Antipsychotic Medications

Antipsychotics (AKA
neuroleptics)
Divided into 3 groups: 1) typical (1st
generation), 2) atypical (2nd
generation), and 3) novel (3rd
generation)
2nd & 3rd generation are
characterized by improved response
of negative symptoms, less harmful
effects on cognition & fewer
extrapyramidal effects

Indications for Use

Effective in treating psychosis (Psychosis from
secondary causes may benefit from short-term
treatment while underlying causes are treated)
Symptoms of psychosis grouped into 3 domains
positive symptoms that are associated with
increased mental and physical activity that most
people dont experience. (An excess or distortion of
normal functions)
negative symptoms that are related to absence or
diminution of normal mental and physical activity
cognitive symptoms that result in difficulties in
organizing thoughts, in learning, and in executive
functions

Goals of Therapy
Overall goal of treatment is to return control to
the individual.
Antipsychotic meds are used to decrease
psychotic signs and symptoms, including
hallucinations, delusions and feelings of paranoia.
These drugs are very potent & overmedication
places control of individual in the hands of the
clinician.
Goal of returning control to the individual is
achieved through monitoring specific psychotic
symptoms and improvement in the clients ability
to provide self-care.

Medication Forms
Most troubling symptom is lack of insight,
client who believes he is not sick will have little
motivation to take any medication.
Liquid most antipsychotics are available as
liquids
Injectable
Acute Situations - Immediate-release
injectable forms of medications are available
for emergencies; A one-time IM injection
can be rapidly effective for clients who pose
a danger to themselves and others

Injectable Forms, cont.

Chronic Situations - Some antipsychotics are
available as long-acting injections (LAI), also
known as depot injections, for clients who are
reluctant to take medications everyday.
Critical to monitor the medication in outpatient setting,
long half-lives of drugs result in steady state levels not
reached until 2-3 months after injections are initiated.
Thus, loss of efficacy or increases in side-effects can
develop over time as serum levels fall or rise toward
steady state.
Long-acting injections can last up to 1 month (frequently
given every 2 weeks) so give with long needle, deep IM
(deltoid or gluteal) and Z track - to keep liquid from
seeping back out.

Injectable Forms, cont.

Haloperidol decanoate (Haldol Decanoate 50 & Haldol

Decanoate 100) - half-life 21 days (not approved for older
adults w/dementia related psychosis). Steady state
achieved after 3rd or 4th dose
Fluphenazine decanoate (Prolixin Decanoate) - half-life 14
days. Range of 2550 mg every 23 weeks. Less
hypotension than other 1st generation
Risperdal Consta - typical starting dose is 25 mg every 2
weeks (available in strengths of 25 mg, 37.5 mg and 50 mg
injections) - (not approved for older adults w/dementia
related psychosis). Depending on the individual and
symptoms present, the dose can be increased to a
maximum of 50 mg every 2 weeks

Injectable Forms, cont.

Invega Sustenna - (paliperidone palmitate) - half-life 28

days (not approved for older adults w/dementia related
psychosis). Steady state achieved after 3rd or 4th dose.
Loading dose of 234 mg on treatment day 1 and 156 mg
one week later.

Zyprexa RELPREVV (olanzapine Extended Release

injectable suspension) - (not approved for older adults
w/dementia related psychosis) - 150 mg to 300 mg
administered every 2 weeks and 405 mg administered
every 4 weeks. Clients must be informed of risk for Postinjection Delirium Sedation Syndrome (PDSS), which can
occur with unexplained rapid serum increases

Antipsychotics - Mode of Action

All known antipsychotics are dopamine
blockers
The drug occupies the dopamine receptor
on the postsynaptic neuron
2nd & 3rd generation -block dopamine
receptors and block, or partially block,
serotonin receptors resulting in improved
response of negative symptoms, improved
cognitive functioning, and reduced EPS.

Mode of Action, cont.

1st generation haloperidol,
fluphenazine, & chlorpromazine
frequently in injectable form
2nd generation antipsychotics are firstline therapy for psychotic disorders
Block serotonin more than dopamine
Improved negative symptom response
and minimal EPS + fewer problems
with cognition

Older Adults

Older adults with dementiarelated psychosis treated with

atypical antipsychotic drugs are
at an increased risk of death
compared to placebo
Must be used with caution!!!

2nd generation
Antipsychotics
Clozapine (Clozaril), risperidone
(Risperdal), olanzapine (Zyprexa),
quetiapine (Seroquel), ziprasidone
(Geodon), paliperidone (Invega),
asenapine (Saphris), lurasidone (Latuda)

2nd generation
Antipsychotics, cont.

Mode of Action - reduced EPSEs, 10 times

more serotonin blockade than dopamine
blockade
Clinical Use and Efficacy - first-line therapy
for psychotic disorders, reduced incidence of
EPSEs & reduced risk of causing TD, lack of
EPSEs contribute to improved adherence

Clozapine
Clinical Use and Efficacy
Gradual titration essential b/c of
hypotension, tachycardia & sedation
Risk of agranulocytosis

Clozapine Protocol
Institute therapy only if WBC above
3500/mm3 and ANC = 2000/mm3 or
higher
Monitor WBC weekly
If counts normal for 6 months,
monitor level every 2 weeks
If counts normal for 1 year, monitor
level every 4 weeks

Clozapine Protocol, cont.

