic depression • Bipolar II: soft bipolar, hypomania • Hypomania • Mixed episodes • Cyclothymic: mild but chronic

  6. Epidemiology • Lifetime prevalence • Bipolar I: 0.4%-1.6% • Bipolar II: 0.5% • Discussion: Is actual incidence much higher based on self medication or misdiagnosis?

  7. Epidemiology • Reoccurrence rates: greater than 90% • Prognosis: Number and severity, as well as delay in treatment may have negative impact on the subsequent prognosis • Suicide: 25% of patients attempt suicide, while 15% complete suicide if untreated

  8. Epidemiology • Comorbidities: substance abuse, sexual and dangerous behaviors, spending sprees, gambling • Disability: Bipolar disorder is among the leading causes of disability • Cost: billions of dollars annually • Emotional costs: to patients and family members, society at large

  9. Who can we blame? • Our parents! 1st degree relative: 8-18x prevalence • Our environment: seasonal, stress, sleep disruption, family relationships, unconscious conflicts • Medical conditions: thyroid, GI, heart • Biological and brain chemistry • Drugs

  10. Brain Chemistry • Dysfunction in norepinephrine, serotonin, dopamine, GABA neurotransmitters • Deregulation in the adrenal, thyroid, and growth hormones • Abnormalities in the sleep cycle and in the regulation of circadian rhythms

  11. Characteristic Symptoms of Manic Phase of Bipolar Disease • Abnormally and persistently elevated, irritable or expansive mood lasting >1 week • Presence of 3 or more of the following: • A. Inflated self esteem • B. Decreased need for sleep • C. More talkative than usual or need to keep talking • D. Flight of ideas or racing thoughts

  12. Characteristic Symptoms of Manic Phase of Bipolar Disease • Three or more of the following (cont) • E. Distractibility • F. Increased goal oriented activity or psychomotor retardation • G. Excessive involvement in pleasurable activities with high potential for painful consequences

  13. Characteristic Symptoms of Manic Phase of Bipolar Disease • Mood disturbance is sufficiently severe to cause • Marked impairment in work or social functioning, usual social activities, or relationships with others • May cause need for hospitalization • May have psychotic features

  14. Characteristic Symptoms of Manic Phase of Bipolar Disease • Symptoms should be evaluated and determined to not be due directly to one or more of the following: • Substance abuse • Medical conditions eg. Mania due to antidepressant therapy or steroid usage

  15. Characteristics of Depressive Phase of Bipolar Disease • Five or more symptoms present nearly every day during same 2 week period: • A. Depressed mood • B. Markedly diminished interest or pleasure • C. Significant change in weight or appetite • D. Insomnia or hypersomnia • E. Fatigue or loss of energy • F. Feeling of worthlessness or excessive or inappropriate guilt

  16. Characteristics of Depressive Phase of Bipolar Disease • Five or more symptoms (cont) • G. Decreased ability to think or concentrate, or inability to make decisions • H. Recurrent thought of death, or thoughts of suicide

  17. Characteristics of Depressive Phase of Bipolar Disease • Symptoms cause clinically significant distress or impairment in social and/or occupational functioning • Symptoms need to be evaluated as not to be due to substance abuse or medical conditions • Symptoms should not be better attributed to normal bereavement patterns

  18. Psychosocial Interventions for the Optimal Management of Bipolar Disorder • Provide psychoeducation • Encourage participation in individual, family, group therapies and support groups • Manage comorbid conditions • Minimize noncompliance Huxley NA, et al. Harvard Review of Psychiatry. 2000;8(3):126-40.

  19. The Bipolar Patient:Treatment Goals • The best treatments result in the fewest, briefest, or mildest episodes • Primary therapeutic objectives • Treat acute depression • Treat acute mania • Prevent depressive recurrence • Prevent manic recurrence • Monotherapy is usually not effective for all therapeutic objectives Sachs GS, et al. Postgrad Med. 2000.

