Page last updated: 2024-11-06

haloperidol decanoate

Description Research Excerpts Clinical Trials Roles Classes Pathways Study Profile Bioassays Related Drugs Related Conditions Protein Interactions Research Growth Market Indicators

Cross-References

ID SourceID
PubMed CID52919
CHEMBL ID1200986
CHEBI ID31664
SCHEMBL ID120575
MeSH IDM0104068

Synonyms (65)

Synonym
haldol dec
bdbm50053408
r-13672
decanoic acid, 4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)-4-piperidinyl ester
r 13,672
haldol decanoas
haldol decanoate
r 13672
kd 16
decanoic acid, ester with 4-(4-(p-chlorophenyl)-4-hydroxypiperidino)-4'-fluorobutyrophenone
kd-136
haloperidol decanoate
4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)-4-piperidyl decanoate
kd 136
einecs 277-679-7
D01898
haloperidol decanoate (jan/usp)
halomonth (tn)
74050-97-8
neoperidole
halomonth
CHEMBL1200986
r-13,672
FT-0669103
[4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl] decanoate
ac20pj4101 ,
depot haloperidol
haloperidol depot
unii-ac20pj4101
haloperidol decanoate [usan:usp:ban:jan]
haloperidol decanoate [usp impurity]
haloperidol decanoate [usan]
haloperidol decanoate [orange book]
haloperidol decanoate [who-dd]
haloperidol decanoate [ep monograph]
haloperidol decanoate [jan]
haloperidol decanoate [mi]
haloperidol decanoate [ep impurity]
haloperidol decanoate [usp-rs]
haloperidol decanoate [mart.]
haloperidol decanoate [usp monograph]
SCHEMBL120575
DTXSID50224951 ,
l-ornithineacetate
KS-1419
AKOS025392169
haloperidol decanoate hcl
CHEBI:31664
HY-107969
haloperidol decanoate; 4-(4-chlorophenyl)-1-[4-(4-fluorophenyl)-4-oxobutyl]piperidin-4-yl decanoate
halomonth; haloperidol decanoate; kd 136; kd 16; neoperidole; r 13762
HMS3887C07
haloperidol-decanoate
NCGC00508704-02
Q27273855
4-(4-chlorophenyl)-1-(4-(4-fluorophenyl)-4-oxobutyl)piperidin-4-yl decanoate
CS-0031068
haloperidol decanoate (usp impurity)
haloperidol decanoate (usan:usp:ban:jan)
haloperidol decanoate (ep impurity)
haloperidol decanoate (ep monograph)
haloperidol decanoate (usp monograph)
dtxcid80147442
haloperidol decanoate (usp-rs)
haloperidol decanoate (mart.)

Research Excerpts

Overview

Haloperidol decanoate is an ester for intramuscular injection. It is a long-acting depot antipsychotic agent used for the treatment of schizophrenia.

ExcerptReferenceRelevance
"Haloperidol decanoate is a typical antipsychotic drug used as maintenance therapy for schizophrenia and mood disorders formulated as an ester for intramuscular injection. "( An acute oral intoxication with haloperidol decanoate.
Dekkers, BGJ; Eck, RJ; Ter Maaten, JC; Touw, DJ, 2017
)
2.18
"Haloperidol decanoate is a long-acting depot antipsychotic agent used for the treatment of schizophrenic patients. "( A practical loading dose method for converting schizophrenic patients from oral to depot haloperidol therapy.
Chang, WH; Jann, MW; Lin, HN; Piao-Chien, C; Wei, FC, 1996
)
1.74
"Haloperidol decanoate is a depot preparation of haloperidol, a commonly used butyrophenone derivative with antipsychotic activity. "( Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis.
Beresford, R; Ward, A, 1987
)
3.16

Effects

ExcerptReferenceRelevance
"Haloperidol decanoate has no intrinsic activity: its pharmacodynamic actions are those of haloperidol--primarily that of central antidopamine activity."( Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis.
Beresford, R; Ward, A, 1987
)
2.44

Treatment

ExcerptReferenceRelevance
"The haloperidol decanoate-treated rats showed lower levels of DOPAC and/or HVA than the rats of the other two groups."( [Effect of haloperidol decanoate on the dopaminergic system in the rat brain].
Fujiwara, Y; Harada, T; Kashihara, K; Ogawa, T; Otsuki, S; Sato, M, 1986
)
1.14

Toxicity

ExcerptReferenceRelevance
" Adverse events related to movement disorders were reported in 3%."( Long-acting injectable risperidone: safety and efficacy in stable patients switched from conventional depot antipsychotics.
Eerdekens, E; Eerdekens, M; Jacko, M; Turner, M, 2004
)
0.32

Pharmacokinetics

The purpose of the study was to investigate clinical and pharmacokinetic parameters concerning perphenazine decanoate (PD) and haloperidol decanoat (HD) with an interval of 3 weeks during a study period.

