Quetiapine Treatment for Pediatric Delirium

Medical College of Wisconsin

Status and phase

Withdrawn

Phase 3

Phase 2

Conditions

Delirium

Treatments

Drug: Quetiapine

Other: Placebo

Study type

Interventional

Funder types

Other

Identifiers

NCT03572257

1195004

Details and patient eligibility

About

This is a prospective, double-blind, randomized controlled trial to begin determining the efficacy of quetiapine as a treatment for pediatric delirium in patients admitted to the pediatric intensive care unit (PICU)

Full description

Delirium is an acute syndrome with fluctuation in mental status with altered cognition and consciousness. It is a common occurrence (17% to 38%) in critically ill children with serious short-term consequences. Its pathophysiology is complex and incompletely understood. Dopaminergic, serotoninergic, glutaminergic, and cholinergic pathways in the cerebral cortex, striatum, substantia nigra, and thalamus have been implicated. Imbalance in the synthesis, release, and inactivation of neurotransmitters can result in altered cognitive function, behavior, and mood. The Society of Critical Care Medicine set the adult practice guidelines including widespread delirium screening as well as treatment to decrease duration of delirium and ameliorate its long-term effects (12). The cornerstone of pharmacologic therapy for delirium in adults is antipsychotics, both first and second-generation (13-20).

The current foundation of treatment for pediatric delirium is identifying and addressing the underlying etiology. Iatrogenic factors should be minimized, such as avoiding benzodiazepines and restraints, optimizing pain control, minimizing sedation, and treating withdrawal. The ICU environment should also be optimized to create a quiet, well-lit space with clustered care to allow for uninterrupted sleep. When non-pharmacologic treatment measures prove insufficient to manage the symptoms of delirium, we believe the second-generation antipsychotic (SGA) quetiapine may have a role in the treatment of delirium. However, there are currently no FDA-approved medications to treat delirium in this population.

The European Society of Paediatric and Neonatal Intensive Care (ESPNIC) has recently recommended that all children in the ICU be monitored for delirium but provided no guidance on recommended treatments (21), likely due to the lack of evidence of proven delirium treatment in children. An adult systematic review and meta-analysis by Kishi et al concluded that antipsychotics are superior to placebo in decreasing severity of delirium and time to response with there was no significant difference in the side effects between the two groups. Additionally, SGAs are associated with a shorter time to response and lower side effect profile than haloperidol (a first-generation antipsychotic).

A growing body of pediatric literature suggests that delirium is a serious and under recognized problem in critically ill children as well, however little research has been focused on treatment . A recent retrospective series looking at the use of quetiapine in suggested that quetiapine use for delirium treatment is a safe option in this population.

With proven efficacy in adults with delirium, an established track record in children for indications other than delirium, a favorable safety profile, and a wide therapeutic window, quetiapine is a logical choice for the next phase of research into pediatric delirium treatment. In this study are looking prospectively at the effectiveness of quetiapine as a treatment for pediatric delirium.

Sex

All

Ages

Under 21 years old

Volunteers

No Healthy Volunteers

Inclusion criteria

Age 0 - 21 years old
PICU admission
Positive CAPD scoring
- For developmentally normal children a CAPD score of ≥ 9
- For developmentally delayed a CAPD score of ≥ 9 and a Richmond Agitation Sedation Scale (RASS) fluctuation of at least 2 points in the last 24 hours

Exclusion criteria

Patients under neuromuscular blockade and/or therapeutic hypothermia.
Patients undergoing treatment of alcohol withdrawal.
Patients unable to tolerate enteral medications
Patients on antipsychotics
Patients with a history of:
- hepatic encephalopathy, hepatitis
- elevated liver enzymes defined ALT or AST above normal range for age since hospitalization
- baseline QTc prolongation (defined as greater than 97th percentile for age or greater than 20% increase from baseline or previous QTc)
- major depressive disorder or bipolar disorder, and movement disorder.
Patients who are pregnant
Non-English and non-Spanish speaking subjects and/or parent/guardian