Download Management of delirium in children and adolescents

Psychopharmacotherapy of
Aggression &
Psychiatric Emergencies in
Children & Adolescents
Mental Health Services
Elham Salari
Child & Adolescent Psychiatrist
Psychiatric Emergencies
• Aggression
• Delirium
Aggression
PRN Sedation–patterns
• Aggressive behaviors, may
be associated with a variety
of psychiatric disorders and
are often the reason for
referral to psychiatric
treatment.
PRN Sedation–patterns
• Acute episodes of
aggression or agitation are
common in children and
adolescents receiving
inpatient psychiatric
treatment.
PRN Sedation–patterns
• Although behavioral
techniques are usually first-line
interventions, psychotropic
medications with sedative
effects are widely used on an
‘as needed’, or prn (Pro Re
Nata) basis to treat acute
aggressive episodes.
The use of p.r.n medication
to control aggression
in child and adolescent
mental health inpatient services
France, 2009
• The study was carried out on the
psychiatry ward of a paediatric
teaching hospital in Paris, France.
• P.r.n prescriptions were written, for
27% of the patients (51) but only
14% (26) received a total of 76
administrations.
France, 2009
• Anxiety was the reason
given for 67% of the p.r.n
administrations, with
hydroxyzine used in 69%
of these cases.
France, 2009
• Disruptive behaviour accounted for 22%
of prn administrations, with antipsychotic
drugs accounting for 88% of these
administrations.
Australia, 2006
• A retrospective chart review examined 122
medical charts from a child and youth
mental health inpatient service in South
Brisbane.
Australia, 2006
• 71.3% of patients were prescribed prn
sedation and 50.8% were administered
prn sedation.
• Patients received an average of 8.0 doses
of prn sedation, with 9.8% receiving 10 or
more doses.
Australia, 2006
• Chlorpromazine
and
• diazepam
were the most
commonly utilised
agents.
Drugs prescribed and
administered for prn sedation
Drugs prescribed
and administered
for prn sedation
Diazepam
Chlorpromazine
Temazepam
Droperidol IM
Haloperidol
Olanzapine
Quetiapine
Others
Dose range (mg)
2-20
10-100
10–20
2.5–10
2–2.5 (oral)
2.5–5 (IM)
2.5–10
25–100
Comparison
with other studies
• The nature of drugs
utilized for prn sedation
varies with other studies
reporting predominance of
• thioridazine,
• thioridazine or
lorazepam
• or chlorpromazine in
combination with chloral
hydrate
Comparison
with other studies
• The lower rate of use of atypical
antipsychotics is noteworthy as it
contrasts with other reports describing
escalating utilization rates of atypical
antipsychotics for nonprn use in children
and adolescents
Antihistamines
Antihistamines
• Antihistamines, particularly first generation
(older) antihistamines, are known to have
effects on the central nervous system by
causing rapid sedation and slowing down
psychomotor performance and cognitive
function.
Antihistamines
• Despite the common use of antihistamines
for aggression and agitation, there is only
one published, controlled study for an
antihistamine (diphenhydramine) on
managing child and adolescent aggression
on psychiatric inpatient units on acute
basis.
Diphenhydramine
• In this double-blind, placebo-controlled,
pilot study of an antihistamine for 21 male
patients (aged 5–13 years old), PRN
diphenhydramine was not superior to
placebo in reducing aggression, as there
was a significant placebo effect.
Typical
Antipsychotics
Atypical
Antipsychotics
Atypical Antipsychotics
• For acute treatment of aggression on child
and adolescent inpatient units, ziprasidone
is the most extensively studied atypical
antipsychotic medication.
Ziprasidone
Ziprasidone
• Ziprasidone was the first atypical
antipsychotic available in IM form and this
might be the reason that it was observed
as the most extensively studied
antipsychotic for managing aggression in
inpatient children and adolescents.
Ziprasidone
• A case report of youths treated with IM
ziprasidone reported an immediate
beneficial effect on controlling the
aggressive episode on the inpatient child
psychiatry unit.