ExcerptReferenceRelevance
" Results suggested an absorption half-life of 4 weeks, although, in three cases steady state was only achieved after 11 monthly injections."( Pharmacokinetics of haloperidol and fluphenazine decanoates in chronic schizophrenia.
McCreadie, RG; Whitehead, A; Wiles, DH, 1990
)
0.28
" However, there is large interindividual, but not intraindividual, variability in plasma haloperidol concentrations and most pharmacokinetic parameters."( Pharmacokinetics of haloperidol.
Davis, CM; Froemming, JS; Jann, MW; Lam, YW, 1989
)
0.28
" The enanthate produces peak plasma concentrations on days 2 to 3 and declines with an apparent elimination half-life (i."( Clinical pharmacokinetics of the depot antipsychotics.
Ereshefsky, L; Jann, MW; Saklad, SR,
)
0.13
" Moreover pharmacokinetic data increasingly have been clinically applied."( Chemotherapy with neuroleptics. Clinical and pharmacokinetic aspects with a particular view to depot preparations.
Knudsen, P, 1985
)
0.27
"Precise pharmacokinetic data of long-acting neuroleptics: apparent half life (T 1/2), time of peak plasma concentration (Tmax), bioavailability, has been a major contribution to determine optimal dosage of the drug."( [Clinical pharmacokinetics of haloperidol decanoate. Comparison with other prolonged-action neuroleptics].
Levron, JC; Ropert, R,
)
0.42
" Haloperidol decanoate has no intrinsic activity: its pharmacodynamic actions are those of haloperidol--primarily that of central antidopamine activity."( Haloperidol decanoate. A preliminary review of its pharmacodynamic and pharmacokinetic properties and therapeutic use in psychosis.
Beresford, R; Ward, A, 1987
)
2.63
" Within each interval between doses, haloperidol plasma levels were maximal within the first week after each dose, decaying with an average half-life of three weeks."( Pharmacology, pharmacokinetics and clinical development of haloperidol decanoate.
Gelders, YG, 1986
)
0.51
"The purpose of the study was to investigate clinical and pharmacokinetic parameters concerning perphenazine decanoate (PD) and haloperidol decanoate (HD) with an interval of 3 weeks during a study period of 51 weeks."( A long-term cross-over pharmacokinetic study comparing perphenazine decanoate and haloperidol decanoate in schizophrenic patients.
Dencker, SJ; Giös, I; Mårtensson, E; Nordén, T; Nyberg, G; Persson, R; Roman, G; Stockman, O; Svärd, KO, 1994
)
0.72

Bioavailability

ExcerptReferenceRelevance
" Large doses of haloperidol can safely be given intravenously and intramuscularly for rapid neuroleptisation; the bioavailability of this agent administered orally ranges from 60 to 65%."( Pharmacokinetics of haloperidol.
Davis, CM; Froemming, JS; Jann, MW; Lam, YW, 1989
)
0.28
" The absorption rate constant is slower than the elimination rate constant and therefore, the depot antipsychotics exhibit 'flip-flop' kinetics where the time to steady-state is a function of the absorption rate, and the concentration at steady-state is a function of the elimination rate."( Clinical pharmacokinetics of the depot antipsychotics.
Ereshefsky, L; Jann, MW; Saklad, SR,
)
0.13
" Optimal dose has been determined from the bioavailability of the oral formulation and the interval between two injections, it averages 15, 20 times the oral daily dose for haloperidol decanoate."( [Clinical pharmacokinetics of haloperidol decanoate. Comparison with other prolonged-action neuroleptics].
Levron, JC; Ropert, R,
)
0.61

Dosage Studied

Clinicians were instructed to target dosing at 500 mg/day of quetiapine or 200 mg of haloperidol decanoate every 4 weeks. It was concluded that 4-week intramuscular treatment provides appropriate control of schizophrenic symptoms, but flupenthixol should be dosed at shorter intervals.

