TOPLINE

Antipsychotic-benzodiazepine combinations were more effective than haloperidol monotherapy for rapid sedation in patients with psychomotor agitation in emergency settings, new research showed. Haloperidol was associated with a higher risk for extrapyramidal side effects, whereas benzodiazepines carried a higher risk for hypotension.

METHODOLOGY

• A multi-country systematic review and individual participant data (IPD) meta-analysis of randomized controlled trials compared intramuscular or intravenous pharmacologic treatments for rapid tranquilization in patients with psychomotor agitation in psychiatric and general emergency settings.
• Thirteen trials with more than 2700 participants (mean age, 35.5 years; 56% men; 67% with severe agitation) provided IPD for the use of antipsychotics, benzodiazepines, and their combinations.
• The antidopaminergic antipsychotic haloperidol was used as a reference comparator.
• The primary outcome was sedation within 15-30 minutes after treatment, with preference given to clinical judgment or cutoffs on rating scales indicating calm or asleep status. Secondary outcomes were additional tranquilization, restraint, and adverse events.

TAKEAWAY

• In moderate agitation, all treatments were more effective than haloperidol alone for achieving sedation within 15-30 minutes, with the biggest effect for antipsychotic-benzodiazepine combinations (odds ratio [OR], 12.9; relative risk [RR], 1.58) followed by benzodiazepines alone (OR, 5.5; RR, 1.49) and other antipsychotics (OR, 4.5; RR, 1.45).
• In severe agitation, antipsychotic-benzodiazepine combinations were more effective than haloperidol (OR, 4.9; RR, 1.73), whereas results were considered uncertain for benzodiazepines or other antipsychotics alone.
• Haloperidol monotherapy was associated with higher odds of extrapyramidal side effects than other treatments (OR range, 10-50), and benzodiazepines, alone or in combination, were associated with higher odds of hypotension (OR range, 2.5-11.6).
• Effects of other treatments vs haloperidol monotherapy for achieving sedation within 15-30 minutes were smaller in severe agitation than in moderate agitation (ratio of ORs, 0.4), with baseline severity of agitation identified as the strongest prognostic factor and effect modifier.

IN PRACTICE

“Antipsychotic-benzodiazepine combinations might be among the most effective options for rapid tranquilization in patients with psychomotor agitation but carry a risk of hypotension, whereas haloperidol monotherapy appeared among the least effective and is associated with extrapyramidal side effects,” the investigators wrote.

The author of an accompanying editorial added that “future research should employ a broader range of outcomes (efficiency, safety, cost-effectiveness, feasibility, and acceptability) across diverse patient populations and increase patient involvement in research and the practice of agitation management.”

SOURCE

The study was led by Spyridon Siafis, MD, Technical University of Munich, Munich, Germany. The editorial was authored by Subho Chakrabarti, Postgraduate Institute of Medical Education and Research, Chandigarh, India. Both articles were published online on June 8 in The Lancet Psychiatry.

LIMITATIONS

The sample size was insufficient for fine-grained analysis of individual medications and oral medications were not considered. Confidence in the estimated treatment effects was very low, mainly due to imprecision and heterogeneity. Additionally, there was substantial heterogeneity across studies and the research excluded trials conducted before 2002.

DISCLOSURES

The study was funded by Germany’s Federal Ministry for Research, Technology, and Space and the Swiss National Science Foundation. Disclosure information for the study investigators is available in the original article. The editorialist reported no relevant conflicts of interest.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.