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225 Cards in this Set
- Front
- Back
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In bipolar, how much of their adult lives are spent in the hospital and disabled?
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1/4 of their adult lives in the hospital and 1/2 of their lives disabled
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What is difference in manic and hypomanic episode?
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hypomanic are less intense
manic are severe enough to impair functioning hypomanic only has to be present for 4 days |
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What is usually the initial presenting symptom of bipolar?
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depressed mood
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What is a mixed episode?
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pt meets criteria for both a major depressive episode and a manic episode concurrently for at least 1 week period
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What symptoms with mixed episode?
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agitation, insomnia, changes in appetite, psychosis, and suicidality
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How is diagnosis of bipolar I disorder made?
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one or more manic or mixed episodes with or without a depressive episode
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How is diagnosis of bipolar II disorder made?
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one or more episodes of both hypomania and depression, without a history of manic or mixed episodes
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How is diagnosis of cyclothymic disorder made?
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experienced at least 2 years of mood cycling characterized by numerous periods with hypomanic symptoms and separate periods with depressive symptoms that don't meet criteria for major depressive episode
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How is diagnosis of bipolar disorder not otherwise specified made?
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disorders with features of mania or hypomania that don't meet criteria for a specific bipolar disorder
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How long does mood disturbance have to be present for mania diagnosis?
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1 week
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What is prevalence of bipolar I disorder?
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1%
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What is prevalence of bipolar II disorder?
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1.1%
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What is the prevalence of all bipolar disorders?
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4.4%
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Is bipolar I and II more common in males or females?
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females
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Is subthreshold bipolar more common in males or females?
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males
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Is there a genetic linkage to bipolar?
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yes
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Are monozygotic or dizygotic twins more likely to both have bipolar?
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monozygotic
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table 80-1 pg 80-2
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80-2
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What are the target symptoms of bipolar?
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increased talkativeness, staying awake all night, bursts of energy during which projects are begun but rarely completed
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What is flight of ideas?
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rapid speech that switches amonth multiple ideas or topics
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What is delusions of grandeur?
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false beliefs of special powers, knowledge, abilities, importance, or identity
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What is the behavior of manic pts characterized as?
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intrusive, loud, intense, irritable, suspicious, and challenging
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How long does it take for symptoms to develop in mania?
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gradually over several days to more than a week
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What is stage I mania?
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euphoria, irritability, labile affect, grandiosity, overconfidence, racing thoughts, increased psychomotor activity, and increase in the rate and amount of speech
corresponds to hypomania |
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What is stage II mania?
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increased dysphoria (feeling of extreme discomfort and unrest), hostility, anger, delusions, and cognitive disorganization without apparent cause
corresponds to acute mania |
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What is stage III mania?
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manic episode progresses to an undifferentiated psychotic state
experiene terror and panic, behavior is bizarre and psychomotor activity is frenzied, may experience hallucinations progress from disorganized thought patterns to incoherence and disorientation |
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Which symptoms resolve first in mania?
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psychotic
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What is the mean age of onset of bipolar?
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21 years
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Which bipolar has the earliest onset?
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bipolar I, 18 years
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What is age of onset of bipolar II?
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20 years
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What is age of onset of subthreshold bipolar disorder?
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22 years
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At what age does the onset of bipolar decrease?
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age 60, mania later in life may be from underlying medical problem
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What are considered rapid cyclers in bipolar?
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people diagnosed with either bipolar I or II disorder who experience shorter cycle lengths and who suffer from 4+ episodes of depression, hypomania, mania, or a mixed episode in a year
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How often does rapid cycling occur?
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20%
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Are men or women more likely to be rapid cyclers?
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women
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What is prognosis of rapid cycler?
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refractory to conventional tx and suffer significant morbidity and mortality because of rapid changes in mood
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Is relapse common in bipolar?
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yes
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What contributes to higher mortality in bipolar?
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CV disease (natural), suicide and excessive risk taking (unnatural)
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What are risk factors for suicide in bipolar?
