4.3 Pharmacotherapy of schizophrenia Flashcards
What are the key features that define psychotic disorders?
- Delusions
- Hallucinations: usually auditory
- Disorganized thinking and speech
- Disorganized or abnormal motor behavior
- Negative sxs
What is the avg diagnosis age by sex and disease course progression in schizophrenia?
- Onset late adolescence to early adulthood
- Late teens/early 20’s for men
- Late 20’s, early 30’s for women
Why is it thought that women have a later age of schizophrenia onset?
Estrogen might be protective against schizophrenia
What is the link between smoking and schizophrenia?
- Smoking is associated w 1A2 induction due to the hydrocarbons
- Hydrocarbons decreases serum conc. of 1A2 substrate antipsychotics (olanzapine, asenapine, clozapine, loxapine)
Which substances are linked to hastening the onset of schizophrenia, but not causing it?
Marijuana, cocaine, and amphetamine can hasten the onset, but not exacerbate sxs, and reduce time to relapse
How can substance abuse with schizophrenia be treated?
- Substance use tx can be successfully achieved along w mental health tx in pts w schizophrenia
- Should be undertaken at the same time
What must be considered during antipsychotic drug therapy?
- Doses per day
- SEs
- Previous drug therapy
- Cost of drug therapy
- Concomitant drug therapy
- Need for monitoring: labs, weight, ECG
Which therapy is considered 1st line?
Oral antipsychotic drug therapy is generally considered 1st line, unless the pt presents w reasons to consider IM depot drug therapy first
What are typical antipsychotics?
Older agents: primarily D2 receptor antagonists
What is the efficacy of typical antipsychotics?
Efficacy for positive sxs, similar to atypical antipsychotics
What drugs are typical antipsychotics?
- Haloperidol
- Fluphenazine, chlorpromazine, perphenazine, thioridazine
- Loxapine (atypical in practice)
What is the most commonly used typical antipsychotic?
Haloperidol, routine and PRN
What do higher potency typicals have?
EPS (extrapyramidal SEs) w higher potency typicals
What are typical antipsychotics effective for?
Very effective for treating the positive sxs, but are likely to worsen negative and cognitive sxs
What drugs are partial agonists (atypical)?
Aripiprazole, Brexpiprazole, Cariprazine
How do partial agonists (atypical) work?
“Stabilize” dopamine transmission
What are partial agonists (atypical) associated more with?
Associated with more akathisia than other antipsychotics
What are partial agonists (atypical) approved for?
Approved for adjunct tx in depression so all have boxed warning for suicidal thoughts/behavior
Aripiprazole drug info.
- 2D6 and 3A4 substrate
- Moderate akathisia
- Low weight gain
Brexpiprazole drug info.
- 2D6 and 3A4 substrate
- Moderate akathisia
- Low-moderate weight gain
Cariprazine drug info.
- 3A4 substrate
- Moderate akathisia
- Low-moderate weight gain
Which drugs are the “pines” atypicals?
- Asenapine
- Clozapine
- Olazapine
- Quetiapine
Asenapine drug info.
- Sublingual and patch formulations
- UGT and 1A2 substrate
- QTc prolongation
Clozapine drug info.
- 1A2 substrate
- Boxed warnings: neutropenia, orthostasis, bradycardia, syncope, seizures, myocarditis, cardiomyopathy
- SEs: sedation, weight gain, constipation, hypersalivation, dry mouth, GI hypomotility w obstruction risk
- QTc prolongation
- Most weight gain
Olanzapine drug info.
- 1A2 substrate
- Significant weight gain and sedation
- High risk metabolic syndrome
- DRESS warning
Quetiapine drug info.
- 3A4 substrate
- QTc prolongation
- Weight gain and sedation
- Boxed warning for suicidal ideation
What are application directions for asenapine transdermal patch (secuado)?
Apply one patch q24h, rotate patch site to minimize application site rxns
Asenapine transdermal patch (secuado) is a UGT and 1A2 substrate. What must be done if given w strong 1A2 inhibitors?
