Lecture 6 - Schizophrenia Spectrum Disorder Flashcards
Positive Schiz symptoms
Delusions = false beliefs
Hallucinations = sensory perception w/ no basis
Disorganized speech
Grossly disorganized/catatonic behavior
Negative Schiz symptoms
Blunted affect
Alogia = cant speak
Avolition
Anhedonia = trouble w/ pleasure
Asociality
DSM - 5 Schiz Diagnosis
2> symptoms (pos/neg/cognitive) for atleast 1 month
> 1 symptoms must be Delusions, Hallucinations, disorganized speech
1> areas of function (work, relationships, self care) marked below prev lvl
Duration lasting at least 6 month, at least 1 month of symptoms
** Doesn’t meet criteria for Schizoaffective or modo disorders, substance/general medical condition, or hx of autism spectrum disorder **
Mesolimbic pathophysiology
Excess DA = Positive sx
txm w/ DA antagonist = relief of positive sx
Mesocotical pathophysiology
Low DA = negative n cognitive sx
txm w/ DA antagonist = worsen neg symptoms
Nigrostriatal pathophysiology
Normal DA = no dysfunction
txm w/ DA antagonist = extrapyramidal sx
Tuberoinfundibular pathophysiology
Normal DA = no dysfunction
txm w/ DA antagonist = hyperprolactinemia
Schiz Txm approach
acute phase = 1-2 wks ( dec symptoms, develop plan)
Stabilization = 3-4 wks ( dec symptoms, optimize regimen)
Maintenance = Life long, inc QoL, Functioning, prevent relapse
1st Gen anti psych indications
Acute agitation n delirium usually what used for
Which FGA used for Tourettes syndrome
Haloperidol
pimozide
Which FDA used in N/V
Chlorpromazine
Perphenazine
Prochlorperazine
Which FGA used for Intractable hiccups
Chlorpromazine
First Gen Antipsychotic MoA
1st = blockade of DA2 receptors in mesolimbic area and mesocortical area of brain
FGA Dosing
start low, titrate to lowest effective dose
usually see effects within few days, full benefit 4-6wk
D/c should be slow taper over several weeks to months
FGA acute txm
inc dose until behavior improves or SE
IM/Iv formulations are 2-4x more potent and should only be used in acute setting
Extrapyramidal symptoms
most common w/ FGA, onset within 2-3wk of starting txm or dose inc
Pseudoparkinonism = symptoms of Parkinson’s disease (rest tremor, shuffle, etc)
Akathisia = unable to stay still
Acute dystonia = spastic muscle movement w/in 24-96hr dose change
How to help treat Pseudoparkinonism symptoms
dose dc or add anticholinergic (benzotropine)
How to help treat Akathisia symptoms
dose dc or switch antipsychotic, add propranolol or anticholinergic
How to help treat Acute dystonia symptoms
Mod/severe = IV/IM benztropine 1-2mg or diphenhydramine 25-50mg
Mild = PO benzotropine 1-2mg QD or BID
How to help treat Acute dystonia symptoms
Mod/severe = IV/IM benztropine 1-2mg or diphenhydramine 25-50mg
Mild = PO benzotropine 1-2mg QD or BID
Tardive Dyskinesia info
Myoclonic jerks, tics…often involving face/mouth
usually long term antipsychotic use and potentially irreversible
Risk factors = Long term, high dose/potency FGA, older age n females
Monitoring = AIMS or DISCUS (Q6M FGA, Q12M SGA)
Tardive Dyskinesia TXM
D/c antipsychotic and switch to one with lower risk
VMAT2 Inhibitor
VMAT2 inhibitors MOA
reversible inhibition of VMAT2 which is transporter that packages DA into presynaptic vesicles in prep for release into synaptic cleft
Deutetrabenazine (Austere)
VMAT 2 inhib
Warning = QTc prolongation, Parkinsonism, Depression or suicidality
ADE = Somnolence, Fatigue, Diarrhea
DI = Strong 2D6 = reduce dose, other QTc prolong drugs
Counseling = Take with food
Valbenazine (Ingrezza)
VMAT2 inhib