ExcerptRelevanceReference
" HD dosage was highly correlated with both RBC H and plasma H, but RBC RH and plasma RH were not significantly related to dosage at any time point."( Haloperidol decanoate pharmacokinetics in red blood cells and plasma.
Dysken, MW; Holden, L; Johnson, SB; Kim, SW; Skare, S; Thomsyck, L; Vatassery, G, 1992
)
1.73
" The study indicates that haloperidol decanoate even in low dosage is effective maintenance therapy is preventing relapse."( Duration of neuroleptic treatment and relapse rate: a 5-year follow-up study with haloperidol decanoate.
Youssef, HA, 1991
)
0.81
"We have evaluated the efficacy and safety of different dosing regimens of haloperidol decanoate (HLD)."( Kinetics and clinical evaluation of haloperidol decanoate loading dose regimen.
Davis, CM; Ereshefsky, L; Lyman, RC; Saklad, SR; Toney, G; Tran-Johnson, T, 1990
)
0.78
" The dosage equivalency of haloperidol decanoate (1."( A randomized clinical trial of haloperidol decanoate and fluphenazine decanoate in the outpatient treatment of schizophrenia.
Annable, L; Campbell, W; Chouinard, G, 1989
)
0.86
" Therefore, it is critical to establish dosing strategies for long-term therapy that emphasize a minimal effective dose."( Dosage strategies with long-acting injectable neuroleptics, including haloperidol decanoate.
Kane, JM, 1986
)
0.5
"Precise pharmacokinetic data of long-acting neuroleptics: apparent half life (T 1/2), time of peak plasma concentration (Tmax), bioavailability, has been a major contribution to determine optimal dosage of the drug."( [Clinical pharmacokinetics of haloperidol decanoate. Comparison with other prolonged-action neuroleptics].
Levron, JC; Ropert, R,
)
0.42
"This article reviews the role of a new depot antipsychotic dosage form, haloperidol decanoate (HD), in relationship to other comparable pharmacotherapies (oral and injectable)."( Haloperidol decanoate: a depot antipsychotic.
Evans, RL; Hemstrom, CA; Lobeck, FG, 1988
)
1.95
" These determinations demonstrate that the release of haloperidol with the decanoate form is sustained throughout the 4-week dosing interval."( A clinical trial comparing intramuscular haloperidol decanoate and oral haloperidol in chronic schizophrenic patients: efficacy, safety, and dosage equivalence.
Achim, A; Lizondo, E; Nayak, R; Schwartz, G; Suranyi-Cadotte, B; Thavundayil, JX; Vasavan Nair, NP, 1986
)
0.54
" It was concluded that 4-week intramuscular administration of haloperidol decanoate provides appropriate control of schizophrenic symptoms, but that flupenthixol decanoate should be dosed at shorter intervals."( Haloperidol decanoate and flupenthixol decanoate in schizophrenia. A long-term double-blind cross-over comparison.
Eberhard, G; Hellbom, E, 1986
)
1.95
" The dosage schema can be adapted individually whenever necessary."( [Long-term therapy of chronic schizophrenic patients with haloperidol decanoate].
Roncoroni, D, 1984
)
0.51
" At the end of the trial, the mean dosage of HD administered and BPRS (Brief Psychiatric Rating Scale) mean scores were significantly lower than the initial ones (70."( Haloperidol decanoate in schizophreniform disorders. Clinical and neuroendocrine aspects.
Attenni, M; Casacchia, M; Castellana, F; Ecari, U; Iafrate, A; Meco, G,
)
1.57
"During a 4-week interval of haloperidol decanoate dosage (dose range = 30-50 mg), the patients' D2 receptor occupancy was determined with positron emission tomography on two occasions."( D2 dopamine receptor occupancy during low-dose treatment with haloperidol decanoate.
Bertilsson, L; Dahl, ML; Farde, L; Halldin, C; Nyberg, S, 1995
)
0.83
" In this case, it seems necessary to diminish the interval between injections than to give higher dosage in order to maintain plasma concentrations."( Do enzyme inducers modify haloperidol decanoate rate of release?
Agenet, C; Barges-Bertocchio, MH; Levron, JC; Pupeschi, G, 1994
)
0.59
" In addition, the clinician should consider the dosage schedule of each medication and balance this against the probability of extrapyramidal side effects and noncompliance."( Dose response of prophylactic antipsychotics.
Brauzer, B; Casey, DE; Davis, JM; Gierl, B; Hassan, M; Kane, JM; Marder, SR; Schooler, N, 1993
)
0.29
" Patients were maintained on monthly depot treatment for 40 weeks after the loading dose regimen and only one patient relapsed during treatment despite dosage increases."( Haloperidol and reduced haloperidol plasma concentrations after a loading dose regimen with haloperidol decanoate.
Chang, WH; Jann, MW; Lin, HN; Piao-Chien, C; Wei, FC, 1996
)
0.51
"A dose-response relationship between dopamine D(2) occupancy and acute extrapyramidal symptoms (EPS) has been well established."( The relationship between dopamine D2 receptor occupancy and the vacuous chewing movement syndrome in rats.
Kapur, S; Nobrega, JN; Remington, G; Turrone, P, 2003
)
0.32
" Clinicians were instructed to target dosing at 500 mg/day of quetiapine or 200 mg of haloperidol decanoate every 4 weeks."( Long-term maintenance therapy with quetiapine versus haloperidol decanoate in patients with schizophrenia or schizoaffective disorder.
Glick, ID; Marder, SR, 2005
)
0.8
" The RLAI group needed a lower dosage of biperiden compared with the control group, even though they had similar risperidone-equivalent daily dosages."( The influence of switching from haloperidol decanoate depot to risperidone long-acting injection on the clinical symptoms and cognitive function in schizophrenia.
Gen, K; Suzuki, H, 2012
)
0.66
"9% of the total antipsychotic dosage on average."( Ten year outcomes of outpatients with schizophrenia on conventional depot antipsychotics: a systematic chart review.
Den, R; Mimura, M; Sakurai, H; Suzuki, T; Tsutsumi, C; Uchida, H; Uchida, T, 2013
)
0.39
[information is derived through text-mining from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Drug Classes (1)

