Mood Stabalizers Flashcards
1
Q
Bipolar I disorder
A
Manic episodes with or without psychosis and/or major depression
- 1 or more manic or mixed episodes (the manic episode
may have been preceded by and may be followed by
hypomanic or major depressive episodes, but these are
not required for diagnosis) * Distinct period of abnormally and persistently elevated,
expansive, or irritable mood, and increased goaldirected activity or energy lasting ≥1 week (any duration
if hospitalized), present most of the day, nearly every day - During the mood disturbance and increased energy or activity, ≥3 (or 4 if irritable mood only) of the following: ▪ Inflated self-esteem or grandiosity ▪ Decreased need for sleep
▪ Pressured speech
▪ Racing thoughts or flight of ideas ▪ Distractibility ▪ Increased activity
▪ Excess pleasurable or risky activity
2
Q
Normal dosing for lamotrigine
A
Start with 25mg for 2 weeks; then 50mg for 2weeks…..and 100mg for 2 weeks…etc.
Dosing usually doesn’t go behind 200mg.
3
Q
Dosing lamotrigine with Depakote
A
(increases plasma levels of Lamictal…..so start at a lower dose of Lamictal):
Start ‘every other day’ 25mg for 2 weeks, then will resume the normal dosing of lamotrigine: 25mg every day for 2
weeks, 50mg every day for 2 weeks….
Dosing not usually beyond 100mg.
4
Q
Dosing lamotrigine with carbamazepine
A
(lowers plasma levels of Lamictal so start at a higher dose):
Start 50mg every 2 weeks, then 100mg every day for 2 weeks…..until reach a level that works for the patient….
Dosing max of 400mg/day.
5
Q
ANC monitoring for patients taking Clozapine
A
recognize what is considered a low ANC and when it may require holding clozapine, and doing follow-up lab work
6
Q
Identify major mood stabilizing drugs
A
7
Q
Apply the pharmacological concepts underlying the use of mood stabilizers.
A
8
Q
Describe the mechanism of action of how the various mood stabilizers work.
A
9
Q
Examine how mood stabilizers act upon, amplify, and modify neural functions, ultimately affecting mood and behavior
A
10
Q
Analyze the use of mood stabilizers in clinical practice, including combination or augmentation strategies
A
11
Q
Understand the art of psychopharmacology including potential advantages, disadvantages and primary target symptoms of various mood stabilizers
A
12
Q
Bipolar II disorder
A
Hypomanic episode with major depression; no history of manic or mixed episode
13
Q
Cyclothymia
A
Hypomanic and depressive symptoms that do not meet criteria for bipolar II disorder; no major depressive episodes
14
Q
Bipolar disorder not otherwise specified
A
Does not meet criteria for major depression, bipolar I disorder, bipolar II disorder, or cyclothymia (e.g., less than one week of manic symptoms without psychosis or hospitalization).
15
Q
Bipolar Clinical Pearls
A
Historically bipolar disorder was referred to as manic depression or manic-depressive illness.
A neurobiological psychiatric disorder is characterized by sustained extreme mood swings from extremely low (depression) to extremely high (manic) and an abnormal increase in energy and activity.
Both phases adversely affect thoughts, behaviors, judgment, and relationships.
Patients rarely present in a manic phase.
16
Q
is it Bipolar
A
Extreme mood swings that occur hourly or daily are very rarely associated with bipolar disorder, and other medical and/or psychiatric diagnoses should be considered and ruled out first (e.g. hypothyroidism, borderline personality disorder, PTSD).
Mania onset after age 40 years of age is more likely due to medical or substance use.
Newly diagnosed mania is uncommon in children and adults older than 65 years.
17
Q
Bipolar w/ Comorbidity - Anxiety Disorders
A
Greater than 50% lifetime comorbidity of anxiety disorders with bipolar illness and these patients appear to have a more difficult course of illness.