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drug abuse, hospitalization for depression, age younger than 35 years, hospitalization within 2 years, previous suicide attempt, family history of affective disorders
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Is mortality reduced in treated bipolar?
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yes
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Are bipolar pts prone to substance abuse?
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yes
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How does bipolar rank for causes of disability adjusted life years in the world?
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6th
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Are bipolar pts more likely to get a divorce?
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yes
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What tx for mixed episodes?
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valproate or atypical antipsychotic more than lithium
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When is carbamazepine used?
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manic episodes, not first line
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When are BDZ used?
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short term, for severely ill or agitated persons
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When is 2 drug combo recommended?
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severe manic symptoms or partially responsive to adequate trial of 1 drug (1-2 weeks)
2 drug combos: lithium, valproate, and atypical antipsychotics |
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What is used for tx resistant bipolar?
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electroconvulsive therapy, clozapine, or 3 drug tx with lithium + anticonvulsant (CBZ, oxcarbazepine, valproate) + AAP
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What are preferred tx for bipolar depression?
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lithium or lamotrigine
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How is lamotrigine used for depression if there is history of severe, recent or recurrent mania?
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only use in combo with antimanic agent
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What are the only FDA approved tx for bipolar depression?
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quetiapine and olanzapine/fluoxetine
2nd line because of metabolic SE |
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What is tx for bipolar depression after failure of 2nd line?
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2 drug combo of lithium, lamotrigine, quetiapine, or olanzapine/fluoxetine
SSRI or SNRI may be used in combo with antimanic |
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What is maintenance for bipolar?
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continue acute phase tx while periodically simplifying and moving toward monotherapy with lithium, valproate, or lamotrigine
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What is the hallmark of a manic episode?
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changes in mood, behavior, cognition, and perception
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What drugs are the most common cause of mania?
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antidepressants (MAOIs, TCA, SSRI, SNRI) and stimulants the most
also CS, anabolic steroids, isoniazid, levodopa, caffeine, OTC stimulants table 80-2 pg 80-5 |
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Can sleep loss cause mania?
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yes
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What can result if mania is untreated?
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confusion, fever, exhaustion, and even death
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What limits lithiums use as a first line?
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narrow therapeutic index, DI, and SE
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When is lithium preferred?
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euphoric mania
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What characteristics predict a poor response to lithium?
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substance abuse, rapid cycling, mixed states, multiple prior episodes
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What is the minimum concentration threshold for valproate?
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45mcg/mL
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At what valproate concentration does risk of SE increase?
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125mcg/mL
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What baseline tests for valproate?
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CBC w/ diff and platelets, LFTs, wt, neurologic status, pregnancy test
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What DI with valproate?
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aspirin, phenytoin, phenobarbital, lamotrigine, rifampin, warfarin, felbamate, carbamazepine
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How long for symptom improvement with valproate?
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5 days
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What AE from valproate?
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GI (nausea, diarrhea, dyspepsia, anorexia), sedation, ataxia, tremor, benign, hepatic transaminase elevations, thrombocytopenia, alopecia, wt gain
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How can GI AE be reduced?
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reducing dose, changing to ER, or administering antacid or H2A
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How are CNS AE (ataxia and sedation) reduced?
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dosage reduction
sedation may resolve with continued tx |
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How is tremor treated for valproate?
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dosage reduction or ER
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How is alopecia treated in valproate?
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dose reduction
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When should valproate be d/c based on LFTs?
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2-3x ULN
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What can be done to minimize wt gain from valproate?
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dose reduction
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What AE from valproate in women?
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polycystic ovary syndrome: oligomenorrhea and hyperandrogenism
clinical features: menstrual irregularities, infertility, hirsutism, alopecia, insulin resistance, hyperlipidemia, obesity |
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What severe AE for valproate presents as a coma or mental status changes?
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valproate induced hyperammonemic encephalopathy
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What is test for hyperammonemic encephalopathy?
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serum ammonise and LFTs, d/c
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What other serious AE for valproate?
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fulminant hepatic failure, agranulocytosis, pancreatitis, d/c
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What is monitoring for valproate after initiation?