• Ziprasidone has been found to be
beneficial in treating aggression in child
and adolescent inpatients as well as
adolescents in the emergency room
Ziprasidone vs haloperidol
Ziprasidone
Haloperidol
with Lorazeoam
Ziprasidone vs haloperidol
• Both treatment groups had similar
outcomes in regards to restraint time and
use of rescue medications.
• The Behavior Activity Rating Scale(BARS)
scores in subjects started decreasing
immediately after the IM ziprasidone
injection and had a significant decrease
after one half hour and continued to
decrease up to two hours.
Ziprasidone vs haloperidol
• Although no severe side effects were
found, side effects may not have been
monitored or documented carefully.
• Nonetheless, the authors conclude that
IM ziprasidone should be considered since
it leads to a similar clinical outcome while
avoiding potential severe adverse events
associated with typical antipsychotic
medications such as haloperidol.
Olanzapine
(Zyprexa)
olanzapine vs ziprasidone
olanzapine
ziprasidone
olanzapine vs ziprasidone
• A retrospective study comparing the
efficacy of IM ziprasidone and IM
olanzapine PRN in 100 juvenile (younger
than 18 years) psychiatric inpatients found
that these medications were similar in
terms of their ability to address inpatient
Aggression.
olanzapine vs ziprasidone
• However, patients taking IM ziprasidone
received significantly more doses of IM
ziprasidone, as well as other potentially
calming medications, such as
antihistamines or lorazepam.
olanzapine vs ziprasidone
• Somnolence was the most common side
effect noted during this study for either IM
ziprasidone or IM olanzapine.
• Neither medication had any documented
significant effect on QTc interval, blood
pressure, or heart rate.
Risperidone
(Risperdal)
Risperidone
• Most of the risperidone studies were
conducted in outpatient settings and are
targeted to treat chronic aggression rather
than acute inpatient aggression.
• As per our search, only one study has
attempted to observe the effects of
risperidone in treating the aggression in an
inpatient unit.
Risperidone
• In this study, 38 aggressive adolescent
inpatients with CD and other oppositional
problems were randomly assigned to
risperidone or placebo treatment for six
weeks in a doubleblind, placebocontrolled, randomized clinical trial.
• Risperidone was superior to placebo in
reducing aggression.
Orally Dissolvable Form
Risperidone
Zyprexa Zydis
Olanzapine
Orally disintegrating tablet
Risperdal m-tab
Orally disintegrating tablet
Orally Dissolvable Form
• Orally Disintegrating Tablets (ODTs) which
disintegrate rapidly in saliva, usually in a
matter of seconds, without the need to
take it water.
Orally Dissolvable Form
• Absorption through the cheek allows the
drug to bypass the digestive tract for rapid
systemic distribution.
• Drug dissolution and absorption as well as
onset of clinical effect and drug
bioavailability may be significantly greater
than those observed from conventional
dosage forms.
Orally Dissolvable Form
• The need for non-invasive delivery
systems persists due to patients’ poor
acceptance of, and compliance with,
existing delivery regimes, limited market
size for drug companies and drug uses,
coupled with high cost of disease
management.
Orally Dissolvable Form
• A patient in a psychiatric institutional
setting who may try to hide a conventional
tablet under his or her tongue to avoid
their daily dose of a psychotropic drug.
• Patients who are unwilling to take solid
preparation due to fear of choking.
• Pediatric and geriatric patients who have
difficulty in swallowing or chewing solid
dosage forms.
Orally Dissolvable Form
• Risperidone and olanzapine, both are
available in an orally dissolvable form
(Risperdal M-tab and Zyprexa Zydis),
• Risperidone is also available as a liquid
concentrate, again broadening the clinical
situations in which it may be of benefit.
Risperidone
• Risperidal
Oral Solution
Quetiepine
(seroquel)
Quetiepine
• In one short-term (eight week), open-label,
outpatient study (including 6–12 year old
children with CD), quetiepine was found to
be helpful and well tolerated when
targeting aggression.
