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what are the suptypes of bipolar?
- BIPOLARI-manic or mixed episode +/- major depressive episode
- BIPOLARII- hypomanic episode + major depresseive episode (more common in women)
- CYCLOTHYMIA--fluctuations between subsyndromal depressive and hypomanic episodes
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what is DSMIV criteria for manic episodes
- more than 1 week period of abnormal and persistent elevated mood associated with atleast three:
- inflated self esteem (grandiosity)
- decreased need for sleep
- increased talking (pressure of speech)
- racing thoughts (flight of ideas)
- distractible (poor attention)
- increased activity (either socially, at work or sexually) or increased motor ativity or agitation
- excessive involvement in activities that are pleasrueable but have a high risk of serious consequences --buying sprees, poor judgment in business venture
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what are symptoms of a manic episode?
- decresae sleep**KEY**
- euphoria
- irritability
- expansiveness
- others--psychotic symptoms
- manifestations--pressure speech
- hypererbosity
- physical hyperactivity and agitation
- decresaed need for sleep
- hypersexuality
- extravagance
- impraired judgment
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what is presentation of manic episode
- usually escalates quickly over several days
- changes in sleep cycyle often first clue to episode
- seasonal changes, stressors, sleep deprivation, antidepresssants can precipitate episode
- attention span is usually very short resultuing in flight of ideas
- severe stages o fepisode may resembe schizo with bizarre behavior hallucinations and delusions
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atypical fatures of bipolar
- hypersomnia
- hyperphagia
- leaden paralysis
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what is hypomania?
what is mixed episode?
what is rapid cycling?
- HYPOMANIA--similar to manic episode, however needs only to be present for 4 days and does not impair functioning
- MIXED EPISODE--simultanesou occurence of mania and depressive symptoms for nearly ever day for atleast 1 week period (unresponsive to monotherapy)
- RAPID CYCLING-->= 4 major depressive or manic episodes (manic mixed or hypomanic) in 12 months associated frequcntly with clinicl or subclinical hypothyroidism
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what are factors that affect compliance
- human nature
- side effects
- substance abuse
- missing highs
- lack of insight
- complex medication schedules
- lack of psychosocial support
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what are the agents used to treat bipolar
- LITHIUM--actue and prophylatcic treatment of bipolar dz
- DIVALPROEX SODIUM--approved for treatment of acute mania
- CARBAMAZEPINE--acute manic and mixed episodes
- OLANZAPINE, RISPERIDON, QUETIAPINE, ARIIPRAZOLE, ZIPRASIDONE, ASENAPINE---approved for treatment of actue manic or mixed episodes
- Olanzapine/fluoxetine, quetiapine--fda approved for depressive episodes assoiated with bipolar dz
- lamotrigine, olanazpine, aripiprazole, fda approved for maintenance treatment of bipolar I
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what drugs treat acute mania
- lihium
- valproic acid
- atypical antipsychotics
- carbamazepine
- ADJUNCTIVE--benzos
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treatment for acute bipolar depression
- lamotrigine
- lithium
- valproic acid
- atypical antisychotics
- carbamazepine
- ANTIDEPRESSANTS--use cautiously
-
what are lithium pharmacokinetic
- rapidly and completely absorbed
- widely distributed--distributes to muscle bone and thyroid and approximates
- no protein binding
- excreted renally with no metabolism
- t1/2 20 hours
- enters and leaves the CNS slowly
- narrow therapeutic index
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what is lithium treat
- classic euphoric mania
- good predictors of response--fam history of lithium response, few prevoius episodes
- POOR RESPONSe--rapid cycling disorder, numerous previous episodes ofmania, dysphoric mania, psychotic mania
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what is dosing00intial/maintenance and plasma concentrations
- INITIAL--600mg/day prophylaxis, 900-1200 mg/day acute mania
- MAINTENANCE--titrate by 300-600 mg/day q 2-3 days, target dose usually 900-2400 me/day to reach desired plasma concentrations
- PLASMA CONCENTRATIONS
- acute mania--0.8-1.5 meq/L
- maintenance 0.6-1.2meq/L
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what are intial lithium adverse effects
- abdominal discomfort/nausea
