Term
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Definition
SCHIZOPHRENIA - disorganized in language and behavior; hallucinations
schizophreniform disorder - not quite classified as schizophrenia
bipolar disorder with psychotic features
major depression with psychotic features
schizoaffective disorder - schizophrenia and a mood portion
delusional disorder - parinoid about one particular thing or delusional about one thing
psychosis due to medical condition - treatment for PD, syphilis, tumor
substance-induced psychotic disorder: cocaine, LSD |
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Term
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Definition
complete physical and neurological exam
conduct mental status exam
full laboratory screen
toxicological screen
brain imaging (CT or MRI) - not routinely done |
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Term
| age of onset of schizophrenia in men and women |
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Definition
males (15-30)
females (20-35)
stress is significant in onset (1st semester of college)
90% of males and 25% of females develop before 30 yo |
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Term
| dopamine pathways in the brain |
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Definition
mesolimbic: modulates arousal, memory, and behavior; excess DA in schizophrenia
mesocortical: responsible for higher-order thinking and executive functioning; loss of DA in schizophrenia
nigrostriatal: modulates motor movements
tuberoinfundibular: prolactin regulation (DA inhibits prolactin secretion) |
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Term
| dopamine blockade in which pathway is responsible for EPS? |
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Definition
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Term
| positive symptoms of schizophrenia |
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Definition
HALLUCINATIONS: of the 5 senses; auditory (most common), visual (second most common), tactile, gustatory, olfactory
DELUSIONS: fixed, false beliefs; paranoid, somatic (feeling like something is physically wrong with them, but there isn't), grandiose (feeling like they have special powers, communicating with a special power), ideas of reference, thought broadcasting/insertion
DISORGANIZED THINKING: loose association, tangential thinking, circumstantial, thought blocking, neologisms, word salad (words all over the place and not connected), word clanging, echolalia (repeating everything)
DISORGANIZED BEHAVIOR: disheveled, bizarre, agitated, poor hygiene, inappropriate affect/dress |
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Term
| negative symptoms of schizophrenia |
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Definition
flat affect - no expression on the face
alogia - loss of ability to formulate speech
avolition - lack of motivation or drive
asociality - not socializing with people
anhedonia - decreased ability to experience pleasure
ambivalence - decreased ability to make decisions
lack of insight/judgement |
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Term
| 3 main symptoms of schizophrenia |
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Definition
positive symptoms
negative symptoms
cognitive symptoms |
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Term
| diagnosis of schizophrenia |
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Definition
A.
active psychotic symptoms greater than or equal to 1 month
greater than or equal to 2 of the following: delusions, hallucinations, disorganized speech, disorganized behavior, negative symptoms
only 1 criteria is necessary if delusions are bizarre or hallucinations are running commentary
B.
social/occupational dysfunction: functioning below the highest expected level
C.
duration of illness greater than or equal to 6 months
D.
schizoaffective and mood disorder exclusion
E.
