Pharmacotherapy of Schizophrenia Flashcards
Key features that define psychotic disorders
- Delusions: fixed false beliefs that are not amenable to change even with conflicting evidence
- Hallucinations-perception-like experiences that occur without external stimulus
- Disorganized thinking and speech-switching from one topic to another, unrelated answers to questions
- Disorganized or abnormal motor behavior
- Negative symptoms
Disease course in Schizophrenia
Onset late adolescence to early adult
Men-late teens, early 20s
Women–late 20s, early 30s
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, clozapine, loxapine)
Marijuana, cocaine, and amphetamine use can hasten the onset of schizophrenia, exacerbate symptoms, adn reduce time to relapse
Substance use treatment can be successfully achieved along with mental health treatment with schizophrenia, should be undertaken at the same time
Antipsychotic Drug Therapy overview
Doses per day
Side effects: what will patients tolerate? What are their other disease states?
Previous drug therapy: success or failure? Do family members have this disease?
Cost of drug therapy
Concomitant drug therapy
Need for monitoring: labs? weight? ECG?
Antipsychotic Drug Selection
Oral antipsychotic drug therapy is generally considered first-line, unless the patient presents with reasons to consider IM depot drug therapy first
Typical antipsychotics
Older agents–primarily D2 receptor antagonists
Efficacy for positive symptoms is similar to atypical antipsychotics
Typical antipsychotics clinical pearls
Haloperidol is most commonly used–routine PRN
More EPS with high potency typical–and atypical antipsychotics risperidone and paliperidone
Are very effective for treating the positive symptoms, but are likely to worsen negative and cognitive symptoms
Partial agonists
“stabilize” dopamine transmission–not too much, not too little
Associated with more akathisia than other antipsychotics
Approved for adjunct treatment in depression so all have boxed warning for suicidal thoughts/behavior
Aripiprazole
Partial Agonist
2D6 and 3A4 substrate
Moderate akathisia
Low weight gain
Brexpiprazole
Partial agonist
2D6 and 3A4 substrate
Moderate akathisia
Low-moderate weight gain
Cariprazine
Partial agonist
3A4 substrate
Moderate akathisia
Low-moderate weight gain
Asenapine
Sublingual and patch formulations
1A2 substrate
QTc prolongation
Clozapine
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
REMS: monitoring timelines weekly x 6 months, biweekly x 6 months, then every 4 weeks
Olanzapine
1A2 substrate
Significant weight gain and sedation
High risk metabolic syndrome
DRESS warning
Quetiapine
3A4 substrate
QTc prolongation
Weight gain and sedation
Boxed warning for suicidal ideation
Asenapine Transdermal Patch
Secuado
Apply 1 patch q24hrs, rotate patch site to minimize application site reactions
Warning for QTc prolongation
UGT and 1A2 substrate–reduce dose of patch if given with strong 1A2 inhibitors
Olanzapine/Samidorphan
Lybalvi
Samidorphan is an opioid antagonist with preferential activity at the mu opioid receptor
Iloperidone
High risk for orthostasis and syncope
QTc prolongation
2D6 substrate
Lurasidone
3A4 substrate
Higher risk for akathisia
Warning for suicidal thoughts
Adjunct for bipolar depression
Taken with food (350 calories) to increase bioavailability
Ziprasidone
QTc prolongation
DRESS warning
Take with food to increase absorption
3A4 substrate (1/3) and aldehyde oxidase (2/3) (less worry for P450 interactions)
Risperidone
2D6 substrate
EPS, hyperprolactinemia, weight gain, sedation, orthostasis
Paliperidone
Renally-eliminated–dose adjustments in renal impairment
Similar side effects with risperidone
QTc prolongation
Lumateperone
Low risk for weight gain or metabolic side effects
Low risk for EPS or akathisia
3A4 substrate
Pimavanserin
Approved for the treatment of hallucinations or delusions in a patient with PD
Inverse agonist and antagonist at the serotonin (5HT) 2A
3A4 substrate
Warnings for all antipsychotics
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
Fall risk assessment should be performed for patients taking other medications or having other disease states that also have a fall/fracture or hypotension risk
Haloperidol Injection
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 antipsychotic) for the first few weeks of treatment (week 4)
Perseris
risperidone
Abdominal subcutaneous injection
3A4 inducers: use 120 mg dose or may need oral supplementation
Rykindo
risperidone
Every 2 week IM injection
Oral overlap is shorter than Risperdal Consta (7 days vs. 21 days)
Gluteal injection only
Uzedy
Abdominal or upper arm subcutaneous injection
Given once monthly for every 2 months
Invega Sustenna
paliperidone
Loading dose, then booster, then every 4 weeks (starting 5 weeks after loading injection)
Initial loading dose and booster doses must be given in deltoid to improve absorption consistency
If loading dose strategy followed, no need for oral overlap antipsychotic treatment
May require dose adjustment in moderate to severe renal impairment
Invega Trinza
May be initiated for a patient who has been on a stable monthly IM injection of Invega Sustenna, at least 4 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
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
PDSS-post-dose delirium sedation syndrome
Abilify Maintena
aripiprazole
Must overlap with oral aripiprazole for at least 14 days after first injection
Deltoid or gluteal injection
Abilify Maintena Dose adjustments for P450 interactions
If taking 2D6 or 3A4 inhibitors or 3A4 inducers for more than 14 days as concomitant therapy
Abilify Asimtufii
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 the first injection
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 2 mg, diphenhydramine)
Drug-induced Parkinson’s: Oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine)
Akathisia: Beta blocker (propranolol 1st line), Benzodiazepine– usually lorazepam
Tardive Dyskinesia: VMAT inhibitors
VMAT inhibitors
50% reduction in AIMS score for tardive dyskinesia
Valbenazine
2D6/3A4 substrate
QTc prolongation
Deutetrabenazine
2D6 substrate
QTc prolongation
Neurologic 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 Averse Effects
Hyperglycemia, hyperlipidemia, hypertension
clozapine=olanzapine >
quetiapine=risperidone=paliperidone=asenapine=iloperidone=cariprazine=brexpiprazole>
ziprasidone=lurasidone=aripiprazole
Metabolic monitoring
Personal/family hx
Weight
Waist circumference
BP
FPG/A1c
Fasting lipids