ClassDescription
organic molecular entityAny molecular entity that contains carbon.
[compound class information is derived from Chemical Entities of Biological Interest (ChEBI), Hastings J, Owen G, Dekker A, Ennis M, Kale N, Muthukrishnan V, Turner S, Swainston N, Mendes P, Steinbeck C. (2016). ChEBI in 2016: Improved services and an expanding collection of metabolites. Nucleic Acids Res]

Protein Targets (6)

Inhibition Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
D(2) dopamine receptorHomo sapiens (human)Ki0.00110.00000.651810.0000AID1184607; AID1184608
D(4) dopamine receptorHomo sapiens (human)Ki0.00580.00000.436210.0000AID1184610
D(3) dopamine receptorHomo sapiens (human)Ki0.00350.00000.602010.0000AID1184609
Kappa-type opioid receptorCavia porcellus (domestic guinea pig)Ki0.00350.00000.20186.4240AID1184609
D(1A) dopamine receptorSus scrofa (pig)Ki0.14000.00051.22238.8000AID1184611
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Activation Measurements

ProteinTaxonomyMeasurementAverageMin (ref.)Avg (ref.)Max (ref.)Bioassay(s)
Potassium channel subfamily K member 2Homo sapiens (human)EC50 (µMol)5.50000.18702.72248.1800AID1802150
[prepared from compound, protein, and bioassay information from National Library of Medicine (NLM), extracted Dec-2023]

Biological Processes (134)

