MH 701-Atypical_antipsychotics

a. i.
b. List of SGA’s:
i. Clozapine (Clozaril)
ii. Risperidone (Risperdal)

iii. Olanzapine (Zyprexa)
iv. Quetiapine (Seroquel)
v. Ziprasidone (Geodon)
vi. Aripiprazole (Abilify)
vii. Paliperidone (Invega)
viii. Asenapine (Saphris)
ix. Iloperidone (Fanapt)
x. Lurasidone (Latuda)
xi. Brexpiprazole (Rexulti)
xii. Cariprazine (Vraylar)
d. Undesirable Effects:
i. S: sedation/sunlight sensitivity skin effects/sexual side effects
T: tardive dyskinesia
A: anticholinergic effects & agranulocytosis
N: neuroleptic malignant syndrome
C: cardiac arrhythmias (orthostatic hypotension)
E: extrapyramidal symptoms /akathisia; endocrine effects – increased prolactin
eye effects
e. Instructor notes:
i. Sunlight sensitivity – can be easily sunburned; educate pt to protect their skin (ie,
sunblock, hats, etc)
ii. TD – abnormal movements, this is a permanent SE, need to monitor with the
AIMS at baseline and again every few months to assess for changes.
1. Can be lip, eye, tongue, shoulder shrugging, torso movements, movement
of the feet/legs
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a. We’ll discuss tx of TD later
iii. Anticholinergic SE
1. Can’t see, can’t spit, can’t pee, can’t shit
iv. Agranulocytosis (reduced WBC counts)
1. Check for fevers, sore throat, malaise
2. If above sx are there, and they are on a known med that causes
agranulocytis, check their WBC count with a CBC
v. NMS
1. Kind of like serotonin syndrome
2. Happens when you deplete dopamine too much
3. Meds can be given to reverse the dopamine blockade being caused by the

Extrapyramidal Symptoms Treatment

Duration to
EPS symptom Treatment options
Minutes-Hours Acute Dystonic Reaction
● Reversible
● Torticollis (neck flexion),
laryngospasm (throat spasm),
oculogyric crisis (eyes are rolled up
into the head)
● This reaction comes on pretty
fast, within minutes to hours
Benztropine or other anticholinergic
PO or IM
Depending on the severity, the pt
may need it IM.
Days Pseudoparkinsonism
● Reversible
● Bradykinesia, rigidity, masklike
face, cogwheel rigidity, perioral
Days-Weeks Akathesia
• Reversible

Benzodiazepine, beta blocker
These meds (beta blocker/benzo)
can help a pt to stay on their
antipsychotic med.

Long Term Tardive Dyskinesia
● Permanent
● Involuntary mild to severe twitching,
shaking, or jerking in the face,
hands, torso, or feet. Involuntary,
unintentional blinking or tongue

Vesicular Monoamine transporter 2
inhibitor (VMAT2)
● These are new meds, which means
they’re expensive. Many pts with
schizophrenia don’t have jobs, don’t
have great insurance. We have to
wait until they become more
affordable; more studies will be
done to assess their efficacy in the
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Another thing you can do with TD is
switch to an atypical antipsychotic, or

5. Common lab work for patient taking atypical antipsychotics?
a. Weight
b. Waist circumference
c. BP
d. Fasting plasma glucose
e. Fasting lipid profile
f. Prolactin (if having symptoms)
g. ECG (if cardiac dz)
h. Usual Assessment (labs)
i. CBC (wbc)
ii. LFTs
iii. EKG
1. Can be expensive, weight the pros and cons
6. Which of the atypical antipsychotics has less sedating side effects?
a. Answers found in reading – “Comparison of Atypical Antipsychotics” Prescriber’s Letter
in mod 5
b. Low sedating SE:
i. Abilify/Aripiprazole (includes injections Maintena & Aristada)
ii. Brexipiprazole / Rexulti)
iii. Iloperidone (Fanapt)
iv. Paliperidone (Invega) (includes injections sustenna & trinza)
v. Risperidone (Risperdal (includes consta injection)
c. Low to moderate sedating SE:
i. Asenapine / Saphris
ii. Cariprazine (Vraylar)
iii. Iloperidone (Fanapt)