Discontinue drug if WBC drops below
3000/mm3 or ANC drops below
1500/mm3
Monitor counts daily
If no infection present, resume drug
when counts return to normal
Permanently discontinue drug if WBC
drops below 2000/mm3 or ANC drops
below 1000/mm3

Risperidone (Risperdal)
High-potency drug - well absorbed w/
or
w/o food
Dose-related EPS usually seen @ > 6
mg/d; other side effects include
anxiety, rhinitis, somnolence,
tachycardia & weight gain

Olanzapine (Zyprexa)
Medium-potency drug
Mild EPS, particularly akathisia; other
side effects include postural
hypotension, dizziness, constipation
& substantial weight gain

Quetiapine (Seroquel)
Low-potency drug; serum half-life is 7
hours
Few EPSEs nor increased serum
prolactin
Side effects include postural
hypotension, somnolence, dizziness,
weight gain, tachycardia

Ziprasidone (Geodon)
Tx of psychotic disorders, as well as
bipolar mania
Affinity for dopamine, serotonin,
noradrenergic & histaminic receptors
Less weight gain than others

Paliperidone (Invega)
Metabolite of risperidone for tx of
schizophrenia. Blocks dopamine type
2, serotonin type 2, and alpha 2
adrenergic receptors.
Extended-Release Tablets, Decanoate
IM

Asenapine (Saphris)
Tx of schizophrenia & acute mania,
mixed episodes
Dosed sublingually, poorly absorbed if
swallowed
Side effects: anticholinergic &
cardiac effects, weight gain
Possible gynecomastia, galactorrhea,
amenorrhea, and low libido due to
increased prolactin levels

Latuda - lurasidone
Indication: schizophrenia
Must be taken with food
No controlled studies for longer than
six weeks
Side effect profile similar to other 2nd
& 3rd antipsychotics

3rd generation
Antipsychotics
aripiprazole (Abilify)
Mode of Action partial
dopamine/serotonin agonist
Clinical Use and Efficacy Less
weight gain than 2nd generation
antipsychotics. As w/ other 2nd
generation decreased EPS.

Neuroleptic Malignant
Syndrome (NMS)
Medical emergency rare abnormal
reaction to neuroleptics and result of
dopamine blockade
Can occur at any stage of treatment,
but more likely to occur early
Potentially fatal complications: MI,
hepatic failure, disseminating
intravascular coagulation (DIC), and
pulmonary edema

(NMS), cont.
Characterized by muscular rigidity,
hyperthermia, altered consciousness &
autonomic dysfunction
Increased creatinine, increased leukocytes
Treatment Stop medication!
Hydration & cooling of patient
IV admin. of muscle relaxant, dopaminergic
drugs (bromocriptine [Parlodel] and
amantadine [Symmetrel]) &
anticholinergics have been used

Extrapyramidal Side-effects
(EPSEs)
Movement-related effects caused by
the dopamine blockade of
medications, esp., but not limited to
antipsychotics
A major reason for non-adherence
EPSEs present as acute dystonia,
neuroleptic induced
pseudoparkinsonism, akathisia, and
tardive dyskinesia.

Anticholinergic drugs
Promptly effective for relieving EPSEs.
Mild presentations may be treated with
oral drugs and severe presentations
will benefit from rapid onset of IM or IV
treatment. Benztropine (Cogentin) 1mg
IM/IV (may be increased incrementally
up to 6 mg) and diphenhydramine
(Benadryl) 50-100 mg IM/IV used most
often. Continue 1-3 days.

Extrapyramidal Side-effects
(EPSEs)
Akathisia most common occurs
with many drugs (see drug guide)
Motor restlessness, feelings of inner
restlessness, pacing, foot-tapping
and rocking. Irritability and/or
inability to sit still and/or lie down.
(similar to S&S of Restless Leg
Syndrome)

Akathisia
Differentiating between akathisia and
psychomotor agitation/irritability of
worsening psychosis is difficult
Mistaking akathisia for psychomotor
agitation could result in increasing
dosage thus worsening akathisia
If severe, patients at risk for suicide

Acute Dystonias
Spontaneous, painful muscle spasm
Blepharospasm (eye closing)
Torticollis (neck muscle contraction - 'twisting'
side to side)
Oculogyric crisis (severe upward deviation of
the eyeballs)
Opisthotonos (severe dorsal arching of the
neck and back)
Laryngospasm can result in dysphagia
(difficult swallowing)

Acute Dystonias, cont.

Treatment:
Anticholinergics quickly relieve symptoms
May be prescribed concurrently w/ antipsychotics

Mild S&S may be treated with oral

anticholinergic drugs
Severe S&S use rapid onset of IV or IM treatment
Benzotropine (Cogentin) 2 mg IM or
diphenhydramine (Benadryl) 50 mg IM or IV
Airway management sometimes needed if
severe

Neuroleptic-Induced
Pseudoparkinsonism
Dopamine & acetylcholine exist in
balance in brain
Dopamine blockade results in
cholinergic predominance leading to
symptoms similar to those seen in
patients w/ Parkinsons Disease

Neuroleptic-Induced
Pseudoparkinsonism, cont.
Tremors
Bradykinesia/akinesia (slowness, absence of
movement)
Cogwheel rigidity (slow, regular muscular
jerks)
Postural instability, hunched posturing,
shuffling gait
Masked facies (loss of mobility in facial
muscles)
Hypersalivation & drooling

Tardive Dyskinesia
Late occurring, abnormal movements
that may occur anywhere on body, but
usually oral, buccal, lingual &
masticatory movements (tongue
writhing, lip pursing, smacking, facial
grimaces.)
May also occur on arm, finger, leg, feet
and truncal movements
Potentially irreversible

Tardive Dyskinesia, cont.

Late occurring, abnormal movements that
may occur anywhere on body (truncal),
but usually oral, buccal, lingual &
masticatory movements (tongue writhing,
lip pursing, smacking, facial grimaces)
Potentially irreversible prevention key
The Abnormal Involuntary Movement
Scale (AIMS) - assessment tool used to
identify EPSEs