BIPOLAR Disorder

Objectives Challenges to Diagnosis Why is this important? What are the treatment options? Atypical Antipsychotics Anti Convulsants Lithium Why is this important? Epidemiology Diagnostic Criteria What are the Screening Tools?

Why is this important? Many patients with bipolar disorder seek treatment in primary care practices first Among patients presenting with depression 21- 26% will meet criteria for bipolar disorder Delay in recognition is common - BPD are at high risk for suicide Bipolar disorder is often improperly diagnosed (as MDD) Strong genetic component Children of parents with bipolar disorders have a 4 to 15% risk of also being affected Caution with SSRIs – obtain good history 1st degree relatives of bipolar patients are bipolar 50% of the time

Epidemiology ~5.7 million American adults (~2.6% of the U.S. population) 12th most common moderately to severely disabling condition M=F in Bipolar I | F>M in Bipolar II Only 39.1% of individuals make treatment contact in the first year of onset Average age of onset is ~20yrs old Onset of new manic episode after age 65 extremely rare Environmental factors are strongly associated with the inheritance pattern.12 These factors include stressful life events, particularly suicide of a family member; disruptions in the sleep cycle; and family members or caregivers with high expressed emotion, a communication pattern de ned as emotionally overinvolved, hostile, and critical 69.3% of individuals with BPD had previous diagnoses, including affective disorders, attention deficit hyperactivity disorder, and substance use disorder.14

Diagnostic Criteria – DSM V Bipolar I Disorder A distinct period of abnormally and persistently elevated, expansive, or irritable mood, lasting at least one week (or any duration if hospitalization is necessary) During the period of mood disturbance, three (or more) of the following symptoms have persisted (four if the mood is only irritable) and have been present to a significant degree Grandiosity may reach a delusions state DIGFAST Distractibility. Increase in goal directed Activities Irresponsibility Talkativeness/pressured speech Grandiosity Flight if ideas Decreased need for Sleep

Diagnostic Criteria – DSM V Bipolar I Disorder The mood disturbance is sufficiently severe to cause marked impairment in occupational functioning or in usual social activities or relationships with others, or to necessitate hospitalization to prevent harm to self or other, or there are psychotic features The symptoms are not due to the direct physiological effects of a substance (e.g., a drug of abuse, a medication, or other treatment) or a general medical condition (e.g. hyperthyroidism)

Diagnostic Criteria – DSM V Bipolar II Disorder For the diagnosis of Bipolar II, it is necessary to meet the following criteria for a current or past hypomanic episode AND the criteria for a current or past Major Depressive Episode. As opposed to Bipolar I A. A distinct period of persistently elevated, expansive or irritable mood, lasting throughout at least 4 days, that is clearly different from the usual nondepressed mood. B. Criterion B the same as for mania – DIG FAST C. The episode is associated with an unequivocal change in functioning that is uncharacteristic of the person when not symptomatic. D. The disturbance in mood and the change in functioning are observable by others. E. The mood disturbance not severe enough to cause marked impairment in social or occupational functioning, or to necessitate hospitalization, and there are no psychotic features.

Clues to Diagnose Bipolar Disorders

Etiology and Workup Labs to Order: CMP CBC EKG Lipid Profile Pregnancy Test [if relevant] TSH Urine tox screen

Screening Tools Mood Disorders Questionnaire (MDQ) Sensitivity 0.28 Specificity 0.97 General Behavior Inventory (GBI) Longer test, 52- 73 questions Can be hard to understand Time consuming Young Mania Rating Scale (YMRS) Pediatric Bipolar screening tool Has a parent version Ask all patients with depression if they have ever had symptoms of mania or hypomania! http://www.integration.samhsa.gov/images/res/MDQ.pdf

MDQ Scoring In order to screen positive for possible Bipolar Disorder, all 3 parts of the following criteria must be met: 1. Yes to 7 or more of the 14 items in Question 1 AND 2. Yes to question 2 AND 3. “Moderate Problem” or “Serious Problem” to question 3

Challenges to Diagnosis Can be difficult to diagnose on initial assessment when patients are depressed if they actually have Bipolar PD Depressed mood present more often and is lengthier 60% initially present with depression Most patient spend time in depressed state as compared to manic state Tend to have extensive psychiatric comorbidity Substance use disorders - frequently self-medicate Anxiety Attention deficit hyperactivity, Axis II disorders https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3225131/

Bipolar Disorder treatment options

Treatment Options – Mood Stabilizers Antipsychotics Olanzapine Quetiapine Risperidone Ziprasidone Aripiprazole Lurasidone Anti Convulsants - Valproic acid - Topiramate - Carbamazapine - Oxcarbamazapine - Lamotrigine - Gabapentin Lithium

Mood Stabilizers Chose based on side effect profile Is it acute treatment? Or maintenance treatment? Maintenance pharmacotherapy usually consists of the same regimen that successfully treated the acute bipolar mood episode Women of childbearing age should be educated about the teratogenic effects of most mood stabilizers and the importance of using reliable contraception