Reduce dose of patch if given w strong 1A2 inhibitors (e.g. fluvoxamine)
What is required for a clozapine prescription?
Absolute neutrophil count (ANC) monitoring; within last 7 days
What is the required ANC count for clozapine and what are the monitoring timelines?
- ANC to 1500 uL or higher to initiate therapy
- Monitoring weekly x6 months, biweekly x6 months, then q4 weeks
Lybalvi is the brand product of olanzapine/samidorphan. Why is samidorphan in the mix?
Samidorphan added to mitigate weight gain
What is samidorphan?
An opioid antagonist w preferential activity at the mu opioid receptor
When is samidorphan CI?
CI in pts currently taking opioids or in opioid withdrawal
What drugs are the “dones” atypicals?
Iloperidone, lurasidone, ziprasidone, risperidone, paliperidone
Iloperidone drug info.
- Highest risk for orthostasis
- QTc prolongation
- 2D6 substrate
Lurasidone drug info.
- 3A4 substrate
- Higher risk for akathisia
- Warning for suicidal thoughts, adjunct for bipolar depression
- Take w food (350 calories) to increase bioavailability
Ziprasidone drug info.
- QTc prolongation (CI)
- DRESS warning
- Take w food to increase absorption and bioavailability
- 3A4 substrate (1/3) and aldehyde oxidase (2/3) (less worry for P450 interactions)
Risperidone drug info.
- 2D6 substrate (minor 3A4 substrate)
- EPS, hyperprolactinemia, weight gain, sedation, orthostasis, gynecomastia
Paliperidone drug info.
- Renally eliminated: dose adjustments in renal impairment
- Similar SEs w risperidone
- QTc prolongation
Lumateperone (Caplyta) drug info.
- Low risk for weight gain or metabolic side effects
- Low risk for EPS or akathisia
- 3A4 substrate
What is pimavanserin (Nuplazid) indicated for?
FDA approved for tx of hallucinations or delusions in a pt w Parkinson’s disease
What is pimavanserin’s MOA?
Inverse agonist and antagonist at 5HT2A and 2C receptors
What is pimavanserin a substrate for?
3A4 substrate
What are the warnings for all antipsychotics?
- Boxed warnings: increased risk of death in elderly pts treated w antipsychotics for dementia w related behaviors
- Metabolic AEs
- EPS
- Risk of somnolence, postural hypotension, and motor and/or sensory instability increases the risk for falls/fractures
- Fall risk assessment should be done
Haloperidol decanoate drug info.
- Given q4 weeks
- Load: 20x oral dose
- Maintenance: 10x oral dose, if only used for maintenance may need oral overlap, oil based is Z track
What must be supplemented with risperdal consta (risperidone)?
MUST supplement w oral risperidone (or another oral antipsychotic) for first few weeks of tx
What is the dosage form of Perseris (risperidone)?
Abdominal subq injection
What should the dose of Perseris (risperidone) be if given w 3A4 inducers?
120 mg or may need oral supplementation
Rykindo (risperidone) drug info.
- Every 2 week IM injection
- Oral dose overlap is shorter than risperdal consta (7 days v 21 days)
Uzedy (risperidone) drug info.
- Abdominal or upper arm subq injection
- Given once monthly or every 2 months
What is the administration timeline for invega sustenna (paliperidone)?
Loading dose, then booster, then every 4 weeks (starting 5 weeks after loading injection)
Where must initial loading and booster doses be given for invega sustenna (paliperidone) and why?
Initial loading and booster doses must be given in deltoid to improve absorption consistency
For invega sustenna (paliperidone), if the loading strategy is followed, is oral overlap required?
No need for oral overlap antipsychotic tx
When could dose adjustments be required for invega sustenna (paliperidone)?
May require dose adjustments in moderate to severe renal impairment
When can invega trinza (paliperidone q3m) be initiated?
May be initiated for a pt who has been on a stable monthly IM invega sustenna injection, at least 4 stable invega sustenna doses
Where can invega trinza (paliperidone q3m) be given?
