Antipsychotic Use in the Hospital Setting

Treatment of the Agitated Patient

Dallas Erdmann, MDMedical Director and Department Chair

Behavioral Health

Riverside Methodist Hospital

Ohio Health

Objectives

• 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 forPotential Violence

The MacArthur Violence Risk Assessment Study Fixed-risk Factors

• Prior violence

• Antisocial behavior form of

psychopathy

• Male gender

• Father who used drugs

• Victim of child abuse

• Personality disorder

Treatable-risk Factors• Unemployment• Violent thoughts• Living in disadvantaged

neighborhood• Poor anger control

• Postictal state• Adjustment disorder• Involuntary status• Command hallucinations

Assessing Etiology and Setting Goals

Diagnosis Associated with Violent Behavior as an Essential Feature

• 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

• 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• Voluntary

medication

• Show of force

• Emergency

medication

(Postgrad Med Special Report 2001. May : 1-88)

• Unlocked seclusion• Locked seclusion

• Leave the area

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– 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 q1-2h 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)

• 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– 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 ZydisRisperidone 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 ofAripiprazole and Haloperidol on Hostility/Excitability Symptoms

*P<0.001.

†P<0.01.Data on file, Bristol-Myers Squibb Company and Otsuka Pharmaceutical Co., Ltd.

Mean Change from Baseline

PANSS Hostility/Excitability Cluster

Mean Change from Baseline

PlaceboHaloperidolAripiprazole

* *

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†

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n= 160 153 304 88 92 198

Mean baseline = 12.6 12.4 12.4 12.4 12.0 12.0

Aripiprazole Dosing

• 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

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

• Substance abuse• Male gender• Young adult• Antisocial PD• Homeless• Friday admit• Cognitively impaired• Psychosis

Clinical Management Considerations

• 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 patientVerbal communication NOT intactAgitation 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