substance/general medical condition exclusion |
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Term
| subtypes of schizophrenia |
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Definition
paranoid
disorganized
catatonic: staring off, non-responsive, repeating what people say
undifferentiated: didn't meet criteria for other 4
residual: no positive symptoms, just negative/cognitive symptoms (common in older age) |
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Term
|
Definition
symptoms of both schizophrenia and mood disorder present
symptoms of schizophrenia are independent of mood episodes
recurrent mood episodes occur over a substantial period of time over the course of the illness (in addition to psychotic symptoms)
patient requires maintenance treatment with BOTH antipsychotic and mood stabilizer |
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Term
|
Definition
PRODROMAL PHASE:
the early stages of schizophrenia
social isolation or withdrawal, impairment of functioning, impaired personal hygiene, blunted affect
ACTIVE PHASE:
bizarre delusions or hallucinations (usually when diagnosed)
RESIDUAL PHASE:
continual negative symptoms |
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Term
| general properties of 1st generation antipsychotics (typicals) |
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Definition
alder
used less often for maintenance treatment
better for positive symptoms of schizophrenia
possible worsening of negative symptoms
generic (cheaper) |
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Term
| general properties of 2nd generation antipsychotics (atypicals) |
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Definition
newer, less risk for EPS
more commonly used; 1st line therapy
positive and negative symptoms improve
may enhance cognitive functioning |
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Term
| first generation antipsychotics: low potency |
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Definition
chlorpromazine
thioridazine |
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Term
| first generation antipsychotics: mid potency |
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Definition
loxapine
molindone
perphenazine |
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Term
| first generation antipsychotics: high potency |
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Definition
trifluoperazine
thiothixene
fluphenazine
haloperidol |
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Term
| properties of high potency first generation antipsychotics: haloperidol, fluphenazine, thiothixene, trifluoperazine |
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Definition
high potency = high D2 blockade
high incidence of EPS - movement disorders
low anticholinergic ADRs
effective for acute psychotic agitation, aggression, positive symptoms |
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Term
| which high potency first generation antipsychotics are available as a long acting injections? |
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Definition
haloperidol decanoate
fluphenazine decanoate |
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Term
| max recommended dose of haloperidol (most prescribed 1 generation antipsychotic) |
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Definition
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Term
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Definition
EPS (dystonic reaction, akathisia, pseudoparkinsonism)
increased prolactin |
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Term
| vehicle of haloperidol decanoate |
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Definition
SESAME OIL VEHICLE
slowly absorbed at IM site
more painful injection |
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Term
| DOSE CONVERSION of haloperidol po to haloperidol IM |
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Definition
| 10-15 x daily PO dose of haloperidol = monthly IM dose |
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Term
| dosing of haloperidol decanoate |
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Definition
CONTINUE PO DOSE x 2-4 weeks after 1st injection
max initial dose = 100 mg (give the rest over 3-7 days) |
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Term
| properties of mid potency first generation antipsychotics: molindone, loxapine, perphenazine |
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Definition
lower risk of EPS and anticholinergic ADRs
Molindone: weight neutral, possible weight loss with use
loxapin: some 5HT-2 antagonism, similar to an atypical AP
perphenazine: used in CATIE trial |
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Term
| properties of low potency 1st generation antipsychotics: chlorpromazine and thioridazine |
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Definition
more sedating (H1 blockade)
orthostatic hypotension (a1 blockade)
high incidence of anticholinergic ADRs: dry mouth, constipation, urinary retention, blurred vision, memory impairment
NOT 1ST LINE AGENTS
too many ADRs and not well tolerated |
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Term
EPS: Acute Dystonia
When does it occur?
risk factors
treatment |
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Definition
acute dystonia - sustained and PAINFUL muscle contractions involving the neck, back, eyes, larynx (laryngospasm can be fatal)
OCCURS: hours to days after initiation of medication
RISK FACTORS: young, male, high doses of high potency typical antipsychotics
TREATMENT:
IM benztropine
OR
IM diphenhydramine |
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Term
EPS: akathisia
when does it occur?
treatment |
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Definition
restlessness, pacing, foot tapping, anxiety, agitation
OCCURS: days to weeks after initiation of mediation
often misdiagnosed as agitation or worsening psychosis
TREATMENT:
beta blockers (propranonlol is better b/c it isn't cardiac specific)
OR
benzodiazepines |
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Term
EPS: pseudoparkinsonism
when does it occur?
risk factors
treatment |
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Definition
mask-like face, shuffled gait, stooped posture, drooling, resting tremor, rigidity
OCCURS: weeks to months after initiation of medication
RISK FACTORS: elderly, female, high-dose antipsychotics
TREATMENT:
benztropine
OR
trihexyphenidyl |
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Term
EPS: tardive dyskinesia
when does it occur?
risk factors
treatment |
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Definition
smooth abnormal movements in mouth, face, eyes, hands, back, or trunk
OCCURS: months to years after initiation of medication
RISK FACTORS: long duration of treatment with typical antipsychotics, older age, female, high dose antipsychotics
possibly irreversible!
