Goldilocks and Bipolar Disorder Getting Treatment Just Right

Transcription

1 Event Type Live Online ACPE Expiration Date 10/22/2016 Credits 1 Contact Hour Target Audience Nurses, Pharmacists, Pharmacy Technicians Program Overview Patients with bipolar disorder and their health care providers search for a treatment solution that is just right, much like Goldilocks. This program will focus on what health care providers can do to refine and adjust treatment until they get it "just right." The science of treating bipolar disorder continues to improve; getting the art of treatment continues to be a challenge. A combination of education, safe prescribing and appropriate monitoring will help us eventually eliminate the consequences of poorly managed bipolar disorder. As the bridge between patients and physicians, pharmacists are in the position to plan an integral part of a multi-pronged solution to this challenge and have the potential to ensure that bipolar disorder is not a chronic drain on patient health. Nurse Educational Objectives Outline the basic signs and symptoms of patients living with bipolar disorder and in particular, those patients that appear to be inadequately treated Review the current and emerging pharmacological approaches to the management of bipolar disorder (pharmacologic profiles, efficacy, side effects, & adverse events) Identify counseling techniques that nurses can use with patients and caregivers, about the benefits of managing bipolar disorder according to prescription indication to include adherence and life style changes to improve patient quality of life on long term maintenance of bipolar disorder

2 Pharmacist Educational Objectives Outline the basic signs and symptoms of patients living with bipolar disorder and in particular, those patients that appear to be inadequately treated Review the current and emerging pharmacological approaches to the management of bipolar disorder (pharmacologic profiles, efficacy, side effects, & adverse events) Identify counseling techniques that pharmacists can use with patients and caregivers, about the benefits of managing bipolar disorder according to prescription indication to include adherence and life style changes to improve patient quality of life on long term maintenance of bipolar disorder Pharmacy Technician Educational Objectives List signs and symptoms of bipolar disorder List medications used to treat bipolar disorder Activity Type Knowledge Accreditation Nurse Pharmacist Pharmacy Technician N L01-P L01-T PharmCon, Inc. is accredited by the Accreditation Council for Pharmacy Education as a provider of continuing pharmacy education. PharmCon, Inc. has been approved as a provider of continuing education for nurses by the Maryland Nurses Association which is accredited as an approver of continuing education in nursing by the American Nurses Credentialing Center s Commission on Accreditation. Faculty Heidi Sawyer, PharmD Medical Writer, Wellness Partners Financial Support Received From Pharmaceutical Education Consultants, Inc.

3 Disclaimer PharmCon, Inc. does not view the existence of relationships as an implication of bias or that the value of the material is decreased. The content of the activity was planned to be balanced and objective. Occasionally, authors may express opinions that represent their own viewpoint. Participants have an implied responsibility to use the newly acquired information to enhance patient outcomes and their own professional development. The information presented in this activity is not meant to serve as a guideline for patient or pharmacy management. Conclusions drawn by participants should be derived from objective analysis of scientific data presented from this activity and other unrelated sources.

4 Page 1 Goldilocks and Bipolar Disorder Getting Treatment Just Right and Getting Treatment Just Right Accreditation Faculty Pharmacists: L01-P Pharmacy Technicians: L01-T Nurses: N-857 Heidi Sawyer PharmD Harborview Medical Center CE Credit(s) Faculty Disclosure 1.0 contact hour(s) Dr. Sawyer has no actual or potential conflicts of interest in relation to this program. Learning Objectives Outline the basic signs and symptoms of patients living with bipolar disorder and in particular, those patients that appear to be inadequately treated Review the current and emerging pharmacological approaches to the management of bipolar disorder (pharmacologic profiles, efficacy, side effects & adverse events) Identify counseling techniques that pharmacists can use with patients and caregivers, about the benefits of managing bipolar disorder according to prescription indication to include adherence and life style changes to improve patient quality of life on long term maintenance of bipolar disorder. Legal Disclaimer The material presented here does not necessarily reflect the views of Pharmaceutical Education Consultants (PharmCon) or the companies that support educational programming. A qualified healthcare professional should always be consulted before using any therapeutic product discussed. Participants should verify all information and data before treating patients or employing any therapies described in this educational activity. Heidi Sawyer, PharmD Bipolar Disorder A cyclical disorder with recurrent fluctuations in mood, energy, and behavior Cycles from mania to depression Mania Hypomania Depression Mixed mood episodes Bipolar Disorder Sixth leading cause of disability 37% relapse within 1 year 50-60% relapse within 2 years Misdiagnosis 60% of patients are misdiagnosed as unipolar depression Illness often begins with depression not mania Depression is much more common than mania Patients may not recognize mania or hypomania

