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Antipsychotic Use in the Hospital
Setting
Treatment of the Agitated Patient
Dallas Erdmann, MD
Medical Director and Department Chair
Behavioral Health
Riverside Methodist Hospital
Ohio Health
Objectives
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•
•
•
Summarize causes of agitation
Review treatment algorithms
Discuss drug therapy options
Discuss the legal complications in
management of patient agitation
Patient Case
• 40 y/o male found sleeping by friend after
allegedly ingesting 30 Percocet for pain
• Recently agitated, involved in a fight injuring back
• At nurse’s station – banging hand, yelling,
screaming – “come and get me”
• Given 2 mg Ativan PO – No behavior change
• Psychiatry Consult called
1. Which is the most appropriate
medication to use in this current
scenario?
A. Haldol PO
B. Haldol IM
C. Ativan PO
D. Ativan IM
2. In this scenario, which regimen is
preferred for ongoing therapy?
A. Scheduled Ativan PO, with prn Haldol IM and
Benadryl IM for emergencies
B. Scheduled Ativan IM, with prn Haldol IM and
Benadryl IM for emergencies
C. Scheduled Haldol PO, with prn Haldol IM and
Benadryl IM for emergencies
D. Scheduled Haldol IM, with prn Haldol IM and
Benadryl IM for emergencies
E. PRN Ativan
3. What are the physician’s legal
responsibilities in this case?
A. Pink slip the individual
B. Get a court order forcing him to take
his medications
C. Transfer to an inpatient psychiatric unit
D. Discharge patient AMA
E. Hold him against his wishes for 24
hours
The Need for Acute Intervention
Prevalence of Aggression:
• Estimated 20% of hospital staff assaulted by patients
- 90% on inpatient units
- nursing staff
• 10% of patients with chronic psychiatric conditions
admitted to hospitals
• 40% of psychiatrists attacked once
• 48% of psychiatric residents assaulted once
Agitation as a Behavioral
Emergency
• Agitation may require immediate medical
intervention when the patient displays:
–
Psychomotor activation
Affective lability
Verbal abuse
Catatonic excitement
Aggression to property
Potential to harm self or others
Allen MH, et al. Postgrad Med Special Report. 2001:1-90.
Predictors of Risk for
Potential Violence
The MacArthur Violence Risk Assessment Study
Fixed-risk Factors
Treatable-risk Factors
• Prior violence
• Unemployment
• Violent thoughts
• Living in disadvantaged
neighborhood
• Poor anger control
• Postictal state
• Adjustment disorder
• Involuntary status
• Command hallucinations
• Antisocial behavior form of
psychopathy
• Male gender
• Father who used drugs
• Victim of child abuse
• Personality disorder
Assessing Etiology and Setting
Goals
Diagnosis Associated with Violent
Behavior as an Essential Feature
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Intermittent explosive disorder
Isolated explosive disorder
Undersocialized conduct disorder, aggressive
Socialized conduct disorder, aggressive
Antisocial personality disorder, aggressive
Borderline personality disorder
Sexual sadism
Diagnoses Associated With Violent
Behavior as an Associated Feature
• Substance use
disorders
• Organic mental
disorders
• Mental retardation
• Attention deficit
disorder
• Brief reactive psychosis
• Schizophrenic disorder
• Schizoaffective disorder
• Paranoid Disorder
• Bipolar Disorder
• Post-traumatic stress
disorder
Diagnoses Associated with Violence
as an Infrequent Behavior
• Atypical psychosis
• Major depression
• Dysthymic disorder
• Cyclothymic disorder
• Atypical depression
• Paranoid personality
disorder
• Schizoid personality disorder
• Schizotypal personality
disorder
• Histrionic personality
disorder
• Psychogenic fugue
• Adjustment disorder with
disturbance of conduct
Common etiologies of organically
induced aggression
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Traumatic brain injury
Stroke and other cerebrovascular disease
Medications
Delirium
Alzheimer’s disease
Chronic Neurological disorders
Brain tumors
Infectious diseases
Epilepsy
Metabolic disorders
Medications and drugs
associated with aggression
• Intoxication and Withdrawal States
• Steroids
• Antidepressants
• Amphetamines and cocaine
• Antipsychotics
• Anticholinergic drugs
TREATMENT
1. Determine etiology
2. Delineate the biopsychosocial context
3. Document and rate the aggression
4. Develop a multifaceted treatment plan
Therapeutic Goal
• Assure the safety of patient and others
• Facilitate treatment course
Ideal endpoint:
Alert and cooperative without falling asleep