AIMS (abnormal involuntary movement scale) q 6 months
TREATMENT:
prevention is the best treatment
use lowest effective dose
switch atypical agent or clozapine (only antipsychotic that can improve TD)
reevaluate need for antipsychotic |
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Term
neuroleptic malignant syndrome
symptoms
treatment |
|
Definition
symptoms: muscular rigidity, hyperthermia, changes in mental status, autonomic dysfunction (changes in BP, tachycardia)
labs: increased CPK
TREATMENT:
DC antipsychotic
supportive care
dopamine agonist (bromocriptine) short term
AND/OR
smooth muscle relaxant (dantrolene)
emergency medical treatment |
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Term
| second generation antipsychotics |
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Definition
clozapine
risperidone
olanzapine
quetiapine
ziprasidone
aripiprazole
paliperidone
asenapine
iloperidone
lurasidone |
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Term
| general properties of 2nd generation antipsychotics |
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Definition
D2 and 5HT-2 blockade
5HT-2 blockade in mesocortical area may enhance DA transmission (relieving negative symptoms)
work well for negative symptoms
inherent "antidepressive" effects
less risk of TD and EPS
EPS occurs and has been reported with most atypicals
FDA class warning:
weight gain, hyperglycemia, new onset of diabetes mellitus
rapid dissociation from the D2 receptors
dissociation from D2 receptors before EPS can develop
5HT-2 blockade regulates DA release
when 5HT-2A is blocked, DA is released in nigrostriatal DA pathway BUT not in the mesolimbic pathway (minimal 5HT-2A receptors here) |
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Term
|
Definition
interacts with 5HT-2 (and other serotonin receptors), M1, H1, alpha1, D1, D2, D3, D4
considered to be the prototype of the atypical antipsychotics
NOT A 1ST LINE AGENT
5HT-2A and D2 antagonist: extremely complex pharmacologic profile |
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Term
|
Definition
decreases violence and aggression
treats refractory psychosis
reduces suicidal ideation (only anti-psychotic that can do this)
improves tardive dyskinesia
least likely to cause EPS |
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Term
|
Definition
LIFE TREATENING AGRANULOCYTOSIS = BBW
SEIZURE RISK (HIGHER DOSES) = BBW
sedation (H1 and M1)
weight gain (H1 and 5HT-2C antagonism) - the worst! (30-40 lbs)
hyperlipidemia/hyperglycemia
sialorrhea (drooling)
anticholinergic effects (constipation)
tachycardia/myocarditis = BBW
orthostasis/hypotension (a1 antagonism)
respiratory depression
QT interval prolongation |
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Term
| MONITORING PARAMETERS FOR AGRANULOCYTOSIS WITH CLOZAPINE |
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Definition
CBC with differential:
WBC must be greater than or equal to 3500/mm^3
ANC must be greater than or equal to 2000/mm^3
watch for clinical s/sx of agranulocytosis:
flu-like symtpoms, fever, sore throat, easy bruising, mouth ulcers |
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Term
| clozapine contraindications |
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Definition
history of drug induced dyscrasia
uncontrolled seizure disorder
WBC < 3500 cells/mm^3
history of a myeloproliferative disorder
current pregnancy
< 16 yo
paralytic ileus |
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Term
|
Definition
brief psychiatric rating scale (BPRS)
CBC with differential (within 7 days of initiation)
physical examination
blood pressure (supine and standing)
oral temperature
pulse
pregnancy test
recommended tests: ECG, liver function tests (AST, ALT, Akl Phos), creatinine, and BUN |
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Term
|
Definition
NON-HEMATOLOGICAL:
supine and standing BP and pulses
HEMATOLOGICAL:
CBC with differential (WBC/ANC):
weekly x 6 months
biweekly x 6 months
monthly thereafter
eosinophils:
eosinophilia = > 4000/mm^3 (hold clozapine)
prolonged elevations -> possible hypersensitivity reaction (fever, rash, myalgias, arthralgias) -> release of vasoactive compounds |
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Term
| clozapine dosing guidelines |
|
Definition
initial dosing: 25 mg/day
monitor for cardiovascular/respiratory collapse
increase by 50 mg/day in first 2 weeks
subsequent increases, no more than once or twice weekly and not to exceed 100 mg/day
maximum dosage = 900 mg/day (over will increase seizure risk)
NO PRN DOSING!!!! |
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Term
| drug interactions with clozapine |
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Definition
phenytoin (inducer) -> decreased clozapine levels
CARBAMAZEPINE -> AGRANULOCYTOSIS
ciprofloxacin (inhibitor) -> increased clozapine levels