Decreased likelihood of recovery
Poorer role functioning and quality of life
Increased risk of suicide attempts
18
Q
Bipolar w/ Comorbidity - Substance-use disorders
A
61% of patients with Bipolar I and 49% of patients with Bipolar II also have coexisting substance-use disorders (most commonly etoh).
19
Q
Bipolar w/ Comorbidity - Personality Disorders
A
One-third of patients with bipolar disorder also have a cluster B (borderline, narcissistic, antisocial, and histrionic) personality disorder.
20
Q
bipolar disorder Etiology
A
The exact cause is not known.
21
Q
bipolar disorder Etiology - predominant theory
A
Kindling Theory - multiple factors that potentially interact and lower the threshold at which mood changes occur. Eventually, a mood episode can start itself and become recurrent. Recurrent mood episodes are associated with repeated physiological insults that add up and kindle, like a spark bursting into fire. This could compromise endogenous compensatory mechanisms, leading to cell apoptosis that in turn causes rewiring of the brain circuits involved in mood regulation and cognition. This can render one more vulnerable to the effects of stressors, increasing risk of future episodes and thus perpetuating the vicious spiral
22
Q
bipolar disorder Etiology - additional theories
A
Environmental:
Sleep deprivation = trigger mania
Hypersomnia = trigger MDE
Traumatic and/or abusive events in childhood
Potential that those with diurnal patterns are affected mostly by both fluctuating light and temperature.
Biological:
Genetics - studies show identical twins are far more concordant for mood disorders than fraternal twins.
Overall heritability of bipolar spectrum disorders has been put at 0.71.
Between 4% - 24% of first-degree relatives of individuals with bipolar I disorder are also diagnosed with bipolar I disorder.
Neural Processes:
Hypersensitivity of melatonin receptors
Structural abnormalities in the amygdala, hippocampus, and prefrontal cortex
Larger lateral ventricles
Biogenic Amines:
Of the biogenic amines, norepinephrine and serotonin are the two neurotransmitters most implicated in the pathophysiology of mood disorders.
White Matter Hyperintensities:
Endocrine Models - Hypothyroidism can cause depression and/or mood instability. Abnormalities have also been found in hypothalamic-pituitary axis due to repeated stress.
23
Q
Treatment of patients with mood disorders should be directed toward several goals.
A
First, the patient’s safety must be guaranteed.
Second, a complete diagnostic evaluation of the patient is necessary.
Third, a treatment plan that addresses not only the immediate symptoms but also the patient’s perspective well-being should be initiated.
24
Q
Treatment of patients with mood disorders first line.
A
Mood stabilizers
25
Treatment of patients with mood disorders w/ si
Lithium - Risk of suicide is reduced 13-fold with long-term maintenance therapy with lithium.
26
Psychopharmacology treatment of bipolar depression
Quetiapine (SGA), olanzapine-fluoxetine (SGA- SSRI), and lurasidone (SGA) have all demonstrated consistent efficacy and are approved for this stage of the disorder.
27
Psychopharmacology treatment of rapid-cycling disorders.
Depakote
28
Psychopharmacology of hypomanic episodes
generally managed with a single mood stabilizer.
29
Psychopharmacology of mild depressive episodes
generally managed with a single mood stabilizer.
30
Psychopharmacology of severe depressive episodes
may require 2 - 3 medications
31
Psychopharmacology of acute mania episodes
may require 2 - 3 medications
32
Acute mania agents
can be used alone or in combination to bring the patient down from the high - think Lithium, Valproate, Carbamazepine/Oxcarbazepine, Clonazepam/Lorazepam, Atypical Antipsychotics
33
Acute Bipolar Depression psychopharmacologic treatment
Many patients who are bipolar in the depressed phase do not respond to treatment with standard antidepressants. In these instances, lamotrigine or low-dose ziprasidone (20 to 80 mg per day) may prove effective.
