Mood Stabilizers Flashcards
Neurochemical theories of BD
- Catecholamine hypothesis
- Permissive theory
- GABA and glutamate involvement
Catecholamine hypothesis of BD
- Mania may be related to excess NE and DA
- Depression may be related to deficits in NE, 5HT, DA
Permissive theory of BD
- Underlying decrease in 5HT with increased NE resulting in mania
- Decreased NE resulting in depression
What is necessary to rule out in evaluation of BD?
- Medical or drug induced causes
- Other psych diagnoses
Complete work-up prior to diagnosing BD?
- PE
- Basic labs (CBC, thyroid, electrolytes)
- Toxicology screen
Treatment goals for BD
- Resolve acute symptoms
- Facilitate pt’s return to pre-morbid functioning
- Prevent further episodes
- Pharm is cornerstone of treatment
Pharm treatment of BD
- Mood stabilizers
- Other agents (adjunctive anxiolytic or short term antipsychotic)
How long does it take mood stabilizers to elicit a response in BD?
7-10 days
How long does it take anxiolytic or short term antipsychotics to elicit a response in BD?
3-5 days
What are mood stabilizer agents used in BD?
- Lithium
- Valproic acid/divalproex sodium
- Lamotrigine
- Carbamazepine
- Oxcarbazepine
Drug of choice for “classic” mania?
Lithium
Lithium is FDA approved for:
- Acute mania
- Maintenance of BPD 1
What is shown to reduce risk of suicide in patients with depressive episodes in BD?
Lithium
Lithium MOA
- Unclear
- May involve 5HT, DA, GABA
Lithium metabolism
Excreted unchanged in the urine
Early ADEs of Lithium
Dose related and worse at peak serum concentrations
- GI
- Muscle weakness/lethargy
- Polydipsia w/polyuria (70%)
- HA, memory impairments, confusion (40%)
- Fine hand tremor (50%)
ADEs of Lithium later in treatment
- Nephrogenic DI
- Morphological renal changes
- Hypothyroidism (30%)
- Cardiac effects (30%)
- Wt gain
- Decreased libido
Monitoring parameters of Lithium
- Plasma concentration taken 8-12 hrs after last dose (trough)
- Renal function
- Thyroid function
- ECG
- CBC
- Serum electrolytes
- Pregnancy test
Lithium toxicity
- Plasma concentrations over 1.5: GI, decrease in coordination
- Plasma concentrations over 2: seizures, cardiac arrhythmias, neuro impairment, kidney damage, coma, death
What situations predispose a patient to Lithium toxicity?
- Na restriction (aka DASH diet)
- Dehydration
- Vomiting, diarrhea
- Drug interactions that lower Li clearance
How to treat Lithium toxicity?
Dialysis
What drugs cause decreased Lithium clearance?
FANTS
- Fluoxetine
- ACE inhibitors
- NSAIDs
- Thiazides
- Salt restricted diets
What drugs cause increased Lithium clearance?
- Caffeine
- Theophylline
Lithium in pregnant/lactating patients
- Category D
- Crosses placenta
- May cause floppy infant syndrome
- Present in breast milk
What is Valproic acid FDA approved for?
- Acute mania in BPD 1
- NOT approved for maintenance, but commonly used as monotherapy or in combo w/other agents
How does Valproic acid compare to Lithium?
Better efficacy for mixed states and rapid cycling
Valproic acid MOA
Proposed mechanisms:
- Increases GABA in CNS
- Antikindling properties (may decrease rapid cycling/mixed states)
Valproic acid drug interactions
Inhibits Lamotrigine and Carbamazepine metabolism (competes with hepatic glucuronidation site)
Valproic acid use in pregnant/lactating pts
- Category D (neural tube defects during 1st trimester)
- Considered compatible with breast feeding
Valproic acid monitoring
- Therapeutic plasma concentrations
- CBC w/diff
- Chem panel w/electrolytes
- LFTs
What is Lamotrigine FDA approved for?
Maintenance of BPD 1
- Has both antidepressant and mood stabilizing effects
- May prevent bipolar depression
Lamotrigine MOA
Proposed mechanisms:
- Modulates or decreases glutamate release
- Antikindling properties
Which mood stabilizers may cause a rash leading to SJS?
- Valproic acid
- Lamotrigine
How does lamotrigine affect weight?
It doesn’t (Li and VA do)
Lamotrigine use in pregnant/lactating
- Category C
- NOT recommended in breast feeding
Lamotrigine monitoring
Derm (assess for rash)
Carbamazepine MOA
Proposed mechanisms:
- Modulates or decreases glutamate release
- Antikindling properties
Use of Carbamazepine in BPD
Monotherapy or in combo for acute and maintenance (NOT 1st line)
What is unique regarding Carbamazepine?
Pan-inducer: induces its own metabolism (and others)
Carbamazepine ADEs
- CNS toxicity (up to 60% pts)
- GI
- Hyponatremia
- Wt gain
- Agranulocytosis
- Derm reactions
Carbamazepine toxicity
- At over 15 mcg/mL
- Ataxia, choreiform movements, diplopia, nystagmus, etc.
Carbamazepine use in pregnant/lactating
- Category D (craniofacial deformities, spina bifida, low birth wt)
- Considered ok w/breast feeding
Carbamazepine serum levels monitoring
- Every 1-2 wks during first 2 mos then every 3-6 mos
- 10-12 hrs post-dose and at least 5-7 days after a dosage change
Carbamazepine monitoring
- CBC w/diff
- LFTs
- Serum electrolytes
- Derm monitoring
Describe oxcarbazepine
- Analog of CBZ
- May have fewer ADEs
- NOT FDA approved for BPD so not 1st line
- Preg Cat C, not recommended in breast feeding
Which meds are FDA approved for acute mania BPD?
Lithium
Divalproex (Depakote)
Carbamazepine
Which meds are FDA approved for acute mixed BPD?
Divalproex (Depakote)
Carbamazepine
Which meds are FDA approved for BPD maintenance?
Lithium
Lamotrigine
Which meds are FDA approved for depressive episodes in BPD?
Lamotrigine
How are antipsychotics used in BPD?
- Acute mania (monotherapy or adjunctive)
- Bipolar depression
Which antipsychotics are used to treat acute mania in BPD?
- Aripiprazole
- Olanzapine
- Risperidone
- Haloperidol
- Quetiapine
- Ziprasidone
- Lithium or VA plus antipsychotic has better efficacy than any of these alone
Which antipsychotics are used for treatment of bipolar depression?
- Quetiapine XR
- Lurasidone
- Fluoxetine/Olanzapine
How are BZDs used in BPD?
- Can be used as an alternative or in combo w/antipsychotics for acute mania
- Alternative to mood stabilizers in 1st trimester of pregnancy
Antidepressant use in BPD
- Concern of mood switching in pts w/BP depression
- Can precipitate a manic episode
- Higher w/TCAs or Venlafaxine
- No better than placebo
