Red flags for potential bipolar disorder:
- Hx of abnormally elevated/irritable mood
- Periods of persistent increased energy
- Period of engaging in out-of-character behavior
- Behavior that is a noticeable change from baseline
- Impulsivity (APA, 2013)
- Cognitive difficulties present even when not depressed (APA, 2013)
- Multiple failed trials of antidepressants (Stahl, 2013)
- Ask about periods of time when it seemed like ‘everyone was picking fights with you’ or conversely periods of time when the individual received feedback from multiple others that might indicate irritability
- East-west travel issues (APA, 2013)
- Sometimes, a lack of clear precipitants for mood episodes (Carlat, 2016)
- Psychosocial history providing evidence of ‘erratic’ behavior over time
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“DIGFAST”
- Distractible
- Indiscretion (excessive pleasurable activities with high potential for painful consequences)
- Grandiosity
- Flight of ideas
- Activities (increased goal direction)
- Sleep deficit (decreased need for sleep)
- Talkativeness (pressured speech)
At least 3 of the above plus expansive mood, 4 of the above if mood is only irritable. In mania, psychosis may e present (APA, 2013; Carlat, 2016)
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Mania vs Hypomania
MANIA
3- 4 DIGFAST x 7 days
Severe impairment in social or occupational functioning
Hospitalizing
is common to prevent harm to self and others
May have psychotic features
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Mania vs Hypomania
HYPOMANIA
3- 4 DIGFAST X 4 days
No marked impairment in social or occupational functioning
No hospitalization required
No psychotic features.
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BIPOLAR I
The only requirement is an occurrence of a manic episode (RED)
In between manic episodes – euthymia, major depressive episodes or hypomanic episodes
Age of onset before 30; mean age of first mood episode = 18
Chronic with relapses
Poorer prognosis than MDD
Lithium – gold standard (RED)
Tegretol and Valproic acid
SGA – Risperdal, Zyprexa, Seroquel, Geodon = monotherapy and adjunct therapy
No antidepressants - concerns with activating mania or hypomania (RED)
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BIPOLAR I - RED PARTS
The only requirement is an occurrence of a manic episode
Lithium – gold standard
No antidepressants – concerns with activating mania or hypomania
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BIPOLAR II
One or more major depressive episodes and at least 1 hypomanic episode.
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ACUTE MANIA TREATMENT
Lithium - gold standard
Depakote
Carbamazepine
Additional benzos/typical/atypical antipsychotics
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Maintenance treatment for mood
Lithium (”gold standard”), but tolerability concerns
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Bipolar = ↑Serotonin; ↑NE
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- Acute mania
Prevent relapses of manic episodes (maintenance treatment) in bipolar and schizoaffective disorder. - Augmentation of antidepressants in patients with MDD
- Potentiate antipsychotics in patients with schizophrenia or schizoaffective disorder
- Treatment of aggression and impulsivity (e.g., in dementias, intellectual disability, personality disorders, other medical conditions)
- Enhancement of abstinence in treatment of alcoholism.
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Etiology of Bipolar Disorder
- GABA dysregulation
- ↑ Noradrenergic activities
Lithium (Eskalith Lithobid)
Carbamazepine (Tegretol)
Valproic acid (Depakote and Depakene)
Lamotrigine (Lamictal)
Oxcarbazepine (Trileptal)
Gabapentin (Neurontin)
Pregabalin (Lyrica)
Tiagabine (Gabitril)
Topiramate (Topamax)
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Red Parts on Lithium:
- Has antisuicidal properties (The only mood stabilizer shown to ↓ suicidality)
- Epstein anomaly – cardiac defect in babies
- Lithium Toxicity: Narrow therapeutic index(0.6-1.2 mEq/L); Toxic >1.5; Potentially Lethal =>2.0
- Emphasize the need for reliable birth control in women of childbearing age
- Good prognostic indicator for Lithium = episode pattern of mania, depression and euthymia
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Lithium Carbonate (Eskalith)
Gold standard for the treatment of Bipolar (acute mania)
Has antisuicidal properties (The only mood stabilizer shown to ↓ suicidality)
Metabolized by the kidney = Special consideration in renal impaired patients
Symptom reduction 2 weeks tx 60 to 80% of manic patients
Effective preventing future manic & depressive episodes; reducing suicide: 6 to 7-fold decrease
Onset of Action= 5-7 days
Has a narrow therapeutic index
Check level 4-5 days after initiation and after every dose change
Before starting: TSH, Creatinine, BUN, pregnancy testing , EKG (over age 50 or risk); CBC, Chemistries
Regular Monitoring: Lithium levels, TSH, Kidney function.
Note: Well documented evidence of causing hypercalcemia and hyperparathyroidism.