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LFTs, valproate serum levels, and CBC w/ diff and plts monthly for first 3 months and every 3-6 months thereafter
wt should be monitored monthly |
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What are signs of thrombocytopenia in valproate?
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easy bruising or bleeding, usually asymptomatic
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Should valproate be d/c for thrombocytopenia?
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usually respond to lower dose, no need to d/c
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What baseline measures for lithium tx?
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pregnancy test, CBC, electrolytes, kidney (BUN/SCr), ECG (45 or older with preexisting cardiac disease), urine specific gravity, TSH, T4, wt/BMI/waist size
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If you have responded to lithium before, are you likely to respond again?
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yes
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What is the goal lithium level for acute management of mania?
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0.5-1.2mEq/L
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How often should lithium level be checked while acute?
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twice weekly until manic episode resolves
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What is t1/2 of lithium?
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24hrs
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When is SS of lithium achieved?
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5 days
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What is onset of action of lithium?
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slow: 1-2 weeks for full therapeutic effects
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What is used as an adjunct in lithium tx until lithiums onset of action?
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BDZ or AAP
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What effects do BDZ work for?
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reduce agitation, anxiety, insomnia
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How often are lithium levels checked?
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weekly x 4 weeks
monthly x 3 months quarterly if symptoms arise |
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What is measured yearly for lithium tx?
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electrolytes, kidney (BUN, SCr), ECG, thyroid function, wt/BMI/waist
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What might happen to lithium level as pt recovers from acute mania?
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increas, because of decreased lithium clearance
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How does tremor present in lithium tx?
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rapid, regular, and fine in amplitude (8-12 cycles/sec)
early in tx and improves over time |
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What increases risk of tremor from lithium?
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caffeine, personal or family history of tremor, alcoholism, anxiety, antidepressants, antipsychotics, possibly increased age
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What is tx for tremor?
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none if not bothered by it
if problematic, can decrease lithium or add BB or switch to SR lithium propranolol 10mg TID |
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What is tx for polyuria in lithium tx?
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decrease dose, once daily dosing with lower trough, amiloride if fail other interventions
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How does amiloride help polyuria?
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antagonize the effect of lithium on free water clearance by reducing the ion entry into renal epithelial cells
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What is diarrhea from lithium associated with?
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high serum levels, once daily dosing, rapidly absorbed preparations
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What is tx for diarrhea from lithium?
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divided doses, lower dose, SR
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What is result of dehydration in lithium tx?
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increasedlithium reabsorption in proximal tubule and results in accumulation to toxic levels
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What is result of SR lithium on serum levels?
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decreased peak and increased trough
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What is used to reduce the risk of renal disease secondary to lithium therapy?
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communication with physician regarding situations that increase the risk of lithium toxicity and cooperation with regular lithium and renal function monitoring
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What ECG changes from lithium?
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T-wave suppression, delayed or irregular rhythm, increase in premature ventricular contraction, sick sinus node syndrome, myocarditis
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How does edema present from lithium?
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primarily ankles and feet, transient and intermittent
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What causes edema from lithium?
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secondary to effects on Na/carbohydrate metabolism
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What can be done to avoid edema from lithium?
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caution about diuretics and Na restriction to avoid lithium toxicity
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What dermatologic AE from lithium?
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Acne, psoriasis, rashes
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What endocrine AE from lithium?
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hypothyroidism (may diminish sex drive), hyperparathyroidism (nonsignificant)
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What AE in pregnancy to fetus from lithium?
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Ebstein anomaly (tricuspid valve malformation, atrial septal defect)
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What hematologic AE from lithium?
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leukocytosis, may counter CBZ induced leukopenia
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Is tremor in lithium worse in men or women?
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men
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What neurologic AE from lithium?
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tremor, cognitive disruption, poor concentration/memore, fatigue/weakness
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Is polyuria a related to more serious renal AE?
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no
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What can increase Li levels?
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dehydration, fever, vomiting, Na restricted diet (should eat diet consistent in amount of Na)
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What are signs of lithium toxicity?
