A double-blind trial of risperidone and haloperidol for the treatment of delirium. Haloperidol prophylaxis for elderly hip-surgery patients at risk for delirium: a randomized placebo-controlled study.
To compare the clinical efficacy of haloperidol and risperidone for the treatment of delirium, the authors performed a double-blind comparative study. Twenty-eight patients with delirium were recruited and randomly assigned to receive a flexible-dose regimen of haloperidol or risperidone over 7 days. The severity of delirium was assessed by using Memorial Delirium Assessment Scale scores. Scores for each group decreased significantly over the study period. However, no significant differences in mean Memorial Delirium Assessment Scale scores between groups were found. The group-by-time effect was not significant. In addition, there was no significant difference in the frequency of response to the drugs between the two groups. One patient in the haloperidol group experienced mild akathisia, but no other patients reported clinically significant side effects. These data show no significant difference in the efficacy or response rate between haloperidol and risperidone in the treatment of delirium. To study the effectiveness of haloperidol prophylaxis on incidence, severity, and duration of postoperative delirium in elderly hip-surgery patients at risk for delirium.
                Randomized, double-blind, placebo-controlled trial.
                Large medical school-affiliated general hospital in Alkmaar, The Netherlands.
                A total of 430 hip-surgery patients aged 70 and older at risk for postoperative delirium.
                Haloperidol 1.5 mg/d or placebo was started preoperatively and continued for up to 3 days postoperatively. Proactive geriatric consultation was provided for all randomized patients.
                The primary outcome was the incidence of postoperative delirium (Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, and Confusion Assessment Method criteria). Secondary outcomes were the severity of delirium (Delirium Rating Scale, revised version-98 (DRS-R-98)), the duration of delirium, and the length of hospital stay.
                The overall incidence of postoperative delirium was 15.8%. The percentage of patients with postoperative delirium in the haloperidol and placebo treatment condition was 15.1% and 16.5%, respectively (relative risk=0.91, 95% confidence interval (CI)=0.6-1.3); the mean highest DRS-R-98 score+/-standard deviation was 14.4+/-3.4 and 18.4+/-4.3, respectively (mean difference 4.0, 95% CI=2.0-5.8; P<.001); delirium duration was 5.4 versus 11.8 days, respectively (mean difference 6.4 days, 95% CI=4.0-8.0; P<.001); and the mean number of days in the hospital was 17.1+/-11.1 and 22.6+/-16.7, respectively (mean difference 5.5 days, 95% CI=1.4-2.3; P<.001). No haloperidol-related side effects were noted.
                Low-dose haloperidol prophylactic treatment demonstrated no efficacy in reducing the incidence of postoperative delirium. It did have a positive effect on the severity and duration of delirium. Moreover, haloperidol reduced the number of days patients stayed in the hospital, and the therapy was well tolerated.
There is no evidence that haloperidol in low dosage has different efficacy in comparison with the atypical antipsychotics olanzapine and risperidone in the management of delirium or has a greater frequency of adverse drug effects than these drugs. High dose haloperidol was associated with a greater incidence of side effects, mainly parkinsonism, than the atypical antipsychotics. Low dose haloperidol may be effective in decreasing the degree and duration of delirium in post-operative patients, compared with placebo. These conclusions must be tempered by the observation that they are based on small studies of limited scope, and therefore will require further corroborating evidence before they can be translated into specific recommendation for the treatment of delirium.