1. BIPOLAR Disorder

2. 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?

3. Why is this important?
Many patients with bipolar disorder seek treatment in primary care practices first
Among patients presenting with depression % 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

4. 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

5. 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

6. 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)

7. 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.

8. Clues to Diagnose Bipolar Disorders

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

10. Screening Tools
Mood Disorders Questionnaire (MDQ)
Sensitivity 0.28
Specificity 0.97
General Behavior Inventory (GBI)
Longer test, 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!

11. 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

12. 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

13. Bipolar Disorder treatment options

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

15. 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

16. 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 ( 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

17. 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

18. 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.

19. 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 

20. 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 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

21. 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

22. 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.

23. 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

24. 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?

25. Summary: Recommendations

26. Any Questions?
Thank you!

27. References https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2902189/