Term
| clinical features of bipolar disorder |
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Definition
age of onset: 15-24 yo
misdiagnosis is common (people will get diagnosed with depression; if bipolar disorder is treated with anti-depressants, it causes mania)
75% of patients report experiencing depression
chronic and recurrent condition
life-long treatment necessary
new-onset bipolar disorder is rare > 60 yo (usually secondary to medication or medical/neurological condition) |
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Term
| etiology of bipolar disorder |
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Definition
NEUROBIOLOGICAL:
disruption of monoamine signaling (DA, NE, serotonin) and the hypothalamic-pituitary-adrenal axis
GENETICS:
multiple genes likely contribute to the risk of developing bipolar disorder
80-90% of patients with bipolar disorder have biological relatives with mood disorders
monozygotic twins - 75% concordance rate
ENVIRONMENT:
obstretric complications, intrauterine viral infections, neurodevlopmental abnormalities in childhood, use of hallucinogenic drugs, psychosocial trauma, change in sleep-wake cycle
PSYCHOSOCIAL STRESSORS:
serve as triggers for initial mood episode |
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Term
| medical conditions that can cause mania |
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Definition
CNS trauma:
brain tumor, stroke, head injury, seizure disorder
endocrine abnormalities:
hyperthyroidism, menstrual related, pregnancy related
infections:
encephalitis, HIV, neurosyphiis
vitamine and nutritional deficiencies (B12)
sleep deprivation |
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Term
| medications that can cause mania |
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Definition
stimulants - amphetamines, cocaine
hallucinogens - LSC, PCP
antidepressants - SSRIs, TCAs
steroids - anabolic, corticosteroids
thyroid hormone - levothyroxine
xanthines - caffeine, theophylline
OTC products - pseudoephedrine, SAM-e, St. John's Wort |
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Term
|
Definition
GIDDINESS
Grandiosity
increased activity
decreased judgment (risky activities)
distractibility
irritability
need for sleep decreased (USUALLY ONE OF THE 1ST SYMPTOMS)
elevated mood
speedy thoughts
speedy speech |
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Term
| DMS-IV criteria for a manic episode |
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Definition
A.
> or equal to 1 week of elevated, expansive, or irritable mood
B.
mood disturbances: > or equal to 3 of the following symptoms (decreased need for sleep, hyperverbal, flight of ideas, distractibility, excessive involvement in pleasurable activities, increase in goal-directed activity
C.
symptoms must NOT meet criteria for mixed episode
D.
mood disturbances severe enought to cause marked impairment, need for hospitalization, or psychosis is present
E.
symptoms not due to substance abuse or general medical condition (hyperthyroidism) |
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Term
| classification of hypomania |
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Definition
less severe form of mania
at least 4 days of persistently elevated mood and associated with > or equal to 3 of the following symptoms:
inflated self-esteem
decreased need for sleep
distractibility
irritability
pressured speech
increased activity or excessive involvement in pleasurable activities
racing thoughts (flight of ideas)
hospitalization NOT required
NO psychotic features |
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Term
|
Definition
D SIGECAPS
depressed mood or anhedonia
sleep (insomnia or hypersomnia)
interest (loss of)
guilt or worthlessness
energy loss
concentration loss
appetite changes (weight loss or gain)
psychomotor agitation or retardation
suicidal ideation |
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Term
|
Definition
males = females
presence of only 1 manic episode (necessary)
episode of depression is not necessary for this diagnosis
the manic episode is not better accounted for by schizoaffective disorder |
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Term
| bipolar disorder: type II |
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Definition
females > males
diagnostic criteria:
presence (or history) of 1 or more major depressive episodes
presence (or history) of at least 1 hypomanic episode
there has never been a manic episode or a mixed episode
the mood symptoms are not better accounted for by schizoaffective disorder
the symptoms cause clinically significant distress or impairment in social, occupational, or other important areas of functioning |
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Term
| bipolar disorder specifiers: mixed episode |
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Definition
characteristics of both MANIA AND DEPRESSION exist at the same time
ex) suicidal with increased agitation/psychomotor movements |
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Term
| bipolar disorder specifiers: rapid cycling |
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Definition
> or equal to 4 mood episodes (mania, depression, mixed episode, hypomania) in 1 year
> women
more difficult to treat |
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Term
| clinical signs and symptoms of bipolar disorder |
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Definition
stage 1 (hypomania):
euphoria, labile mood, grandiosity, overconfidence, racing thoughts, hyperverbal
stage 2 (mania):
irritability, dysphoria, hostility, anger, delusions, cognitive, disorganization
stage 3 (psychosis)
terror, panic, bizarre behavior, hallucinations, disorientation |
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Term
| what is a mood stabilizer? |
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Definition
commonly defined as an agent which treats a phase of bipolar disorder (depression and/or mania) without causing either
in addition, must prevent episodes from occurring (maintenance or prophylaxis)
antidepressants are not mood stabilizers
lithium treats mania and depression and prevents both from occurring |
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Term
|
Definition
acute manic, mixed and hypomanic episodes
acute major depressive episodes in bipolar disorder
maintenance treatment of bipolar disorder