Processvia Protein(s)Taxonomy
cardiac ventricle developmentPotassium channel subfamily K member 2Homo sapiens (human)
G protein-coupled receptor signaling pathwayPotassium channel subfamily K member 2Homo sapiens (human)
memoryPotassium channel subfamily K member 2Homo sapiens (human)
response to mechanical stimulusPotassium channel subfamily K member 2Homo sapiens (human)
response to axon injuryPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of cardiac muscle cell proliferationPotassium channel subfamily K member 2Homo sapiens (human)
cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion transmembrane transportPotassium channel subfamily K member 2Homo sapiens (human)
cochlea developmentPotassium channel subfamily K member 2Homo sapiens (human)
positive regulation of cellular response to hypoxiaPotassium channel subfamily K member 2Homo sapiens (human)
negative regulation of DNA biosynthetic processPotassium channel subfamily K member 2Homo sapiens (human)
stabilization of membrane potentialPotassium channel subfamily K member 2Homo sapiens (human)
phospholipase C-activating dopamine receptor signaling pathwayD(2) dopamine receptorHomo sapiens (human)
temperature homeostasisD(2) dopamine receptorHomo sapiens (human)
response to hypoxiaD(2) dopamine receptorHomo sapiens (human)
negative regulation of protein phosphorylationD(2) dopamine receptorHomo sapiens (human)
response to amphetamineD(2) dopamine receptorHomo sapiens (human)
nervous system process involved in regulation of systemic arterial blood pressureD(2) dopamine receptorHomo sapiens (human)
regulation of heart rateD(2) dopamine receptorHomo sapiens (human)
regulation of sodium ion transportD(2) dopamine receptorHomo sapiens (human)
G protein-coupled receptor internalizationD(2) dopamine receptorHomo sapiens (human)
positive regulation of neuroblast proliferationD(2) dopamine receptorHomo sapiens (human)
positive regulation of receptor internalizationD(2) dopamine receptorHomo sapiens (human)
autophagyD(2) dopamine receptorHomo sapiens (human)
adenylate cyclase-inhibiting dopamine receptor signaling pathwayD(2) dopamine receptorHomo sapiens (human)
neuron-neuron synaptic transmissionD(2) dopamine receptorHomo sapiens (human)
neuroblast proliferationD(2) dopamine receptorHomo sapiens (human)
axonogenesisD(2) dopamine receptorHomo sapiens (human)
synapse assemblyD(2) dopamine receptorHomo sapiens (human)
sensory perception of smellD(2) dopamine receptorHomo sapiens (human)
long-term memoryD(2) dopamine receptorHomo sapiens (human)
grooming behaviorD(2) dopamine receptorHomo sapiens (human)
locomotory behaviorD(2) dopamine receptorHomo sapiens (human)
adult walking behaviorD(2) dopamine receptorHomo sapiens (human)
protein localizationD(2) dopamine receptorHomo sapiens (human)
negative regulation of cell population proliferationD(2) dopamine receptorHomo sapiens (human)
associative learningD(2) dopamine receptorHomo sapiens (human)
visual learningD(2) dopamine receptorHomo sapiens (human)
response to xenobiotic stimulusD(2) dopamine receptorHomo sapiens (human)
response to light stimulusD(2) dopamine receptorHomo sapiens (human)
response to toxic substanceD(2) dopamine receptorHomo sapiens (human)
response to iron ionD(2) dopamine receptorHomo sapiens (human)
response to inactivityD(2) dopamine receptorHomo sapiens (human)
Wnt signaling pathwayD(2) dopamine receptorHomo sapiens (human)
striatum developmentD(2) dopamine receptorHomo sapiens (human)
orbitofrontal cortex developmentD(2) dopamine receptorHomo sapiens (human)
cerebral cortex GABAergic interneuron migrationD(2) dopamine receptorHomo sapiens (human)
adenohypophysis developmentD(2) dopamine receptorHomo sapiens (human)
negative regulation of cell migrationD(2) dopamine receptorHomo sapiens (human)
peristalsisD(2) dopamine receptorHomo sapiens (human)
auditory behaviorD(2) dopamine receptorHomo sapiens (human)
regulation of synaptic transmission, GABAergicD(2) dopamine receptorHomo sapiens (human)
positive regulation of cytokinesisD(2) dopamine receptorHomo sapiens (human)
circadian regulation of gene expressionD(2) dopamine receptorHomo sapiens (human)
negative regulation of dopamine secretionD(2) dopamine receptorHomo sapiens (human)
response to histamineD(2) dopamine receptorHomo sapiens (human)
response to nicotineD(2) dopamine receptorHomo sapiens (human)
positive regulation of urine volumeD(2) dopamine receptorHomo sapiens (human)
positive regulation of renal sodium excretionD(2) dopamine receptorHomo sapiens (human)