Electroconvulsive therapy may also be useful for patients with bipolar depression who do not respond to lithium or other mood stabilizers and their adjuncts, particularly in cases in which intense suicidal tendency present as a medical emergency.
34
Acute Bipolar Depression psychopharmacologic treatment - Use of antidepressants
should be avoided or used short term only and with a mood stabilizer.
Antidepressant monotherapy may precipitate mania or induce rapid-cycling disorders between mania and depression.
Antidepressant drugs are often enhanced by a mood stabilizer in the first-line treatment for a first or isolated episode of bipolar depression.
A fixed combination of olanzapine and fluoxetine (Symbyax) has been shown to be effective in treating acute bipolar depression for an 8-week period without inducing a switch to mania or hypomania.
35
A fixed combination of olanzapine and fluoxetine
(Symbyax) - effective in treating acute bipolar depression for an 8-week period without inducing a switch to mania or hypomania.
36
Maintenance treatment of bipolar disorder -
Preventing recurrences of mood episodes is the greatest challenge facing clinicians. Not only must the chosen regimen achieve its primary goal—sustained euthymia—but the medications should not produce unwanted side effects that affect functioning. Sedation, cognitive impairment, tremor, weight gain, and rash are some side effects that lead to treatment discontinuation.
Lithium, carbamazepine, and valproic acid, alone or in combination, are the most widely used agents in the long-term treatment of patients with bipolar disorder.
Lamotrigine has prophylactic antidepressant and, potentially, mood-stabilizing properties.
Lamotrigine appears to have superior acute and prophylactic antidepressant properties compared with antimanic properties.
Very slow increases of lamotrigine help avoid the rare side effect of lethal rash. A dose of 200 mg per day appears to be the average in many studies. The incidence of severe rash (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis) is now thought to be approximately two in 10,000 adults and four in 10,000 children.
Many patients treated with lithium develop hypothyroidism, and many patients with bipolar disorder have idiopathic thyroid dysfunction.
37
the most widely used agents in the long-term treatment of patients with bipolar disorder are
Lithium, carbamazepine, and valproic acid
alone or in combination
38
Lamotrigine
has prophylactic antidepressant and, potentially, mood-stabilizing properties
appears to have superior acute and prophylactic antidepressant properties compared with antimanic properties
Very slow increases of lamotrigine help avoid the rare side effect of lethal rash. A dose of 200 mg per day appears to be the average in many studies. The incidence of severe rash (i.e., Stevens-Johnson syndrome, toxic epidermal necrolysis) is now thought to be approximately two in 10,000 adults and four in 10,000 children.
39
lithium
Many patients treated with lithium develop hypothyroidism, and many patients with bipolar disorder have idiopathic thyroid dysfunction
Lithi-one - (1.0-1.2 per video) per lecture (0.5-1.5) is the ideal therapeutic level
was in 7up & originally used to treat gout
lowest & most narrow therapeutic window 1.0-1.2
40
Mood Stabilizers to be Intimately Familiar with:
lithium
valproate/Depakote
lamotrigine/Lamictal
carbamazepine/Tegretol
Antipsychotics used for mood stabilization will be reviewed in modules 5 & 6
41
lithium side effects
LMNOP
Lithium side effects
Movement/tremors
Nephrotoxicity
HypOthyroid
Pregnancy Problems
42
A side effect of lithium on a fetus
Ebstein's Anomaly
LIThium
Low
Implanted
Tricuspid
43
Lithium Checklist
Lithium level
electrolytes
BUN & Creatinine
CBC
TSH/Thyroid panel
Preg test
44
Valproic Acid aka
Depakote, Depakene, Divalproax, valproate
45
mood stabilizers that are anticonvulsants
Valproate/Depakote
46
Valproate/Depakote mechanism of action
inhibits voltage gates at Na- channels
&
