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Pharm- Antipsychotics > Mood Stabilizers > Flashcards

Mood Stabilizers Flashcards

1
Q

Complete work-up prior to diagnosis of BD

A

Physical exam
Basic laboratory work-up (CBC w/diff, thyroid function, electrolytes)
Toxicology screen

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2
Q

2 things that need to be ruled out before diagnosis?

A

Medical or drug-induced causes

Other psychiatric diagnoses

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3
Q

Catecholamine Hypothesis of BD

A

Mania may be related to excessive NE and DA

Depression may be related to relative deficits in NE, 5-HT, and DA

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4
Q

Permissive Theory of BD

A

In both mania and depression there is an underlying decrease in 5-HT with increased NE activity resulting in mania or decreased NE activity resulting in depression

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5
Q

4 treatment goals for Bipolar disorder

A

Resolve acute symptoms
Facilitate patient’s return to pre-morbid functioning (social and occupational)
Prevent further episodes of mania and/or depression
Pharmacotherapy is cornerstone of treatment

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6
Q

Nonpharm Therapy for Bipolar

A 
Nutrition
Sleep (decrease need for sleep with hypomanic)
Exercise
Stress reduction
Mood charting
Psychoeducational programs
Self-help, support groups
ECT
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7
Q

5 MC used mood stabilizers in practice

A 
Lithium (Eskalith®, Lithobid®)
Valproic acid (Depakene®); divalproex sodium (Depakote®)
Lamotrigine (Lamictal®)
Carbamazepine (Tegretol®; Equetro®)
Oxcarbazepine (Trileptal®)
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8
Q

Lithium is the drug of choice for?

A

“classic” mania

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9
Q

Lithium (2)

A

FDA approved for treatment of acute mania and maintenance treatment of bipolar I disorder
Shown to reduce risk of suicide in patients with depressive episodes in BD

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10
Q

Lithium is less effective than?

A

Less effective than VA or CBZ for mixed episodes or rapid cycling

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11
Q

Lithium effects what?

A

affects NE, GABA, glutamate and serotonin

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12
Q

What are the pharmacokinetics for Lithium?

A 
Rapidly absorbed
Widely distributed
No protein binding
Not metabolized
Excreted unchanged in the urine
T ½ = 18-27 hours
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13
Q

Lithium Adverse Effects early in therapy

A

GI distress (e.g., nausea, vomiting, dyspepsia, diarrhea)
Muscle weakness and lethargy (30%)
Polydipsia with polyuria and nocturia (70%)
Headache, memory impairments,
Hand tremor

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14
Q

Lithium: Adverse Effects later is therapy

A 
renal changes
nephrogenic diabetic insipidous
hypothyroid
wt gain
sexual dysfunction
cardia effects
dermatologic effects
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15
Q

What needs to be monitored with nephrogenic diabetic insipidous during lithium use?

A

Monitor potassium levels

Monitor for lithium toxicity

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16
Q

Monitoring Parameters (baseline and maintenance) for Lithium?

A 
Plasma concentration taken 8-12 hours after last dose 
Acute Mania: 
Every 4-5 days when first started (until stable)
Maintenance: 
           Every 3 months for first 6 months
           Every 6 months thereafter
Renal Function 
Thyroid Function
ECG
CBC
Serum electrolytes
Pregnancy test
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17
Q

At plasma concentrations of lithium > 1.5 mEq/L

A 
GI symptoms 
Decrease in coordination
Severe hand tremor
Unstable gait
Slurred speech
Muscle twitching
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18
Q

At plasma concentrations of lithium > 2.0

A

Seizures, cardiac arrhythmias, neurological impairment, kidney damage, coma, death

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19
Q

Situations that predispose the patient for lithium toxicity?

Treat with?

A 
Sodium restriction
Dehydration
Vomiting, diarrhea
Drug interactions that  lithium clearance
Treat with dialysis
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20
Q

Increase lithium levels (decrease lithium clearance)

Lithium Drug-Drug Interactions

A

Thiazide diuretics, NSAIDs, ACE inhibitors, fluoxetine, salt-restricted diets

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21
Q

Lithium Drug-Drug Interactions

decrease lithium levels (increase lithium clearance)

A

Caffeine, theophylline

22
Q

Pregnancy and lactation associated with lithium? (4)

A

Crosses the placenta
Pregnancy risk category D
May cause “floppy” infant syndrome
Present in breast milk

23
Q

Lithium should be maintained at what?

A

Maintain patient on lowest therapeutic dose
Maintain adequate hydration
Avoid in patients with pre-existing renal disease

24
Q

Valproic Acid is FDA approved for?

A

FDA approved for treatment of acute mania in bipolar I disorder
Better efficacy for mixed states and rapid cycling compared to lithium

25
Q

Valproic Acid is not FDA approved for?

A

maintenance treatment of BD but commonly used as monotherapy or in combination with other agents (e.g., lithium, CBZ, antipsychotics)

26
Q

Valproic Acid MOA

A 
increases GABA levels in CNS
Antikindling properties (may  rapid cycling and mixed states)
27
Q

What do you need to know about valproic acid?