schizoaffective disorder
refractory schizophrenia
refractory depression
assaultive, aggressive, impulsive behavior |
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Term
| what drugs have the strongest evidence for efficacy as mood stabilizers? |
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Definition
lithium
valproate
carbamazepine
lamotrigine
atypical antipsychotics
possibly effective:
oxcarbazepine
topiramate
NDP CCBs (diltiazem)
NOT effective: gabapentin |
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Term
|
Definition
bipolar disorder
approved for acute and maintenance treatment of bipolar disorder
efficacy for:
bipolar mania and depression
bipolar relapse prevention
unipolar depression augmentation
suicidality prevention
MOST EFFECTIVE FOR BIPOLAR DISORDER TYPE I (mania)
less effective for: rapid cyclers and mixed episodes |
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Term
|
Definition
absorption: almost 100%
METABOLISM: NO HEPATIC CYP450 METABOLISM
elimination:
steady state reached in 5 days
t1/2 = 24 hours
blood levels should be drawn 5 days after a dosage change
excretion:
90-95% excreted unchanged by kidneys
interactions are possible with other drugs excreted by the kidneys |
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Term
| lithium plasma level monitoring |
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Definition
NARROW THERAPEUTIC WINDOW
therapeutic plasma levels:
0.8-1.5 mEq/L (acute mania)
0.6-1.2 mEq/L (maintenance)
toxicity may occur if > 1.5 mEq/L
every 300 mg increase in dose will increase lithium plasma levels by 0.15 - 0.35 mEq/L
draw plasma levels 12 hours post dose
obtain plasma level ~5 days after initiating therapy or after dose change
check plasma levels every 1-2 weeks until patient is stable
maintenance plasma levels may be measured every 3-6 months |
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Term
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Definition
once you reach steady state at a therapeutic plasma level, it takes 3-10 more days to see initial response
it may take 2-4 weeks (~21 days) to see full therapeutic effects
patients may be given a benzodiazepine until the lithium begins working |
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Term
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Definition
BASED ON PHARMACOKINETICS:
dose based on plasma level and symptom control
initial: 300-1200 mg/day bid
increase by 300-600 mg q5d depending on lithium plasma level |
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Term
|
Definition
nausea/vomiting
diarrhea
fine hand tremor
muscle weakness
fatigue
lethargy
headache
polydpsia and polyuria
impaired cognitive functioning
"mental clouding or loss of creativity" |
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Term
| managing lithium ADRs: GI upset |
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Definition
take lithium with food
change to ER product |
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Term
| managing lithium ADRs: polyuria/polydipsia |
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Definition
give total dose q HS to decrease urine volume
ADD HZTZ 25-50 MG/DAY AND DECREASE LITHIUM DOSE
adding HCTZ has a paradoxical effect
HCTZ is the treatment of choice for polyuria with lithium
there is an interaction between HCTZ and lithium (competition between Li and Na for renal excretion) and the patient will become toxic if the lithium dose is not decreased |
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Term
| managing lithium ADRs: intentional hand tremor |
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Definition
check for toxicity and consider decreag lithium dose
change to ER product
add propranolol 20-120 mg/d |
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Term
|
Definition
CARDIOVASCULAR:
prolonged QT interval, T-wave flattening or inversion, AV block, bradycardia
DERMATOLOGICAL:
worsen acne, alopecia
ENDOCRINE:
hypothyroidism - have to treat and continue lithium
METABOLIC:
weight gain
HEMATOLOGIC:
BENIGN REVERSIBLE leukocytosis
NEPHROLOGY:
decreased GFR, diabetes insipidus (polyuria, polydipsia) |
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Term
| lithium baseline monitoring |
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Definition
thyroid (TSH) q6 months
renal function (SCr and BUN) q3 months
CBC with diff
electrolytes (hyponatremia)
ECG (patient > 40 yo or preexisting heart condition)
urinalysis (with specific gravity)
pregnancy test (Ebstein's anomaly - pregnancy category D) - most risk in the 1st trimester, clinically used in the 2nd and 3rd trimester |
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Term
| signs and symptoms of acute lithium toxicity |
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Definition
moderate (>1.5 mEq/L):
confusion, sedation, lethargy, muscle weakness, ataxia, dysarthria, nausea/vomiting, slurred speech, fine to coarse hand tremor
severe (>3 mEq/L):
hyperreflexia, delirium, seizures, coma, renal failure, death
patient should be taken to the ER and lithium should be discontinued |
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Term
| what patients are at an increased risk for lithium toxicity? |
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Definition
elderly patients
drug interactions
sodium restricted diets (< 2 g/day)
dehydration, heavy exercise, hot weather
vomiting and severe diarrhea |
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Term
| pharmacokinetic drug interactions with lithium |
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Definition
INCREASE LITHIUM CONCENTRATIONS:
NSAIDS (including COX2 inhibitors) - MOA-enhance reabsorption of Li secondary to inhibition of PG synthesis
diuretics (thiazide diuretics) - MOA-cause Na depletion which causes an increase in proximal tubular reabsorption of Li
ACE inhibitors, ARBs - MOA-volume depletion = decrease in glomerular filtration rate causing decreased Li excretion and increased Li levels
DECREASE LITHIUM CONCENTRATION:
theophylline and caffeine - increase the renal clearance of lithium
OTHER:
alcohol: results in small increase or decreases in Li concentrations |
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Term
| pharmacodynamic drug interactions with lithium and neurotoxicity |
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Definition
No blood level changes, but can result in neurotoxicity!
