4-12 Mood Stabilizers Flashcards
What are the main mood stabilizers?
Lithium carbonate (Li+) (generic, Eskalith)
Valproate:
Valproic Acid (Depakene)
Divalproex (Depakote)
Carbamazepine (Tegretol)
In addition to LiCO3, valproate, and carbamazepine, what are some additional mood stabilizers discussed?
nLithium carbonate (Li+) (generic, Eskalith)
nValproate
qValproic Acid (Depakene)
qDivalproex (Depakote)
nCarbamazepine (Tegretol)
nLamotrigine (Lamictal)
nAtypical Antipsychotics
qAripiprazole (Abilify)
qOlanzapine (Zyprexa) Olazapine + fluoxetine (Symbyax)
qLurasidone (Latuda)
qQuetiapine (Seroquel)
qRisperidone (Risperdal)
qZiprasidone (Geodon)
What is the epidemiology of bipolar disorder?
nLifetime prevalence rate is 0.7 to 1.6%
nFirst degree relatives 24-times more likely to develop bipolar disorder
nConcordance rate 79% in monozygotic twins and 19% in dizygotic twins
nAverage onset age 21, however first symptoms often present in teen years or earlier
What is a manic episode?
How long must it last?
How often each time?
nElevated, expansive, or irritable mood for 1+ week, present most of the day, nearly every day
What elements/characteristics make up a manic episode? 7
3 or more of the following, 4 if irritable mood: (DTRHIGH)
- Distractible
- Talkative or pressured speech
- Racing thoughts or flight of ideas
- Hyper-alert = decreased need for sleep
- Increased activity or psychomotor agitation
- Grandiose
- Hypersexual = risky acts
What are the symptom domains in mania and mixed mania?
manic mood and behavior
psychotic symptoms
dysphoric or negative mood and behavior
cognitive symptoms
What characteristics make up manic mood and behavior?
a
What characteristics make up psychotic symptoms? 3
What characteristics make up dysphoric or negative mood and behavior?
What characteristics make up cognitive symptoms?
What is lithium?
A Mood Stabilizing Drug
Typically given as Li2CO3
Lithium Carbonate
What are the effects of lithium on NTs and electrolytes? How long until clinical effects are seen?
nEffects on electrolytes (substitutes for Na+)
nEffects on neurotransmitter systems (DA, 5-HT, ACh)
nMany of these effects are seen acutely, yet lithium must be taken for 2-3 weeks before clinical effects are seen.
How does lithium affect a GPCR system/phosphoinositide signaling?
inhibits phosphatase enzyme primarily responsible for the conversion of IP2 to IP1and IP1 to inositol
With chronic lithium treatment there is a depletion of phosphatidylinositol-4,5-bisphosphate (PIP2)– the source of the second messengers inositol triphosphate (IP3) and diacylglycerol (DAG)
What are the consequences of lithium’s effects on IP3 signalling?
nA depletion of PIP2 may lead to a decreased responsiveness to synaptic transmission for those receptors which utilize phosphoinositide second messenger signaling (e.g., muscarinic receptors and others).
nA depletion of PIP2 sufficient enough to produce decreased responsiveness may not occur until lithium has been administered for 2-3 weeks, a time course consistent with the latency to clinical improvement.
What are the ADRs of lithium? 9 one bold
- tremor
- hypothyroidism
- renal dysfunction (polydipsia & polyuria)
- Diabetes insipidus
- weight gain
- cardiac conduction problems
- gastric distress
- mild cognitive impairment
- edema
What is the therapeutic window of lithium?
plasma drug levels must be monitored
acute ~ 1-1.5 meq/L
maintenance ~0.6 - 1.2 meq/L
toxic levels ~ 2.0 meq/L
DEHYDRATION can lead to toxic levels quickly due to increased plasma concentrations and decreased renal excretion
20-40% of bipolar patients do not respond to lithium
In addition ot lithium, what are some other mood stabilizing drugs?
Anticonvulsant Drugs
nValproate
qValproic Acid (Depakene)
qDivalproex (Depakote)
nCarbamazepine (Tegretol)
nLamotrigine (Lamictal)
What is divalproex sodium?
What is it a first line option for within the context of this topic?
Anticonvulsant Drug Used As Mood Stabilizer
One of the first line treatments for bipolar disorder
What are the advantages of divalproex sodium? How does it work?
Wider therapeutic window and faster onset than lithium (4-5 days)
May act through increasing GABA levels
What are the ADRs of divalproex sodium?
GI (N&V) & hepatic problems
Congenital neural tube defects
Alopecia (hair loss)
Increases polycystic ovarian syndrome in women up to nine fold
How does carbamazepine work?
Anticonvulsant Drug Used As Mood Stabilizer
Most probably act through blockade of voltage dependent sodium channels.
What are the ADRs of carbamazepine?
Aplastic anemia and agranulocytosis possible
Hyponatremia (~3%), diplopia, ataxia, GI upset, sedation, weight gain
What is something to consider when prescribing carbamazepine?
Pharmacokinetic tolerance through auto-induction of metabolism
What is lamotrigine?
What is it used for?
What is it NOT used for?
Anticonvulsant Drugs Used As Mood Stabilizers
Not effective in acute mania, used instead for maintenance therapy
How does lamotrigine work?
Blocks sodium and/or calcium channels.
What are some important things to keep in mind in dosing lamotrigine?
It interacts with two other drugs from this section, identify them and describe their respective interactions.
Slow taper in dosing is critical
valproic acid doubles [lamotrigine]
carbamazepine halves [lamotrigine]
What are some ADRs with lamotrigine?
dizziness,
headache
diplopia,
GI upset,
somnolence,
skin rash
*** Steven Johnson Syndrome***
What are the second generation anti-psychotics?
Aripiprazole (Abilify)
Olanzapine (Zyprexa), Olanzapine + fluoxetine (Prozac) = (Zymbyax)
Lurasidone (Latuda)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
What are the second-generation antipsychotics approved for?
Which would you use for bipolar? (oops, I gave away part of question one. Shucksy-darn)
treatment of acute mania and mixed episodes
Quetiapine, lurasidone, and olanzapine for bipolar depression
What are the ADRs of second generation antipsychotics?
diabetes
extrapyramidal symptoms
elevated prolactin
QTc prolongation
weight gain
Discuss the following drugs in terms of ADRs: aripiprazole, asenapine, clozapine, olanzapine, quietiapine, risperidone, ziprasidone.