5 Page 2 Bipolar I Mania +/- depression Includes psychotic features in 50% of patients Mania Elevated, expansive or irritable mood Present for > 1 week or resulting in hospitalization Severe impairment of the normal ability to function Symptoms are not due to substance abuse or another medical condition Mania Symptoms Inflated self-esteem or grandiosity Decreased need for sleep (3 hours/night) More talkative; pressured speech Racing thoughts Distractibility Very goal directed Very bad judgment (excessive spending, bad business or investment decisions etc.) Mania Pathophysiology Largely unknown Linked to dopamine over activity Fluctuations in cortisol and thyroid hormones Sleep deprivation Bipolar II Major depression and hypomania Hypomania Hypomania occurs 1% of the time Symptoms not as severe as mania Many patients view hypomania as desirable Lasts >4 days Physical appearance Involved, busy and planning activities Energy increase is noticeable to others Optimistic or irritable

6 Page 3 Major Depression Most common mood in bipolar disorder Symptoms: Five or more symptoms present for >2 weeks; must include either of following Depressed mood most of day (sad, tearful, irritable) Loss of interest or pleasure in most activities Symptoms of Major Depression Significant weight loss or gain (>5% per month) Insomnia or hypersomnia* every day Psychomotor agitation or retardation* Fatigue or loss of energy* Worthlessness or inappropriate guilt Diminished ability to concentrate; indecisiveness Recurrent thoughts of death; suicidal ideation or attempt * More common with bipolar than unipolar depression Mixed Features Mania with features of depression OR depression with features of mania Includes 3 features from opposite mood Occurs in 20% of patients Bipolar Disorder Cyclothymic Disorder Hypomania and depressive symptoms Duration 2 years in adults, 1 year in adolescents Bipolar Disorder Not Otherwise Specified (NOS) Bipolar features not meeting criteria for bipolar disorders 45% convert to bipolar I or II within 5 years

7 Page 4 Rapid Cycling Defined as >4 episodes of mania, hypomania or depression per year Occurs in 16% of bipolar patients May occur after antidepressant use Relapse more common Medications associated with rapid cycling: TCAs, SNRIs, steroids, pseudoephedrine Abbreviations: SNRI=serotonin -norepinephrine reuptake inhibitor, TCA=tricyclic antidepressant Treatment of Bipolar Disorder 1. Acute Stabilization Achieve euthymia 2. Maintenance Prevent relapse Enhance social and occupational functioning Primary medications Mood stabilizers (lithium) Antiepileptic drugs (AEDs) Atypical antipsychotics FDA Approved Indications Drug Brand Mania Mixed Depression Maintenance Pediatrics Lithium Lithobid X X yo Valproate Depakote X Lamotrigine Lamictal X Carbamazepine XR Equetro X X Aripiprazole Abilify X X X yo Olanzapine Zyprexa X X X yo Risperidone Risperdal X X X (injectable) yo Quetiapine Seroquel X X Adjunct yo Ziprasidone Geodon X X Adjunct Asenapine Saphris X X Lurasidone Latuda X Chlorpromazine Thorazine X Loxapine Adasuve X Mood Stabilizers Lithium Inorganic cation Onset 5-7 days; max effect 2-3 weeks Mechanism: unknown Affects sodium transport Inhibitory effects on dopamine and glutamate Increases GABA and serotonin Not metabolized

8 Page 5 Early Side Effects Polyuria* 70% Tremor* 50% Headache, decreased memory and concentration 40% Muscle weakness, lethargy 30% GI upset * Tolerance does not develop Lithium Late Side Effects Leukocytosis Arrhythmias 30% Weight gain 20% Hypothyroidism 10% Dermatologic effects (acne, alopecia, psoriasis) Sexual dysfunction Thyroid effects Lithium concentrates in the thyroid Interferes with thyroid hormone synthesis Hypothyroidism may occur after 18 months of therapy More common in women Lithium Renal effects Nephrogenic diabetes insipidus Lithium inhibits antidiuretic hormone (ADH) Chronic renal disease Reduced glomerular filtration rates, increasing creatinine Risk factors: longer duration and higher dose of lithium, hypertension, and diabetes Drug interactions Dehydration, diuretics (HCTZ) and NSAIDS Cause reabsorption of sodium and lithium ACE inhibitors cause a delayed incr. lithium concentration Abbreviations: ACE=angiotensin converting enzyme, HCTZ=hydrochlorothiazide, NSAIDs=non-steroidal antiinflammatory drugs Mild Toxicity (<1.5 meq/l) Fine hand tremor GI upset Mild polyuria Polydipsia Muscle weakness Lithium Moderate Toxicity ( meq/l) Coarse tremor Recurring GI upset Slurred speech Vertigo Confusion Sedation Polyuria Narrow therapeutic index drug Therapeutic levels vary ( meq/l) Obtain 12 hours after last dose Check 5-7 days after dose change Monitor q3-6 months in stable patients Severe Toxicity (>2.5 meq/l) Seizures Stupor Coma Cardiovascular collapse Death Antipsychotics Second Generation Antipsychotics (SGAs) Metabolic syndrome Abdominal obesity, elevated triglycerides, low HDL, hypertension, and high fasting glucose Monitor Waist circumference and/or body mass index (BMI) Blood pressure, lipids, fasting blood glucose Prevalence: 45.3% of patients on antipsychotics vs. 32% without

