Pharmacotherpay of Schizophrenia

Question 1

What are the key features that define psychotic disorders?

Answer 1

Delusions,hallucinations,disorganized thinking and speech,disorganized or abnormal motor behavior,negative symptoms

Question 2

what are delusions?

Answer 2

fixed false beliefs that are not amenable to change even with conflicting evidence

Question 3

What are hallucinations

Answer 3

perception-like-experiences that occur without an external stimulus (usually auditory but can also be visual tactile or olfactory)

Question 4

What is disorganized thinking and speech

Answer 4

switching from one topic to another unrelated to answers to questions

Question 5

Disease course in schizophrenia.

Answer 5

onset late adolescence to early adulthood
men late teens early 20s
women late 20s early 30s

Question 6

SZ link to substance use?

Answer 6

smoking is associated with induction of 1A2 not due to nicotine but because of hydrocarbons produced and inhaled which decreases the serum concentration of 1a2 substrate antipsychotics (olanzapine,asenapine,clonapine,loxapine)
marijuana cocaine and amphetamine use can hasten the onset and exacerbate symptoms and reduce time to relapse

Question 7

Antipsychotic drug selection

Answer 7

oral antipsychotic drug therapy is generally considred first line unless the patient presents with reasons to consider IM depot drug therapy first

Question 8

What are typical antipsychotics?

Answer 8

older agents primarily D2 antagonists efficacy for positive symptoms is similar to atypical antipsychotics
Haloperidol,Chlorpromazine Fluphenazine,Perphenazine,loxapine, thioridazine

Question 9

what are typical antipsychotic clinical pearls?

Answer 9

Halloperidol is most commonly used-routine and PRN
More EPS with high potency drugs)
are very effective for treating the positive symptoms but are likely to worsen negative and cognitive symptoms

Question 10

what are Partial Agonists

Answer 10

Stabilize dopamine transmission not too much not to little, associated with more akathisia than other antipsychotic.approved for adjunct tx in depression so all have boxed warning for suicidal thoughts and behaviors
aripiprazole, brexpiprazole and cariprazine

Question 11

what is aripiprazole?

Answer 11

partial agonists 2D6 and 3A4 substrate moderate akathisia low weight gain

Question 12

what is Brexpiprazole?

Answer 12

partial agonists, 2D6 and 3A4 substrate moderate akathisia low moderate weight gain

Question 13

what is Cariprazine?

Answer 13

3A4 substrate moderate akathisia low-moderate weight gain

Question 14

What are the “pines”

Answer 14

have less D2 antagonism more 5HT2A antagonist Asenapine (Saphris®), Clozapine (Clozaril®),Olanzapine (Zyprexa®) Quetiapine (Seroquel®)

Question 15

what is Quetiapine (Seroquel®)?

Answer 15

3A4 substrate
QTc prolongation Weight gain and sedation
Boxed warning for suicidal ideation

Question 16

What is Olanzapine (Zyprexa®)

Answer 16

1A2 substrate
Significant weight gain and sedation
High risk metabolic syndrome
DRESS warning

Question 17

what is Clozapine (Clozaril®)

Answer 17

1A2 substrate
Boxed warnings:neutropenia, orthostasis,bradycardia, syncope, seizures, myocarditis, cardiomyopathy
Side effects: sedation,weight gain, constipation,hypersalivation, dry mouth, GI hypomotility with obstruction risk
QTc prolongation
monitoring timelines weekly x 6 months biweeklyx 6 months then every 4 weeks

Question 18

what is Asenapine (Saphris®)

Answer 18

Sublingual and patch formulations, UGT and 1A2 substrate reduce dose of patch if given with strong 1A2 inhibitorsQTc prolongation, apply one patch every 24 hours rotate patch to minimize site reaction

Question 19

what is Olanzipine/ Samidorphan

Answer 19

Samidorphan added to mitigate weight gain and metabolic syndrome potential of olanzapine it is an opioid antagonist with preferential activity at the mu opioid receptor

Question 20

what are the dones

Answer 20

Iloperidone, lurasidone, ziprasidone, risperidone and paliperidone

Question 21

what is Iloperidone (Fanapt®)

Answer 21

High risk for orthostasis and syncope QTc prolongation, 2D6 substrate

Question 22

what is Lurasidone (Latuda®)

Answer 22

3A4 substrate, Higher risk for akathisia, Warning for suicidal thoughts adjunct for bipolar depression Take with food (350 calories) to increase bioavailability

Question 23

what is Ziprasidone (Geodon®)

Answer 23

QTc prolongation (contraindication)
DRESS warning
Take with food to increase absorption and bioavailability
3A4 substrate (1/3) and aldehyde oxidase (2/3) (less worry for P450 interactions)

Question 24

what is Risperidone (Risperdal®)

Answer 24

2D6 substrate (minor 3A4 substrate) EPS, hyperprolactinemia, weight gain, sedation, orthostasis

Question 25

What is Paliperidone (Invega®)

Answer 25

Renally eliminated – dose adjustments in renal impairment Similar side effects with risperidone QTc prolongation

Question 26

what is lumateperone (caplyta)

Answer 26

primarily 5HT2A antagonism with post synaptic D2 blockade Low risk for weight gain or metabolic side effects Low risk for EPS or akathisia 3A4 substrate

Question 27

What is Pimavanserin (nuplazid)

Answer 27

Antipsychotic medication that is approved for the treatment of hallucinations or delusions in a patient with Parkinson’s Disease inverse agonist and antagonist at the serotonin (5HT) 2A 3A4 substrate

Question 28

Xanomeline/ Trospium (Cobenfy®

Answer 28

M1/M4 agonist, 2D6 substrate,Baseline and continued monitoring: LFTs, heart rate

Question 29

Warnings for all Antipsychotics (except xanomeline/trospium)

