In the Journals

Haloperidol plus lorazepam best treatment for delirium

Results from a large network meta-analysis found that haloperidol plus lorazepam appears to be the best treatment — and ramelteon the best preventive medicine — for patients with delirium.

Although delirium is prevalent, particularly among elderly inpatients, it is underdiagnosed, and prior research has estimated that up to 40% of delirium cases may be preventable, according to Yi-Cheng Wu, MD, of Chang Gung Memorial Hospital at Linkou, Taiwan, and colleagues.

“Despite the widespread use of various psychopharmacological agents for the management of delirium, the relative balance between benefit and harm of the various available treatments remains unclear,” they wrote in JAMA Psychiatry.

To evaluate the available evidence, the researchers reviewed clinical online databases for randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention. Using a random-effects model, the investigators measured treatment response in patients with delirium and the incidence of delirium in patients at risk for delirium (primary outcomes).

Of 58 trials included in the analysis, 20 RCTs encompassing 1,435 participants (mean age 63.5 years) compared the outcomes of treatment and 38 encompassing 8,168 participants (mean age 70.2 years) assessed the prevention of delirium.

Network meta-analysis revealed that haloperidol plus lorazepam provided the best response rate for treatment on delirium (OR = 28.13; 95% CI, 2.38-333.08) compared with placebo/control. Other treatment medications (including rivastigmine tartrate, chlorpromazine hydrochloride, lorazepam, quetiapine fumarate, amisulpride, ziprasidone hydrochloride, olanzapine, etc.) did not show significantly better response rates when compared with placebo/control.

For prevention, analysis revealed that only ramelteon (OR = 0.07; 95% CI, 0.01-0.66), olanzapine (OR = 0.25; 95% CI, 0.09-0.69), risperidone (OR = 0.27; 95% CI, 0.07-0.99) and dexmedetomidine hydrochloride (OR = 0.5; 95% CI, 0.31-0.8) demonstrated a significantly lower delirium occurrence rate than placebo/control. Moreover, midazolam hydrochloride was linkd to a greater rate of delirium occurrence than placebo/control.

Other preventive interventions (including clonidine hydrochloride, melatonin, propofol, haloperidol, lorazepam, rivastigmine tartrate, suvorexant, etc.) did not result in different risks of delirium occurrence compared with placebo/control.

Wu and colleagues also reported that no pharmacological treatments for delirium were significantly associated with a greater risk for all-cause mortality compared with placebo/control.

“When delirium occurs, clinicians should not only prescribe medication to manage delirium symptoms but also begin surveillance to identify any potential abnormal physical conditions behind the delirium,” the researchers wrote. “Future large-scale RCTs investigating the treatment effect of haloperidol plus lorazepam and the preventive effect of ramelteon are warranted to corroborate the findings of our [network meta-analysis].”

When drawing conclusions from network meta-analyses, clinicians should pay attention to the individual trials of participants, Dan G. Blazer, MD, MPH, PhD, from the department of psychiatry and behavioral science, Duke University Medical Center, wrote in a related editorial.

“Given that the use of [network meta-analysis] will most probably become a much more widely used analytic tool in the future, scrutiny of the RCTs, the components of the analyses, is especially important,” Blazer wrote. – by Savannah Demko

Disclosure: The authors and Blazer report no relevant financial disclosures.

Results from a large network meta-analysis found that haloperidol plus lorazepam appears to be the best treatment — and ramelteon the best preventive medicine — for patients with delirium.

Although delirium is prevalent, particularly among elderly inpatients, it is underdiagnosed, and prior research has estimated that up to 40% of delirium cases may be preventable, according to Yi-Cheng Wu, MD, of Chang Gung Memorial Hospital at Linkou, Taiwan, and colleagues.

“Despite the widespread use of various psychopharmacological agents for the management of delirium, the relative balance between benefit and harm of the various available treatments remains unclear,” they wrote in JAMA Psychiatry.

To evaluate the available evidence, the researchers reviewed clinical online databases for randomized clinical trials (RCTs) examining pharmacological interventions for delirium treatment and prevention. Using a random-effects model, the investigators measured treatment response in patients with delirium and the incidence of delirium in patients at risk for delirium (primary outcomes).

Of 58 trials included in the analysis, 20 RCTs encompassing 1,435 participants (mean age 63.5 years) compared the outcomes of treatment and 38 encompassing 8,168 participants (mean age 70.2 years) assessed the prevention of delirium.

Network meta-analysis revealed that haloperidol plus lorazepam provided the best response rate for treatment on delirium (OR = 28.13; 95% CI, 2.38-333.08) compared with placebo/control. Other treatment medications (including rivastigmine tartrate, chlorpromazine hydrochloride, lorazepam, quetiapine fumarate, amisulpride, ziprasidone hydrochloride, olanzapine, etc.) did not show significantly better response rates when compared with placebo/control.

For prevention, analysis revealed that only ramelteon (OR = 0.07; 95% CI, 0.01-0.66), olanzapine (OR = 0.25; 95% CI, 0.09-0.69), risperidone (OR = 0.27; 95% CI, 0.07-0.99) and dexmedetomidine hydrochloride (OR = 0.5; 95% CI, 0.31-0.8) demonstrated a significantly lower delirium occurrence rate than placebo/control. Moreover, midazolam hydrochloride was linkd to a greater rate of delirium occurrence than placebo/control.

Other preventive interventions (including clonidine hydrochloride, melatonin, propofol, haloperidol, lorazepam, rivastigmine tartrate, suvorexant, etc.) did not result in different risks of delirium occurrence compared with placebo/control.

Wu and colleagues also reported that no pharmacological treatments for delirium were significantly associated with a greater risk for all-cause mortality compared with placebo/control.

“When delirium occurs, clinicians should not only prescribe medication to manage delirium symptoms but also begin surveillance to identify any potential abnormal physical conditions behind the delirium,” the researchers wrote. “Future large-scale RCTs investigating the treatment effect of haloperidol plus lorazepam and the preventive effect of ramelteon are warranted to corroborate the findings of our [network meta-analysis].”

When drawing conclusions from network meta-analyses, clinicians should pay attention to the individual trials of participants, Dan G. Blazer, MD, MPH, PhD, from the department of psychiatry and behavioral science, Duke University Medical Center, wrote in a related editorial.

“Given that the use of [network meta-analysis] will most probably become a much more widely used analytic tool in the future, scrutiny of the RCTs, the components of the analyses, is especially important,” Blazer wrote. – by Savannah Demko

Disclosure: The authors and Blazer report no relevant financial disclosures.