positive regulation of multicellular organism growthD(2) dopamine receptorHomo sapiens (human)
response to cocaineD(2) dopamine receptorHomo sapiens (human)
negative regulation of circadian sleep/wake cycle, sleepD(2) dopamine receptorHomo sapiens (human)
dopamine metabolic processD(2) dopamine receptorHomo sapiens (human)
drinking behaviorD(2) dopamine receptorHomo sapiens (human)
regulation of potassium ion transportD(2) dopamine receptorHomo sapiens (human)
response to morphineD(2) dopamine receptorHomo sapiens (human)
pigmentationD(2) dopamine receptorHomo sapiens (human)
phosphatidylinositol 3-kinase/protein kinase B signal transductionD(2) dopamine receptorHomo sapiens (human)
positive regulation of G protein-coupled receptor signaling pathwayD(2) dopamine receptorHomo sapiens (human)
negative regulation of blood pressureD(2) dopamine receptorHomo sapiens (human)
negative regulation of innate immune responseD(2) dopamine receptorHomo sapiens (human)
positive regulation of transcription by RNA polymerase IID(2) dopamine receptorHomo sapiens (human)
negative regulation of insulin secretionD(2) dopamine receptorHomo sapiens (human)
acid secretionD(2) dopamine receptorHomo sapiens (human)
behavioral response to cocaineD(2) dopamine receptorHomo sapiens (human)
behavioral response to ethanolD(2) dopamine receptorHomo sapiens (human)
regulation of long-term neuronal synaptic plasticityD(2) dopamine receptorHomo sapiens (human)
response to axon injuryD(2) dopamine receptorHomo sapiens (human)
branching morphogenesis of a nerveD(2) dopamine receptorHomo sapiens (human)
arachidonic acid secretionD(2) dopamine receptorHomo sapiens (human)
epithelial cell proliferationD(2) dopamine receptorHomo sapiens (human)
negative regulation of epithelial cell proliferationD(2) dopamine receptorHomo sapiens (human)
negative regulation of protein secretionD(2) dopamine receptorHomo sapiens (human)
release of sequestered calcium ion into cytosolD(2) dopamine receptorHomo sapiens (human)
dopamine uptake involved in synaptic transmissionD(2) dopamine receptorHomo sapiens (human)
regulation of dopamine uptake involved in synaptic transmissionD(2) dopamine receptorHomo sapiens (human)
positive regulation of dopamine uptake involved in synaptic transmissionD(2) dopamine receptorHomo sapiens (human)
regulation of synapse structural plasticityD(2) dopamine receptorHomo sapiens (human)
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionD(2) dopamine receptorHomo sapiens (human)
negative regulation of synaptic transmission, glutamatergicD(2) dopamine receptorHomo sapiens (human)
excitatory postsynaptic potentialD(2) dopamine receptorHomo sapiens (human)
positive regulation of growth hormone secretionD(2) dopamine receptorHomo sapiens (human)
prepulse inhibitionD(2) dopamine receptorHomo sapiens (human)
negative regulation of dopamine receptor signaling pathwayD(2) dopamine receptorHomo sapiens (human)
positive regulation of ERK1 and ERK2 cascadeD(2) dopamine receptorHomo sapiens (human)
regulation of locomotion involved in locomotory behaviorD(2) dopamine receptorHomo sapiens (human)
postsynaptic modulation of chemical synaptic transmissionD(2) dopamine receptorHomo sapiens (human)
presynaptic modulation of chemical synaptic transmissionD(2) dopamine receptorHomo sapiens (human)
negative regulation of cellular response to hypoxiaD(2) dopamine receptorHomo sapiens (human)
positive regulation of glial cell-derived neurotrophic factor productionD(2) dopamine receptorHomo sapiens (human)
positive regulation of long-term synaptic potentiationD(2) dopamine receptorHomo sapiens (human)
hyaloid vascular plexus regressionD(2) dopamine receptorHomo sapiens (human)
negative regulation of neuron migrationD(2) dopamine receptorHomo sapiens (human)
negative regulation of cytosolic calcium ion concentrationD(2) dopamine receptorHomo sapiens (human)
regulation of dopamine secretionD(2) dopamine receptorHomo sapiens (human)
negative regulation of adenylate cyclase activityD(2) dopamine receptorHomo sapiens (human)
phospholipase C-activating dopamine receptor signaling pathwayD(2) dopamine receptorHomo sapiens (human)
negative regulation of voltage-gated calcium channel activityD(2) dopamine receptorHomo sapiens (human)
positive regulation of MAPK cascadeD(2) dopamine receptorHomo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathwayD(2) dopamine receptorHomo sapiens (human)
positive regulation of MAP kinase activityD(4) dopamine receptorHomo sapiens (human)
