Comparative effectiveness of second-generation antipsychotics and haloperidol in acute schizophrenia. Intramuscular aripiprazole for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder: a double-blind, placebo-controlled comparison with intramuscular haloperidol.
There is little information on the comparative effectiveness of second-generation antipsychotic agents.
                To determine if any of five second-generation antipsychotics or haloperidol is more effective in treating acutely ill patients with schizophrenia, schizoaffective disorder or schizophreniform disorder.
                A sample of 327 newly admitted patients were randomised to open-label treatment with aripiprazole, haloperidol, olanzapine, quetiapine, risperidone or ziprasidone for a minimum of 3 weeks. Measures of effectiveness were improvement in mental status so that the patient no longer required acute in-patient care, and changes in Brief Psychiatric Rating Scale (BPRS) scores.
                By the first measure, haloperidol (89%), olanzapine (92%) and risperidone (88%) were significantly more effective than aripiprazole (64%), quetiapine (64%) and ziprasidone (64%). Changes in BPRS ratings were not significant among treatments.
                Haloperidol, olanzapine and risperidone are superior to aripiprazole, quetiapine and ziprasidone for the acute treatment of psychosis in hospitalised patients with schizophrenia, schizoaffective disorder or schizophreniform disorder. This double-blind, placebo-controlled study investigated the efficacy and safety of intramuscular (IM) aripiprazole and IM haloperidol for the treatment of acute agitation in patients with schizophrenia or schizoaffective disorder.
                Four-hundred and forty-eight patients were randomized (2:2:1 ratio) to IM aripiprazole 9.75 mg, IM haloperidol 6.5 mg, or IM placebo. Patients could receive up to three injections over the first 24 h, with second and third injections administered > or =2 and > or =4 h, respectively, after the first if deemed clinically necessary. Primary efficacy measure was mean change in Positive and Negative Syndrome Scale Excited Component (PEC) score from baseline to 2 h.
                Mean improvement in PEC at 2 h was significantly greater for IM aripiprazole (-7.27) vs placebo (-4.78; p<0.001); IM aripiprazole was noninferior to IM haloperidol (-7.75) on PEC. All secondary efficacy measures showed significantly greater improvements at 2 h for IM aripiprazole and IM haloperidol over placebo. Mean number of injections/patient and percentage of patients requiring benzodiazepines were significantly lower for IM aripiprazole vs placebo (p<0.01). IM aripiprazole was well tolerated. Extrapyramidal symptom-related adverse events were similar for aripiprazole (1.7%) and placebo (2.3%) and lower than with haloperidol (12.6%).
                These results show that IM aripiprazole is an effective treatment, comparable to IM haloperidol, and well-tolerated for acute agitation in patients with schizophrenia.
Aripiprazole differs little from typical antipsychotic drugs with respect to efficacy, however it presents significant advantages in terms of tolerability. Clearly reported pragmatic short, medium and long term randomised controlled trials are required to replicate and validate these findings and determine the position of aripiprazole in everyday clinical practice.