A

what it is used for

migraine prophylaxis, bipolar, seizures

28
Q

Valproic Acid: Adverse Effects (8)

A 
GI upset
Tremor
Rash
Alopecia
Somnolence 
Dizziness
Weight gain
Mild and transient  in LFTs
29
Q

Drug interaction with Valproic Acid

A

Potential drug-drug interaction when used concomitantly with lamotrigine
VA inhibits lamotrigine metabolism by competing with hepatic glucuronidation enzyme site

30
Q

Pregnancy and Lactation for Valproic Acid

A

Pregnancy risk category D: risk of neural tube defects (1-5%) during 1st trimester
Considered compatible with breastfeeding

31
Q

Monitoring (Baseline and maintenance) for Valproic Acid

A

Therapeutic plasma concentrations
Acute Mania and Maintenance: 50-125 mcg/mL (trough)
Toxicity :Serum levels > 200 mcg/mL (can occur as low as 150 mcg/mL)
Visual hallucinations, new onset tremor, motor restlessness, deep sleep, coma
CBC with differential
Chemistry panel with electrolytes
Liver function tests

32
Q

Lamotrigine

A

FDA approved for maintenance treatment of bipolar I disorder
Has both antidepressant and mood-stabilizing effects
May have efficacy for prevention of bipolar depression

33
Q

Lamotrigine MOA

A

Modulates or decreases glutamate release

Antikindling properties

34
Q

Lamotrigine drug interaction

A

When combined with VA, initial and titration dosing should be decreased by 50%

35
Q

Lamotrigine Pharmacokinetics

A

Metabolized via glucuronide conjugation (no CYP involvement)
T ½ = 25 hrs (’d to 59 hrs with VA)
No well-established therapeutic range

36
Q

Lamotrigine adverse effects

A 
Headache, nausea, dizziness, ataxia, diplopia, drowsiness, tremor, rash
Weight neutral (vs. Li+ and VA)
Rash can progress to Stevens-Johnson Syndrome with rapid dose escalation
37
Q

Lamotrigine in Pregnancy

A

Pregnancy risk category C

Not recommended in breast-feeding

38
Q

Carbamazepine MOA

A

Modulates or decreases glutamate release

Antikindling properties

39
Q

Carbamazepine

A

Used as monotherapy or in combination with other agents (e.g., lithium, VA, antipsychotics) for acute and maintenance therapy – NOT 1st Line
autoinducer
2-3wks before effects seen

40
Q

Carbamazepine Pharmacokinetics

A

Hepatically metabolized via CYP 2C8 and 3A4
Pan-inducer of CYP
Induces its own metabolism
T ½ 25-65 hrs initially; 12-17 hrs with multiple dosing
Therapeutic serum levels:
Acute: 4-12 mcg/mL
Maintenance: 4-8 mcg/mL

41
Q

Carbamazepine Adverse effects

A 
Hyponatremia 
Weight gain
Agranulocytosis 
GI
CNS toxicity
42
Q

Carbamazepine Toxicity

A

(at > 15 mcg/mL)

Ataxia, choreiform movements, diplopia, nystagmus, cardiac conduction changes, seizures, coma)

43
Q

Carbamazepine pregnancy and lactation

A

Pregnancy risk category D
Craniofacial deformities, spina bifida, low birth weight
Considered compatible with breast feeding

44
Q

Carbamazepine drug interactions

A

Pan-inducer

increases metabolism of many medications

45
Q

Monitoring parameters of carbamazepine

A

Serum levels every 1-2 weeks during first 2 months of therapy; then every 3-6 months during maintenance
10-12 hours post-dose and at least 5-7 days after a dosage change
CBC with differential
Liver function tests
Serum electrolytes
Dermatologic monitoring

46
Q

Oxcarbazepine

A

10-keto analog of carbamazepine
May have fewer adverse effects and be better tolerated than CBZ
Not FDA approved for treatment of bipolar disorder – NOT 1st line

47
Q

Oxcarbazepine Pharmacokinetics

A 
Hepatic conjugation (? Oxidation at CYP450)
T ½ = 9 hrs (active metabolite)
No established therapeutic range
48
Q

Oxcarbazepine Pregnancy risk?

A

Pregnancy risk category C; not recommended in breastfeeding

49
Q

Acute Mania: Monotherapy or adjunctive therapy antipsychotics for bipolar disorder

A

Aripiprazole - Haloperidol
Olanzapine - Quetiapine
Risperidone - Ziprasidone
Lithium or valproic acid + antipsychotic > efficacy than any of these agents alone

50
Q

Benzodiazepines in Bipolar Disorder

A

Can be used as an alternative to or in combination with antipsychotics for acute mania
Can ↓ agitation, anxiety, panic, insomnia symptoms
Alternative to mood stabilizers in 1st trimester of pregnancy
Lorazepam (Ativan®): intramuscular and oral formulations

51
Q

Antidepressants in Bipolar Disorder

A

Concern of mood switching in patients with bipolar depression
Can precipitate a manic episode
Higher with TCAs or venlafaxine
Recent data suggests adjunctive antidepressant therapy (with mood stabilizers) no better than placebo for acute bipolar depression

Pharm- Antipsychotics (2 decks)

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