Less Invasive Rapid Tranquilization in LMIC Emergency Settings: Comparison of Oral Risperidone Plus Clonazepam Versus Intramuscular Haloperidol in a Randomized Trial

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Abstract

Psychomotor agitation is a common mental emergency that requires immediate, safe treatment. Intramuscular haloperidol is frequently used; however oral alternatives may be safer and more tolerated. In many low- and middle-income settings, resource constraints, cultural norms, and emergency department coercion shape agitation prescribing. This study compared the efficacy and safety of oral risperidone plus clonazepam versus injectable haloperidol for psychomotor agitation in primary psychotic patients. In this single-blind, randomized comparative trial, 260 patients (mean age 32.38; 95% CI [31.13-33.64], 119 males and 141 females) with severe psychomotor agitation in a general hospital emergency room were randomly assigned oral risperidone 3 mg plus clonazepam 3 mg (RC) or intramuscular haloperidol 5 mg. Behavioral Activity Rating Scale (BARS) agitation was measured at 30, 1, and 2 hr. The primary outcome was the percentage of patients reported as tranquil (BARS = 4) or tranquil/asleep (BARS = 2-4) at all time points, with an equivalency margin of ±20%. Secondary outcomes included tranquil/tranquil or asleep after 2 hr, restraint use, adverse effects (during the 2 hr of assessment), and necessity of additional medication after 1 hr. RC and IH were equally tranquil or sleeping at all time points for primary outcomes (adjusted ARR 9 percentage points, 95% CI -1.8 to +19.8). Neither tranquility at 2 hr nor extra medication were equal for secondary outcomes (adjusted ARR 15 p.p., 95% CI [1.35, 28.65]). At 2 hr, tranquil or asleep, restraint utilization, and side effects were equivalent. In conclusion, besides oral risperidone plus clonazepam met the prespecified criterion for equivalence to intramuscular haloperidol for the primary composite outcomes of maintaining tranquility or tranquility/asleep at all time-points during the 2-hr observation period, the equivalence was not demonstrated for all secondary outcomes. The oral regimen was associated with a greater need for additional medication. Therefore, the two regimens should not be considered fully interchangeable in all emergency presentations. We found that oral techniques may enable more humane, less invasive, and culturally acceptable emergency care in LMICs due to the social burden of injectable medication, which typically requires restraint.

Abstract as published, via PubMed.