EBM Question C/L

Delirium Definition
Delirium

is a neuropsychiatric disorder characterized by disturbances of

Consciousness Attention Cognition Perception With an abrupt onset and fluctuating course

Delirium is Common
Delirium

usually has an underlying physiological etiology In a general hospital setting the occurrence of Delirium may approach
30% in medically ill patients 40% in the hospitalized elderly 85% in cancer patients and for those with terminal illness

Delirium worsens prognosis

Delirium

is associated with poor functional outcome, prolonged hospitalization, and increased morbidity and mortality

APA Guidelines in the Treatment of Delirium

(i)

the identification of underlying etiologies (ii) appropriate medical intervention to treat reversible etiologies (iii) initiation of environmental interventions to provide safety and support (iv) relief of distressing symptoms with antipsychotics

Antipsychotic Delirium Treatment Recommendations @ URMC

Haldol

(IV or PO)

Has historically been the treatment for delirium

Seroquel
Ideally Treats delirium and provides sedation without significant EPS

Abilify

(once patient was already on Abilify)

Case
Patient

with bipolar d/o presenting with hyperactive delirium (but not in a manic episode). Was on Abilify 15 mg Recommendation go up to 20 mg Patient improved clinically

Intriguing case?
Somewhat

surprised the intervention of increasing Abilify from 15 mg to 20 mg worked Lack of experience using or hearing about Abilify (specifically) used for delirium

Intriguing case?
Abilify

differs from all other antipsychotics by being a partial agonist (not a D2 blocker). . . Mechanism by which antipsychotics treat delirium unclear By being a partial D2 agonist could there be a difference could there be a difference in efficacy for treating delirium?

PICO Question
Patient

population: Delirious patients Intervention: Abilify Comparison: Other antipsychotics (non partial agonists either FGA or SGA) Outcome: Resolution of Delirium
In

patients with delirium, is Abilify as effective as other anti-psychotics in clearing the delirium?

Article
Aripiprazole

and haloperidol in the treatment of delirium

Soenke Boettger , Miriam Friedlander, William Breitbart Australian and New Zealand Journal of Psychiatry 2011; 45:477 482

Article Aim
To

further explore the efficacy and tolerability of Abilify (as compared with Haldol) in the treatment of delirium
Previous studies on this topic include a single published case series and two published case reports examining the safety & tolerability of Abilify Results from these studies showed a significant reduction in symptoms of delirium

Methods
This

paper performed a secondary analysis on patients with delirium who received Abilify and then compared this data to a case matched sample of subjects treated with Haldol. Retrospective chart review Essentially they compared reduction in MDAS scores between Haldol / Abilify.

MDAS - Memorial Delirium

Assessment Scale

10-item, four-point (0-3), clinician-rated scale The MDAS items reflect the diagnostic criteria

for delirium in the DSM-IV-TR and assess disturbance in arousal and level of consciousness, cognitive functioning (memory, attention, orientation, and perceptual disturbances) and psychomotor activity. MDAS scores greater than 10 identified the presence of delirium MDAS scores of less than 10 indicated the resolution of delirium in this analysis

MDAS Sample Items

Limitations
Paper based on retrospective analysis of prospectively collected data (Level 4 Evidence). Selection of neuroleptic based on psychiatrists preference Severely agitated patients were excluded from the analysis 21 Patients in each medication group (not a large analysis) This paper acknowledged the need for further randomized, double blind, controlled studies.

Evidence Based Strength

Quality 1a 1b

Type of Evidence Systematic review of RCTs Individual RCT (with narrow confidence interval) 2a Systematic review of cohort studies 2b Individual cohort study 3 Case control studies 4 Case Series (retrospective chart review) 5 (Worst) Expert Opinion, Editorials

Strengths
Authors

attempted to case match patients treated with Abilify to those treated with Haldol with both groups having similar:
Age Initial MDAS Scores Similar etiologies of delirium Similar ratios of subtypes of delirium: Hypoactive / hyperactive delirium were

Strengths
Analysis

was not sponsored by a pharmaceutical company. Although some of the authors had received grants from companies such as Lilly and Purdue-Pharma none reported affiliations to Bristol-Myers Squibb (Abilify pharmaceutical company) The authors alone are responsible for the content and writing of the paper.

Analysis MDAS Scores

Abilify

Time 1: 18.1 Time 2: 10.8 Time 3: 8.3

Haldol

Time 2: 48 72 h later Time 3: 7 days later

Time 1: 19.9 Time 2: 9.9 Time 3: 6.8

Time 2: 48 72 h later Time 3: 7 days later

***No significant difference in MDAS scores *** At times 2 and times 3

Analysis of Safety: Side effects

Abilify

none Haldol EPS (parkinsonism and dystonia). More likely at higher doses

Article Conclusions
There

was no significant difference in the ability of Abilify to ameliorate the symptoms of delirium more effectively than haloperidol at time points T2 and T3 in either subtype of delirium, hypoactive or hyperactive.
OR

Abilify

may be as effective as haloperidol in the management of delirium and its subtypes

Article Conclusions
Abilify

demonstrated an advantage in tolerability by the absence of extrapyramidal side effects.

This article alluded to the conclusion that Abilify, in general, is a better choice over Haldol simply because it has less incidence of EPS.

My Conclusions
At

this time given the available evidence (although of lower grade) it seems reasonable to believe that Abilify and Haldol likely have relatively similar efficacies in treating delirium. However, more research is needed.
Again noting: this study was not strong enough to conclude this definitively (it was not a superiority trial, equivalence trial, a non-inferiority trial OR even a trial at all [it was a retrospective chart review])

My Thoughts
Article

conclusions seems in line with first principles but why limit to just Abilify and not all SGA vs. Haldol since SGAs as a class tend to have less EPS?