Comparison of risperidone oral solution and intramuscular haloperidol with the latter shifting to oral therapy for the treatment of acute agitation in patients with schizophrenia

Abstract

This randomized, parallel-group, open study investigated the efficacy and safety of risperidone oral solution (RIS-OS) in combination with clonazepam and intramuscular haloperidol for the treatment of acute agitation in patients with schizophrenia, and the study explored the possibility of decreasing the efficacy of an acute 6-week treatment by switching intramuscular haloperidol injection to RIS-OS. Two hundred and five agitation-exhibiting schizophrenic inpatients at six hospitals were originally included in the study. The 47-day trial consisted of 5 days (session I) of receiving either oral treatment (RIS-OS plus clonazepam) or intramuscular treatment (intramuscular haloperidol) and a 42-day (session II) period of either withdrawing from clonazepam or shifting from intramuscular haloperidol to a RIS-OS period. The primary efficacy outcome was measured as the change in the Positive and Negative Syndrome Scale-Excited Component (PANSS-EC) in session I and the change in the PANSS in session II. Safety was assessed by the frequency of the adverse events. Mean PANSS-EC improvement was significant after 5 days of treatment in both groups (P>0.05) and was similar between the two treatment groups (P<0.01). Most patients' PANSS-EC scores improved or remained stable during the drawback/shift treatment period. Efficacy was not significantly different between the two treatment groups after the 6-week treatment (P>0.05). However, combination treatment exhibited greater efficacy, and adverse events, especially extrapyramidal symptoms, were lower with the oral treatment than with the intramuscular treatment in session I. These results show that RIS-OS in combination with clonazepam is an effective treatment, comparable with intramuscular haloperidol, and is well-tolerated for acute agitation in patients with schizophrenia.

Pharmacological treatment of acute agitation associated with psychotic and bipolar disorder: a systematic review and meta-analysis

“…(Meehan et al ., ; Zimbroff et al ., ). Three trials employed a combined treatment approach: one assessed the use of risperidone with lorazepam (Currier et al ., ), one risperidone with clonazepam (Fang et al ., ) and two trials used haloperidol with lorazepam(Currier et al ., ; Hwang et al ., ). The trials assessing inhaled loxapine (Allen et al ., ; Lesem et al ., ; Kwentus et al ., ) all included two dose sizes of loxapine (5 mg and 10 mg), a range of dose sizes of olanzapine were included in another trial (Breier et al ., ) whilst a range of doses of aripiprazole were included in a third trial (Tran‐Johnson et al ., ).…”

Rapid tranquilization of severely agitated patients with schizophrenia spectrum disorders: a naturalistic, rater-blinded, randomized controlled study with oral haloperidol, risperidone, and olanzapine

“…Two controlled trials over 5 days also reported no difference between oral aripiprazole and oral olanzapine 14 and between oral risperidone and intramuscular haloperidol. 11 Likewise, an observational, nonrandomized study in a mixed psychiatric emergency population failed to find differences between olanzapine, risperidone, and haloperidol over 5 days. 24 In contrast, longer trials seem to favor olanzapine.…”

“…The severity of agitation as measured with the PANSS-EC is in the same range as reported in 1 controlled trial and 3 observational studies 10,13,24,27 but clearly higher than in most controlled trials. 11,12,14 We have used higher PANSS cutoff scores for inclusion than the cutoff used in most other studies.…”

“…10Y15 Most previous studies on acute agitation in mixed patient populations report outcomes only in the first 24 to 72 hours after admission, 12,13,15Y17 and only a few studies extend over 5 days. 11,14 However, efficacy of antipsychotic agents may vary widely over an observation period, with some exhibiting superior performance only during the initial hours. 11,13 Despite this, we are unaware of any trials comparing oral formulations of first-and second-generation antipsychotics beyond the first day in acutely agitated schizophrenia patients.…”

“…11,14 However, efficacy of antipsychotic agents may vary widely over an observation period, with some exhibiting superior performance only during the initial hours. 11,13 Despite this, we are unaware of any trials comparing oral formulations of first-and second-generation antipsychotics beyond the first day in acutely agitated schizophrenia patients. Furthermore, interventional trials must obtain prior informed consent from study participants, precluding prospective studies in severely agitated or aggressive patients.…”