Pharmacotherpay of Schizophrenia Flashcards
What are the key features that define psychotic disorders?
Delusions,hallucinations,disorganized thinking and speech,disorganized or abnormal motor behavior,negative symptoms
what are delusions?
fixed false beliefs that are not amenable to change even with conflicting evidence
What are hallucinations
perception-like-experiences that occur without an external stimulus (usually auditory but can also be visual tactile or olfactory)
What is disorganized thinking and speech
switching from one topic to another unrelated to answers to questions
Disease course in schizophrenia.
onset late adolescence to early adulthood
men late teens early 20s
women late 20s early 30s
SZ link to substance use?
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
Antipsychotic drug selection
oral antipsychotic drug therapy is generally considred first line unless the patient presents with reasons to consider IM depot drug therapy first
What are typical antipsychotics?
older agents primarily D2 antagonists efficacy for positive symptoms is similar to atypical antipsychotics
Haloperidol,Chlorpromazine Fluphenazine,Perphenazine,loxapine, thioridazine
what are typical antipsychotic clinical pearls?
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
what are Partial Agonists
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
what is aripiprazole?
partial agonists 2D6 and 3A4 substrate moderate akathisia low weight gain
what is Brexpiprazole?
partial agonists, 2D6 and 3A4 substrate moderate akathisia low moderate weight gain
what is Cariprazine?
3A4 substrate moderate akathisia low-moderate weight gain
What are the “pines”
have less D2 antagonism more 5HT2A antagonist Asenapine (Saphris®), Clozapine (Clozaril®),Olanzapine (Zyprexa®) Quetiapine (Seroquel®)
what is Quetiapine (Seroquel®)?
3A4 substrate
QTc prolongation Weight gain and sedation
Boxed warning for suicidal ideation
What is Olanzapine (Zyprexa®)
1A2 substrate
Significant weight gain and sedation
High risk metabolic syndrome
DRESS warning
what is Clozapine (Clozaril®)
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
what is Asenapine (Saphris®)
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
what is 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
what are the dones
Iloperidone, lurasidone, ziprasidone, risperidone and paliperidone
what is Iloperidone (Fanapt®)
High risk for orthostasis and syncope QTc prolongation, 2D6 substrate
what is Lurasidone (Latuda®)
3A4 substrate, Higher risk for akathisia, Warning for suicidal thoughts adjunct for bipolar depression Take with food (350 calories) to increase bioavailability
what is Ziprasidone (Geodon®)
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)
what is Risperidone (Risperdal®)
D6 substrate (minor 3A4 substrate) EPS, hyperprolactinemia, weight gain,
sedation, orthostasis
What is Paliperidone (Invega®)
Renally eliminated – dose adjustments in renal
impairment
Similar side effects with risperidone
QTc prolongation
what is lumateperone (caplyta)
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
What is Pimavanserin (nuplazid)
Antipsychotic medication that is FDA-approved for
the treatment of hallucinations or delusions in a patient with Parkinson’s Disease
inverse agonist and antagonist at the serotonin (5HT) 2A and (to a lesser extent) 2C receptors
3A4 substrate
Xanomeline/ Trospium (Cobenfy®
M1/M4 agonist, 2D6 substrate,Baseline and continued monitoring: LFTs, heart
rate
Warnings for all Antipsychotics (except xanomeline/trospium)
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
What is haloperidol
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
Risperdal® Consta (risperidone)
MUST supplement with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment – I tell providers until 3rd injection (week 4)
what is Rykindo® (risperidone)
Every 2 week IM injection, Oral dose overlap is shorter than Risperdal
Consta (7 days vs 21 days)
what is Perseris® (risperidone)
Every 4 week LAI dosage form of risperidone, Abdominal subcutaneous injection, 3A4 inducers – use 120 mg dose or may need oral supplementation
What is Uzedy® (risperidone)
Abdominal or upper arm subcutaneous injection, Given once monthly or every 2 months
What is Invega®
Sustenna (paliperidone)
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
Invega® Trinza (paliperidone q3mo)
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
Invega® Hafyera (paliperidone q6mo)
May be initiated after stable Invega Sustenna for 4 months or stable Invega Trinza after one 3- month dose Gluteal injection only
Zyprexa® Relprevv (olanzapine)
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
Abilify® Maintena (aripiprazole)
MUST overlap with oral aripiprazole (or another oral antipsychotic) for at least 14 days after first injection
Deltoid or gluteal injection
Abilify® Maintena – Dose Adjustments for P450 Interactions
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
Abilify® Asimtufii (aripiprazole)
Every-2-month dosing
Gluteal injection only continue oral aripiprazole for 2 weeks after first injection
Aristada® (aripiprazole lauroxil)
Overlap with oral aripiprazole for 3 weeks after first injection unless Aristada Initio given first
Aristada Initio
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
immediate Release Antipsychotic Injections/ Psychiatric Emergencies
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®)
Clinical Treatment Strategies for EPS
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
what are VMAT inhibitors
Tetrabenazine (Xenazine® Valbenazine (Ingrezza®) Deutetrabenazine (Austedo®)
Valbenazine (Ingrezza®)
2D6/3A4 substrate
Side effects: QTc prolongation
Deutetrabenazine (Austedo®)
2D6 substrate
Side effects: QTc prolongation,
Neuroleptic Malignant Syndrome
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
Metabolic Adverse Effects
Hyperglycemia, hyperlipidemia, hypertension
clozapine = olanzapine >
quetiapine = risperidone = paliperidone = asenapine =
iloperidone = cariprazine = brexpiprazole >
ziprasidone = lurasidone = aripiprazole