- metallic taste
- fine tremor
- muscle weakness
- lethargy
- polydipsia/polyuria
- headache
- confusion
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what are long term lithium adverse effects
- polydipsia/plyuria
- goiter/hypothryoidism
- benign reversible leukocytosis
- fatigue/lethargy
- weight gain
- ekg changes
- dermatologic effects
-
when serum concentration monitor lithium
- once to twice weekly to start
- once desired concentration attained monitor every 1-2 weeks for 2 months or until concentrations stabilized
- four to five days to reach steady state
- maintenance concnetrations monitorying ever 3-6 months
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what symptoms fall under lithium intoxication at 1.2-1.5 meq/l
- imparied concentration
- lethargy/fatigue
- irritability
- muscle weakenss
- nausea/vomiting/diarrhea
- worsening tremor
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what symptoms fall under lithium intoxicatino at 1.6-2.5meq/l
- disorientation
- confusion
- drowsiness
- coarse rtremor
- vomiting
- ataxia
- muscle fasciculation
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what symptoms fall under lithium intoxication at levels >2.5meq/l
- imparied consciousness
- coma
- arrhtyhmias
- eps
- seizures
- deliurium
- hypotensin
- death
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what is treatment for lithium intoxication
- reduce dose/discontinue
- gastric lavage
- hydration
- incresa sodium intake
- dialysis
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what are lithium drug interactions
- diuretics--primarly thiazide type, reduce clearance by 25-30%
- ace inhibitors--some incresd lithium levels
- xanthings--increas lithium excretion
- NSAIDS caseu reabsorption of NA and LI
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what are good things to take valporate for
- effective in patients less responsive to lithium--rapid cycling patterns, mixed mania
- LOADING DOSE--20mg/kg for rapid stabilization--normal dose being at 5-10mg/kg/day
- dose titrated based on respose and adverse effects--plasma concentrations 50-125mcg/ml
-
adverse effects of valporate
- GI upset
- sedation
- tremor
- weight gain
- hair loss
- increased liver function
- LESS COMMON--impaired platelet function, thrombocytopenia, polycystic ovary disease
- RARE--irreversible hepatic failure, pancreatitis
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what do you use carbamazepine for
- mixed states
- rapid cycling
- neurologia dz
- TEHRAPUETIC RANGE--4-12 mcg/ml
- AUTOINDUCER
- CYPA3A4 substrate
- induced multiple isoenzymes
- response seen in 1-2 weeks
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ADVERSE EFFECTS carbamazepine
- neurotoxic--sedation, dizziness, sipolopia, ataxia
- headache
- gastrointestinal
- leukopenia
- thromocytopenia
- increased LFTs
- rashhyponatreamia
- RARE--agranulocytosis/aplasitc anemia
- SJS
- hepatic failure
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contraindications for carbamazepin
- hypersensitivity to TCAs
- concomitant use of MAOIs
- history of bone marrow depleation
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what do you use olanzapine for
- acute mania
- 10mg/day initially, adjust 5-20 mg/day based on clinical response
- adverse reactions--somnolence, drymouth, dizziness, and weight gain
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what are metabolisms you need tobe aware of of atyical antipsychoitcs
- olanzapine--cyp1a2 and glucuronidation
- asenapine cyp1a2 and glucuronidation
- risperidonecyp2d6
- quetiapine cyp3a4
- aripiprazole cyp 2d6 nad cyp3a4
- ziprasidone primarily non cyp 450 metabolism
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what is treatment for maintanenceof bipolar
- lamotrigine, lithium, olanzapine, aripipraozle, and valporate decrase relapse rate in most studies
- after remission of acute episode continue mood stabilizer wile discontinuing adjunctive treatments treat breakthrough episodes of hypomania or depression wiht short term adjunctive medications
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what is lamotrigene for
- bipolar depression--delays time to occurence of mood episodes, greater effect on depressive episodes, drug interations, enzyme inhibiors increase levels
- adverse effects--headache, dizziness, ataxia, diplopia, drowsiness, tremor, nausea, rash--higher dose for faster tiration, SJS
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whats dosing for lamotrigene
- need to adjust based on concommit drugs--25, 50, 100.
- valproate 25 qod, 25 q day, 25-50 qday
- carbamazepine 50, 100, 100
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