  20. Multiphase Treatment Strategy Start Treatment Euthymic Natural Course Treated Course Depressed Maintenance/ Discontinuation Acute Continuation

  21. Consensus Practice Guidelines • Acute treatment of manic, mixed, and hypomanic episodes • Selecting a mood stabilizer • Selecting adjunctive treatments for psychosis, agitation, and insomnia • Inadequate response to first treatment • Acute treatment of bipolar depression • Selecting an overall strategy • Selecting specific medications • Inadequate response to first treatment • Continuation and maintenance treatment • General issues in all treatment phases Sachs GS, et al. Postgrad Med. 2000.

  22. Acute Phase Treatment of Bipolar Disorder

  23. Goals of Oral Loading • Stabilize the patient • Ameliorate the mood symptoms • Ameliorate psychotic and other symptoms • Do it as rapidly as possible • Do it safely • Establish a maintenance medication

  24. Continuation and Maintenance Phase Treatment of Bipolar Disorder

  25. Continuation Phase: Mania • Continue successful acute therapies at full dose • To maintain effective serum levels • To allow patient to tolerate medication • Dependent on prior duration • Average mania lasts 19 weeks JAMA. 1986.

  26. Maintenance Phase: General Principles • Continue treatments that worked acutely- mood stabilizers • If patient has significant history of depression • Consider adding lithium • Use an antidepressant as a second-line option • Taper antipsychotic medications • If patient is left on antipsychotic, consider an atypical antipsychotic over conventional ones Sachs GS, et al. Postgrad Med. 2000.

  27. Mood Stabilizer Usage in Maintenance Phase of Bipolar Disease

  28. The Expert Consensus Guideline Series

  29. Lithium • 1950-1970’s: alters the distribution and exchange of ions involved in the process of conduction of electrical impulses in the brain • Toxicity especially with low sodium • Salt (chloride, carbonate), nonsedating, prophylactic properties, inexpensive • Weigh effectiveness vs. side effects

  30. Lithium • Therapeutic levels: 0.6 mEq/L-1.5 (2-3 300mg tabs of lithium carbonate/day), fine hand tremor, thirst, nausea, excessive sweating • Toxic signs: diarrhea, vomiting, drowsiness, confusion, muscle weakness • Levels>2.0: ataxia, tinnitus, kidney dysfunction • Levels>3.0: coma, respiratory depression, death

  31. Lithium • Half life: 20-24 hours • Slow release product: Lithobid • May be better alternative with less potential for side effects

  32. Classic Mood Stabilizers • Lithium Carbonate Summary: • More effective for true Bipolar Type I disorder but may be helpful as adjunct • Need to periodically monitor levels, BUN, Cr, TSH and free T4 • Concern for toxicity, Nephrogenic drug interactions • Need to consider med selection for other disorders (e.g. NSAIDS, diuretics, COX-2 inhibitors)

  33. Predictors of Good Prophylactic Response to Lithium • Few previous episodes (Bouman, 1986; Gelenberg 1989) • No rapid cycling course (Dunner, Fieve, 1974) • Depressive mania in index episode (Bowden, 2000) • Sustained higher lithium levels (Gelenberg, 1989; Maj, 1998) • No comorbidity or delusions (Greil, 1998) Bouman TK, et al. J Affect Disord. 1986; Bowden CL, et al. Arch Gen Psychiatry. 2000. In press; Dunner DL, Fieve RR. Arch Gen Psychiatry. 1974; Gelenberg AJ, et al. N Engl J Med. 1989; Greil W, et al. J Clin Psychopharmacol. 1998; Maj M, et al. Am J Psychiatry. 1998; O’Connell RA, et al.Br J Psychiatry. 1991.

  34. Depakene (Valproic Acid) and Depakote (Valproate) • Pharmacokinetics • Depakote tablets lag in absorption ( 1hr on empty stomach, up to 8 hrs w/food) • Depakote tablets are coated to reduce possible GI side effects (Do not crush) • Depakene are liquid filled capsules, and appear to have more GI side effects (TID or QID) • Dosage strengths: 125, 250 and 500mg tablets

  35. Mood Stabilizers (Divalproate) • Very effective for mood stabilization (efficacy in both manic as well as depressive stages) and aggression • Less medication interactions than Carbamazepine • Need to monitor liver functions and platelet counts (especially in elderly) • May require doses higher than antiepileptic doses for good control of impulsivity/aggression (blood levels of 100-150 mcg/ml) • Dose related side effects: tremor and gait disturbance (back off on the dose)