Mood stabilizers First Line ** Remember – If appears to be acute mania, these patients should likely be hospitalized! Valproic Acid (VPA) Carbamazapine Lamotrigine Maintenance + Acute Most commonly prescribed** Maintenance Bipolar Depression Migraine Prophylaxis Trigeminal Neuralgia Not helpful in acute phase Levels available (50-100 mcg/mL) Levels available (6-12 mcg/mL) No levels available Side Effects: Hepatotoxic (LFTs PCOS Weight Gain Hair Loss P450 Inhibitor Side Effects Hyponatremia Blood Dyscrasias (CBC) Bone Marrow Suppression P450 Inducer Steven Johnson Syndrome - Slow Titration (~6wks) Tremors Category D (?autism) Reduces risk of relapse by 30% Category D Category C MS is often given in conjunction with an antipsychotic and a benzodiazepine in the acute phase Combination therapy with lithium or valproate plus an antipsychotic is superior to either agent alone in the resolution of acute mania

Other Anticonvulsants Topirimate Oxcarbamazapine Gabapentin Not FDA Approved Maintenance Not FDA approved Acute + Maintenance Side Effects: Cognitive problems Renal Stones Metabolic acidosis Hyponatremia Tremor Angioedema Memory Impairment Dizziness No blood Levels Adjunctive Treatment Monotherapy Weight loss Alcoholics Less chance blood dyscrasia Chronic Pain

Atypical Antipsychotics with Mood Stabilizing Effects Olanzapine, Quetiapine, Risperidone, Ziprasidone, Aripiprazole, Lurasidone FDA indicated for acute mania Aripiprazole, Olanzapine, Quetiapine are for maintenance (monotherapy or adjunct) Have both antidepressant and manic effects Use lower doses than for psychosis Lurasidone; Bipolar Depression Ziprasidone; adjunct to lithium or valproate for maintenance treatment Olanzapine; combined with fluoxetine for bipolar depression [Symbyax] Combination therapy for patients whose manic symptoms fail to respond to monotherapy frequently consists of a mood stabilizer plus an atypical antipsychotic Randomized maintenance trials for bipolar disorder have found that lithium or divalproex plus a second-generation antipsychotic is superior to lithium or valproate monotherapy SGAs are among the most used agents in acute mania.

Lithium FDA approved for acute mania and maintenance Response is 70-80% Still considered the drug of choice though not used often anymore: Risk of toxicity/side effects/compliance Almost entirely eliminated by the kidneys Do not use in patients with kidney disease Avoid dehydration and diuretics, careful with NSAIDs Side effects: Ebstein anomaly Leukocytosis Tremor – dose related Heart block Hypothyrodism (5%) Diabetes Insipidus Acne/Weight gain – most common Using lithium reduces the risk of relapse by approximately 30 percent Reduced risk of suicide 

Lithium Cont... Therapeutic trial of lithium should last 4-6 weeks Takes a number of days to reach steady state Lithium levels should be a range of 0.8-1.2. Narrow Therapeutic Window Suicide Risk Lithium levels should be monitored Weekly for the first month Monthly for months 2 and 3 Every 2-3 months thereafter What to monitor in Lithium? 6-12 month check of serum creatinine and TSH is required EKG Electrolytes BUN/Creatinine Takes a number of days to reach steady state

Tips on choosing a mood stabilizer Depakote: Avoid in young females Lithium; Don’t be afraid to use! Suicidal, recurrent mania, avoid in renally compromised Latuda; Bipolar Depression Lamictal; Bipolar Depression Antipsychotics: Acute/quick action of onset, Psychosis

What About Antidepressants in Bipolar Depression? Controversial topic STEP BD - Study comparing the efficacy of an antidepressant (sertraline or bupropion) plus mood stabilize Did not differentiate between the two groups in the rates of recovery Use has not demonstrated favorable outcomes HOWEVER If individuals had previous response to antidepressants, it may be beneficial as an adjunct The risk of manic switch with anti depressants is higher in Bipolar I versus Bipolar II Generally, continue antidepressants for approx 2-4 months after remission Venlafaxine was more likely than the other antidepressants to induce a switch into mania.

Psychosocial Interventions and Social Supports Psychosocial stress is known to trigger manic and depressive episodes Faster recognition of early warning signs, fewer and hospitalization and better functioning Sleep disturbance, agitation, increased goal orientation, disruption in usual routine Intensive psychotherapy  fewer relapses and longer periods wellness Behavioral interventions are considered 1st-line adjuncts to pharmacotherapy to improve social function, reduce number of hospitalizations, and improve relapse rates

When to refer to a psychiatrist? Acute Mania If symptoms do not improve after adequate trials of mood stabilizers patient appears to be decompensating on maintenance treatment [DIG FAST symptoms appearing] Patients with strong indication toward Bipolar Disorder [based on screening tools or clinical suspicion] If time to psychiatric appointment is lengthy, and suspicion for Bipolar Disorder is high – air on side of caution and start Mood stabilizer > Anti Depressant Situations where find need to start medications – at what point out of scope?? Case example – what would you chose; and why?

Summary: Recommendations

Any Questions? Thank you!

References https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902189/ http://psycheducation.org/treatment/mood-stabilizers/ http://psychiatryonline.org/doi/10.1176/appi.books.9781615370047.AS05#x10359 9.1080183