Mood stabilizers

Question 1

Drug List: Mood Stabilizers

Answer 1

Lithium carbonate (Li+)

Valproate

• Valproic Acid (Depakene)
• Divalproex (Depakote)

Carbamazepine

Question 2

Epidemiology of Bipolar Disorder

Answer 2

Lifetime prevalence rate is 0.7 to 1.6%
* First degree relatives 24-times more likely to develop bipolar disorder
Concordance rate 79% in monozygotic twins and 19% in dizygotic twins
Average onset age 21, however first symptoms often present in teen years or earlier

Question 3

Manic Episode

Answer 3

Elevated, expansive, or irritable mood for 1+ week, present most of the day, nearly every day

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

Question 4

Symptom domains in Mania and mixed mania

Answer 4

Manic mood and behavior (euphoria, grandiosity, pressured speech, impulsivity, excessive libido, recklessness, diminished need for sleep)

Psychotic symptoms (delusions, hallucinations, sensory hyperactivity)

Dysphoric or negative mood and behavior (depression, anxiety, irritability, hostility, violence or suicide)

Cognitive symptoms (racing thoughts, distractability, poor insight, disorganization, inattentiveness, confusion)

Question 5

Lithium: A Mood Stabilizing Drug

Answer 5

Typically given as Li2CO3

Lithium Carbonate

Question 6

Lithium: Multiple & Variable Effects

Answer 6

Effects on electrolytes (substitutes for Na+)
Effects on neurotransmitter systems (DA, 5-HT, ACh)
Many of these effects are seen acutely, yet lithium must be taken for 2-3 weeks before clinical effects are seen.

Question 7

Lithium: Effects on Phosphoinositide Signaling

Answer 7

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)

Question 8

Lithium: IP3 Signaling

Answer 8

A 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).

A 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.

Question 9

Lithium: Adverse Effects

Answer 9

** tremor
hypothyroidism
renal dysfunction (polydipsia & polyuria)
Diabetes insipidus
weight gain
cardiac conduction problems
gastric distress
mild cognitive impairment
Edema
Use with caution in pregnant patient

Question 10

Lithium

Narrow Therapeutic Window

Answer 10

plasma drug levels must be monitored

• acute ~ 0.8-1.2 meq/L
• maintenance ~0.6 - 1.0 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

Question 11

Other Mood Stabilizing Drugs: Anticonvulsant Drugs

Answer 11

Valproate

• • Valproic Acid (Depakene)
• • Divalproex (Depakote)

Carbamazepine (Tegretol)

Lamotrigine (Lamictal)

Question 12

Anticonvulsant Drugs Used As Mood Stabilizers

Answer 12

Divalproex Sodium =
Valproic Acid + Sodium Valproate

• One of the first line treatments for bipolar disorder
• Wider therapeutic window and faster onset than lithium (4-5 days)
• May act through increasing GABA levels
• GI (N&V) & hepatic problems
• Congenital neural tube defects
• ** Contraindicated in pregnant patients
• Alopecia (hair loss)
• Increases polycystic ovarian syndrome in women up to nine fold

Question 13

Carbamazepine

Answer 13

(Anticonvulsant Drugs Used As Mood Stabilizers)

Most probably act through blockade of voltage dependent sodium channels.
Aplastic anemia and agranulocytosis possible
Pharmacokinetic tolerance through auto-induction of metabolism
Hyponatremia (~3%), diplopia, ataxia, GI upset, sedation, weight gain
*** Contraindicated in pregnant patients

Question 14

Lamotrigine

Answer 14

(Anticonvulsant Drugs Used As Mood Stabilizers)

Not effective in acute mania, used instead for ** maintenance therapy
Blocks sodium and/or calcium channels.
dizziness, headache diplopia, GI upset, somnolence, skin rash * Steven Johnson Syndrome*
** Slow taper in dosing is critical**
valproic acid doubles [lamotrigine]
carbamazepine halves [lamotrigine]

Question 15

Second Generation Antipsychotics

Answer 15

See Dr. Linger’s Lecture on Antipsychotics
Aripiprazole (Abilify)
Olanzapine (Zyprexa)
Olanzapine + fluoxetine (Prozac) = (Zymbyax)
Lurasidone (Latuda)
Quetiapine (Seroquel)
Risperidone (Risperdal)
Ziprasidone (Geodon)
All are approved for treatment of acute mania and mixed episodes. Quetiapine, lurasidone, and olanzapine for bipolar depression.