Aripiprazole
(Abilify)
Aripiprazole
• Although the inpatient studies on
aripiprazole for pediatric aggression are
also lacking, one open-label study of 15day duration suggests that it is effective
and safe in reducing aggression in
children and adolescents with CD
Benzodiazepines
Benzodiazepines
• Although these agents are generally safe,
several clinical caveats should be kept in
mind with their use.
• It is found that the use of benzodiazepines
in children and adolescents can be
associated with a paradoxical reaction
including agitation and other adverse side
effects.
Benzodiazepines
• When used for longer durations,
habituation to and physiologic dependence
on any of the benzodiazepines may occur.
Benzodiazepines
• Despite these risks, benzodiazepines are
still being preferred to treat pediatric
agitation,
• even though standardized studies
assessing the usefulness and adverse
effects of benzodiazepine monotherapy in
treating inpatient aggression in children or
adolescents are lacking.
Comparison of the most commonly
used benzodiazepines
for acute agitation and aggression.
Agent
Routes
Dose
equivalency
(mg)
Typical dose (mg)
Alprazolam
PO, SL
0.5
0.25–0.5 t.i.d. to q.i.d.
Clonazepam
PO
0.25
0.125–0.5 q.d. to t.i.d
Diazepam
PO,
IM, IV
5
1–5 b.i.d. to t.i.d
Lorazepam
PO,
IM, IV
1
0.25–2 b.i.d. to t.i.d
Oxazepam
PO
15
15–30 b.i.d. to t.i.d
Pharmacological Treatment of
Aggression
in Children & Adolescent
Guidelines
Summary
• Medication must be appropriate to the
severity of the aggression.
• Mild aggression can be managed with
psychosocial interventions.
• A weight-based dose of diphenhydramine
PRN can be considered for mild
aggression but it should be noted that the
beneficial effect may be due to a placebo
effect.
Summary
• Moderate-to-severe aggression or
threatening behavior with severe distress
can be treated with either IM ziprasidone
(20mg for both children and adolescents)
• or
• Olanzapine
(5mg for children and 10mg for adolescents)
American Academy of
Child and Adolescent Psychiatry
If patient is already taking psychiatric medications
If taking benzodiazepine or
antipsychotic:
Give usual PO medicines on
schedule
If not at usual dose time,
consider one fourth to one half
of total daily amounts as a single
dose
General agitation treatments
(PO preferred over IM)
PO risperidone
PO olanzapine
PO/IM/IV diazepam
PO/IM/IV lorazepam
IM ziprasidone
IM haloperidol plus IM lorazepam
May add on benzodiazepine to an
antipsychotic after 30 min as needed
Symptom-specific treatments
(PO preferred over IM)
Anxiety
• lorazepam, diazepam,
• or possibly diphenhydramine
Psychotic
thoughts or
mania
• risperidone, olanzapine,
• IM ziprasidone, or haloperidol
Impulsive,
maladaptive
aggression
• risperidone or olanzapin
Delirium
• risperidone
• or haloperidol
Suggested dose ranges
Diazepam
0.04 - 0.2 mg/kg/dose PO/IM/IV
(max 10 mg/dose)
Diphenhydramine
1 mg/kg/dose
to max 50 mg PO/IM/IV
Haloperidol
0.025-0.075 mg/kg/dose IM
(max 5 mg/dose)
Lorazepam
0.05 mg/kg/dose PO/IM/IV
(max 2 mg/dose)
Olanzapine
2.5 mg (school age) to
10 mg (late adolescence) PO
Risperidone
0.25 mg (school age) to
2 mg (late adolescent) PO
Ziprasidone
10 mg IM if 12-16 y
10-20 mg IM if ≥16 y
The Royal Children`s
Hospital Melbourne
If the patient can tolerate
oral medications
Diazepam
oral
0.2mg - 0.4mg/kg
(Max 10mg/dose
if benzodiazepine naive)
Lorazepam
Oral
Olanzapine
wafer
sublingual
(SL)
0.5mg - 1mg (<40kg)
1mg - 2.5mg (>40kg)
2.5mg - 5mg (<40kg)
5mg - 10mg (>40kg)
If oral medication not possible
Midazolam
IM / IV
0.1mg - 0.2mg/kg
(Max 10mg/dose)
Olanzapine
IM
only
IM / IV
5mg (<40kg)
10mg (>40Kg
0.1mg - 0.2mg/kg
(Max 5mg/dose,
usually 2.5mg - 5mg/dose)
Give above doses combined
in one syringe
Haloperidol
Midazolam /
Haloperidol
Combination
IM
Delirium
Mortality
• As with adult and elderly
patients, delirium in children
and adolescents in
consultation–liaison
psychiatry settings is
associated with high
mortality rates,
• ranging from 12.5%,
through 20% to 29%.