increases GABA (causing a benzo type effect of sedation)
47
Valproate/Depakote
ValproATE the FOLATE causing neural tube defects such as SpinaBidifa
Rare but fatal hepatic necrosis
48
Drugs that cause fatal hepatic necrosis
Ha Ve A Seat
Halothane
Valproic Acid
Acetaminophen
49
carbamazepine/Tegretol uses
CBZ
Cranial Nerve V - Trigeminal defect
Bipolar Disorder
Epilepsy - Zeisures
49
carbamazepine/Tegretol uses
CBZ
Cranial Nerve V - Trigeminal defect
Bipolar Disorder
Epilepsy - Zeisures
50
carbamazepine/Tegretol
risk of Agranulocytosis
- anticonvulsant (acts at the Na- channel receptors & increases GABA)
51
lamotrigine/Lamictal
anticonvulsant (acts at the Na- channel receptors BUT does not affect the GABA receptors)
better suited for the depressive episode
52
lamotrigine/Lamictal side effect
Lam-ITCH-tal
Rash that can progress to Stephen Johnson's Syndrome
53
Oxcarbazepine/Trileptal
Anticonvulsant
54
Topiramate/Topamax
Anticonvulsant
Not FDA approved for mood stabilizers
DOPEamax - a weight loss of 5-15 lbs. but have difficulty with word finding & c/o mental dulling
55
Bipolar II
* Never had a full manic episode; at least 1 hypomanic episode and at least 1 major depressive episode
* Distinct period of abnormally and persistently elevated,
expansive, or irritable mood, and increased goal-directed activity or energy lasting ≥4 but <7days, and
clearly different from usual nondepressed mood,
present most of the day, nearly every day
* During the hypomanic episode, ≥3 (or 4 if the irritable mood only) of the following:
▪ Inflated self-esteem or grandiosity
▪ Decreased need for sleep
▪ Pressured speech
▪ Racing thoughts or flight of ideas
▪ Distractibility
▪ Increased activity
▪ Excess pleasurable or risky activity
* Change in functioning that is uncharacteristic of a person
* Not severe enough to cause marked impairment; not
due to a medical condition or substance use; no psychosis
* Change in functioning that is uncharacteristic of person* Not severe enough to cause marked impairment; not
due to a medical condition or substance use; no psychosis
56
Bipolar I and II - Major depressive episode
* During the major depressive episode, ≥5 of the following symptoms
are present during the same 2-week period, and represent a change
from previous functioning. At least one of the symptoms is either depressed mood or loss of interest or pleasure:
▪ Depressed mood most of the day, nearly every day
▪ Markedly diminished interest or pleasure, nearly every day
▪ Significant weight loss when not dieting or weight gain, or
decrease or increase in appetite, nearly every day
▪ Insomnia or hypersomnia, nearly every day
▪ Psychomotor agitation or retardation, nearly every day
▪ Fatigue or loss of energy, nearly every day
▪ Feelings of worthlessness or excessive or inappropriate guilt (which may be delusional), nearly every day
▪ Diminished ability to think or concentrate, or indecisiveness,
nearly every day
▪ Recurrent thoughts of death (not just fear of dying), recurrent
suicidal ideation with or without a specific plan.
57
Cyclothymia is
For at least a two-year period, there have been episodes of hypomanic and depressive experiences which do not meet the full DSM-5 diagnostic criteria for hypomania or major depressive disorder.
58
Cyclothymia - Criteria:
* Present at least half the time during a two year period, with not more than two months of symptom remission.
* There is no history of diagnoses of manic, hypomanic, or a depressive episode.
* The symptoms cannot be accounted for by a psychotic
disorder, such as schizophrenia, schizoaffective disorder,
schizophrenifrom disorder, or delusional disorder.
* The symptoms cannot be accounted for by substance
use or a medical condition.
* The symptoms cause distress or significant impairment
in social or occupational functioning.
59
Lithium is FDA approved for
Manic episodes & Maintenance treatment of manic depressive patients with a history of mania
60
Lithium off label uses
Bipolar Depression
MDD (Adjunct)
61
Lithium & Dementia???