methyldopa
carbamazepine
CCB (diltiazem, verapamil)
phenytoin
SSRIs (fluoxetine) |
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Term
| indications for valproate for bipolar disorder, advantages and disadvantages |
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Definition
valproate is good to use for rapid cycling or mixed mania
advantages:
lower risk of toxicity
safer in renal disease
less drug interactions (compared to lithium)
disadvantages:
less evidence for relapse prevention
hepatotoxicity
no IM dosage form available |
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Term
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Definition
initial loading dose (give in divided doses): add "0" to weight in lbs (i.e. 150 lbs + 0 = 1500 mg/day)
more of the dose should be given at HS (sedating drug) |
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Term
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Definition
dose-related ADRs:
GI upset (nausea, diarrhea, dyspepsia)
sedation, ataxia
intentional hand tremor
transient elevated LFTs
thrombocytopenia (<100,000 caution; <50,000 DC)
weight gain
amenorrhea - PCOS
other ADRs:
alopecia - zinc and selenium can treat
hyperammonemia = changes in mantal status
rash
pancreatitis |
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Term
| valproate black box warnings |
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Definition
teratogenicity:
fetal neural tube defects - pregnancy category D
should NOT be used in pregnancy (lithium can be used in pregnancy)
hepatotoxicity:
hepatic failure
pancreatitis |
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Term
| monitoring of valproate plasma levels |
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Definition
obtain plasma level 2-3 days after initiating treatment or after dose change
draw plasma levels 12 hours post dose
obtain plasma levels monthly until stable then q3 months
THERAPEUTIC PLASMA LEVEL: 50-125 mcg/mL |
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Term
| other valproate monitoring parameters |
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Definition
LFTs - elevated transaminases, hepatotoxicity
CBC with diff - thrombocytopenia
measure weight - weight gain
check ammonia level - hyperammonemia (unexpected lethargy, vomiting, changes in mental status)
OB/GYN exam - PCOS
pregnancy test - neural tube defects; pregnancy category D |
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Term
| drug interactions with valproate |
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Definition
aspirin and anticoagulants (warfarin):
displacement from protein binding sites
effect: increased risk of bleeding
lamotrigine, lorazepam:
valproate inhibits glucuronidation
effects: increased blood levels of lamotrigine and lorazepam
alcohol and CNS depressants:
augmented CNS depression
effect: increased toxicity of CNS depressants |
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Term
| indications for lamotrigine for bipolar disorder |
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Definition
controlled trials show efficacy for depressed phase of bipolar I and II
FDA indicated for maintenance phase of bipolar I disorder
no anti-manic efficacy
CLINICALLY, MOST USED FOR BIPOLAR TYPE II, DEPRESSIVE EPISODE |
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Term
| lamotrigine dosing: not taking carbamazepine or valproate; taking valproate; taking carbamazepine, phenytoin, phenobarbitol, primidone, rifampin (enzyme inducing drugs) |
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Definition
PATIENTS NOT TAKING CARBAMAZEPINE:
initiate with 25 mg da
max 200 mg da
PATIENTS TAKING VALPROATE:
initiate 25 mg every other day
max 100 mg da
PATIENTS TAKING CARBAMAZEPINE, PHENYTOIN, PHENOBARBITOL, PRIMIDONE, RIFAMPIN (enzyme inducing drugs):
initiate with 50 mg da
max: > 200 mg bid |
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Term
| lamotrigine ADRs and monitoring |
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Definition
ADRs:
dizziness, somnolence, ataxia, N/V, blurred vision, HA
BBW: serious rashes (SJS)
monitoring parameters:
skin for rash
LFTs annually
no plasma blood monitoring necessary |
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Term
| indications for carbamazepine for bipolar disorder |
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Definition
2nd line for bipolar disorder in patients unresponsive to lithium or valproate
treatment of bipolar disorder (mania or major depression) alone or in combo with lithium
less weight gain than lithium or valproate |
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Term
|
Definition
CNS:
sedation, slurred speech, dizziness, ataxia, diplopia
HYPONATREMIA
TRANSIENT LFT INCREASES; cholestatic jaundice
severe rash: rare
BBW:
agranulocytosis (contraindicated to use clozapine and carbamazepine together b/c of agranulocytosis risk)
aplastic anemia |
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Term