Answer 29

Boxed Warning: Increased risk of death in elderly patients treated with antipsychotics for dementia with related behaviors. Metabolic adverse effects EPS Risk of somnolence, postural hypotension, and motor and/or sensory instability increases the risk for falls/fractures. Fall risk assessment should be performed for patients taking other medications or having other disease states that also have a fall/fracture or somnolence/hypotension risk; assess when initiating antipsychotic and repeat routinely if on continuous long-term treatment

Question 30

What is haloperidol

Answer 30

Given every 4 weeks Load: 20 times oral dose Maintenance: 10 times oral dose If only use maintenance, may need oral overlap Oil-based – Z-track

Question 31

Risperdal® Consta (risperidone)

Answer 31

MUST supplement with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment – I tell providers until 3rd injection (week 4)

Question 32

what is Rykindo® (risperidone)

Answer 32

Every 2 week IM injection, Oral dose overlap is shorter than Risperdal Consta (7 days vs 21 days)

Question 33

what is Perseris® (risperidone)

Answer 33

Abdominal subcutaneous injection, 3A4 inducers – use 120 mg dose or may need oral supplementation

Question 34

What is Uzedy® (risperidone)

Answer 34

Abdominal or upper arm subcutaneous injection, Given once monthly or every 2 months

Question 35

What is Invega® Sustenna (paliperidone)

Answer 35

Loading dose, then booster, then every 4 weeks (starting 5 weeks after loading injection),Initial loading and booster doses must be given in deltoid to improve absorption consistency, If loading strategy followed, no need for oral overlap antipsychotic treatment,May require dose adjustment in moderate to severe renal impairment

Question 36

Invega® Trinza (paliperidone q3mo)

Answer 36

May be initiated for a patient who has been on a stable monthly (every 4 week) IM injection of Invega Sustenna (only way that it should be used), at least FOUR stable Invega Sustenna doses Recommended to be given deltoid; gluteal administration results in a lower Cmax Not recommended if CrCl < 50 mL/min

Question 37

Invega® Hafyera (paliperidone q6mo)

Answer 37

May be initiated after stable Invega Sustenna for 4 months or stable Invega Trinza after one 3- month dose Gluteal injection only

Question 38

Zyprexa® Relprevv (olanzapine)

Answer 38

REMS, DSS – post-dose delirium sedation syndrome Oral 10mg once daily, 15mg once daily,20mg once daily IM Depot 210mg IM every 2 weeks, 405mg IM every 4 weeks, 300mIM every 2 weeks

Question 39

Abilify® Maintena (aripiprazole)

Answer 39

MUST overlap with oral aripiprazole (or another oral antipsychotic) for at least 14 days after first injection Deltoid or gluteal injection

Question 40

Abilify® Maintena – Dose Adjustments for P450 Interactions

Answer 40

Patients Taking 400mg of Abilify Maintena 300mg Strong CYP 2D6 OR CYP 3A4 Inhibitors 200mg CYP 2D6 AND CYP 3A4 Inhibitors Avoid Use CYP 3A4 Inducers Patients Taking 300mg of Abilify Maintena 200mg Strong CYP 2D6 OR CYP 3A4 Inhibitors 160mg CYP 2D6 AND CYP 3A4 Inhibitors Avoid Use CYP 3A4 Inducers

Question 41

Abilify® Asimtufii (aripiprazole)

Answer 41

Every-2-month dosing Gluteal injection only continue oral aripiprazole for 2 weeks after first injection

Question 42

Aristada® (aripiprazole lauroxil)

Answer 42

Overlap with oral aripiprazole for 3 weeks after first injection unless Aristada Initio given first

Question 43

Aristada Initio

Answer 43

Developed to avoid need for 21-day oral overlap of antipsychotic Avoid in patients who are 2D6 poor metabolizers or with strong 3A4 or 2D6 inhibitors

Question 44

immediate Release Antipsychotic Injections/ Psychiatric Emergencies

Answer 44

Haloperidol, chlorpromazine, fluphenazine are used, haloperidol most commonly Olanzapine immediate release IM – CANNOT be given at the same time as a benzodiazepine immediate release injection – boxed warning for respiratory depression Loxapine for inhalation (Adasuve®)

Question 45

Clinical Treatment Strategies for EPS

Answer 45

Acute Dystonia;IM anticholinergic NOW dose (benztropine 2mg, diphenhydramine 50mg) Drug-Induced Parkinson’s:Oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine) Akathisia:Beta-blocker – propranolol preferred first-line - ~ Benzodiazepine – usually lorazepam Tardive Dyskinesia:VMAT inhibitors

Question 46

what are VMAT inhibitors

Answer 46

Tetrabenazine (Xenazine® Valbenazine (Ingrezza®) Deutetrabenazine (Austedo®)

Question 47

Valbenazine (Ingrezza®)

Answer 47

VMAT inhibitor 2D6/3A4 substrate Side effects: QTc prolongation

Question 48

Deutetrabenazine (Austedo®)

Answer 48

2D6 substrate Side effects: QTc prolongation,

Question 49

Neuroleptic Malignant Syndrome

Answer 49

Life- threatening – IS a medical emergency Hyperpyrexia, tachycardia, labile blood pressure Muscle rigidity – elevated (significantly) CK, myoglobinuria Treatment is supportive Future antipsychotic use is NOT contraindicated

Question 50

Metabolic Adverse Effects

Answer 50

Hyperglycemia, hyperlipidemia, hypertension clozapine = olanzapine > quetiapine = risperidone = paliperidone = asenapine = iloperidone = cariprazine = brexpiprazole > ziprasidone = lurasidone = aripiprazole