BENZODIAZEPINES (LORAZEPAM; CLONAZEPAM) -> RESPIRATORY DEPRESSION
BENZTROPINE OR DIPHENHYDRAMINE -> INCREASED ANTICHOLINERGIC ADRS
epinephrine (contraindicated) -> hypotension
CIGARETTE SMOKING -> DECREASE CLOZAPINE LEVELS |
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Term
|
Definition
dosage: 4-6 mg/day
maximum: 16 mg/day
start dosing low and BID for best tolerability |
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Term
|
Definition
orthostasis
weight gain
EPS
increased prolactin: decreased libido, amenorrhea, osteoporosis, galactorrhea, gynecomastia |
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Term
|
Definition
| water based injection, less painful |
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Term
| dosing frequency of risperdal consta |
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Definition
IM injection given every 2 weeks
microspheres are hydrolyzed over time
CONTINUE PO X 3 WEEKS |
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Term
|
Definition
10-20 mg/day
smokers may require 30-40 mg/day
maximum recommended: 30 mg/day |
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Term
| dosage forms of olanzapine |
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Definition
tablets
OCT
short acting injection (IM)
long acting injection |
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Term
|
Definition
IM ADMINISTRATION WITH BENZODIAZEPINES = SEVERE HYPOTENSION
sedation
dry mouth
constipation
weight gain (second only to clozapine)
hyperlipidemia
hyperglycemia/diabetes |
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Term
| ADRs to zyprexa relprevv (long acting olanzapine injection) |
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Definition
WARNING: POST-INJECTION DELIRIUM/SEDATION SYNDROME
severe sedation (including coma) and/or delirium after each injection
patient must be OBSERVED FOR AT LEAST 3 HOURS in registered facility with ready access to emergency response services |
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Term
|
Definition
300-800 mg/day
max: 800 mg/day
higher doses needed for antipsychotic efficacy
commonly underdosed
25 or 50 mg q HS? only a histamine blocker that is very sedating (not an antipsychotic at lower doses) |
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Term
|
Definition
orthostasis
headache
sedation
weight gain (after olanzapine)
hypertriglyceridemia (after olanzapine) |
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Term
| dose of ziprasidone (geodon) |
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Definition
80-160 mg/day (given BID)
BIOAVAILABILITY INCREASES 2 FOLD WHEN GIVEN WITH FOOD
NEEDS TO BE GIVEN WITH A 500 CAL MEAL BID
maximum: 160 mg/day
Geodon IM (short acting injection): 2 x 20 mg doses in 24 hours |
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Term
| ADRs of ziprasidone (geodon) |
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Definition
IM ADMINISTRATION WITH BENZODIAZEPINES = SEVERE HYPOTENSION
insomnia, nausea, headache
QT prolongation longest among atypicals
ECG required before initiation at some facilities |
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Term
|
Definition
10-30 mg/day
MAX: 30 mg/day
available as a short acting injection (IM)
CAN administer benzodiazepines concomitantly with IM |
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Term
| receptor affinity of aripiprazole |
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Definition
D2 partial agonist/antagonist
5HT-1A partial agonist
5HT-2 antagonist |
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Term
|
Definition
insomnia
anxiety
akathisia - worst of the 2nd generations
headache
nausea |
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Term
|
Definition
6 mg/day (titrate weekly)
MAX: 12 mg/day
taken with food increases bioavailability
dosage forms: OROS capsules, long acting injection paliperidone pamitate |
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Term
|
Definition
tachycardia
nausea
weight gain
dizziness
anxiety
EPS
paliperidone is the major active metabolite of risperidone |
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Term
| dosage of invega sustenna (paliperidone IM) |
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Definition
q monthly dosing (NO ORAL OVERLAP)
initial dose: 234 mg IM deltoid
1 week later: 156 mg IM deltoid
maintenance dose: 117 mg IM deltoid or gluteal |
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Term
|
Definition
| only available as a sublingual tablet |
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Term
|
Definition
ORTHOSTASIS (more potent a1 blockade)
dizziness
sedation
HA
weight gain
nausea
no/minimal anticholinergic ADRs |
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Term
|
Definition
hypothesized to possibly improve cognition (5HT-1 partial agonist)