9 Page 6 Second Generation Antipsychotics Risperidone (Risperdal) Olanzapine (Zyprexa) Quetiapine (Seroquel) Aripiprazole (Abilify) Ziprasidone (Geodon) Weight gain /- +/- Sedation +/ /- +/- Anticholinergic effects Orthostatic hypotension Prolactin elevation /- ++ +/ EPS* / QT prolongation *EPS=extrapyramidal symptoms +3.6 ms +1.7 ms +5.7 ms No change ms Typical Antipsychotics Haloperidol, chlorpromazine Few studies Adverse effects more common Sedation Extrapyramidal symptoms Anticholinergic effects Chlorpromazine High Moderate Moderate Haloperidol Very low Very High Very low Loxapine Moderate High Low Antipsychotics Loxapine (Loxitane, Adasuve) Approved for treatment of mania Inhalation powder Adverse events: bronchospasm, respiratory distress and arrest REMS program: administer only in facilities experienced with intubation and mechanical ventilation Monitor q15 min x1 hour Antiepileptic Drugs (AEDs) Valproic Acid (VPA) Mechanism: May be related to enhanced GABA Indicated for acute mania Adverse effects GI upset and sedation (tolerance develops) Ataxia, tremor, alopecia, incr LFTs Weight gain Rare: hepatitis, thrombocytopenia Drug interactions: VPA lamotrigine; CBZ VPA Abbreviations: REMS=risk evaluation and mitigation strategies Abbreviations: CBZ=carbamazepine, CNS=central nervous system, GI=gastrointestinal, LFTs=liver function test

10 Page 7 AEDs Lamotrigine (Lamictal) Approved for maintenance in adults with Bipolar I Mechanism: unknown Drug interactions Interacting drug Oral contraceptives (30 mcg ethinyl estradiol mcg levonorgestrel) Effect on Lamotrigine lamotrigine 50% CBZ, phenobarbital, phenytoin, rifampin lamotrigine 40% VPA lamotrigine >2-fold Lamotrigine Adverse events Headache 25%, benign rash 11%, dizziness 10%, diarrhea 8%, abnormal dreams 8%, pruritus 6% Rash Stevens-Johnson syndrome % in bipolar patients Risk factors: VPA, high doses, fast dose titration Discontinue with rash Abbreviations: AEDs=antiepileptic drugs, CBZ=carbamazepine, VPA=valproic acid Lamotrigine Aseptic meningitis warning 40 cases reported from 1994 to 2009 Symptoms: headache, fever, stiff neck Ave. onset 16 days after initiating lamotrigine Symptoms worsen with restarting med in 15 cases Treatment of Mania FDA approved agents: Lithium, VPA, CBZ 2 nd generation antipsychotics Risperidone, olanzapine, quetiapine, ziprasidone, asenapine 1 st generation antipsychotics Chlorpromazine, loxapine Tarr meta-analysis (9 trials, 1,631 patients) SGAs significantly improve mania scores, responder rates and risk of drop out vs. mood stabilizers (lithium or VPA) Abbreviations: CBZ=carbamazepine, VPA=valproic acid

