Describe the different Thought Processes Patterns for getting from A to B?
Goal Directed - direct and normal
Tangential and Circumstantial are within the normal range but takes a long time to get back to the question or only sort of answers it
Flight of Ideas - Abnormal topic to topic and never comes back to main point but can tell connections between each topic
Loose Associations - most severe pathology of thought process and can NOT make connections (typically manic or psychotic)
What are the typical thought processsing patterns seen in Bipolar disorder/mania?
see Flight of Ideas
Circumstantial or loose associations at other times
What is the definition/symptoms of a Manic Episode?
At LEAST 1 week (7 days) duration of elevated mood + 3 other symptoms [or irritability + 4other symptoms bc irritability is non-specific] PLUS Persistently increased activity/energy
Additional symptoms: decreased NEED for sleep, grandiosity, increased self esteem, pressured speech, increased goal-directed actiity, Flight of Ideas/Racing thoughts, distractibility, Risk behavior
Can have psychotic symptoms
How is a Hypomanic episode different than a Manic episode?
Lesser extent and shorter period of time than a manic episode
NO PSYCHOTIC symptoms
What is an episode with Mixed Features?
Pt has symptoms of both a manic or hypomanic episode with concurrent depressive symptoms at the same week
For at least 1 week
What is the definition of rapid cycling? Who is more likely to be a rapid cycler? What are some triggers?
BPAD 1 or 2 in which 4 or more mood episodes occur in a year (frequently depressive or manic) and has a worse prognosis overall
70-90% are rapid cyclers are WOMEN!!!
More common in BPAD 2 vs BPAD 1
can be triggered by lithium-induced hypothyroidsim or antidepressants
Bipolar 1 vs Bipolar 2 vs Mixed Episodes - compare simply
Bipolar 1 - manic - euthymic - MDE alternating
Bipolar 2 - MDE - hypomania - Euthymia (get full depressive eposides but never up to mania)
Mixed - Euthymic then to either Mania or MDE and then both at the same time
What are underlyng causes of BPAD that must be ruled out prior to diagnosis?
Co-morbid medical conditions
Medication side effects
What are substance abuse problems that could cause similar symptoms to BPAD?
Acute Cocaine intoxication can look like mania/psychosis or an anxiety disorder and then like depression after the drug wears off
Heroin intoxication looks like depression with cognitive deficits and withdrawal can look like anxiety disorder or hypomania
Alcohol withdrawal can look like anxity, mania, hypomania or psychosis
What are co-morbid medical conditions that can cuase similar symptoms to BPAD?
Complex Partial Seizure
MS, SLE, Syphilis, Cushing's
Acute HIV encephalitis, hypoglycemia, hypoxia....
BPAD 1 in men vs women
Average Age Onset
Women = Men but affects them differently
Women are more likely to be rapid cyclers, have mixed states, and have more depressive episodes
Average Age of Onset is 18 yo (very rare after 50 so make sure you haven't missed another medical diagnosis)
What is the clinical course of BPAD 1?
Untreated mania lasts 3 months, untreated depression lasts 6-12 months, untreated mixed episodes last 6 months
Patients will have on average 9 episodes
Most are Manic into Depression - which is when there is significant Suicide Risk!!!!!
Many develop substance problems
What are the co-morbidities with BPAD type 1?
60% substance use disorders
75% anxiety disorders
>50% Alcohol use disorder
all increase risk for suicide (esp alcohol)
What are the genetics of BPAD 1? What chromosmoes are implicated?
STRONG genetic component:
10fold increased risk in first degree relatives
50% have at least one parent w/ a mood disorder
1 PArent has Bipolar, then 25% risk in kid
If both parents have, then 50-75% risk
Concordance for twins: HIGH
Chromosomes 5, 11, 18, and X
How is the Epidemiological picture different for BPAD Type 2 vs type 1?
How are the Co-Morbidities different from Type 2 vs Type 1?
How does Suicide rate compare for type 2 vs Type1?
Prevalence is a little higher and age of onset is a little higher (20 vs 18)
Anxiety 75%!!!! HIGH
Substance Abuse is less common
Increased incidence of at least one lifetime eating disorder
1/3 pts attempt (same as 1) but LETHALITY is HIGHER
What is the clinical course for BPAD 2?
Many patients originally diagnosed with MDD then later get BPAD 2
Some patients go on to develop full blown manic episodes
*MORE lifetime mood episodes than type 1
**Depressive episodes are more frequent than hypomanic episodes and get more disabling over time
What is Cyclothymia? Who gets it? What are symptoms?
Cyclothymia - like one step down on level of intensity of symptoms
Pts have hypomanic periods and dysthymic periods but never have symptoms severe enought to meet criteria for mania/hypomania/MD
Symptoms last for > 2 years without going for more than 2 months symptoms free
Male = Female from adolescence to early adult years
*Increased chance will evolve into BPAD Type 1/2
How do you treat BPaD?
