Antipsychotics

Question 1

What are the five core symptoms of schizophrenia?

Answer 1

Delusions
Hallucinations
Disorganized speech
Disorganized behavior
Negative symptoms (deficits in emotional, social, and cognitive experience)

Question 2

What needs to be present, according to DSM-5, to make a diagnosis of schizophrenia?

Answer 2

At least 2 of the 5 core symptoms for a period of at least 6 months.

Remember: Think that patients with schizophrenia have “BeN 2 HaDeS” and back.

Behavior
Negative symptoms
2 or more of these symptoms
Hallucinations
Delusions
Speech (disorganized)

Question 3

T or F: Antipsychotic drugs are much more effective to treat the positive symptoms of schizophrenia, but are much less effective at addressing the negative symptoms.

Answer 3

True

Question 4

What are the 2 classes of antipsychotics and how do they differ?

Answer 4

First Generation- Typical

Second Generation- Atypical

They do not differ in efficacy, they differ in their side effects.

Question 5

First Generation (Typical)

Answer 5

Neurological side effects
Decreased dopamine
No effect on serotonin
Equivalent efficacy

Question 6

Second Generation (Atypical)

Answer 6

Metabolic side effects
Decreased dopamine
Increased serotonin
Equivalent efficacy

Increased risk for weight gain, diabetes, and dyslipidemia.

Can be split into 3 groups:
-apine’s (sedating, weight gain)
-idone’s (extrapyramidal)
-piprazole’s (partial agonists at dopamine receptor)

Question 7

Effects of dopamine-
DOPAMINE mnemonic

Answer 7

D- Drugs
O- psychOsis
P- Prolactin inhibition (increased!)
A- Attention
M- Motivation
I- Involuntary movements
N- Nausea
E- Energy

Question 8

Extrapyramidal Effects

Answer 8

Arise from neurons outside of the medullary pyramids.

Occurs more with first generation, but are possible with second generation antipsychotics.

4 main types:

Acute dystonia
Akathisia
Parkinsonism
Tardive dyskinesia

Remember: how long the body needs to AdAPT to an antipsychotic.

A- Acute dystonia (hours)
A- Akathisia (days)
P- Parkinsonism (weeks)
T- Tardive dyskinesia (years)

Question 9

What is acute dystonia?

Answer 9

An extrapyramidal side effects caused by antipsychotics. Can hit within a few hours of the first dose.

Sustained and often painful involuntary contraction of a muscle group, often involving muscles in the face or neck.

Treatment: an anticholinergic drug, like diphenhydramine or benztropine. Dramatic improvement usually seen within a few minutes. No long term side effects.

Question 10

What is akathisia?

Answer 10

Extrapyramidal effect from taking antipsychotic drugs. Starts a few days after starting an antipsychotic for most people, but some notice it right away.

Constant restlessness or jitteriness of the muscles. Patients report being “on edge” or unable to sit still and anxiety.

Treatment involves either starting propranolol (Inderol), a benzodiazepine, or an anticholinergic drug. Stopping or decreasing the antipsychotic should be tried if able. Usually reversible, sometimes not.

Question 11

What is Parkinsonism?

Answer 11

An extrapyramidal effect when taking antipsychotic drugs. Tends to occur several weeks after starting the drug.

Motor deficits resembling the signs and symptoms seen in patients with Parkinson’s disease and indistinguishable from it, including:

Bradykinesia (trouble initiating movement)
Tremor
Rigidity
Postural instability
Shuffling gait

Effects slowly go away after discontinuation of antipsychotic drug over several days.

Question 12

What is tardive dyskinesia?

Answer 12

The most feared outcome (extrapyrimidal effect) of long-term use of first generation antipsychotic use.

Constant involuntary and rhythmic movements, generally involving the perioral muscles. Resembles grimacing, lip smacking, chewing, tongue flicking, or excessive eye blinking.

Slowly occur over time. Can become irreversible if it goes on too long, often permanent. Treatment is to discontinue the typical antipsychotic for an atypical (clozapine is helpful).

Question 13

Neuroleptic Malignant Syndrome

Mneumonic: FEVER

Answer 13

More common with typical than atypical. 15% mortality.

F- Fever
E- Encephalopathy
V- Vital sign instability
E- Elevated WBC and CPK
R- Rigidity

Treat neuroleptic malignant syndrome by discontinuing the antipsychotic, initiating cooling measures, and using either dantrolene or bromocriptine.

Remember: Dan, a Bro with dance FEVER who Never Misses a Step.

Question 14

PO before depot!

Answer 14

Always give the oral form of an antipsychotic before administering it as an IM depot.

Question 15

Short-acting intramuscular antipsychotics

Answer 15

Into the CHAOZ Flu an IM.

C- Chlorpromazine
H- Haloperidol
A- Aripiprazole
O-Olanzapine
Z- Ziprasidone
Flu- Fluphenazine

Question 16

Long-acting intramuscular antipsychotic drugs

Answer 16

One Flu OPRAH the cuckoo’s nest.

F- Fluphenazine
O- Olanzapine
P- Paliperidone
R- Risperidone
A- Aripiprazole
H- Haloperidol

Question 17

Chlorpromazine (Thorazine)
First-generation antipsychotic

Answer 17

Blocks dopamine, also antagonizes acetylcholine, norepinephrine, and histamine.

Memory impairment (anticholinergic)
Hypotension (antiadrenergic)
Sedation (antihistaminergic)

Rare- causes sediment deposits in the cornea when used long-term. Think- CHLORpromazine causes CHLORneal deposits.

Primarily used for sedating effect in very agitated people.

Question 18

Haloperidol (Haldol)
First-generation antipsychotic

Answer 18

Frequently used to treat schizophrenia.