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worsening tremor, slurred speech, muscle weakness or twitches, or difficulty walking
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What OTC should be avoided with Lithium?
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NSAIDs
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What effect does caffeine have on lithium?
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short term: worsen lithium tremor
longterm: lower lithium levels |
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When are lithium levels drawn?
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12hrs after dose, take evening dose and have level drawn before morning dose
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What is mild lithium toxicity?
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levels less than 1.5mEq/L: felling of apathy, lethargy, and muscle weakness accompanied by nausea and irritability
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What is moderate toxicity in lithium tx?
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1.5-2.5mEq/L: symptoms progressing to coarse tremor, slurred speech, unsteady gait, drowsiness, confusion, muscle twitches, blurred vision
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What is severe toxicity in lithium tx?
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greater than 2.5mEq/L: seizures, stupor, coma, renal failure, CV collapse
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What is tx for lithium toxicity?
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stat lithium levels, electrolytes, renal function tests
IV solutions started to hydrate adequately, correct electrolyte abnormalities promptly hemodialysis |
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What is lithium level for IR if drawn before 12hrs?
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falsely elevated
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What is lithium level for SR drawn to soon?
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falsely low
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How does lithium cause hypothyroidism?
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lithium affects the incorporation of iodine into thyroid hormone, interferes with secretion of thyroid hormones, and may interfere with peripheral degradation of T4 to T3
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What are risk factors for hypothyroidism from lithium?
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female, family history in first degree relatives, wt gain, elevated baseline TSH, preexisting autoantibodies, iodine deficient diet, rapid cycling, elevated lithium levels
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Is d/c needed if hypothyroidism?
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no, levothyroxine to normalize
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What s/s of hypothyroidism?
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lethargy, tired, wt gain, depressed, feel cold
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What is result of ingestion of large amounts of salt or caffeine when taking lithium?
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increased levels
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What effect does acute mania have on lithium clearance?
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increase lithium clearance, decrease lithium levels
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What drugs increase lithium levels?
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NSAIDs, diuretics, ACEI
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What causes increase in lithium from NSAIDs?
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enhanced reabsorption of Na and Li secondary to inhibition of prostaglandin synthesis
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What causes increased Li from diuretics?
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Na depletion results in increased proximal tubular reabsorption of Na and Li
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What causes increased Li from ACEI?
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volume depletion and reduction in GFR
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What drugs decrease Li levels?
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theophylline, caffeine, acetazolamide, Na
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How does theophyline and caffeine decrease Li levels?
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increase renal clearance of Li
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How does acetazolamide decrease Li?
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impair proximal tubular reabsorption
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How does Na decrease Li?
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promotes renal clearance of Li
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What drugs increase Li toxicity?
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methyldopa, carbamazepine, CCB, antipsychotics, SSRI
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What causes DI from AP and Li?
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increase in phenothiazine levels, changes in tissue uptake of Li, or DA blocking effects of Li
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What PC is lithium?
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D
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When do most malformations to fetus from Li occur?
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1st trimester
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What effects to fetus from Li?
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cardiac malformations, hypotonia, nephrogenic diabetes insipidus, thyroid abnormalities
increased risk of premature |
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What PC valproate and CBZ?
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D, should be avoided
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What AP is associated with the highest exposure, highest rate of low birth wt and neonatal ICU admission?
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olanzapine
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What monitoring if use Li in pregnancy?
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levels monitored closely, Li clearance increases in 3rd trimester and need dose adjustment
16-18wks after conception: screening tests, high resolution ultrasound, fetal echocardiography used to determine cardiac defects |
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What should be considered before delivery when on Li?
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decrease Li dose before delivery to minimize Li in newborn and to offset reduction in Li excretion that occurs after delivery
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How long for Li d/c?
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gradually over 4 weeks
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How soon can pt restart lithium if d/c for pregnancy?
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as soon as urine output is established and fully hydrated, but it is in breast milk and can affect baby if nursing
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What risk to newborn from Li in breast milk?
