Ott Pharmacotherapy of Schizo Flashcards
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 answers to questions
When is the typical onset of schizophrenia for men?
Late teens, early 20s
When is the typical onset of schizophrenia for women?
Late 20s to early 30s
Which substances are linked to schizophrenia?
-Cigarette smoking
-Marijuana
-Cocaine
-Amphetamine
How does smoking cigarettes cause schizophrenia?
The 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)
How does marijuana, cocaine, and amphetamine use affect schizophrenia?
Can hasten the onset of schizophrenia, exacerbate symptoms, and reduce time to relapse
What must be considered in antipsychotic drug therapy?
-Dose per day
-Side effects
-Previous drug therapy
-Cost of drug therapy
-Concomitant drug therapy
-Need for monitoring
Which route of antipsychotic drug therapy is considered first-line?
Oral antipsychotic drug therapy is generally considered first-line, unless the patient presents with reasons to consider IM depot drug therapy first
What are the typical antipsychotics?
-Haloperidol
-Fluphenazine
-Loxapine
-Chlorpromazine
-Perphenazine
-Thioridazine
Typical antipsychotic clinical pearls
-Older agents - primarily D2 receptor antagonists
-Efficacy for positive symptoms is similar to atypical antipsychotics
-Haloperidol is most commonly used - routine and PRN
-More EPS with higher potency typicals
-Are very effective for treating the positive symptoms, but are likely to worsen negative and cognitive symptoms
What are the atypical antipsychotics?
-Aripiprazole
-Asenapine
-Brexpiprazole
-Cariprazine
-Clozapine
-Iloperidone
-Lumateperone
-Lurasidone
-Olanzipine
-Paliperidone
-Quetiapine
-Risperidone
-Ziprasidone
Which atypical antipsychotics are partial agonists?
-Aripiprazole
-Brexpiprazole
-Cariprazine
Partial agonist mechanism of action/CP
Stabilize dopamine transmission - not too much, not too little
Aripiprazole effects
-2D6 and 3A4 substrate
-Moderate akathisia
-Low weight gain
Brexpiprazole effects
-2D6 and 3A4 substrate
-Moderate akathisia
-Low-moderate weight gain
Cariprazine side effects
-3A4 substrate
-Moderate akathisia
-Low-moderate weight gain
Partial agonist clinical pearls
-Associated with more akathisia than other antipsychotics
-Approved for adjunct treatment in depression so all have boxed warning for suicidal thoughts/behavior
What are the “pines”
-Asenapine
-Clozapine
-Olanzapine
-Quetiapine
Asenapine clinical pearls
-Sublingual and patch formulations
-1A2 substrate
-QTc prolongation
Clozapine clinical pearls
-1A2 substrate
-QTc prolongation
Clozapine boxed warnings
-Neutropenia
-Orthostasis
-Bradycardia
-Syncope
-Seizures
-Myocarditis
-Cardiomyopathy
Clozapine side effects
-Sedation
-Weight gain
-Constipation
-Hypersalivation
-Dry mouth
-GI hypomotility with obstruction risk
Olanzapine clinical pearls
-1A2 substrate
-Significant weight gain and sedation
-High risk of metabolic syndrome
-DRESS warning
Quetiapine clinical pearls
-3A4 substrate
-QTc prolongation
-Weight gain and sedation
-Boxed warning for suicidal ideation
Pines clinical pearls
-Less D2 antagonism, more 5HT2A antagonist - significantly less EPS
-Higher weight gain than other agents
Asenapine patch clinical pearls
-Apply one patch every 24 hours, rotate patch site to minimize application site reactions
-Warnings for QTc prolongation
-UGT and 1A2 substrate - reduce dose of patch if given with strong 1A2 inhibitors
How often do neutrophils have to be monitored with clozapine?
Monitor timelines weekly for 6 months, biweekly for 6 months then every 4 weeks
What is samidorphan?
An opioid antagonist with preferred activity at the mu opioid receptor
Why is samidorphan given in combination with olanzapine?
Clinical trials showed less weight gain with the combination vs monotherapy
What are the dones?
-Iloperidone
-Lurasidone
-Ziprasidone
Dones clinical pearls
-D2 and 5HT2A antagonists
-Variable EPS and metabolic side effects
Iloperidone clinical pearls
-High risk for orthostasis and syncope
-QTc prolongation
-2D6 substrate
Lurasidone clinical pearls
-3A4 substrate
-Higher risk for akathisia
-Warning for suicidal thoughts - adjunct to bipolar depression
-Take with food (350 calories) to increase bioavailability
Ziprasidone clinical pearls
-QTc prolongation (contraindication)
-DRESS warning
-Take with food to increase absorption and bioavailability
-3A4 substrate (1/2) and aldehyde oxidase (2/3) (less worry for P450 interactions)
More dones clinical pearls
-Highest D2 blockade for atypical antipsychotics
-High risk EPS, moderate risk metabolic side effects
What are the more dones?