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Lithium SE:
SE: Weight gain, cognitive slowing or dulling; Impaired thyroid function, GI disturbance, Sedation, fine tremor, ECG changes(T-wave inversion), Leukocytosis; hypothyroidism; Epstein anomaly – cardiac defect in babies
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Lithium Toxicity:
Narrow therapeutic index(0.6-1.2 mEq/L); Toxic >1.5; Potentially Lethal =>2.0
Early: Nausea, vomiting, diarrhea, coarse tremors, ataxia
Late: Seizures, Coma, death
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Lithium
Patient Education: Drink @ least 6-8 glasses of water per day ; Caution in the summer – exercising outdoors
Emphasize the need for reliable birth control in women of childbearing age
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Factors that can increase lithium levels
NSAIDS (e.g. ibuprofen)
Aspirin
Thiazide diuretics
Dehydration (especially in the elderly)
Salt deprivation
Sweating (salt loss)
Impaired renal functioning
Ace Inhibitors
Antihypertensives
Lithium Adverse Effects
Renal
- diabetes insipidus, nephrotic syndrome, interstitial fibrosis, renal failure
Thyroid
- benign & transient decreases in thyroid hormone, goiter (5%), hyperthyroidism, hypothyroidism (10%)
Cardiac
- T-wave flattening or inversion (benign), sinus dysrhythmias, heart block, ventricular arrhythmia & CHF (rare)
Weak teratogen: potential for Ebstein’s anomaly (congenital heart defect)
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Lithium toxicity
Early signs: slight apathy, lethargy, decrease concentration, mild ataxia, muscle weakness, course tremor, slight twitching
Mod toxicity: severe diarrhea, N/V, ataxia, slurred speech, tremor, tinnitus, blurred vision, frank muscle twitch
Severe toxicity: nystagmus, muscle fasciculation, deep tendon hyperreflexia, V/T halluc, oliguria or anuria, imp consciousness, seizure, coma, death
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Carbamazepine (Tegretol) 800-1600 mg
Useful in treating mania w/ mixed features and rapid –cycling bipolar disorder
Gold Standard for = Rapid- cycling mania
Onset of Action: 5-7 days
Blackbox warning for Agranulocytosis & Aplastic Anemia
S/E: drowsiness; ataxia, nausea, dizziness, sedation, dry mouth, constipation
Therapeutic Level= 8-12 mcg/ml
Rare= Depakote induced thrombocytopenia
Elevation of liver enzymes causing hepatitis
Labs before initiating: Pregnancy test, CBC, LFTs
Regular Labs: CBC, LFTs
Associated w/ Neural tube defects
Note: Auto-induction of its own metabolism;
Starts 3-5 days after initiating
Translates as decrease plasma levels
May need a dose increase in the first few weeks to months
Potential for dangerous skin rash (Stevens Johnson Syndrome)
Toxicity: Confusion, stupor, motor restlessness, ataxia, tremor, nystagmus, twitching and vomiting
***Acute intoxication can produce Ataxia
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Carbamazepine (Tegretol) Red Parts
- Blackbox warning for Agranulocytosis & Aplastic Anemia
- Therapeutic Level= 8-12 mcg/ml
- Rare= Depakote induced thrombocytopenia
- Elevation of liver enzymes causing hepatitis
- Associated w/ Neural tube defects
- Note: Auto-induction of its own metabolism;
***Acute intoxication can produce Ataxia
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Valproic acid (Depakote and Depakene) 500mg -2000mg
MOA: Blocks sodium channels and increases GABA concentrations in the brain
PO (Depakote) Liquid (Depakene) and IV formulation
Blackbox warning for hepatotoxicity & pancreatitis
Therapeutic level = 80-120 ug/ml
Check level after 4-5 days
S/E: Nausea, diarrhea, Abdominal cramping, sedation, tremor
Rare= Depakote induced thrombocytopenia
Labs: CBC, LFTs
Associated w/ Neural tube defects specifically spina bifida, atrial septal defects, cleft palate and possible long-term developmental deficits
(Care with women at childbearing age) – Some studies have linked Depakote to PCOS.
S/E: GI distress, sedation, cognitive slowing, weight gain, LFT elevations, hyper ammonia, pancreatitis, hair loss
Fatal hepatotoxicity
Pancreatitis
Hyperammonemia-induced encephalopathy
Thrombocytopenia
Highly teratogenic (neural tube and other defects)
Concerning drug interaction
- VPA more than doubled when taking lamotrigine, therefore increases risk Steven Johnson syndrome
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Valproic Acid Red Parts
Therapeutic level = 80-120 ug/ml
Check level after 4-5 days
Rare= Depakote induced thrombocytopenia
Associated w/ Neural tube defects specifically spina bifida, atrial septal defects, cleft palate and possible long-term developmental deficits
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