11 Page 8 Treatment of Mania Cipriani meta-analysis (68 RCTs, 16,073 pts) Most effective (in order) Haloperidol, risperidone, and olanzapine Followed by lithium, quetiapine, aripiprazole and CBZ Least drop outs Olanzapine, risperidone and quetiapine Worse than placebo Lamotrigine, topiramate and gabapentin Treatment of Mania Stop antidepressants Benzodiazepines Sedative effects Useful before antimanic medications take effect Electroconvulsive therapy (ECT) Effective for acute mania and depression Consider if symptoms severe or lack of response to medications Adverse effects: cognitive impairment Abbreviations: CBZ=carbamazepine, RCT=randomized controlled trials Treatment of Depression Antidepressants Used in 50% of patients with bipolar disease Trial data Meta-analysis: no benefit vs. placebo Paroxetine: no benefit vs. placebo STEP-BD trial: Adjunctive paroxetine or bupropion vs. placebo No difference in remission, mania or effects of discontinuation of antidepressant Olanzapine + fluoxetine: more effective than placebo or olanzapine alone Treatment of Depression Antidepressants Controversy: risk of mania and rapid cycling Switching more common with bipolar I than II Risk of switching Bupropion 5-10% Sertraline and SSRIs 7-9% Venlafaxine and SNRIs 15-29% TCAs 43% Abbreviations: SSRI=selective serotonin reuptake inhibitor, SNRI=serotonin -norepinephrine reuptake inhibitor, TCA=tricyclic antidepressant

12 Page 9 ISBD Antidepressant Guidelines Use recommended: Adjunctive use with acute depression if history of positive response Patients whose depression relapses after stopping antidepressants Use adjunctive TCAs or SNRIs as second line antidepressants Avoid use: Acute depression with >2 manic symptoms with agitation or rapid cycling Antidepressant monotherapy with BP I Antidepressant monotherapy with BP II with >2 manic symptoms Mixed features or mixed state Abbreviations: BP=bipolar, SNRI=serotonin-norepinephrine reuptake inhibitor, TCA=tricyclic antidepressant Treatment of Depression FDA approved Quetiapine, lurasidone, olanzapine/fluoxetine Meta-analysis of 19 trials for bipolar depression Most effective agents Quetiapine, olanzapine/fluoxetine More effective than placebo VPA, olanzapine No difference from placebo Lamotrigine, aripiprazole, lithium Lurasidone (Latuda) Effective vs. placebo as monotherapy and adjunct Maintenance Treatment Lithium FDA indicated for maintenance Most evidence of long-term efficacy Meta-analysis of 5 trials in 770 patients: Decreased risk of manic relapse by 38% (p=0.0008) Decreased risk of depression relapse by 28% (p=0.06) Some data supports decreased risk of suicide Meta-analysis found 60% decreased risk of suicide with lithium vs. placebo No difference vs. active treatments except CBZ Maintenance Treatment Valproic Acid (VPA) Little data in long-term prevention More effective vs. depression than mania BALANCE trial large 2 year trial Lithium more effective than VPA (RR 0.71, 95% CI , p=0.0472) Lithium + VPA: more effective than VPA alone (RR 0.59, 95% CI , p=0.002) Combo therapy vs. lithium- no difference in efficacy Abbreviations: CI=confidence interval, RR=relative risk, VPA=valproic acid

13 Page 10 Maintenance treatment Lamotrigine FDA indicated for maintenance only More effective for preventing depression relapse than mania relapse Pooled analysis of 2 trials of lamotrigine and lithium vs. placebo Lamotrigine and lithium more effective than placebo 36% decrease in relapse with lamotrigine Lamotrigine more effective than placebo for depression Maintenance Treatment Antipsychotic agents FDA approved monotherapy Risperidone long-acting injection, aripiprazole Olanzapine No difference in efficacy vs. lithium or VPA overall More effective than lithium, VPA for mania FDA approved adjunctive agents Quetiapine, ziprasidone Effective for prevention of mania, not depression Exception: quetiapine effective for both Maintenance Treatment Overview For prevention of mania Lithium Antipsychotics (risperidone, olanzapine, aripiprazole, quetiapine, ziprasidone) For prevention of depression Valproic acid Lamotrigine Quetiapine Psychotherapy Educate patients and caregivers Stress management Signs of recurrence Maintain healthy lifestyle (sleep, exercise etc.) Improve adherence with drug therapy Improve social and occupational function

14 Page 11 Psychotherapy Evidence based methods Cognitive-behavioral therapy Family-focused therapy Interpersonal and social rhythm therapy Exercise, sleep schedule, healthy diet Group psycho-education Systematic care management Does it work? Acute mania or depression Long-term maintenance Pharmacists and Adherence Up to 50% of patients are non-adherent to treatment Lost meds (37%) Feel med is not needed (23%) Med not wanted (19%) Adverse events (15%) Patient Education Health beliefs model Susceptibility to illness Severity of illness Barriers to a behavior (compliance) Benefits to a behavior Patient education Address patient beliefs Importance of adherence Expected benefits and adverse effects Pharmacist Interventions Community setting Extra education time with new starts Extra information on adherence Refill reminders Notify provider if meds not picked up Outpatient clinics/hmos/va Follow-up with pharmacist (telephone or in person) Pharmacist med reviews Clinical monitoring of patients Unit of use packaging

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