-Risperidone
-Paliperidone
Risperidone clinical pearls
-2D6 substrate (minor 3A4 substrate)
-EPS, hyperprolactinemia, weight gain, sedation, orthostasis
Paliperidone clinical pearls
-Renally eliminated - dose adjustments in renal impairment
-Similar side effects with risperidone
-QTc prolongation
Lumateperone clinical pearls
-Low risk for weight gain or metabolic side effects
-low risk for EPS or akathisia
-3A4 substrate
Primavanserin clinical pearls
-FDA approved for the treatment of hallucinations or delusions in patients with Parkinson’s disease
-Inverse agonist and antagonist at the serotonin 2A receptor
-3A4 substrate
Warnings for all antipsychotics
-Boxed warning: increased risk of death in elderly patients treated with antipsychotics for dementia 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 preformed for patients taking other medications or having other disease states that also have fall/fracture or somnolence/hypotension risk; assess when initiating antipsychotic and repeat routinely if on continuous long-term treatment
Haloperidol decanoate (IM) dosing
-Given every 4 weeks
-Load: 20 times the oral dose
-Maintenance: 10 times the oral dose
-If only using maintenance, may need oral overlap
-Oil-based - Z-track
How do you start Risperdal Consta (IM risperidone)?
Supplement with oral risperidone (or another oral antipsychotic) for the first few weeks of treatment (third injection/week)
Perseris (risperidone SC) clinical pearls
-Abdominal SC injection
-3A4 inducers - use 120 mg dose or may need oral supplementation
Rykindo (risperidone IM) dosing
-Every 2 weeks IM injection
-Oral dose overlap is shorter than Risperdal Consta (7 days vs 21 days)
Uzedy (risperidone SC) dosing
-Abdominal or upper arm SC injection
-Given once monthly or every 2 months
Invega Sustenna (paliperidone IM) dosing
-Loading dose, then booster, then every 4 weeks (starting 5 weeks after loading dose injection)
-Initial loading dose 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 IM) clinical pearls
-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 lower Cmax
-Not recommended if CrCl is less than 50
Invega Hafyera (paliperidone q6mo IM) clinical pearls
-May be initiated after stable Invega Sustenna for 4 months or stable Invega Trinza after 3-month dose
-Gluteal injection only
Zyprexa Relprevv (olanzapine) clinical pearls
-REMS requires registration of patient, facility giving injection, prescriber, and pharmacy with Eli Lilly
-Can cause PDSS - post-dose delirium sedation syndrome
Abilify Maintena (aripiprazole) clinical pearls
-MUST overlap with oral aripiprazole for at least 14 days after first injection
-Deltoid or gluteal injection
Abilify Asimtulfi (aripiprazole) clinical pearls
-Every 2 month dosing
-Gluteal injection only
-Continue oral aripiprazole for 2 weeks after first injection
How to start Aristada (aripiprazole lauroxil)
Overlap with oral aripiprazole for 3 weeks after first injection
Aristada Initio clinical pearls
-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
Which medications are used for psychiatric emergencies?
Immediate release antipsychotics:
-Haloperidol (most common)
-Chlorpromazine
-Fluphenazine
-Olanzapine (cannot be given at the same time as immediate release injection benzodiazepines
-Loxapine for inhalation (not commonly used)
EPS symptoms
-Acute dystonia
-Drug-induced Parkinson’s
-Akathisia
-Tardive dyskinesia
How to treat acute dystonia
IM anticholinergic asap (benztropine 2mg, diphenhydramine 50mg)
How to treat drug-induced Parkinson’s
Oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine)
How to treat akathisia
-Beta-blocker - propranolol preferred first-line
-Benzodiazepine - usually lorazepam
How to treat tardive dyskinesia
VMAT inhibitors
VMAT inhibitor clinical pearls
-Inhibit the vesicular monoamine transporter to decrease storage/increase release of dopamine, serotonin, norepinephrine
-Efficacy expected to be around 50% reduction in AIMS score for tardive dyskinesia
What are the VMAT inhibitors
-Tetrabenazine
-Valbenazine
-Deutetrabenazine
Valbenazine clinical pearls
-2D6/3A4 substrate
-QTc prolongation
Deutetrabenazine clinical pearls
-2D6 substrate
-QTc prolongation
What is neuroleptic malignant syndrome
-Life-threatening - IS a medical emergency
-Hyperpyrexia, tachycardia, labile blood pressure
-Muscle rigidity - elevated (significantly) CK, myoglobinuria
-Treatment is supportive - discontinue antipsychotics, consider dopamine agonists
-Future antipsychotic use is NOT contraindicated
Antipsychotic metabolic adverse effects
-Hyperglycemia
-Hyperlipidemia
-Hypertension
Drug risk of metabolic adverse effects from highest to lowest risk
-Clozapine, olanzapine
-Quetiapine, risperidone, paliperidone, asenapine, iloperidone, cariprazine, brexpiprazole
-Ziprasidone, lurasidone, aripiprazole