Warning = QTC prolong (2D5/3A4 inhib), Parkinsonism, Depression or suicidality
ADE = Somnolence, Fatigue, Sedation
DI = Strong 3A4/2D6 inhib (dec dose), Avoid MAOI and strong 3A4 inducer, Digoxin
Counseling = avoid driving or operating heavy machinery
Neuroleptic Malignant Syndrome (NMS) info
V low incidence
Presentation = muscle rigidity, hyperthermia, altered mental status, autonomic dysfunction
Onset = 1-2 weeks after initiation/change in dose, can occur as soon s 1-3 days
Txm = should last 10 das after symptoms subside (d/c med immediately)
Recurrence = 30-50%, wait atleast 2wk before restarting antipsychotic therapy or use dif class of lower potency
FGA monitoring parameters
AIMS/DISKUS screening for EPS
QTc prolongation
Hyperprolactinemia
Pro vs Con of FGA
Pro = Xtremely effective at reducing positive symptoms
Con = Doesn’t treat neg symptom, can make worse
High risk SE
Movement disorder common maybe permanent
Many interactions
SGA used for Tx-fractory or suicidal behavior in schiz
Clozapine
SGA dosing info
start low and titrate based on response/tolerability
acute psychosis = inc until symptoms improve or AE limit dose
divides doses for 1-2 wks to dec AE, then change to daily dosing
SGA Tapering or Dc’ing
consider 1/2 life and patient specific factors
25% reduction in Total daily Dose weekly or slower
D/c symptoms start 2-3 days after stop, can last up to 14 days
Metabolic Syndrome Highest to lowest risk SGA
Highest -> Lowest
Clozapine/Olanzapine
Quetiapine
Risperidone/Paliperidone
Lioperidone
Asenapine/Aripiprazole/Lurasidone/Ziprasidone
Monitoring for SGAs metabolic syndrome
Baseline = BMI, Waist, A1c, Lipid BP
Annually = Waist, A1c, Lipid, BP
SGA Hyperprolactinemia
Symptoms: Females = change in menstrual cycle, painful sex, hirsutism, Males = ED or gyno
** lvls dont correlate with symptoms, only Tx symptoms **
Worst offenders = Risperidone, Paliperidone
Lowest Risk = Aripiprazole, Brexpiprazole, Cariprazine
ECG monitoring SGA
Inc risk = Ziprasidone > Quetiapine over others
encourage freq monitoring or d/c if QTc > 500ms
Treatment Resistance Definition
lack of sig improvement in symptoms despite txm with at least 2 antipsychotic from 2 iff classes at recommended dosage for atleast 2-8wks
Clozapine CI
Myeloproliferative disorders
Clozapine-induced agranulocytosis
Severe CNS Depression
Paralytic ileus
Clozapine Warning n Precautions
Boxed: Agranulocytosis, Orthostasis/Syncope, Myocarditis n cardiomyopathy, seizures
QTc prolongation
Clozapine Blood monitoring
ANC has to be > 1500
weekly 6 months, then every 2 wks for 6 month, then monthly after 12 month
Long acting injectable pro n con
Pro = good for long time, dec OD risk, more stable, more contact with med staff
Con = one time before effective dose/SS reached, less flexibility, have to go to place o get inj n inj site reactions
Pregnancy and Lactation special pop
Not recommended to stop during preg
Avoid ones with anticholinergic SE
Breast feeding not recommended
Children Special pop
Children tend to gain more weight than adults and have more EPS
Elderly Special pop
more susceptible to antiadrenergic (falls/orthostasis) n antimuscarinic (urinary retention,constipation,memory) SE
Box warning = inc mortality in dementia related psychosis
drugs that have to be taken together with food?
Ziprasidone ( 500+ cal meal)
Lurasidone (350+ cal meal)
Quetiapine, olanzapine, clozapine SE to consider
heavy sedation
Aripiprazole SE to consider
Restlessness
Risperidone, paliperidone SE to consider
Gyno
TLC for Schiz
smoking cessation, can have major effect on drug lvls
diet
exercise
Limit alc