7. Which of the atypical antipsychotics has less metabolic side effects?
a. Low metabolic risk-ziprasidone, aripiprazole, lurasidone/latuda, fanapt/iloperidone (low
for dyslipidemia, good for cholesterol, has moderate weight gain profile), asenapine
b. From the reading – – “Comparison of Atypical Antipsychotics” Prescriber’s Letter:
i. Abilify/Aripiprazole (includes injections Maintena & Aristada)
ii. Cariprazine (Vraylar)
iii. Lurasidone (Latuda)
iv. Ziprasidone (Geodon,
8. Neuroleptic Malignant syndrome—Symptoms to recognize this? What do you do if your
suspect your patient has this?
a. NMS is a life-threatening emergency and is fatal is 10% of cases. It usually occurs later
in tx, but can occur earlier.
b. It is characterized by:
i. Reduced consciousness
ii. Increased muscle tone
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iii. Autonomic dysfunction
1. Hyperpyrexia (high fever); HTN, tachycardia, tachypnea, diaphoresis, and
iv. Cogwheeling
1. Ask the pt to flex their arm, it should be easy. However, pt will shake, feel
tight and stiff.
2. A cogwheel moves in spurts
c. Treatment consists of early detection, discontinuation of antipsychotics, management of
fluid balance, temperature reduction, and monitoring for complications
9. Extrapyramidal side effects-interventions for treating:
a. Akathisia, Acute Dystonic Reactions, Parkinsonism
i. These three are the most common
ii. These three are also reversible by:
1. Taking a medication
2. Stopping the antipsychotic
3. Decreasing the dose of the antipsychotic
b. Chronic dopamine blockage can lead to Tardive Dyskinesia (TD)
i. Usually this is a permanent side effect
ii. If it’s caught early, and the medication is decreased or changed, then sometimes
the TD might wane a little bit.
c. If EPS symptoms develop, give Benztropine/Cogentin (an anticholinergic med) or
Trihexyphenidyl or Diphenhydramine
d. Propranolol more beneficial for akathisia
i. And sometimes a benzodiazepine
e. If develops TD you can give Diphenhydramine.
i. Weak studies also show Vitamin E use,
ii. You can also change to different antipsychotic with less potential to cause TD
f. akathisia
g. Pseudoparkinsonism
i. Mimics Parkinson’s
ii. Slow motion
iii. Drooling
h. Acute Dystonia
i. Laryngeal spasms = trouble swallowing. Hence the word acute. This pt may
need IM or IV Cogentin injection to reverse it.
ii. Happens fast
10. Dystonia
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a. b. More common with high potency typical antipsychotics (rare with atypical
antipsychotics); D2 blockade
i. Onset in hours to days after antipsychotic started or dose increased; 90% within
first 5 days
c. Benztropine 1-2mg 1-twice /day
i. (Benztropine Anticholinergic SE: dry mouth, blurred vision, constipation, urinary
retention, cognitive changes)
d. Diphenhydramine – you can take up to 50mg/day
e. If the dystonic reaction
is severe, stop
medication and give
above agents IV or IM
once or twice to stop
the dystonia; then
prescribe oral
medication to prevent
another episode

