Bipolar I
Disorder where one has at least one episode of mania
Bipolar II
Major Depressive and hypomanic esisodes. In contrast to BPI there does not need to be a full blown manic episode
Cyclothymia
Less severe form of Bipolar Disorder which has numerous periods of hypmanic symptoms and numerous periods of depressive symptoms
Bipolar, NOS
Not otherwise specified means it does not quite fit the checklist
Symptoms of Mania
Irritability, Excessive High Risk Activity, Inflated Self-Esteem, Flight of ideas, distractibiliyy,decreased need for sleep
Difference between BP induced depression and MDD
The depression associated with BP is one that is briefer in duration, more rapid onset, contain anergia, psychomotor retardation ad reversed vegetative symptoms
Reversed vegetative symptoms
Overeating (hyperphagia) and ovversleep (hypersomnia) … this is in contrast to vegetative symptoms which are insomnia and a loss of appetite
Prevelance of BP I and BP II (W/respect to M F)
Affects around 1% of population, BDI is equally impactful to males and females while BDII appears to impact females more than males
Age of onset of BP
First symptoms around 15-19 while there is a long delay for diagnosis and treatment
Mortality of BP
25-50% attempt suicide wherein 19% succeed (high lethality)
Why is differential diagnosis difficukt?
Not diagnostic test to say wether or not it is BP. BP depression also can look like MDD< antioscoial behavioral disorder, ADHD, conduct disorder or substance induced disorder
Difference between BP and MDD
BP is earlier onset, has more episodes, more familial mania, more equal in sex distribution, HIGHLY heritable,
T/F BP has a high concordance rate among identical twins
TRUE
Mood stabilizers
Potential pharmacologic use for treatment against BP. Similar in nerobiological action to antidepressants
Structural Changes to brain from MDD
Reduction in volume of prefonrtal cortext and hipposcampus, decreases in the number of neurons and glial cells in prefrontal cortext
Chemical Changes to brain from MDD/BD
Lower levels of neurochemical N-acetyl-aspartate
N-acetyl-aspartate
A neurochemical that is often used as a marker for neuronal health. It shows reduced leves in those with MDD and BD
BDNF
Brain derived trophic factor. BDNF is a neurotrophic factor. The use of mood stabilizers is said to reverse impairments toward the level of BDNF in the brain
Neurotrophins
Neurotrophins are proteins that induce the survival, development, function and plasticity of neurons
Rita Levi-Montalcini
A Nobel Prize winning physiologist that discovered the nerve growth factor (NGF) in the brain which causes develpoing cells to grow by stimulating surronding nerve tissue
Four classes of drugs for the treatment of Bipolar disorder
(1) Lithium (2) Anticonvulsant Mood Stabilizers (3) Atypical antipsychotics (4) Omega-3-fatty acids
Why Lithium probably used less than other drugs
Lithium, being an element, is not patentable which means companies cannot make a profit from it so there is little incentive to provide it when there are other drugs that are profitable.
Why was Lithium not super effective
Compliance is poor, side effects are intolerable and people usually miss the highs and the mood swings. The Lithium serves to really placate and calm the mood swings but some can perceive this as boring
Lithum excretion
Lithium is usually excreted unmetabolized. It is less impacted by liver disease as it will just be excreted out and does not need to be broken down by liver enzymes however kidney damage or fluid imbalanence would cause severe problems
What improvement to Lithium treatment could increase compliance
More routine blood monitoring and management of symptoms…Though costs and convenience make this hard
What can Lithium be perscribed for?
