Optimal Injectable Haloperidol Dose Assessment in the Older Hospitalized Inpatient.

BACKGROUND: Haloperidol can be used off-label for agitation and/or delirium in older individuals. The recommended initial intramuscular or intravenous dose is 0.5 to 1 mg. However, the evidence to support these doses is nominal. OBJECTIVES: The primary outcome was to determine whether low-dose injectable haloperidol (≤0.5 mg) was similar in effect to higher doses by assessing the need for repeat doses within 4 hours as a surrogate marker. Secondary outcomes include comparison of length of stay, utilization of restraints, and discharge outcomes between dosage groups. METHODS: This was a retrospective, single-center, cohort study. Patients aged ≥65 years who received haloperidol injectable who were not on antipsychotics prior to admission were reviewed. RESULTS: In the low-dose group (n = 15), no patients required additional haloperidol doses within 4 hours compared with 1 patient each in the medium-dose (n = 23) and high-dose (n = 19) groups (P = 0.94). There was a difference regarding length of stay, utilization of restraints, and discharge to facility when admitted from home favoring low-dose haloperidol. CONCLUSIONS AND RELEVANCE: While limited by sample size and retrospective design, patients who received low-dose haloperidol demonstrated similar efficacy to those who received higher doses of haloperidol. In addition, secondary outcomes mentioned above favored the use of low-dose haloperidol as well. Based on these findings, low-dose haloperidol is a reasonable initial dose for the agitated older patient.

Efficacy and Safety of Paliperidone Extended Release 1.5 mg/day-A Double-blind, Placebo- and Active-Controlled, Study in the Treatment of Patients with Schizophrenia.

BACKGROUND: Paliperidone extended-release (paliperidone ER) is an approved oral antipsychotic medication (dosing range 3-12 mg/day) for treatment of schizophrenia and schizoaffective disorder in adults. METHODS: In this 3-arm, double-blind, placebo- and active-controlled, parallel-group study, paliperidone ER 1.5 mg was assessed to determine the lowest efficacious dose in patients (N = 201) with acute schizophrenia. Paliperidone ER 6 mg was included for assay sensitivity. RESULTS: Patients (intent-to-treat analysis set) had a mean age of 39.4 years; 74% were men, 43% Asian, and 40% black. The baseline mean (SD) Positive and Negative Syndrome Scale (PANSS) total score was 92.6 (13.02) and the mean (SD) change from baseline to endpoint was: placebo group, -11.4 (20.81); paliperidone ER 1.5 mg group, -8.9 (23.31); and paliperidone ER 6 mg group, -15.7 (26.25). Differences between paliperidone groups versus placebo were not significant (paliperidone ER 1.5 mg [p = 0.582], paliperidone ER 6 mg, [p = 0.308]). Safety results of paliperidone ER 1.5 mg and placebo were comparable. The most frequently reported treatment emergent adverse events (≥10%) were: placebo group-headache (15.6%) and psychotic disorder (14.1%); paliperidone ER 1.5 mg group-insomnia (13.6%); and paliperidone ER 6 mg group-headache (11.4%), insomnia (10%), and tremor (10%). CONCLUSIONS: In this study, paliperidone ER 1.5 mg did not demonstrate efficacy in patients with acute schizophrenia. A markedly high placebo response was noted. Assay sensitivity with the 6 mg dose was not established. Paliperidone ER 1.5 mg was generally tolerable with a safety profile comparable to placebo.