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Psychopharmacotherapy of Aggression & Psychiatric Emergencies in Children & Adolescents Mental Health Services Elham Salari Child & Adolescent Psychiatrist. Psychiatric Emergencies. Aggression Delirium. Aggression. PRN Sedation–patterns.

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Psychiatric emergencies

Psychopharmacotherapy of Aggression &PsychiatricEmergencies in Children & AdolescentsMental HealthServicesElham SalariChild & Adolescent Psychiatrist


Psychiatric emergencies

PsychiatricEmergencies

  • Aggression

  • Delirium


Psychiatric emergencies

Aggression


Prn sedation patterns

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 patterns1

PRN Sedation–patterns

  • Acute episodes of aggression or agitation are common in children and adolescents receiving inpatient psychiatric treatment.


Prn sedation patterns2

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.


Psychiatric emergencies

The use of p.r.n medication

to control aggression

in child and adolescent

mental health inpatient services


France 2009

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 20091

France, 2009

  • Anxiety was the reason given for 67% of the p.r.n administrations, with hydroxyzine used in 69% of these cases.


France 20092

France, 2009

  • Disruptive behaviour accounted for 22% of prn administrations, with antipsychotic drugs accounting for 88% of these administrations.


Australia 2006

Australia, 2006

  • A retrospective chart review examined 122 medical charts from a child and youth mental health inpatient service in South Brisbane.


Australia 20061

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 20062

Australia, 2006

  • Chlorpromazine and

  • diazepam

    were the most commonly utilised agents.


Drugs prescribed and administered for prn sedation

Drugs prescribed and administered for prnsedation


Comparison with other studies

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 studies1

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


Psychiatric emergencies

Antihistamines


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.


Antihistamines1

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

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.


Psychiatric emergencies

Typical

Antipsychotics


Psychiatric emergencies

Atypical

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.


Psychiatric emergencies

Ziprasidone


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.


Ziprasidone1

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 vs haloperidol

Ziprasidone

Haloperidol

with Lorazeoam


Ziprasidone vs haloperidol1

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 haloperidol2

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.


Psychiatric emergencies

Olanzapine

(Zyprexa)


Olanzapine vs ziprasidone

olanzapine vs ziprasidone

olanzapine

ziprasidone


Olanzapine vs ziprasidone1

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 ziprasidone2

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 ziprasidone3

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.


Psychiatric emergencies

Risperidone

(Risperdal)


Risperidone

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.


Risperidone1

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, placebo-controlled, randomized clinical trial.

  • Risperidone was superior to placebo in reducing aggression.


Psychiatric emergencies

Orally Dissolvable Form


Risperidone2

Risperidone

Zyprexa Zydis

Olanzapine

Orally disintegrating tablet

Risperdal m-tab

Orally disintegrating tablet


Orally dissolvable form

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 form1

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 form2

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 form3

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 form4

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.


Risperidone3

Risperidal

Oral Solution

Risperidone


Psychiatric emergencies

Quetiepine

(seroquel)


Quetiepine

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.


Psychiatric emergencies

Aripiprazole

(Abilify)


Aripiprazole

Aripiprazole

  • Although the inpatient studies on aripiprazole for pediatric aggression are also lacking, one open-label study of 15-day duration suggests that it is effective and safe in reducing aggression in children and adolescents with CD


Psychiatric emergencies

Benzodiazepines


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.


Benzodiazepines1

Benzodiazepines

  • When used for longer durations, habituation to and physiologic dependence on any of the benzodiazepines may occur.


Benzodiazepines2

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

Comparison of the most commonly used benzodiazepines for acute agitation and aggression.


Psychiatric emergencies

Pharmacological Treatment of Aggression

in Children & Adolescent

Guidelines


Summary

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.


Summary1

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)


Psychiatric emergencies

American Academy of

Child and Adolescent Psychiatry


If patient is already taking psychiatric medications

If patient is already taking psychiatric medications


General agitation treatments po preferred over im

General agitation treatments (PO preferred over IM)


Symptom specific treatments po preferred over im

Symptom-specific treatments (PO preferred over IM)


Suggested dose ranges

Suggested dose ranges


Psychiatric emergencies

The Royal Children`s Hospital Melbourne


If the patient can tolerate oral medications

If the patient can tolerate oral medications


If oral medication not possible

If oral medication not possible


Psychiatric emergencies

Delirium


Mortality

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

Prevalence

  • The paucity of epidemiological data is striking given the children represent a population at heightened risk of Delirium.


Psychiatric emergencies

Symptom profile of delirium

in children and adolescent:

does it differ from

adults and elderly?


Symptom profile of delirium in children and adolescent

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 Scale-Revised-98 (DRS-R-98) and compared with DRS-R-98 data on adults and elderly patients, 2012.


Symptom profile of delirium in children and adolescent1

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 adolescent2

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 adolescent3

Symptom profile of delirium in children and adolescent

  • Compared to adults, children and adolescents had lower frequency of long-term 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 adolescent4

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 adolescent5

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 adolescent6

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 adolescent7

Symptom profile of delirium in children and adolescent

  • Developmental regression with transient loss of previously acquired skills


Symptom profile of delirium in children and adolescent8

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

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 adolescents1

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

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 factors1

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

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 adolescents1

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 adolescents2

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 adolescents3

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 adolescents4

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 adolescents5

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 adolescents6

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 adolescents7

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 adolescents8

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 adolescents9

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

  • 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.


Droperidol1

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.


Droperidol2

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


Droperidol3

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 adolescents10

Management of delirium in children and adolescents

  • Other psychotropic medications:

  • Benzodiazepines

  • Psychostimulants


Benzodiazepines3

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.


Benzodiazepines4

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.


Benzodiazepines5

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

Psychostimulants

  • A number of authors have described the successful use of psychostimulants such as methylphenidate for the treatment of hypoactive delirium in adults.


Psychostimulants1

Psychostimulants

  • However, there is no literature relating to the treatment of hypoactive delirium in children and adolescents with psychostimulants.


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