Expert Consensus Guidelines on
Tx of Behavioral Emergencies
• Verbal intervention
• Unlocked seclusion
• Voluntary
medication
• Locked seclusion
• Show of force
• Leave the area
• Emergency
medication
(Postgrad Med Special Report 2001. May : 1-88)
Treating Agitation:
Acute Intervention
Drug Selection
• Effectiveness (vs. efficacy)
• Patient preference/ Hx of med response
• Limited intolerable or dangerous side effects
• Clinically useful sedation
• Speed of onset, duration
• Dosing alternatives
• Long term considerations
Medications used in Acute
Situations
• Benzodiazepines
–
Lorazepam
– Diazepam
• Antihistamines
–
Diphenhydramine
– Hydroxyzine
• Typical Antipsychotics
–
Haloperidol
– Droperidol
– Chlorpromazine
– Thioridazine
• Atypical Antipsychotics
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–
–
–
Risperidone
Olanzapine
Ziprasidone
Aripiprazole
Benzodiazepines
• Preferred by patients
• Superior to haloperidol for aggression
• Drug of choice for agitation from EtOH,
BZD WD, cocaine, amphetamine
ingestions (Bath Salts)
• Safer than neuroleptics
• Allow reduced dose of neuroleptic
• Lorazepam most studied
BENZODIAZEPINES
 Generally safe, particularly in cardiac dz.
 Short and long half life choices
 PO, IV, and IM options
 Few drug interactions
Benzodiazepine Adverse
Effects
• Excessive sedation
• Poor coordination
• Memory impairment
• Mood disturbance
• Deliriogenic
• Paradoxical hostility possible
(disinhibiting)
– Elderly, mentally retarded may be at
higher risk
• Abuse/Dependence (long-term
use)
• Respiratory depression when
combined with other sedatives
• Can cause Hypotension
Benzodiazepines - Dosing
• Lorazepam 1-4
mg IM/PO/IV q12h prn
- May give as
often as q30” in
select patients
• Diazepam 5-10
mg PO q2-4h prn
- Avoid IM if
possible
- If not possible,
same dose and
frequency as PO
TRADITIONAL
ANTIPSYCHOTICS
ADVANTAGES
– PO/IV/IM option
– Well known
– Not amnestic/deliriogenic
– Not disinhibiting
– No abuse potential
– Less suppression of respiratory drive than
BZs
• Haldol primary choice
– Droperidal (Inapsine) black box warning
TRADITIONAL
ANTIPSYCHOTICS
• DISADVANTAGES
– Does not treat alcohol or sedative/hypnotic
withdrawal
– Risk of arrhythmias (prolongs QT)
– Significant risk of EPS
• Dystonia, akathisia, NMS
– Can cause hypotension
• Particularly droperidol
Droperidol (Inapsine)
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•
•
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Antipsychotic structurally related to haloperidol
Potent antimetic
2.5 to 5 mg IM for behavioral indications
vs. haloperidol
– quicker onset
– shorter duration
– more sedating
• Not part of the usual long-term treatment for any
psychiatric condition
Droperidol Pharmacokinetics
• Rapidly absorbed when given IM
- therapeutic effect in 3-10 min, 30 min to max effect
- effect declining by 60 min
- sedating/tranquilizing properties last 2 to 4 hours
- alteration of consciousness lasts up to 12 hours
• Metabolized by the liver
Droperidol – Adverse Effects
• EPS
- dystonia, akathisia
• Hypotension, tachycardia
• Increased QTc interval, ventricular arrhythmias
• Withdrawn from the European market
- baseline ECG recommended
- extreme caution in those at risk for prolonged QTc
- dose-dependent but has occurred at standard doses
Haloperidol (Haldol)
Benefits/Limitations
• Flexible dosing/ onset of effect
– IM administration
- 30 to 60 minutes to peak level
- Therapeutic effect still rising at 1 hour
– PO administration
- 2 to 6 hours to peak effect
- oral bioavailability 60%
• Adverse Effects
- Acute dystonia
- Akathisia
Haldol
• Usual dosing
- 2-10 mg PO/IM/IV q2-4h prn
- Start with 2 mg in the elderly or
w/comorbidities
• 21 hour half-life
– detectable for several weeks
Chlorpromazine (Thorazine)
• Low potency phenothiazine
• Not first line
• 25-100 mg IM q1-4h prn NTE 1 gm/day
• Common side effects
- sedation
- hypotension, tachycardia, QT prolongation
- blurred vision, constipation, urinary retention
- ocular effects
- less EPS than haloperidol
ATYPICAL
ANTIPSYCHOTICS
• ADVANTAGES
– Not amnestic/deliriogenic
– Not disinhibiting
– No/low abuse potential
– Treats psychotic symptoms regardless of
cause
– Available in Oral and IM options
• Geodon, Zyprexa, Abilify
Potential Advantages of
Atypical Antipsychotics
• Reduced risk of EPS*1
• Reduced risk of prolactin elevation†1
• Reduced risk of TD1
• Improvement of depressive symptoms2
*May
be dose-related; †Except risperidone.