Lithium studies in humans show a
strong association of reduced risk of dementia. ▪ At present very low doses 25 mg/day of lithium can be
considered for at risk persons such as those with genetics
for dementia or middle-aged
62
Lithium Pharmacologic Actions
Rapidly absorbed by oral administration
Excreted by kidneys
Half-life 18-24 hours in young adults, shorter in children, and longer in older adults
Peak serum concentrations occurring 1 to 1.5 hours with standard preparations, 4 to 5 hours with controlled release
Equilibrium reached 5 to 7 days of regular intake
Excretion increases during pregnancy but decreases after delivery; Excreted in breast milk
63
Lithium Therapeutic Indications - Manic Episodes
▪ Controls acute mania and prevents relapse in 80% of persons with Bipolar 1 disorder
▪ Relatively slow onset of action for antimanic effects over 1 to 3 weeks
▪ Use uses a benzo, antipsychotics, or Depakote added the first few weeks.
64
Lithium Therapeutic Indications - * Bipolar Depression:
Shown to reduce incidence of suicide with Bipolar six or sevenfold
* Can be augmented with Depakote or Tegretol with little risk of precipitation of mania
* When depression occurs while the patient taking maintenance Lithium,
* Rule out differential diagnosis
* Can increase lithium concentrations to 1-1-1.2mEq/L or add liothyronine (Cytomel) - thyroid hormone
65
Lithium Therapeutic Indications - additional uses
OCD,
ADHD,
Eating Disorders,
Phobias,
Aggression,
PMDD,
Cognitive Disorders
66
Drug Interactions with Lithium & NSAIDs
may reduce lithium clearance and
increase serum concentration
67
Drug Interactions with Lithium & Thiazide diuretics
reduced renal clearance and
increased serum concentrations
68
Drug Interactions with Lithium & ACE inhibitors
reduced lithium clearance,
increase concentrations, and toxicity
69
Drug Interactions with Lithium & Metronidazole
increases lithium concentration
70
Lithium Adverse Effects - Neurological
Tremor, slowed reaction time, memory difficulties *
Toxic: ataxia, coarse tremors, neuromuscular irritabilities, seizures, coma, and death
71
Lithium Adverse Effects - Endocrine
Goiter
hypothyroid
(rare) - hyperthyroidism
72
Lithium Adverse Effects - Cardiac
Benign T wave changes
73
Lithium Adverse Effects - Renal
Morphological changes
polyuria
reduced GFR
74
Lithium Adverse Effects - Dermatological
Acne
hair loss
psoriasis
rash
75
Lithium Adverse Effects - GI
N/V/D
Appetite loss
76
Lithium Adverse Effects - other
Weight gain
fluid retention
77
Signs & Symptoms of Lithium Toxicity - Mild to moderate (1.5-2.0)
* Vomiting, abdominal pain
* Ataxia, dizziness, slurred speech, nystagmus, muscle
weakness
78
Signs & Symptoms of Lithium Toxicity - Moderate to severe (2.0-2.5)
Anorexia, persistent N/V
Blurred vision, clonic limb movements, hyperactive deep
tendon reflexes, convulsions, delirium, coma, stupor
79
Signs & Symptoms of Lithium Toxicity - Severe (>2.5)
* Convulsions, oliguria and renal failure, and death
80
Management of Lithium Toxicity
Contact the provider or go to the emergency room
D/c lithium
Vital signs and neurological exam
Draw lithium levels, serum electrolytes,
renal tests, and EKG
Emesis, gastric lavage, and absorption
with activated charcoal
For any patients with lithium levels greater
than 4.0 mEq/L hemodialysis
81
Lithium Dosing - For oral dosage forms (capsules, solution, and tablets):
* For acute mania:
* Start 300mg 2 to 3 times daily then titrate upward as
indicated by plasma levels.
* For long-term treatment of mania:
* Adults and children 7 years of age and older weighing
more than 30 kilograms (kg)—300 mg to 600 mg 2 to 3
times a day.