BPADtreatment is based upon the stage that the patient is in but likely involves lithium
Stages: Acute Mania, Bipolar Depression, Maintenance
What are the treatment goals for Acute Mania? How can you achieve those goals? What meds?
Goals: SLEEP!, decrease though disorganization, address psychotic symptoms, prevent dangerous behavior
**MOOD STABILIZER - Lithium!!! (or Valproate or Carbamazepine)
can add antipsychotic (also helps with sedation for sleep symptoms)
Can add Benzodiazepine (lorazepam) for continued agitation
*Eliminate Mood De-stabilizing agents like Anti-depressants!!!!
What is the treatment in Bipolar depression? What is the order of agents to use?
Mood Stabilizer: Maximize lithium Dose!!! >.8 mEq and takes 3-4 days to work (also acts as anti-depressant)
Then try Valproate or Carbamazepine as mood stabilizer but don't act as anti-depressants
Then consider Lamotrigine
Then can try Quetiapine, Lurasidone Monotherapy or Olanzapine/Fluoxetine
THEN consider Mood Stabilizer + Antidepressant but NEVER treat with just anti-depressant alone!!
Lastly - ECt is an option for bipolar depression, elderly, and pregnant women
What is the Maintenance treatment to maintain euthymia?
Mood stabilizer like Lithium valproate or carbamazepine
Lamotrigine is helpful only for biplar depression but does not control mania so should not be given alone
Pts may be able to come off the anti-depressant or anti-psychotic during this phase if they are doing well
Ex. Lithium + Risperidone and eventually can slowly wean off the Risperidone and maintain just the Lithium
What is Lithium? What is its MOA?
Li is a naturally occuring cation
Don't really know MOA but acts via second messenger to enhance serotonergic treansmission
Treatment of choice for BPAD!!!!! 1/3 Pts dont respond to it
What are the Side effects of Lithium?
Pregnancy Class D - causes Ebstein's Anomaly malformation of tricuspid valve
EKG changes and prolongation of ST interval
Thyroid Abnormalities - Goiter, Hyperglycemia, Hypothyroidism
Kidney - Polydypsia, polyuria, nephrogenic Diabetes Insipidus
Weight gain, edema, dry mouth,
What is the toxic level of lithium and what are the signs and symptoms of Lithium Toxicity?
Levels > 1.2
Levels 1.2-1.5 see Ataxia, dysarthria, incoordination; Increased GI and Renal Symptoms; increased tremor
Levels 1.5-2: see confusion, N/V/D, slurred speech, tremor and ataxia
Levels 2-2.5: see Delirium, EKC changes and cardiac arrhythmia, ataxia
Levels >2.5: see change in consciousness, acute renal failure, seizure, coma death
How do you treat a toxic Lithium level?
What is the warning for Lithium dosing? What should you be cautious of in patients taking lithium?
Lithium is 100% Renally Filtered so warning to pts with Kidney problems!!!
Be careful in dehydration, NSAID use, Thiazide diuretics, ACE inhibitors, CCB and Ibuprofen
they can all increase lithium level due to decreased renal clearance
What is the target dosing for Lithium in Bipolar disorder?
Aim for lower in elderly
What is Valproic Acid? How does it work? Who is it more effective for?
VA is a mood stabilizer and anti-epileptic
MOA: increases brain levels of GABA inhibitory NT
May be more effective for Rapid Cyclers and Mixed States
Caution - Lots of P450 interactions through liver clearance
What are the side effects of Valproic Acid?
Common: N/D, tremor, sedation, hair loss, weight gain, Increased Ammonia levels
Rare: Thrombocytopenia, Hemorrhagic pancreatitis, polycystic ovary disease
Hepatotoxicity (Not food for Hepatitis pts or alcoholics)
Pregnancy Category D: High risk of Neural tube defects, liver disease, dysphormphic facial features, cardiac abnormalities, reduced IQ
What are symptoms of Valproic Acid toxicity? What level do you see those at? What do you do at toxic levels?
See toxicity at levels >125 ug/ml
See Deep sleep, coma
Can get Hemorrhagic pancreatitis
Do HEMODYALISIS to clear toxic levels
What is Carbamazepine? How is it used? what is it's MOA?
Carbamazepine (Tegretol) is not as good as lithium for bipolar depression but may be more effective for rapid cyclers and mixed states
MOA: inhibits Voltage-dependent Na chnanels and decreases repetitive neuron firing and inhibits presynaptic Na channels
What do you need to remember about Carbamazepine?
MANY drug-drug interactions - is a P450 inducer and even auto-inducer and so decreases levels of itself and other drugs
DECREASES levels of Oral Contraceptives!!!
What are the side effects of Carbamazepine?
N, Ataxia, Sedation
Aplastic Anemia and agranulocytosis
Autoinduction and Hepatitis
Pregnancy Class D: Teratogeniticity of Spinal malformation, dysmorphic features, cranial and cardiac defects