| carbamazepine plasma monitoring |
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Definition
obtain plasma level 7 days after initiating therapy or after dose change
draw plasma levels 12 hours post dose
monitoring for toxicity
obtain level weekly during titration; every 3 months or as clinically necessary thereafter |
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Term
| carbamazepine monitoring parameters |
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Definition
liver (ALT/AST) - elevated LFTs, liver damage, hepatitis
CBC - aplastic anemia, agranulocytosis, pancytopenia, bone marrow suppression, thrombocytopenia, leukopenia, eosinophilia
urinalysis and BUN - renal dysfuunction
metabolic panel (electrolytes) - hyponatremia
ECG - aggravation of CHF and arrhythmias
pregnancy test - teratogenicity (pregnancy category D) |
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Term
| drug interactions with carbamazepine |
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Definition
ANTICONVULSANTS: PHENYTOIN, BARBITURATES
induction of AED metabolism, induction of CBZ metabolism
decreased levels of AEDs
decreased CBZ clearance
CYP450 INHIBITORS: DILTIAZEM, ERYTHROMYCIN, ISONIAZID, CIMETIDINE, AZOLE ANTIFUNGALS, FLUOXETINE, FLUVOXAMINE, NEFAZODONE
inhibition of metabolism of CBZ
increased toxicity of CBZ
CYP450 SUBSTRATES: WARFARIN, CYCLOSPORINE, THEOPHYLLINE, VPA, ORAL CONTRACEPTION
induction of metabolism of substrates
reduced effects of concomitant drug therapy
carbamazepine is a potent enzyme inducer (CYP3A4) and autoinducer
onset of enzyme induction ~1 week and max effect at 5 weeks |
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Term
|
Definition
treatment of bipolar disorder, including mania
initiate at 300 mg bid
maintenance dose 1200-2400 mg da given in divided doses |
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Term
|
Definition
better tolerated than CBZ
CNS:
sedation, dizziness, ataxia, HA
HYPONATREMIA: twice as common than with CBZ
rash
nausea |
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Term
| oxcarbazepine monitoring parameters |
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Definition
therapeutic plasma concentration monitoring generally not necessary
metabolic panel (Na): significant hyponatremia may develop |
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Term
| indication of topiramate in bipolar disorder |
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Definition
no established efficacy as monotherapy
may help as an add-on for bipolar I mania/mixed episode with partial response to lithium or VPA
patients ask for this because it causes weight loss (all others can cause weight gain) |
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Term
|
Definition
weight loss (nausea, dyspepsia)
kidney stones
narrow angle glaucoma
oligohydrosis - decreased ability to sweat
metabolic acidosis
COGNITIVE DYSFUNCTION |
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Term
| atypical antipsychotics in bipolar disorder |
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Definition
usually used to help stabilize patients who are acutely manic or agitated
generally not accepted as monotherapy for maintenance, although OLANZAPINE, QUETIAPINE, RISPERIDONE, ARIPIPRAZOLE are indicated for maintenance treatment
PATIENTS WITH MOOD DISORDERS MAY BE MORE SENSITIVE TO EPS, which is a possibility with the atypical antipsychotics |
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Term
|
Definition
feeling more relaxed
improved sleep habits
improved appetite
getting along better with others
improved concentration
feeling less irritable or upset
prevention of relapse of depression or mania
decreased risky behavior (IV drug use, sexually promiscuous behavior) |
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Term
| APA guidelines for bipolar disorder: bipolar type I (mania) |
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Definition
1st line: lithium, VPA, or olanzapine
2nd line: carbamazepine or oxcarbazepine |
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Term
| APA guidelines for bipolar disorder: bipolar type II (depressed) |
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Definition
1st line: lithium or lamotrigine or quetiapine (may add on anti-depressant in more severely ill patients)
other: fluoxetine + olanzapine combination
psychosis or high suicide rate: add olanzapine or electro-convulsive therapy |
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Term
| APA guidelines for bipolar disorder: bipolar mixed or rapid cycling |
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Definition
| 1st line: combination therapy (rapid cycling DC all antidepressants); VPA may be more effective than lithium |
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Term
| antidepressants and mania |
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Definition
| AVOID ANTIDEPRESSANT MONOTHERAPY FOR BIPOLAR DEPRESSION |
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