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hypothyroidism, cyanosis, hypotonia, lethargy, cardiac dysrhythmias
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What are FDA approved meds for mania in bipolar?
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CBZ, Li, valproate, aripiprazole, olanzapine, quetiapine, risperidone, ziprasidone
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What are FDA approved meds for mixed bipolar?
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CBZ, valproate, aripiprazole, olanzapine, risperidone, ziprasidone
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What are FDA approved meds for depression in bipolar?
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olanzapine/fluoxetine, quetiapine
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What are FDA approved for maintenance bipolar?
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lamotrigine, lithium, aripiprazole, olanzapine
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What concerns from use of AAP?
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metabolic complications: wt gain, glucose dysregulation, dyslipidemia
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Which AAP have the highest metabolic complications?
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clozapine and olanzapine
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Which AAP have intermediate risk for metabolic complications?
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quetiapine and risperidone
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Which AAP have the lowest risk for metabolic complications?
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ziprasidone and aripiprazole
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What other AE for clozapine?
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agranulocytosis, seizures, sialorrhea, anticholinergic SE, orthostasis, sedation
needs frequent monitoring of WBC |
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When is clozapine effective?
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tx resistant mania and long term mood stabilization
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Which AAP cause sedation?
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clozapine, olanzapine, quetiapine, may be beneficial in acute mania
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Which AAP are least sedating?
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aripiprazole and ziprasidone, usually need adjunctive use of BDZ for acute mania
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What is over all best tolerated AAP?
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risperidone, higher risk of serum prolactin elevation and EPS
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If no initial response to AAP, may a different AAP work?
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yes
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Which AAP doesn't require titration?
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aripiprazole
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What is alternative if Li, valproate, and AAP fail?
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CBZ
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How is CBZ dosed?
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100-200mg BID and increase by 200mg every 3-4 days until adequate serum levels reached
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What is recommended target serum level for CBZ?
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4-12mcg/mL, no correlation between levels and response in bipolar established
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What occurs at CBZ levels over 12mcg/mL?
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sedation and ataxia
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What AE for CBZ?
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Neurologic: ataxia blurred vision, diplopia, fatigue are most frequent
hematologic: transient leukopenia, agranulocytosis (rare), thrombocytopenia, aplastic anemia others: hyponatremia, skin rashes, elevation of liver enzymes, wt gain, GI complaints |
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What PC CBZ?
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D
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What does CBZ cause in fetus?
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neural tube defects
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What baseline tests for CBZ?
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CBC w/ diff and plts, LFTs
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How often are LFTs and hematologic tests in CBZ?
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every 2 weeks for 2 months, every 3 months thereafter
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What signs should be monitored for in CBZ tx?
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abnormal bleeding or petechiae, skin rashes, s/s infection, signs of hyponatremia (mental status changes)
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What DI for CBZ?
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induce metabolism/reduce effect: OC, warfarin, theophylline, haloperidol, lamotrigine, TCAs
Increase levels of CBZ/toxicity: erythromycin, cimetidine, fluoxetine, CCB |
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What DI for CBZ and valproate?
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CBZ increase metabolism of valproate, resulting in reduced serum concentrations and efficacy
valproate may inhibit the metabolism of CBZ leading to increased serum concentrations and AE |
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What AE from CBZ/Li combo?
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neurotoxicity, avoid in pts with preexisting neurologic disease
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What advantages of oxcarbazepine over CBZ?
|
improved tolerability and fewer DI
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Does lamotrigine have effect in acute mania?
|
no
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What serious SE from tiagabine?
|
seizures
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What useful combos in bipolar?
|
Li/AAP, valproate/AAP, Li/valproate
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What combo should be avoided in bipolar?
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CBZ/clozapine: increased risk of hematologic AE
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What are BDZ and AP useful in treating?
|
agitation, irritability, hyperactivity associated with acute mania
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What dosage form is preferred for acute mania?
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PO (liquid/ODT)
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What is used for uncooperative pts?
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IM BDZ or AP
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What AAP are available in rapid acting IM?
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ziprasidone, aripiprazole, olanzapine, effective for manic and mixed episodes
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When can dose of IM AAP be repeated?