More selective with D2 receptors, less anticholinergic, antihistaminic, or antiadrenergic side effects.

However, because it bonds so strongly to D2 receptors, much higher risk of extrapyramidal side effects.

IV haloperidol requires cardiac monitoring to watch for QTc prolongation and torsades des pointes!!

Question 19

Fluphenazine (Prolixin)
First-generation antipsychotic

Answer 19

Has both IM depot formulation as well as short-acting IM for agitation.

Question 20

Olanzapine (Zyprexa)
Second-generation antipsychotic

Answer 20

Popular, very effective and fast.

Very sedating (night time dosing!).

Worst for metabolic side effects- weight gain on low calorie diet. High risk for developing diabetes.

Think O for Olanzapine and Obesity.

Question 21

Quetiapine (Seroquel)
Second- generation antipsychotic

Answer 21

Highest rates of sedation, often causes weight gain.

Has street value for benzo-like effect.

Think: QUIETapine is for QUIET time.

Question 22

Risperidone (Risperdol)
Second-generation antipsychotic

Answer 22

Lower risk of metabolic side effects, less sedating, and higher risk of extrapyramidal.

Risperidone is less sedating, but can cause hyperprolactinemia and gynecomastia.

Think: RISE-PAIR-idone can give RISE to a PAIR of breasts.

Question 23

Paliperidone (Invega)
Second-generation antipsychotic

Answer 23

Primary active metabolite of risperidone and acts roughly the same way.

Has both a 1-month and a 3-month intramuscular depot form.

Question 24

Clozapine (Clozaril)
Second-generation antipsychotic

Answer 24

Single most effective agent we have against schizophrenia. Never a first-line treatment. Used for treatment/resistant schizophrenia (only if 2 or more other antipsychotics have failed). Evidence that it also helps improve negative symptoms (not just positive).

Rare/potentially deadly side effect: agranulocytosis (1% during first year of treatment). WBC’s depleted, major infections, sometimes death.

Question 25

Ziprasidone (Geodon) Second-generation antipsychotic

Answer 25

Less weight gain and sedation, but can prolong the QT interval so it requires electrocardiogram. Needs to be taken with food. (Can cause QTc prolongation.)

Question 26

Lurasidone (Latuda) Second-generation antipsychotic

Answer 26

Less sedation, less weight gain, more extrapyramidal side effects. Must be taken with food. Helps with psychosis AND bipolar depression.

Question 27

Aripiprazole (Abilify) Second-generation antipsychotic

Answer 27

Partial dopamine receptor agonist. Helps with both acute and maintenance therapy. Less hyperprolactinemia, is weight neutral, and less sedation. Increased risk for akathisia and other extrapyramidal effects. Can be used as adjunctive treatment for depression.

Question 28

Cariprazine (Vraylar) Second-generation antipsychotic

Answer 28

Partial dopamine receptor agonist. Similar to lurasidone. Approved for the use of bipolar depression.

Question 29

T or F: First and second generation antipsychotics are equally effective.

Answer 29

True They are better tolerated though.

Question 30

Choose based on side effect profile.

Answer 30

Side effects differ much more between each antipsychotic than does the efficacy (except for clozapine). Consider side effects profile to determine which med to give. Don’t give weight increasing meds to diabetics or obese patients. Don’t give short acting drugs to forgetful patients. Consider depot drugs for non compliant patients.

Question 31

T or F: Clozapine is superior for treatment- refractory schizophrenia.

Answer 31

True. If a patient has failed multiple trials, consider clozapine unless contraindicated.

Question 32

Why is it so important to to enroll schizophrenic patients in psychosocial therapies (case management, occupational rehabilitation, and CBT)?

Answer 32

While antipsychotic drugs are effective at improving positive symptoms (like auditory hallucinations and paranoia), they do much less for negative symptoms (like apathy, emotional blunting, and cognitive deficits).

Question 33

A 24 yo male brought to ED by police after running haphazardly into traffic while yelling and screaming. Will not give a history, allow an exam, or allow an IV. He is agitated and attempts to assault staff several times, calling them “interlopers” and “agents of destruction.” What form of antipsychotic medication administration should be pursued?

Answer 33

Intramuscular

Question 34

Patient is admitted to psych unit and continues to be agitated, requiring more doses of antipsychotics. Several hours later the patient appears confused and muscular rigidity is noted. HR 122, BP 172/140, RR 20, T 105.2 F. What steps should be taken?

Answer 34

Withdraw all antipsychotics Admit to medical ICU Administer dantrolene Start aggressive cooling measures (Antipyretics are not shown to be effective for neuroleptic malignant syndrome and should not be used.)

Question 35

T or F: Second generation antipsychotics have a lower rate of neurological side effects than first generation antipsychotics?

Answer 35

True

Question 36

A 33 yr old M comes to Urgent Care with sore throat and fever. HR 104, BP 90/60, RR 16, and T 101.7 F. Lab studies reveal ANC=0.4/uL. On further questioning, the patient admits to having moved across the country one month ago to “start again.” What medication is most likely responsible for his presentation?

Answer 36

Clozapine, the only antipsychotic with a potential side effect of agranulocytosis.

Question 37

T or F: a wide QRS is a common side effect of Ziprasidone?

Answer 37

False It is known for a prolonged QTc interval, not a wide QRS (which is related to tricyclic overdose).

Question 38

-apine’s main side effects

Answer 38

-apine’s (sedating, weight gain)

Question 39

-idone’s main side effects

Answer 39

-idone’s (extrapyramidal)

Question 40

-piprazole’s mechanism of action

Answer 40

-piprazole’s (partial agonists at dopamine receptor)