* Children younger than 7 years of age—Use is not recommended
82
Lithium Dosing - * For oral dosage form (extended-release tablets):
* For long-term treatment of mania:
* Adults and children 12 years of age—600 milligrams
(mg) 2 times a day, or 3 times a day up to 1200 mg per
day.
* Children younger than 12 years of age—Use is not
recommended.
83
Lithium Monitoring - Tests:
Before initiating, kidney function tests, TSH, EKG in those
over 50 yrs.
Monitoring – Kidney function 1 – 2 x per year; frequent
monitoring of trough levels; Monitor for metabolic
syndrome (BMI, Weight, Lipids, A1c)
84
Lithium Monitoring - Patient Education:
* the Last dose of Lithium should be approx. 12 hours before
lab draw
* Avoid sudden changes in diet or fluid intake
* Caffeine and alcohol act as diuretics and can lower serum
concentrations
* Changes in exercise (more vigorous) may affect lithium
levels
85
Valproic Acid (Depakote) - Therapeutic level
50-100 mcg/mL
86
Valproate/Depakote - FDA-approved 4
* Acute mania and mixed episodes (Divalproex ER,
Valproic Acid delayed-release)
87
Valproate/Depakote is used off-label for
* Maintenance treatment of bipolar disorder
* Bipolar depression
* Psychosis, Schizophrenia (adjunctive)
* Dementia with behavioral disturbances
88
Valproic Acid (Depakote) Pharmacologic Actions
- Biochemical basis remains misunderstood
- Possible mechanism with GABA activity, modulation of sodium channels, action on extrahypothalamic neuropeptides
- Readily absorbed 1 to 2 hours after oral administration with peak concentrations occurring 4 to 5 hours after oral administration
- Plasma half-life is 10-16 hours
- Highly protein bound
- Extended-release option produces lower peak
concentrations and higher minimum concentrations
and can be given once a day.
89
Valproic Acid (Depakote) Therapeutic Indications - Acute Mania:
* About 2/3 of persons with acute mania respond within 1 to 4
days of achieving serum concentrations of 50 mmol/L
* Gradual dosing may achieve serum concentrations within 1 week; rapid loading achieve serum concentrations within 1 day and control symptoms within 5 days.
* Can be augmented with Tegretol or Antipsychotics
90
Valproic Acid (Depakote) Therapeutic Indications - Acute Bipolar Depression
More effective in treatment of agitation than dysphoria
Used as adjunct to antidepressant
91
Valproic Acid (Depakote) Therapeutic Indications - Schizoaffective/Schizophrenia:
May accelerate response to antipsychotic therapy
Ineffective if used alone for psychotic symptoms
92
Valproic Acid (Depakote) Therapeutic Indications - other
Alcohol withdrawal and relapse prevention
* Panic disorder
* PTSD
* Impulse control
* Personality disorders
* Behavioral agitation
* Dementia
93
Valproic Acid (Depakote) Adverse Effects - Common
* GI Irritation
* Nausea
* Sedation
* Tremor
* Weight Gain
* Hair Loss
94
Valproic Acid (Depakote) Adverse Effects - Uncommon
V/D,
ataxia,
persistent elevated hepatic transaminases
95
Valproic Acid (Depakote) Adverse Effects - Rare
Platelet dysfunction,
agranulocytosis,
edema
96
Valproic Acid (Depakote) Dosing
Usual dose range Mania: 1,200-1,500 mg/day
97
Valproic Acid (Depakote) How to Dose
Usual starting dose for mania is 15mg/kg in 2 divided
doses (once daily for ER)
Acute mania (adults): initial 1000mg/day increase
dose rapidly; generally 60mg/kg/day
Less acute mania (adults): 250-500mg on first day
and titrate upward as tolerated
97
Valproic Acid (Depakote) How to Dose
Usual starting dose for mania is 15mg/kg in 2 divided
doses (once daily for ER)
Acute mania (adults): initial 1000mg/day increase
dose rapidly; generally 60mg/kg/day
Less acute mania (adults): 250-500mg on first day
and titrate upward as tolerated
98
Valproic Acid (Depakote) Monitoring - Tests:
* Prior to starting: baseline hepatic panel, CBC with
platelet counts, and pregnancy tests
* Recurrent – LFTs, VPA level, and Platelets over first
few months and then 1 – 2 x per year thereafter.