Acute mania, BP, Mixed states, depression, schizophrenia, aggressive outburts
Clinical effect of Lithium on Mania
Decreases the number, frequency and intensity of episodes. The episodes usually shorten in duration. There is a decrease in subtle mood swings between episodes, Takes about 5-10 days for a response. Usually requires a 2nd drug
Overdose impact of Lithium
There is no specific antidote for intoxication,,, one would likely need dialysis and supportive treatment
Side effects of Li
There is a NARROW therapeutic range which means regular monitoring is necessary, around 3-5-95% have adverse reactions. Usually some form of cognititve dsyfunction occurs. Other side effects include: reduced renal clearance, organic brain disorder, vomiting, diuretics, low sodium intake and high sodium excreation,
Most common side effects of Lithium
Hand tremor, incoordination, nystagmus[dancing eyes], muscle weakness, complaints about creativity, lack of excitement
“Other” Lithium side effects
Renal failure, polyuria, inhibition of vasopression (ADH), dipsogenic, weight gain…Lithium also passes into placenta and breast milk
Symptom of severe Lithium toxicity
Choreoathetosis, seizures, coma, detth
Used of anticonvulsants in mood stabilization
Used in bipolar disorder, used to treat relapse to substance abuse, detoxification agent for alcohol withdrawl
Problem with use of anticonvulsants
They are definitie teratogens and are rarely perscribed to those that are carrying
Lamotrigine
Lamictal which has improved saftey for mothers with epilepsy and carrying
Sources of noncompliance for mood stabilizers
Intolerance of side effects, memory impairments, cognitive slowing, weight gain, reduced energy, missing highs and mood swings, feeling the disorder has resolved and that the medication is unnecessary, feeling stigmatized
New guidlines for treating manic or mixed episodes
The new methodology is to initiate treatment with lithium+antipsychotic or valproate+antipsychotic
New guidelines for treating those patients that are less ill for manic/mixed episodes
Monotherapy can be utilized with lithium, valporate, or an antipsychotic such as olanzapine
New guidelines for depressive episodes
First line of treatment for bipolar depression is the initiation of either lihtium or lamotrigine
New guidelines for antidepressants
Antidepressants should be be administered monotheraputicly
New guidelines for treating more severly ill patients
Simultaneous treatment with lithium and an antidepressant
New guidelines for psychoterpahy
New evidence shows strong efficacy of psychoterapy in treatment of unipolar depression but no bipolar depression
Manic Flipping
A process that is called antidepressant-associated hypomania. It can occur with antidepressant administration to a bipolar depressed patient and cause the patient to switch into a state of mania. Most clinicians do not give ADs without Mood stabilizers….
AD most likely to cause Manic Flipping
TCA’s more likely over MAOI’s
Course of action if manic flipping occurs
Taper and discontinue use of AD
Negative effects associated with Carbamazepine
Sedation, ataxia, visual distrubances, skin reactions, cognitive impairments can cause birth defects …can cause decreased WBC and hypoatemia [electrolyte distrubance where Na levels are low]
Metabolic consequence of Carbazepine
It induces its own metabolism by autoinduction of cytochrome P450 enzyme. Needs frequent blood monitoring…Has heptic toxicity
Difference between carbazepine and oxcarbazepine
Oxcarbazepine has an oxygen attached to the heterocycle of the basic unit OXCARBAZEPINE SHOULD BE USED FOR TREATMENT NOT CARBAZEPINE
Benefits of Oxcarbazepine
It is an inactive prodrug that the live converts to the active species. It does not induce hepatic enzymes. It thus has fewer drug-drug interactions compared to carbamazepine.
Side effects of oxcarbazepine
tiredness, headache, dizziness, ataxia, allergic reactions, teratogenic effects
Benefits of oxcarbazepine over carbazepine
No enzyme induction, leukopenia, hepatic toxicities
Mechanism of Valproic Acid
Valproic Acid inhibits GABA transaminase which breaks down GABA. Can inhibit GABA reuptake and inhibit Na+ action potentials….
Valproic Acid used best with
Lithium or olanzapine
Major side effects of Valproic Acid
Teratogenicity (spina bifida) Coma/death in overdose
Valproic Acid in comparison to other AED;s
Does not induce hepatic microsomal enzymes
Treatment for Lamotrigine
Treats bipolar disorder, PTSD, schizoaffective disorder ..inhibits glutamate release making it antieplieptic, antimanic and analgesic
Side effect of lamotrigine
RASH
Use of topiramate
Effective anticonvulsant and antimanic…causes weightloss
Atypical antipsychotics used for mania
Colzapine, olanzapine, risperidone, aripiprazole…dopamine blocakde
Reasoning for why Omega-3 related to BPD
Countries with rich diets in fish oils have a low rate of occurance for BP disorder