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2-4hrs after 1st dose
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Which AAP shouldn't be used with BDZ?
|
IM olanzapine: excessive sedation and cardiorespiratory depression
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What is the preferred BDZ for acute manic agitation?
|
lorazepam
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What benefits from lorazepam?
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IM and PO, lack of active metabolite, safety in hepatic and renal impairment
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What are primary concers for BDZ in agitated mania?
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sedation and potential abuse and addiction
addiction unlikely because inpatient for short term |
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What is risk of acute bipolar depression?
|
suicide
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Is Li effective in acute bipolar depression?
|
yes
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What serum concentration for acute bipolar depression for Li?
|
higher, 0.8mEq/L or higher
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Is lamotrigine effective for tx of acute bipolar depression?
|
yes
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What DI for lamotrigine?
|
lamotrigine metabolism is affected by concomitant use of enzyme inducing (CBZ) and enzyme inhibiting (valproate) drugs, need dose adjustment
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How long is lamotrigine titrated up?
|
6 weeks to 200mg/day from 50mg/day
taking enzyme inducers:7 weeks to 400mg/day from 50mg/day taking enzyme inhibitor (valproate): 6 weeks to 100mg/day from 25mg every other day |
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What common AE for lamotrigine?
|
dizziness, HA, ataxia, sedation, blurred vision, GI disturbances
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What life theatening AE for lamotrigine?
|
SJS, increase dose quickly and receiving valproate
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What is target dose of quetiapine in bipolar depression?
|
300mg/day
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What AE most common from quetiapine cause d/c?
|
dry mouth, sedation, somnolence, dizziness
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How does efficacy of olanzapine/fluoxetine compare to lamotrigine?
|
superior to lamotrigine
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Whay are quetiapine and olanzapine/fluoxetine 2nd line for bipolar depression?
|
metabolic complications
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What are the only FDA approved meds for acute bipolar depression?
|
quetiapine and olanzapine/fluoxetine
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When are antidepressants considered for bipolar depression?
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only after Li, lamotrigine, quetiapine, or olanzapine/fluoxetine have failed
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Should antidepressant monotherapy be used in bipolar?
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no
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What is goal of maintenance therapy in bipolar?
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increase in interval between episodes, decrease in frequency of episodes, reduction in duration and severity of single episodes
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Is Li effective in maintenance of bipolar?
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yes, clearly reduces the frequency and severity of mood episodes in pts with bipolar disorder
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What is added benefit of Li in maintenance?
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reduce suicide
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What are target levels for maintenance therapy for Li?
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0.5-0.8mEq/L
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How often is Li monitored once stable?
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every 3 months
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Will relapse occur if d/c Li?
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most times
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How long for maintenance Li tx?
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may need for lifetime
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When does Li d/c induced refractoriness occur?
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pts who once responded to Li and then had it d/c
fail to respond to reintroduction of Li |
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Do rapid cyclers respond to Li?
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most have poor response
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What are alternatives to Li for maintenance?
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valproate and lamotrigine
AAP (aripiprazole and olanzapine approved) |
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Is CBZ used for maintenance?
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little evidence
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What limits the use of olanzapine longterm?
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metabolic complications
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Is exercise encouraged in bipolar?
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yes
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What herbals/dietary supplements for bipolar?
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omega-3 FA (may cause mania or hypomania symptoms)
inositol (bipolar depression) St. John's wort and S-adenosyl-L-methionine (depressive episodes, should be avoided because of risk of switching to mania) chromium (acute depressive episodes IV Magnesium (tx resistant acute mania) |
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When is ECT beneficial?
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acute mania, mixed states, depression, and tx to prevent relapse
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What is pretx for ECT?
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short acting barbiturate, skeletal muscle depolarizing agent, and atropine
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What meds may raise seizure threshold and interfere with seizure induction in ECT?
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anticonvulsants and BDZ
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What AE for Li in ECT?
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increase confusion and memory impairment after ECT
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What meds seem safe in ECT?
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AP
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