Prevalence
• The paucity of
epidemiological data is
striking given the children
represent a population at
heightened risk of Delirium.
Symptom profile of delirium
in children and adolescent:
does it differ from
adults and elderly?
Symptom profile of delirium
in children and adolescent
• In India: children and adolescents (age 8–
18 years) diagnosed with delirium by the
consultation–liaison psychiatry team were
rated on the Delirium Rating ScaleRevised-98 (DRS-R-98) and compared
with DRS-R-98 data on adults and elderly
patients, 2012.
Symptom profile of delirium
in children and adolescent
• Severity of symptoms, compared to
adults, the children and adolescents had
lower severity of sleep–wake
disturbances, abnormality of thought,
motor agitation, orientation, attention,
short-term memory, long-term memory
and visuospatial abilities impairment.
Symptom profile of delirium
in children and adolescent
• When compared to elderly patients,
• children and adolescents had higher
severity of lability of affect
• and lower severity of language
disturbances, short-term memory and
visuospatial abilities.
Symptom profile of delirium
in children and adolescent
• Compared to adults, children and
adolescents had lower frequency of longterm memory and visuospatial
disturbances.
• Compared to the elderly, children and
adolescents had higher frequency of
lability of affect.
Symptom profile of delirium
in children and adolescent
• certain features (irritability, affective
lability, agitation, sleep–wake disturbance,
fluctuation of symptoms) were reported
more commonly in children.
Symptom profile of delirium
in children and adolescent
• while other features (delusions, speech
disturbance, memory deficits) were
reported less commonly.
Symptom profile of delirium
in children and adolescent
• Although studies suggest strong continuity
in the clinical manifestations of the
syndrome across the age span, additional
features of delirium in children were
identified by the systematic literature
review, which have not been described in
adults.
Symptom profile of delirium
in children and adolescent
• Developmental regression with transient
loss of previously acquired skills
Symptom profile of delirium
in children and adolescent
• The inability of a usual carer to console
the child,
• reduced eye contact with the usual carer,
• and other subtle changes in the quality of
the parent–child interaction have been
suggested as relatively unique features of
delirium in children and adolescents.
Delirium subtypes
in children and adolescents
• Schieveld et al. reported that only 35% of
children and adolescents presenting with
delirium in the setting of a PICU
conformed to the hyperactive subtype.
• 22.5% of patients were classified as
hypoactive,
• while the remaining 42.5% patients were
classified as having a subsyndromal
“emerging delirium.”
Delirium subtypes
in children and adolescents
• The authors noted that the different forms
were not always clear-cut and that some
cases fluctuated markedly over time.
Possible predisposing factors
• young age are particularly at
risk of emergence delirium,
with those aged 2 to 5 years
being most vulnerable,
• male gender,
• mental retardation,
• caregiver factors such as
carer anxiety or absence
Possible predisposing factors
• preexisting emotional and behavioral
problems:
• children with higher levels of preoperative
anxiety
• temperamentally more impulsive,
• less social, and less adaptable to
environmental changes have also been
identified as being at higher risk of
emergence delirium
Management of delirium in
children and adolescents
• “two-track” treatment approach using both
psychosocial and pharmacological
interventions
• in conjunction with attempts at reversing
the cause(s) of the delirium.
