Rapid tranquilization for agitated patients in emergency psychiatric rooms: a randomized trial of olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone

Abstract

OBJECTIVE: To compare the effectiveness of intramuscular olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol alone as the first medication(s) used to treat patients with agitation and aggressive behavior. METHOD: One hundred fifty patients with agitation caused by psychotic or bipolar disorder were randomly assigned under double-blind conditions to receive olanzapine, ziprasidone, haloperidol plus midazolam, haloperidol plus promethazine or haloperidol alone. The Overt Agitation Severity Scale, Overt Aggression Scale and Ramsay Sedation Scale were applied within 12 hours after the first dosage. RESULTS: All medications produced a calming effect within one hour of administration, but only olanzapine and haloperidol reduced agitation by less than 10 points, and only olanzapine reduced aggression by less than four points in the first hour. After twelve hours, only patients treated with haloperidol plus midazolam had high levels of agitation and aggression and also more side effects. Ziprasidone, olanzapine and haloperidol alone had more stable results for agitation control, while ziprasidone, haloperidol plus promethazine and olanzapine had stable results for aggression control. CONCLUSION: Olanzapine, ziprasidone, haloperidol plus promethazine, haloperidol plus midazolam and haloperidol were effective in controlling agitation and aggression caused by mental illness over 12 hours. Although all the drugs had advantages and disadvantages, haloperidol plus midazolam was associated with the worst results in all the observed parameters.

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) 2018 guidelines for the management of patients with bipolar disorder

“…Because of the strength of evidence for efficacy in alleviating agitation in this population, aripiprazole IM (level 2),125, 126 lorazepam IM (level 2),125, 127 loxapine inhaled (Level 1)128, 129 and olanzapine IM (level 2)127, 130, 131, 132, 133 are recommended as the first‐line option. Sublingual asenapine (level 3),134 haloperidol IM (level 3),131, 135, 136 haloperidol IM + midazolam IM (level 3),131, 137 haloperidol IM + promethazine IM (level 3),131, 137, 138 risperidone ODT (level 3),136 and ziprasidone IM (level 3)131, 137, 139 are recommended as a second‐line treatment. Haloperidol per os (PO) (level 4),140, 141 loxapine IM (level 4) (clinical opinion), quetiapine PO (level 4),141 and risperidone PO (level 4)140 are included as third‐line options (Table 11).…”

Canadian Network for Mood and Anxiety Treatments (CANMAT) and International Society for Bipolar Disorders (ISBD) collaborative update of CANMAT guidelines for the management of patients with bipolar disorder: update 2013

“…In patients who refuse oral medications, intramuscular olanzapine (level 2) (32-35), ziprasidone (level 2) (35)(36)(37)(38), and aripiprazole (level 2) (39) or a combination of intramuscular haloperidol and a benzodiazepine should be considered (level 2) (29,35,38,40,41). In general, benzodiazepines should not be used as monotherapy, but are useful adjuncts to sedate acutely agitated patients (1).…”

Potenciais interações medicamentosas em um serviço de urgência psiquiátrica de um hospital geral: análise das primeiras vinte e quatro horas

“…Nevertheless, the benefit of using this combination does not exclude its risks (18)(19) . The database Drugs® accused several pairs of drugs administered at the same time with moderate potential interaction.…”

“…Nevertheless, this approach comes with several disadvantages, as benzodiazepines can cause respiratory depression, thus requiring strict monitoring. The association of these classes can be related to the patient profile attended at the psychiatric emergency services, as it demands care related to agitation through drug barriers (22) .…”