Recommended to be given deltoid
Gluteal admin of invega trinza (paliperidone q3m) results in what?
Gluteal admin results in a lower Cmax
When is invega trinza (paliperidone q3m) not recommended?
If CrCl <50 ml/min
When can invega hafyera (paliperidone q6m) be initiated?
May be initiated after stable invega sustenna for 4 months or stable invega trinza after one 3 month dose
What is only location for invega hafyera (paliperidone q6m) admin?
Gluteal injection only
What is required for zyprexa relprevv (olanzapine)?
REMS (risk evaluation mitigation strategy)
What can zyprexa relprevv (olanzapine) cause?
PDSS - post dose delirium sedation syndrome
What is the oral and IM depot dosing of zyprexa relprevv (olanzapine)?
What is required for abilify maintena (aripiprazole)?
MUST overlap w oral aripiprazole (or another oral antipsychotic) for at least 14 days after first injection
Where is abilify maintena (aripiprazole) admin?
Deltoid or gluteal injection
What is the abilify maintena (aripiprazole) dose adjustments for P450 interactions?
If taking 2D6 or 3A4 inhibitors or 3A4 inducers for more than 14 days as concomitant therapy:
What is the dosing schedule for abilify asimtufii (aripiprazole)?
Every 2 month dosing
Where is abilify asimtufii (aripiprazole) administered?
Gluteal injection only
What is required after the first injection of abilify asimtufii (aripiprazole)?
Continue oral aripiprazole for 2 weeks after first injection
What must be overlapped w Aristada (aripiprazole lauroxil)?
Overlap w oral aripiprazole for 3 weeks after first injection
Why was aristada initio developed?
Developed to avoid need for 21 day oral overlap of antipsychotic
When should aristada initio (aripiprazole lauroxil) be avoided?
Avoid in pts who are 2D6 poor metabolizers or w strong 3A4 or 2D6 inhibitors
Which immediate release antipsychotic injections are commonly used for psychiatric emergencies?
- Haloperidol, chlorpromazine, fluphenazine are used
- Haloperidol most commonly
When can olanzapine immediate release IM NOT be used and why?
CANNOT be given at the same time as a benzodiazepine immediate release injection - boxed warning for respiratory depression
What inhalation dosage form med is available for psychiatric emergencies?
Loxapine for inhalation (Adasuve)
What is the tx for acute dystonia of EPS?
IM anticholinergic NOW dose (benztropine 2mg, diphenhydramine 50 mg)
What is the tx for drug induced parkinson’s of EPS?
Oral anticholinergic (benztropine, trihexyphenidyl, diphenhydramine)
What is the tx for akathisia of EPS?
- BB (propranolol preferred 1st line)
- Benzodiazepine (usually lorazepam)
What is the tx for tardive dyskinesia of EPS?
VMAT inhibitors
Which drugs are the VMAT inhibitors?
Tetrabenazine (Xenazine), Valbenazine (Ingrezza), Deutetrabenazine (Austedo)
Valbenazine (Ingrezza) drug info.
- 2D6/3A4 substrate
- QTc prolongation
Deutetrabenazine (Austedo) drug info.
- 2D6 substrate
- QTc prolongation
What is the danger of neuroleptic malignant syndrome?
Life threatening - is a medical emergency
What are characteristics of neuroleptic malignant syndrome?
- Hyperpyrexia, tachycardia, labile BP
- Muscle rigidity: elevated (significantly) CK, myoglobinuria
What is not CI in tx of neuroleptic malignant syndrome?
Future antipsychotics
What characterizes metabolic AEs?
Hyperglycemia, hyperlipidemia, HTN
What are the atypical antipsychotic risk comparisons for metabolic AEs?
- Clozapine, olanzapine >
- Quetiapine, risperidone, paliperidone, asenapine, iloperidone, cariprazine, brexipiprazole >
- Ziprasidone, lurasidone, aripiprazole
What are the metabolic monitoring parameters during antipsychotics use?
