antipsychotic updatedesired antipsychotic medicine (one that has an lai formulation) 2. give trial...
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Antipsychotic
Update
Carrie L. Kreps
Pharm.D., BCGP, FASCP
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Objectives
● Define and classify antipsychotic drugs (APD).
● Explain the mechanism of action of antipsychotic drugs.
● List various indications of APDs.
● Explain adverse effects of antipsychotic drugs.
● Understand how a pharmacist can monitor side effects.
● Describe new atypicals on the market.
● Explain differences in cost of APDs.
● Recognize which APDs are long-acting injectables.
● Predict which APDs are more/less desirable in various
scenarios.
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Definition
● Class of medication primarily used to manage psychosis
(including delusions, hallucinations, paranoia, or
disordered thoughts)
● Increasingly being used in the management of non-
psychotic disorders
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Most Common Uses
● Schizophrenia
● Schizoaffective disorder
● Bipolar disorder
● Psychotic depression
● Treatment resistant major depression
● Adjunctive treatment in some anxiety disorders
● Acute treatment of agitation
● Dementia or insomnia where no other treatments have
worked
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Classification of Antipsychotics
Typical (1st generation) APD
● D2 antagonist
● Higher risk of EPS
Atypical (2nd generation) APD
● D2/5-HT2A antagonist
● Higher risk of metabolic
effects
● Lower risk of EPS
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APD Effects
Pathways Function 1st Generation APD 2nd Generation APD
Nigrostriatal Movement Higher risk for EPS Lower risk for EPS
Mesolimbic Arousal, memory,
motivation
Decreased positive
symptoms
Decreased positive
symptoms
Mesocortical Cognition,
communication,
social function,
response to stress
Increased negative
symptoms
Decreased or no effect
on negative symotins
Tuberoinfundibular Regulates prolactin
release
Higher risk for
Hyperprolactinemia
Lower risk for
Hyperprolactinemia
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Extrapyramidal Symptoms (EPS)
EPS Acute Dystonia Akathisia Pseudoparkinsonism Tardive dyskinesia
Looks like Stiff neck, muscle rigidity,
eye deviation, trouble
swallowing, spasm of the
body
“Ants in pants”, severe
internal restlessness,
can’t sit still
Shuffling gait,
expressionless face,
rigidity/tremors
Involuntary
movement of facial
muscle, jerky limb
movement
Onset Hours to days of treatment
initiation or dosage
increase
≤ 1-4 weeks of treatment
initiation or dosage
increase
≤ 1-3 months of
treatment initiation or
dosage increase
After Months to
years of therapy
Treatment 1. parenteral:
-anticholinergic (Cogentin)
or benadryl
-benzodiazepine (ativan)
2. Follow-up with oral
anticholinergic (Cogentin)
-beta blocker
(propanolol)
-benzodiazepine(ativan)
-anticholinergic
(Cogentin)
-anticholinergic
(Cogentin)
-amantadine
-valbenazine
(Ingrezza)
-deutetrabenazine
(Austedo)
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APDs: Dirty Drugs
Other receptors Dopamine inhibition
Alpha-1 Orthostatic hypertension
H-1 Sedation, weight gain
5-HT2C Weight gain, mood, cardiovascular effect
Muscarinic receptors anti-SLUD effects, tachycardia, impaired
cognition/memory
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1st Generation (Typical)
Low potency
● Chlorpromazine
● Prochlorperazine
● Thioridazine
High potency
● Fluphenazine
● Haloperidol
● Pimozide
● Thiothixene
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2nd Generation (Atypical)
● Asenapine (Saphris)
● Clozapine (Clozaril)
● Iloperidone (Fanapt)
● Ziprasidone (Geodon)
● Lurasidone (Latuda)
● Olanzapine (Zyprexa)
● Quetiapine (Seroquel)
● Paliperidone (Invega)
● Risperidone (Risperdal)
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Newer Atypical
● D2 partial agonist
○ Aripiprazole (Abilify) 2002
○ Brexpiprazole (Rexulti) 2015
● D3-preferring D3/D2 receptor partial agonist
○ Cariprazine (Vraylar) 2015
● 5HT2A inverse agonist/antagonist with no D2 affinity
○ Pimavanserin (Nuplazid) 2014
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Cost
● LAIs can cost up
to four times as
much as the oral
equivalent, but
this cost increase
can be offset by
a reduction in
hospitalization
related medical
costs.
● Most 2nd gen
APDs cost
>$1000/month
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Long-acting Injectables (LAI)
● LAIs ensure medication delivery, NOT efficacy.
● Ideally used in patients who respond to and tolerate antipsychotic
medications that are available in LAI formulations.
● Allows for better ability to distinguish between lack of efficacy and poor
adherence.
● Not for short-term therapy (<3 months).
● Consider for any patient with schizophrenia and risk factors for non-
adherence (history on non-adherence, substance abuse, cognitive
impairment, ambivalence towards medicine).
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LAI Dosing
1. Start or convert patient to an oral dosage form of the
desired antipsychotic medicine (one that has an LAI
formulation)
2. Give trial of oral dosage form to determine clinical
response, tolerability, and effective dose (at least 3-7
days)
3. Convert from oral dosage form to LAI
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LAIs and Dosing Intervals
● Risperdal consta - every 2 weeks
● Fluphenazine decanoate - every 2-3 weeks
● Zyprexa relprevv - every 2-4 weeks
● Haloperidol decanoate - every 4 weeks
● Invega sustenna - every 4 weeks
● Abilify maintena - every month
● Aristada (aripiprazole lauroxil) - every 1-2 months
● Invega trinza - every 3 months
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LAI Advantages vs Disadvantages
● Varying pharmacokinetics
and dosing intervals
● Adverse effects may persist
after stopping/reducing
dose
● Injection related adverse
effects
● Some patients may feel a
lack of autonomy
● High cost
● Improved adherence
● Reduced risk of overdose
● Reduced hospitalization rates
● Bypasses pharmacokinetic
hurdles of absorption and
first pass hepatic elimination
● Improved relapse prevention
Disadvantages Advantages