1. Nemeroff. J Clin Psychiatry. 2000;61(suppl 13):19.
2. McElroy and Keck. Biol Psychiatry. 2000;48:539.
ATYPICAL
ANTIPSYCHOTICS
• DISADVANTAGES
– Does not treat alcohol or sedative/hypnotic
withdrawal
– Risk of arrhythmias (prolongs QT)
• Particularly Geodon
– Small risk of EPS
• Particularly Risperdal
– Can cause hypotension
• Particularly Zyprexa
Risperidone Dosing
• Liquid
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–
–
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1 mg/ml concentration, 30 ml bottle
May mix with OJ, coffee, water, milk
Peak level in 60 minutes
2-4 mg dose
• Tablet
Olanzapine Zydis
Risperidone M-TAB
Abilify Disc-Melt
• Freeze dried tablet dissolves into saliva
- non-carbonated beverages (Olanzepine &
Risperidone)
• Absorbed in normal way
• 5 to 15 seconds to initial disintegration
• Can be suspended in liquid
• Bioequivalent to regular tablets
• Onset no quicker than oral tablet
Olanzapine
• Dosing
- 2.5 to 20 mg tablets
• Benefits
– Efficacy in positive and negative sx
– Sedation
• Limitations
– Uncooperative patients
– Long term side effect profile
– Sedation
Olanzapine IM
• Dosing
- 10 mg dose
- q 2-4 hours max 30 mg.
• Benefits
– Efficacy in positive and negative sx
– Sedation
• Limitations
– Benzodiazepines used with caution
– Long term side effect profile
– Sedation
Ziprasidone IM
• Efficacy of IM Ziprasidone demonstrated in
two pivotal double-blind trials
• Very favorable response compared to IM
haloperidol
• Rapid clinical improvement after ziprasidone
10 mg and 20 mg consistent with short Tmax
(>1 hour)
• Well tolerated IM up to 80 mg per day
• Adverse events mild to moderate
• No significant effects on BP or heart rate
Aripiprazole (Abilify)
• Potent partial agonist at D2 dopamine receptors1-2
– Functional antagonist at D2 receptors in a
hyperdopaminergic environment1
– Functional agonist at D2 receptors in a
hypodopaminergic environment1
• Serotonin antagonist at 5-HT2A and partial agonist
at 5-HT1A receptors
• Not generally sedating
Short-Term Effect of
Aripiprazole and Haloperidol on
Hostility/Excitability Symptoms
Mean change from baseline
PANSS Hostility/Excitability Cluster
2.0
1.5
1.0
0.5
0
-0.5
-1.0
-1.5
-2.0
-2.5
-3.0
LOCF
*
*
†
*
ge from
nge
fromBaseline
Baseline
n=
160
Mean baseline =
OC
153 304
12.6 12.4 12.4
88
92 198
12.4 12.0 12.0
*P<0.001.
†P<0.01.
Data on file, Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co., Ltd.