* Plasma drug levels – Assist with monitoring efficacy,
side effects, compliance
* Monitor Metabolic syndrome
99
Lamotrigine (Lamictal) - FDA-approved
Maintenance of bipolar I
100
Lamotrigine (Lamictal) - off label
Bipolar Depression
* Bipolar mania (Adjunct and second line)
* Neuropathic pain//chronic pain
* MDD (Adjunct)
101
Lamotrigine (Lamictal) - Actions
* Completely absorbed
* Steady-state plasma half-life of 25 hours
* Rate of metabolism depends on which drugs are coadministered
* Dosing is escalated slowly to BID dosing
* Food does not affect absorption
* Modestly increases serum serotonin concentrations,
possibly through inhibition of serotonin reuptake
* “Stabilize mood from below”
102
Lamictal Adverse Effects
Dizziness
* Ataxia
* Somnolence
* Headaches
* Blurred vision
* Nausea
* **Rash-common and occasionally very severe drug should be d/c if develops can manifest to Steven Johnson’s syndrome.**
▪ Concurrent Depakote doubles Lamictal serum concentrations
103
Lamotrigine - Dosing
* Usual dosing is to 200 mg/day
* 100 mg/day with the combination of Depakote
* 400 mg/day with inducer antiepileptic drugs
carbamazepine, phenobarbital, and phenytoin
104
Lamotrigine - How to Dose
▪ Adults start 25 milligrams (mg) of lamotrigine once a day for 2 weeks, then 50 mg once a day for 2 weeks. You may increase to 100mg/day thereafter. Dose is usually not more than 200 mg a day.
▪ Adults taking Depakote start 25 mg of lamotrigine once every other day for 2 weeks, then 25 mg once a day for 2 weeks. After this, you may increase to 50 mg/day for 2 more week. Dose is usually not more than 100 mg a day.
▪ Adults taking carbamazepine, phenobarbital, phenytoin, or primidone start 50 mg of lamotrigine once a day for 2 weeks, then a total of 100 mg divided into 2 smaller doses each day for 2 weeks. Dose is usually not more than 400 mg a day.
105
Carbamazepine (Tegretol) - Therapeutic levels
4-12 mcg/mL
106
Carbamazepine (Tegretol) - Off Label
* Bipolar Depression
* Bipolar Maintenance
* Psychosis, Schizophrenia(adjunctive)
107
Tegretol Pharmacologic Action
* Absorption is slow and unpredictable
* Food enhances absorption
* Peak plasma concentrations reached 2 to 8
hours after a single dose; steady-state reached 2
to 4 days on steady dose.
* Half-life ranges from 18 to 54 hours, avg. 26
hours
* Metabolized in the liver
* Activity of treatment of Bipolar Disorder is
unknown
108
Tegretol Drug Interactions
* Decreases serum concentrations of numerous
drugs as a result of hepatic CYP3A4
* Decreases blood concentrations of oral
contraceptives; resulting in breakthrough
bleeding and uncertain prophylaxis against
pregnancy
* Should not be administered with MAOIs and
they should be d/c 2 weeks before starting
Tegretol
* If used with Depakote, decrease Tegretol dose
because Depakote replaces binding on proteins
and the dosage of Depakote may need to be increased.