11. Akathisia
a. b. Sense of restlessness, appear fidgety, can’t sit still, rocking motion; can be inner sense
of restlessness; can lead to agitation and suicidal ideation; appears in days to weeks
after starting medication, and possibly after a dosage change.
i. Severe cases can lead to suicidal thoughts
c. High potency typical agents most likely to cause this (Haloperidol);
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d. Atypical agents most likely to cause this (aripiprazole (abilify), asenapine,
brexpiprazole, cariprazine, lurasidone (Latuda), paliperidone (Invega), risperidone
(Risperdal); SSRIs/Buspirone); D2 blockade
i. paliperidone (Invega) and risperidone (Risperdal) are like brother and sister
e. First line medications to treat:
i. *Propranolol-Start 10mg BID; can go up to 30mg-90mg daily in 2-3 divided doses
(SE: dizziness, fatigue, syncope, low BP)
ii. *Inderal LA—long acting propranolol dosed once a day (60- 80mg daily)
iii. *Benzodiazepines-any of them will work.
1. Short acting (Eg Lorazapam 0.5mg to 1mg BID)
2. Or Long acting (diazepam 10mg BID or more frequently as needed)
f. *Reduce dose of medication; switch to lower potency agent or different atypical agent
g. *Don’t mistake akathisia with agitation for psych disorder symptoms; you may
worsen akathisia. (Clozapine, quetiapine, and lurasidone cause no more akathisia
than placebo)
12. Parkinsonism
a. b. Pseudo parkinsonism—drug induced Parkinson’s like disease (Tremor “pill rolling”,
rigidity or cogwheeling, bradykinesia-(slow movement), shuffling gait; slurred speech,
mask like face, stooped posture, drooling; cognitive dulling, worse negative symptoms,
worse depression.
c. *Decrease dose or switch to a different antipsychotic
d. *First line meds: Benztropine 1-2mg once or twice per day;
e. *trihexyphenidyl (artane) 2-5mg once or twice per day; diphenhydramine 50mg /day
f. *Symptoms can occur at any time; usually occurs within 1-2 months after antipsychotic
initiated; highest risk patients: female, older higher potency agents at higher doses
g. *If patient is high risk for parkinsonism—consider starting benztropine (or one of the first
line agents) at the same time as starting the antipsychotic
h. *Can discontinue the anticholinergic agent after several weeks; many patients will not
need to remain on it long term. (You just have to see how your pt is doing).
i. *Usually caused by typical agents. Atypical can cause less parkinonsism. (Meds least
likely to cause this: clozapine, quetiapine, and ziprasidone / Geodon.)
j. *D2 blockade—disruption of balance b/t dopaminergic vs cholinergic neurons
13. Tardive dyskinesia
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a. b. Treatment for Tardive Dyskinesia:
c. First Line: Deutetrabenazine (Austedo)
i. Dose: 6mg BID for 1 week, then raise based on response by 3mg BID every
week. Max 24mg BID.
1. Take with food.
ii. Risks:
1. QTc prolongation, insomnia, nasopharyngitis, possible depression, and
d. Also first line: Valbenazine (Ingrezza)
i. 40mg QHS for 1 week, then 80mg QHS with or without food
1. Easier for patients, because it’s once a day (more convenient, less
remembering), and it can be taken with or without food.
ii. Risks:
1. QTc prolongation, sedation, possible depression and suicidality
e. Notes about BOTH meds:
i. They’ve been around for awhile, have been used to treat huntington’s dz.
ii. BB warning for depression and suicidality, when taken for huntington’s only
iii. These meds usually need to be ordered through a specialty pharmacy, which
makes them expensive! Can cost 6,000/month. Yikes.
f. Tardive Dyskinesia (TD) Treatment Management
g. Step 1
i. Prevention – minimizing antipsychotics in patients at risk.
1. Risk factors:
a. Age >50
b. h/o SUD, brain injury, DM, HIV+, female gender, mood d/o’s,
African American race, and presence of EPS
2. Minimize the dose and duration if taking an antipsychotic
a. In other words, don’t give them more than they need.
3. Can decrease duration in mood disorders. That said, in schizophrenia, it’s
much more difficult to do that.
a. For pts with a mood d/o, you can change their medication to a
mood stabilizer
h. Step 2
i. Taper off – with first signs of TD; discuss risks/benefits to continued tx with
1. d/c dose – taper by lowering the dose every 2-4 weeks
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2. can have “withdrawal dyskinesias” with worsening dyskinesias for first few
months after med is stopped.
3. Can be permanent, 30-50% of cases can resolve with discontinuation.
i. Step 3
i. Switch – if discontinuation is not successful
ii. Clozapine is the only antipsychotic that does not cause TD (low level of D2
occupancy) (has other risks…) (Quetiapine also has a low level of D2 occupancy
and low EPS rates
iii. Aripiprazole, and olanzapine may be good alternatives
j. Step 4
i. VMAT2 inhibitor – if tapering and switching do not work – attempt to treat the TD
1. Valbenazine (Ingrezza) – take 1 time a day (1 in 4 response rates) &
Deutetrabenazine (Austedo) take BID with food (1 in 7 response rates)
(used to tx huntington’s in the past, remember BB warming for suicidality
in pts with huntingtons)
ii. These VMAT2 inhibitor meds reduce dopamine hypersensitivity. Doesn’t worsen
psychosis; actually have been helpful in the past for treating psychosis
1. Question – what’s reserpine? (skipped in lecture. 2nd video, 29:25.)
k. Step 5
i. Second line agents – dopamine agents that address other pathways such as
glutamate antagonist – amantadine – tx’s dyskinesias in parkinson’s dz; Ginkgo
is neuroprotective; benztropine can worsen TD with its anticholinergic effects, so
be careful to NOT give Cogentin
14. Clozaril-What is important to know about his medication?
a. Risk for agranulocytosis
15. What patient education will you provide regarding Clozaril?
a. Weekly/monthly lab work to start
b. Side effects (Kaplan ch 29):
i. The most common drug-related adverse effects are sedation, dizziness,
syncope, tachycardia, hypotension, electrocardiography (ECG) changes, nausea,
and vomiting. Other common adverse effects include fatigue, weight gain,
various GI symptoms (most commonly constipation), anticholinergic effects, and
subjective muscle weakness. Sialorrhea, or hypersalivation, is a side effect that
begins early in treatment and is most evident at night. Patients report that their
pillows are drenched with saliva. This side effect is most likely the result of
impairment of swallowing. Although there are reports that clonidine or
amitriptyline may help reduce hypersalivation, the most practical solution is to put
a towel over the pillow.
ii. The risk of seizures is about 4 percent in patients taking dosages greater than
600 mg a day. Leukopenia, granulocytopenia, agranulocytosis, and fever occur in
about 1 percent of patients. During the rst year of treatment, there is a 0.73
percent risk of clozapine-induced agranulocytosis. The risk during the second
year is 0.07 percent. For neutropenia, the risk is 2.32 percent and 0.69 percent,
respectively, during the rst and second years of treatment. The only
contraindications to the use of clozapine are a white blood cell (WBC) count
below 3,500 cells per mm3; a previous bone marrow disorder; a history of
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agranulocytosis during clozapine treatment; or the use of another drug that is
known to suppress the bone marrow, such as carbamazepine (Tegretol).

16. What lab work will be required to be monitored while taking Clozaril? Interventions if
patient complains of illness?
a. Regular CBC’s (with differential)

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