Placebo
Haloperidol
Aripiprazole
Aripiprazole Dosing
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Available in 2, 5, 10, 15, 20 and 30 mg tablets
Liquid, discmelt and IM formulations
May be taken with or without food
May be used in combination with BZDs
Low incidence of EPS
Low incidence of weight gain/hyperglycemia
Generally not sedating
Higher incidence of akathisia
Aripiprazole IM
• Dosing
- 9.75 mg (one vial)
- q 2 hours for maximum 30 mg in 24 hours
• Benefits
– Efficacy in positive and negative sx
– Non-sedating
– Can be given with Lorazepam in same syringe
• Adverse events mild to moderate
• No significant effects on BP or heart rate
Seroquel
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Well known
VERY low incidence of EPS
Can cause hypotension – need to titrate
Very sedating – need to titrate
Reports of Seroquel abuse (“Quelling”)
Only available in tablet form – NO IM
Patient Who Wants to Leave
AMA
• Demographics of AMA Discharges
– 1% of all discharges
– Risk factors
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Substance abuse
Male gender
Young adult
Antisocial PD
Homeless
Friday admit
Cognitively impaired
Psychosis
Clinical Management
Considerations
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Try to convince patient to stay
Do MSE
Treat aggravating conditions
Get help from family members
Document, document, document
Consider consultation
Stay open to creative solutions
Medical-Legal Considerations
• The vast majority of successful lawsuits
are from patients being discharged AMA
with consequent bad clinical outcome
vs. from forcing the patient to stay in
hospital against his/her will.
• Progress note entrees will be more
important than signed forms if case
goes to court.
Is the Patient Cognitively
Impaired?
• If yes, strong case for keeping them
hospitalized against their will.
• Try to do MSE
– Ideal = MMSE
– At least orientation and insight into medical
condition and need to treat.
• If acute confusion (delirium)
– Treat cause and document rationale
– Consider family involvement
Is the Patient Imminently at
risk of Violence?
• If yes - risk of harm to self/others, can
hold up to 24 hours without pink slip
– If due to a “psychiatric condition”, get
psych consult
– If primarily a criminal justice issue, notify
police
• If not risk to self or others and not
confused, can AMA discharge
Questions and Answers
Forced Medications:
Steele v. Hamilton County
Community Mental Health Board
In a unanimous decision written by Justice Douglas, the Ohio
Supreme Court affirmed and ruled that a court may authorize the
administration of antipsychotic medication against a patient's
wishes without a finding of dangerousness when clear and
convincing evidence exists that:
1. The patient lacks the capacity to give or withhold informed
consent regarding treatment;
2. The proposed medication is in the patient's best interest;
3. No less intrusive treatment will be as effective in treating the
mental illness.
EMERGENCY MEDICATION
The decision of whether to medicate the patient in an emergency must
be made promptly before an injury occurs. There is not time for a
judicial hearing, and medical personnel must make the determination
whether the patient is dangerous to self or others.
Therefore, a physician may order the forced medication of an
involuntarily committed mentally ill patient with antipsychotic
medications when the physician determines that:
1. The patient presents an imminent danger of harm to
himself or others;
2. There are no less intrusive means of avoiding the
threatened harm;
3. The medication to be administered is medically
appropriate for the patient.
Steele v. Hamilton Cty. Community Mental Health Bd., (OHIO 2000)
When not to use the CIWA…
• The CIWA is not intended to be used for:
- agitation management
- delirious, confused, head injured,
ventilation dependent patients
- any other forms of withdrawal other
than alcohol *
- very complicated/difficult withdrawal
patients
Examples of when NOT to use CIWA
*patient intubated & sedated (on
propofol)
*patient who is a recovering alcoholic
(no recent use)
*a delirious patient
 Verbal communication NOT intact
 Agitation resulting from delirium secondary to
underlying medical issues (metabolic abnormalities,
infection) may lead to inappropriate excess dosing of
benzodiazepines, which may worsen delirium
Top Mistakes seen when working
with Detox Protocols
1) Identifying both protocols as ”CIWA”
2) Attempting to use alcohol detox
protocols for other forms of withdrawal
(cocaine, heroin, nicotine, etc.)
3) Putting patients that cannot be
adequately/thoroughly assessed by
symptom triggered therapy on CIWA