109
Tegretol is induced by
Decreases serum concentrations of numerous
drugs as a result of hepatic CYP3A4
110
Tegretol Adverse Effects
Pancreatitis
Rash - *Steven Johnson’s Syndrome
Hepatic Failure
GI disturbances
Vertigo
Double or blurred vision
Hematologic effects -
*Agranulocytosis
*Aplastic anemia
111
Tegretol Dosing
* Target dose for antimanic is 1,200 mg/day
* For ages 13 and older for Bipolar Disorder:
* Initial 200mg BID daily, each week increase
by 200 mg/day in divided doses (max:
1,200 mg/day for adults and 1,000 mg/day
children under the age of 15).
* Maintenance usually 800-1,200 mg/day
112
Oxycarbamazapine (Trileptal) - Notes
113
Oxycarbamazapine (Trileptal) - Actions
Structurally related to carbamazepine
* Peak concentrations within 45 mins.
* Half-life is 2 hours Tremor
114
Oxycarbamazapine (Trileptal) - Side effects
* Sedation and nausea most common
* Does not have increased risk of serious blood dyscrasias hematologic monitoring not required
* More likely to cause hyponatremia-check BMP
115
Oxycarbamazapine (Trileptal) - Dosing
150-2,400 mg/ day in divided doses of twice a day
Typically used between 900-1,200 mg/day with starting dose of 150-300 mg at night.
116
Gabapentin (Neurontin) Indications
Epilepsy, pain management
117
Gabapentin (Neurontin) - Adverse Effects
somnolence,
ataxia, fatigue (dose-dependent),
is excreted through breast milk
118
Gabapentin (Neurontin) - Interactions
bioavailability may decrease as much as
20% when administered with antacids.
119
Gabapentin (Neurontin) - Dosing
* generally start
300mg day 1,
600mg day 2, and
900mg day 3, and
can increase
subsequently to
1,800 mg/day.
Results can be seen
in as low as 200- 300mg/day
120
Topiramate (Topamax) - Indications
Epilepsy, migraine prevention, obesity treatment, binge eating, bulimia, and alcohol dependence
121
Topiramate (Topamax) - Action
GABAnergic effects and increases cerebral GABA in
humans
Not affected by food; excreted by kidneys
122
Topiramate (Topamax) - Adverse Effects
weight loss, paresthesia, somnolence, dizziness, anorexia, memory problems, activation of suicidal
ideation and behaviors
Affects acid-base balance can assoc. with cardiac
arrhythmias and formation of renal calculi-encourage
plenty of fluids
123
Topiramate (Topamax) - Dosing
usual dose 50-300 mg/day Bipolar Disorder
Start 25-50 mg/day, increase each week by 50
mg/day administered in 2 divided doses
124
Mood Stabilizer Overview
Lithium is recommended for suicidal ideation. Risk of suicide is reduced 13-fold with long-term maintenance therapy with lithium.
* Depakote is preferred for rapid-cycling disorders.
* Hypomanic episodes and mild depressive episodes are
generally managed with a single mood stabilizer. Acute mania and severe depressive episodes may require 2 - 3 medications.
* Use of antidepressants should be avoided or used short term only and with a mood stabilizer. Antidepressant monotherapy may precipitate mania or induce rapid-cycling disorders between mania and depression.
* Antidepressant drugs are often enhanced by a mood stabilizer in the first-line treatment for a first or isolated episode of bipolar depression. A fixed combination of olanzapine and fluoxetine (Symbyax) has been shown to be effective in treating acute bipolar depression for an 8-week period without inducing a switch to mania or hypomania
- Preventing recurrences of mood episodes is the greatest challenge facing clinicians. Not only must the chosen regimen achieve its primary goal---sustained euthymia—but the medications should not produce unwanted side
effects that affect functioning. Sedation, cognitive impairment, tremor, weight gain, and rash are some side effects that lead to treatment discontinuation
- Electroconvulsive therapy may also be useful for patients with bipolar depression who do not respond to lithium or other mood stabilizers and their adjuncts, particularly in
cases in which intense suicidal tendency presents as a medical emergency
