AP
What is the basic APA 2020 Guidelines per DSM 5?
DSM 5 Met: start AP (SGA or FGA) based on target symptoms
If improvement after 6 weeks at therapeutic dose: continue therapy
If moderate or poor response after 6 weeks at therapeutic dose and 80% + adherence: change AP (to check adherence, can check blood level, obtain info from at least 2 sources, obtain past Tx response from pt, caregiver or other source)
What receptor type do FGAs typically act on?
Dopamine
What SGAs are most responsible for causing weight gain?
Olanzapine and clozapine
When is clozapine appropriate?
Treatment resistance: despite at least 2 AP trials at appropriate doses
Risk for suicide is substantial or aggressive behavior remains substantial
What is the AIMS examination? What do the scores represent? What is not documented?
Abnormal involuntary movement scale
+ AIMS exam: 2 of more in 2 movements or a score of 3 or 4 in 1 movement
tremors
What is the expected onset of efficacy for AP?
Initial dose: improvement in acute agitation and aggression, AEs can be seen within 24-96 hrs
1-2 weeks: some improvement in + sx
4-6 weeks: majority of sx may take this length of time to improve
What are the FGAs?
Haloperidol, chlorpromazine, fluphenazine, loxapine, pimozide
Which 2 SGAs need to be taken with food and how many calories?
Ziprasidone: 500 cals
Lurasidone: 350 cals
Does clozapine need titrated? What happens if the patient does not take the medication in over 48 hours?
titrate up slowly, too fast can cause seizures, myocarditis, hypotension, agranulocytosis
Must retitrate
What is tardive dyskinesia? How do we manage it? What needs to be monitored?
Involuntary movements of orofacial area, often restricted to mouth
Onset is typically in months-years and it is often irreversible
Manage with VMAT2 inhibitor: causes a reversible decrease in dopamine release (Valbenazine, Tetrabenazine, Deutetrabenazine)
Monitor AIMS every 6 months
For FGAs, what symptoms do these typically improve more? What are the more common SEs?
+ symptoms, little - symptom change
increased EPS
What are some dose dependent AEs of FGAs?
Antihistamine: weight gain and sedation
Anticholinergic
orthostatic hypotension: tolerance often occurs in 2-3 months
increased risk of aspiration pneumonia
What are the second generation APs?
Aripiprazole, brexpiprazole, asenapine, iloperidone, lurasidone, olanzapine, paliperidone, quetiapine, ziprasidone, clozapine, cariprazine, risperidone
What CYP does clozapine interact with? What are the main AEs we should look out for (BBW)?
CYP1A2
BBW: seizures, myocarditis, agranulocytosis, and other CV/respi
Most sedation, orthostatic hypotension, and metabolic side effects, but least EPS among the atypicals
Sialorrhea (treat with anticholinergics
How do we treat Autism?
Treat the behaviors, not Autism itself
Agents for irritability/aggression: Risperidone and aripiprazole
Get an IEP
For SGAs, what symptoms do these typically improve more? What are the more common SEs?
increased metabolic SEs
What are some serious AEs FGAs can cause? Main offenders?
QTc prolongation: Thioridazine (BBW), pimozide, haloperidol
Hepatic: fluphenazine, perphenazine, trifluperazine, Jaundice most common with chlorpromazine
Seizures: chlorpromazine, least with haloperiodol
Hyperprolactinemia: worse with potent D2 antagonists, Risperidone (consider switch to Abilify or augmentation)
Which SGAs are most likely to cause the following:
Akathisia, movement AEs, hyperprolactinemia, seizures
Akathisia: aripiprazole
Movement: risperidone, paliperidone, lurasidone
hyperprolactinemia: risperidone
seizures: clozapine
What are the major cardiac AEs of clozapine and what should we do if they occur? What should be routinely monitored?
Hypotension: monitor during titration
Tachycardia: tolerance usually develops
EKG changes: dose related
Myocarditis: Discontinue if CRP is greater than 100 or troponin is more than 2x ULN
Cardiomyopathy: D/C drug if occurs
CRP, troponin should be measured at baseline and weekly for first 8 weeks.
What us neuroleptic malignant syndrome (NMS)?
Lead pipe muscle rigidity, hyperthermia, autonomic dysfunction, altered mental status, elevated CPK
D/C antipsychotic ASAP, do not retry, supportive care
Are all antipsychotics considered equally effective?
Yes, except for Clozapine (SGA)
What are extrapyramidal symptoms? What can cause them? How are they monitored?
Acute dystonia, pseudoparkinsonism, akathisia
Most common with high dose, high potency FGAs
Monitor with AIMS
Which SGAs are most likely to cause the following:
Sedation, metabolic AEs, QTc prolongation, anticholinergic SEs
Sedation: clozapine, olanzapine, quetiapine
Metabolic: clozapine, olanzapine, quetiapine
QTc: ziprasidone, iloperidone
Anticholinergic: clozapine
What is the program used for clozapine? What does it monitor?
REMS: for severe neutropenia
Requires baseline ANC to be above 1500 for initiation, stop clozapine if ANC is less than 1000
Prescribers must submit patient status form monthly to REMS before patient can be dispensed clozapine
How do we manage the following EPS SEs?
Acute dystonia, pseudoparkinsonism, akathisia, mod-severe TD
Acute dystonia: give anticholinergic med such as Benztropine or diphenhydramine
Pseudoparkinsonism: lower the dose, switch APs, or add anticholinergic
Akathisia: lower the dose, switch APs, add BZD, or add beta blocker such as propranolol (avoid diphenhydramine)
Mod-sev TD: add reversible VMAT2 inhibitor