Management of delirium in
children and adolescents
• Stoddard et al. (2006) have suggested that
brief use of intravenous haloperidol with
later substitution of an atypical
antipsychotic was increasingly becoming
the case with children presenting with a
delirium in the United States.
Management of delirium in
children and adolescents
• In children with marked
agitation, haloperidol
at a loading dose of
0.15 to 0.25 mg/dose
intravenously was
used,
• followed by a
maintenance dose of
0.05 to 0.5 mg/kg per
24 h.
Management of delirium in
children and adolescents
• Review article:
• Individual haloperidol doses in these
studies ranged from 0.02 to 0.67 mg/kg
per dose.
Management of delirium in
children and adolescents
• If children were able to tolerate oral,
nasogastric, or gastrostomy tube
medications,
• these authors suggested that after 24 to
48 h of intravenous haloperidol,
substitution of an atypical antipsychotic
such as risperidone, olanzapine, or
quetiapine might be appropriate.
Management of delirium in
children and adolescents
• In less acute situations, and
when an enteral route of
administration was possible,
risperidone at a loading
dose of 0.1 to 0.2 mg/dose
by mouth, followed by a
total daily maintenance
dose of 0.2 to 2.0 mg/24 h,
was the treatment of choice.
Management of delirium in
children and adolescents
• The reports of Karnik et al. and Scharko et
al. raise the possibility that risperidone
may be less effective in
hyperactive/agitated cases of delirium
among adolescent patients,
• while having a particular role in hypoactive
cases of pediatric delirium, based on wider
receptor effects and potential to selectively
increase dopamine in the prefrontal area.
Management of delirium in
children and adolescents
• Karnik et al. proposed a theoretical
framework to account for the apparent
better response of hyperactive delirium to
haloperidol and of hypoactive/mixed
delirium to risperidone.
Management of delirium in
children and adolescents
• Ratcliffe et al. assessed the effectiveness
and safety of haloperidol using a
retrospective chart review of acutely ill
children who received haloperidol for
“marked agitation and restlessness” or
delirium.
• Although 43% had an excellent response,
Management of delirium in
children and adolescents
• 23% had adverse reactions to the
medication including dystonic reactions
and hyperpyrexia.
• The authors concluded that the use of
haloperidol was accompanied by an
unacceptably high incidence of side
effects in the critically ill pediatric
population.
Droperidol
• Droperidol, an analog
of haloperidol, has
also been suggested
to have a role in the
treatment of agitated,
violent, or psychotic
pediatric patients and
in adults with delirium.
Droperidol
• Droperidol is more sedating and has a
faster onset of action than haloperidol, an
effect that may have added benefit in
extremely agitated and combative
patients.
Droperidol
• A great deal of controversy has
surrounded droperidol since the US Food
and Drug Administration issued a “black
box” warning in relation to droperidol's
dose-dependent prolongation of the QT
interval on the electrocardiogram.
• However, since then, several published
studies have disputed this point
Droperidol
• For children two to 12 years of age:
• the maximum recommended initial dose is
0.1 mg/kg.
Management of delirium in
children and adolescents
• Other psychotropic medications:
• Benzodiazepines
• Psychostimulants
Benzodiazepines
• Stoddard et al. suggested a role for
• intravenous benzodiazepines in the
management of delirium in the pediatric
critical care setting.
• They warned of the risk of sedation,
paradoxical disinhibition, and worsening
delirium significantly compromising the
assessment and management in some
cases.
Benzodiazepines
• Schieveld et al. reported that 55% of their
cases of PICU delirium were associated
with a recent increase or decrease in
benzodiazepines and/or opioids.
Benzodiazepines
• Williams has suggested that
benzodiazepines generally be
reserved for childhood delirium due
to sedative-hypnotic withdrawal,
• other than those cases in which
lorazepam is used as an adjunct to
haloperidol for persistent agitation
and insomnia.
Psychostimulants
• A number of authors have described the
successful use of psychostimulants such
as methylphenidate for the treatment of
hypoactive delirium in adults.
Psychostimulants
• However, there is no literature relating to
the treatment of hypoactive delirium in
children and adolescents with
psychostimulants.