Lecture 6 - Schizophrenia Spectrum Disorder Flashcards by Patryk Lasiuk

Positive Schiz symptoms

Delusions = false beliefs
Hallucinations = sensory perception w/ no basis
Disorganized speech
Grossly disorganized/catatonic behavior

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Negative Schiz symptoms

Blunted affect
Alogia = cant speak
Avolition
Anhedonia = trouble w/ pleasure
Asociality

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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 **

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Mesolimbic pathophysiology

Excess DA = Positive sx

txm w/ DA antagonist = relief of positive sx

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Mesocotical pathophysiology

Low DA = negative n cognitive sx

txm w/ DA antagonist = worsen neg symptoms

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Nigrostriatal pathophysiology

Normal DA = no dysfunction

txm w/ DA antagonist = extrapyramidal sx

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Tuberoinfundibular pathophysiology

Normal DA = no dysfunction

txm w/ DA antagonist = hyperprolactinemia

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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

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1st Gen anti psych indications

Acute agitation n delirium usually what used for

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Which FGA used for Tourettes syndrome

Haloperidol
pimozide

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Which FDA used in N/V

Chlorpromazine
Perphenazine
Prochlorperazine

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Which FGA used for Intractable hiccups

Chlorpromazine

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First Gen Antipsychotic MoA

1st = blockade of DA2 receptors in mesolimbic area and mesocortical area of brain

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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

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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

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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

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How to help treat Pseudoparkinonism symptoms

dose dc or add anticholinergic (benzotropine)

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How to help treat Akathisia symptoms

dose dc or switch antipsychotic, add propranolol or anticholinergic

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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

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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