  36. Depakote sprinkles and ER formulation • Sprinkles available in 125mg capsules that allow for smoother, extended release flow and more consistent blood levels • Depakote ER formulated in 250 and 500mg tablets that allow for 1-2 times daily dosing minimizing side effects and allowing for a sustained release action

  37. Predictors of Good Prophylactic Response to Valproate • Most subtypes have equivalent response to pure mania, although most data are from open studies • Mixed mania (Calabrese, Delucchi, 1990) • Rapid cycling course (Calabrese, Delucchi, 1990) • Positive acute manic response to divalproex • Substance abuse (Brady, et al, 1995) Calabrese JR, Delucchi GA. Am J Psychiatry. 1990; Bowden CL, et al. Arch Gen Psychiatry. 2000. Brady KT, et al. J Clin Psychiatry. 1995.

  38. Mood Stabilizers • Carbamazepine • Highly effective for aggression and agitation, less so mood stabilization • Inducer of hepatic enzymes and may cause havoc with blood levels of other meds • Need to monitor for liver functions and CBC for marrow suppression • Optimal treatment may be with higher doses (levels of 10-12)

  39. Carbatrol and Tegretol XR • Carbatrol • 200mg and 300mg sustained release capsule • Tegretol XR • 100, 200, and 400mg sustained release tablets • Advantages of both • Ease of dosing (bid) • Smoother blood level • Less potential side effects

  40. Predictors of Good Prophylactic Response to Carbamazepine • Atypical forms of bipolar disorder (Greil, 1998) • Inadequate data for further predictors Greil W, et al. J Clin Psychopharmacol. 1998.

  41. Newer Antiepileptic Medications • Oxcarbazepine (Trileptal) • Topiamate (Topamax) • Gabapentin (Neurontin) • Lamotrigine (Lamictal) • Tiagapine (Gabatril) • Levetiracetam (Keppra)

  42. Lamotrigine (Lamictal) • Pharmacokinetics: • Highly affected by concomitant use of other antiseizure medications, so initial dose must be low, start slow, and titrate over several MONTHS. • Initial dose if on divalproex and enzyme inducers is 25mg qod. • If not on divalproex, but on enzyme inducer, use 50mg/day. • Inducers: carbamazepine, phenobarbital, phenytoin

  43. Lamotrigine (Lamictal) • More than 95% metabolized, many metabolites, some active • Dosage form: 25, 100, 150, 200mg tabs; 2.5 and 25mg chewable tabs

  44. Lamotrigine (cont) • Maintenance dose of 100-150mg/day if on divalproex, • otherwise, 300-500mg/day dosed bid • Half-life: • Ave 25hrs (monotherapy) • Ave 14hrs (inducers) • Ave 27hrs (inducers & VPA) • Ave 70 hrs (VPA)

  45. Lamotrigine (cont) • Steady state: 3-15 days • Side effects: • CNS: drowsiness, diplopia, dizziness, ataxia • Rash • Drug interactions: • carbamezepine and phenytoin decrease half-life • divalproex prolongs half-life

  46. Use of Anxiolytics in the Treatment of Bipolar Disease

  47. Anxiolytic Medications • Benzodiazepines: Use for rapid symptom relief for the shortest duration possible • Example: lorazepam

  48. Management of Psychotic Symptoms

  49. Conventional Introduced in 1950s & 1960s Dopamine-receptor blockade Examples Haloperidol Thioridazine Chlorpromazine Atypical Introduced in the 1990s Dopamine and serotonin receptor blockade Examples Clozapine Risperidone Olanzapine Quetiapine Ziprasidone Aripiprazole Conventional (Typical) vs Atypical Antipsychotics Source: Jeste DV et al. Am J Geriatr Psychiatry. 1999;7:70-76.

  50. Typical agents • Effective for the symptoms of hallucinations, abnormal thoughts, bizarre behavior, hostility, etc • Untoward CNS effects • EPS • Tardive dyskinesia • Sedation • Impairment of cognitive function

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