Feasibility, efficacy, and safety of antipsychotics for intensive care unit delirium: the MIND randomized, placebo-controlled trial.
OBJECTIVE
To demonstrate the feasibility of a placebo-controlled trial of antipsychotics for delirium in the intensive care unit and to test the hypothesis that antipsychotics would improve days alive without delirium or coma.


METHODS
Randomized, double-blind, placebo-controlled trial.


METHODS
Six tertiary care medical centers in the US.


METHODS
One hundred one mechanically ventilated medical and surgical intensive care unit patients.


METHODS
Patients were randomly assigned to receive haloperidol or ziprasidone or placebo every 6 hrs for up to 14 days. Twice each day, frequency of study drug administration was adjusted according to delirium status, level of sedation, and side effects.


RESULTS
The primary end point was the number of days patients were alive without delirium or coma. During the 21-day study period, patients in the haloperidol group spent a similar number days alive without delirium or coma (median [interquartile range], 14.0 [6.0-18.0] days) as did patients in the ziprasidone (15.0 [9.1-18.0] days) and placebo groups (12.5 [1.2-17.2] days; p = 0.66). No differences were found in secondary clinical outcomes, including ventilator-free days (p = .25), hospital length of stay (p = .68), and mortality (p = .81). Ten (29%) patients in the haloperidol group reported symptoms consistent with akathisia, compared with six (20%) patients in the ziprasidone group and seven (19%) patients in the placebo group (p = .60), and a global measure of extrapyramidal symptoms was similar between treatment groups (p = .46).


CONCLUSIONS
A randomized, placebo-controlled trial of antipsychotics for delirium in mechanically ventilated intensive care unit patients is feasible. Treatment with antipsychotics in this limited pilot trial did not improve the number of days alive without delirium or coma, nor did it increase adverse outcomes. Thus, a large trial is needed to determine whether use of antipsychotics for intensive care unit delirium is appropriate.
Girard
Timothy D
TD
Department of Medicine, Division of Allergy, Pulmonary, and Critical Care Medicine, Vanderbilt University School of Medicine, Nashville, TN, USA. timothy.girard@vanderbilt.edu
Pandharipande
Pratik P
PP
Carson
Shannon S
SS
Schmidt
Gregory A
GA
Wright
Patrick E
PE
Canonico
Angelo E
AE
Pun
Brenda T
BT
Thompson
Jennifer L
JL
Shintani
Ayumi K
AK
Meltzer
Herbert Y
HY
Bernard
Gordon R
GR
Dittus
Robert S
RS
Ely
E Wesley
EW
D000328:Adult; D000368:Aged; D014150:Antipsychotic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D003693:Delirium / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006220:Haloperidol / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D010879:Piperazines / Q000009:adverse effects / Q000627:therapeutic use*; D011183:Postoperative Complications / Q000523:psychology; D011569:Psychiatric Status Rating Scales; D012121:Respiration, Artificial / Q000009:adverse effects; D013844:Thiazoles / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome
D014150:Antipsychotic Agents; D010879:Piperazines; D013844:Thiazoles; C092292:ziprasidone; D006220:Haloperidol