must be administered with 350 cal meal for full absorption |
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Term
|
Definition
insomnia, akathisia/restlessness, nausea, elevated prolactin
thus far: weight gain and cholesterol changes are minimal |
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Term
| 2nd generation anti-psychotics with available short acting IM injections |
|
Definition
aripiprazole - can be given with a benzodiazepine
olanzapine - DO NOT GIVE WITH BZDs
ziprasidone - MAX: 40 mg/day for QT prolongation risk |
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Term
| anti-psychotics FDA indicated for < or equal to 13 yo |
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Definition
risperidone
olanzapine
quetiapine
aripiprazole
paliperidone |
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Term
| which anti-psychotic is FDA indicated to treat bi-polar disorder? |
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Definition
|
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Term
| which anti-psychotics are FDA indicated to treat autism |
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Definition
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Term
| which anti-psychotic is FDA indicated to treat suicidal behavior associated with schizophrenia? |
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Definition
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Term
| best and worst SGA for weight gain, hyperlipidemia, diabetes |
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Definition
worst:
clozapine > olanzapine
best:
aripiprazole > ziprasidone |
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Term
| highest and lowest SGAs for D2 receptor blockade and EPS |
|
Definition
highest:
risperidone = paliperidone
lowest:
clozapine (minimal) |
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Term
| best and worst SGA for sedation |
|
Definition
worst:
clozapine > quetiapine
best:
lurasidone = aripiprazole |
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Term
| metabolic complications associated with SGAs |
|
Definition
WEIGHT GAIN:
not dose-related
increased appetite and body weight observed in 1st few months of treatment
at 10 weeks of treatment, estimated average weight gain varies from 0.5 to 5 kg
weight gained is difficult to lose; most gain is fat
sedentary lifestyle and poor nutrition
mechanism not fully understood:
5HT-C antagonism
H1 antagonism
insulin and leptin levels affected
clozapine and olanzapine up to 12 kg in 1 year
HYPERGLYCEMIA:
can occur in absence of weight gain
direct effect of SGAs on insulint sensitive target tissues (liver, muscle tissue) and on beta cell function
insulin resistance due to weight gain or change in body fat distribution
monitor:
waist circumference -> baseline and annually
weight
BP
fasting blood glucose
fasting lipid panel |
|
|
Term
| purpose of the CATIE trial |
|
Definition
Clinical Antipsychotic Trials of Intervention Effectiveness
multicenter
NIMH funded study
tested difference between typical (perphenazine; moderate potency) and atypicals
primary outcome: time to discontinuation of treatment of any cause |
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Term
| Results of the CATIE trial |
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Definition
olanzapine = longest duration of treatment
perphenazine = comparable efficacy to SGAs
trial concerns:
74% of the patients d/c'ed tx within 1st 18 months
patients with preexisting TD did not receive perphenazine
only 1 typical AP (at low dosage) was used to compare
30% of patients receiving olanzapine experienced weight gain, hyperglycemia, elevated cholesterol and TGs
recommendation: selection of an AP agent should be individualized |
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Term
| Antipsychotic treatment guidelines: 1st episode |
|
Definition
1st line: second generation antipsychotic
2nd line: SGA, FGA
3rd line: clozapine |
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Term
|
Definition
|
|
Term
| time course of response to antispychotics |
|
Definition
1st week:
decreased agitation, hostility, aggression and improved sleep and appetite
2-4 weeks:
decreased paranoia, hallucinations, bizarre behavior and more organized thinking
6-12 weeks:
decreased delusions, improvement in negative symptoms, ongoing improvements in positive symptoms
3-6 months:
cognitive symptoms improve (with atypical antipsychotics) |
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Term
| pregnancy and antipsychotic use |
|
Definition
typical antipsychotics: category C
higher potency AP preferred to minimize ACh antihistaminergic and hypotensive effects
atypical antipsychotics: category C
clozapine and lurasidone: category B but would never suggest that clozapine be used during pregnancy!!
DC AP 2 weeks prior to delivery |
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