behavioral fear responseD(4) dopamine receptorHomo sapiens (human)
synaptic transmission, dopaminergicD(4) dopamine receptorHomo sapiens (human)
response to amphetamineD(4) dopamine receptorHomo sapiens (human)
intracellular calcium ion homeostasisD(4) dopamine receptorHomo sapiens (human)
adenylate cyclase-inhibiting dopamine receptor signaling pathwayD(4) dopamine receptorHomo sapiens (human)
dopamine receptor signaling pathwayD(4) dopamine receptorHomo sapiens (human)
adult locomotory behaviorD(4) dopamine receptorHomo sapiens (human)
positive regulation of sodium:proton antiporter activityD(4) dopamine receptorHomo sapiens (human)
positive regulation of kinase activityD(4) dopamine receptorHomo sapiens (human)
response to histamineD(4) dopamine receptorHomo sapiens (human)
social behaviorD(4) dopamine receptorHomo sapiens (human)
regulation of dopamine metabolic processD(4) dopamine receptorHomo sapiens (human)
dopamine metabolic processD(4) dopamine receptorHomo sapiens (human)
fear responseD(4) dopamine receptorHomo sapiens (human)
regulation of circadian rhythmD(4) dopamine receptorHomo sapiens (human)
positive regulation of MAP kinase activityD(4) dopamine receptorHomo sapiens (human)
behavioral response to cocaineD(4) dopamine receptorHomo sapiens (human)
behavioral response to ethanolD(4) dopamine receptorHomo sapiens (human)
rhythmic processD(4) dopamine receptorHomo sapiens (human)
arachidonic acid secretionD(4) dopamine receptorHomo sapiens (human)
negative regulation of protein secretionD(4) dopamine receptorHomo sapiens (human)
positive regulation of dopamine uptake involved in synaptic transmissionD(4) dopamine receptorHomo sapiens (human)
inhibitory postsynaptic potentialD(4) dopamine receptorHomo sapiens (human)
regulation of postsynaptic neurotransmitter receptor internalizationD(4) dopamine receptorHomo sapiens (human)
negative regulation of voltage-gated calcium channel activityD(4) dopamine receptorHomo sapiens (human)
adenylate cyclase-inhibiting serotonin receptor signaling pathwayD(4) dopamine receptorHomo sapiens (human)
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messengerD(4) dopamine receptorHomo sapiens (human)
chemical synaptic transmissionD(4) dopamine receptorHomo sapiens (human)
response to ethanolD(3) dopamine receptorHomo sapiens (human)
synaptic transmission, dopaminergicD(3) dopamine receptorHomo sapiens (human)
G protein-coupled receptor internalizationD(3) dopamine receptorHomo sapiens (human)
intracellular calcium ion homeostasisD(3) dopamine receptorHomo sapiens (human)
G protein-coupled receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
adenylate cyclase-activating dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
adenylate cyclase-inhibiting dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
learning or memoryD(3) dopamine receptorHomo sapiens (human)
learningD(3) dopamine receptorHomo sapiens (human)
locomotory behaviorD(3) dopamine receptorHomo sapiens (human)
visual learningD(3) dopamine receptorHomo sapiens (human)
response to xenobiotic stimulusD(3) dopamine receptorHomo sapiens (human)
regulation of dopamine secretionD(3) dopamine receptorHomo sapiens (human)
positive regulation of cytokinesisD(3) dopamine receptorHomo sapiens (human)
circadian regulation of gene expressionD(3) dopamine receptorHomo sapiens (human)
response to histamineD(3) dopamine receptorHomo sapiens (human)
social behaviorD(3) dopamine receptorHomo sapiens (human)
response to cocaineD(3) dopamine receptorHomo sapiens (human)
dopamine metabolic processD(3) dopamine receptorHomo sapiens (human)
response to morphineD(3) dopamine receptorHomo sapiens (human)
negative regulation of blood pressureD(3) dopamine receptorHomo sapiens (human)
positive regulation of mitotic nuclear divisionD(3) dopamine receptorHomo sapiens (human)
acid secretionD(3) dopamine receptorHomo sapiens (human)
behavioral response to cocaineD(3) dopamine receptorHomo sapiens (human)
negative regulation of oligodendrocyte differentiationD(3) dopamine receptorHomo sapiens (human)
arachidonic acid secretionD(3) dopamine receptorHomo sapiens (human)
negative regulation of protein secretionD(3) dopamine receptorHomo sapiens (human)
musculoskeletal movement, spinal reflex actionD(3) dopamine receptorHomo sapiens (human)
regulation of dopamine uptake involved in synaptic transmissionD(3) dopamine receptorHomo sapiens (human)
negative regulation of phosphatidylinositol 3-kinase/protein kinase B signal transductionD(3) dopamine receptorHomo sapiens (human)
prepulse inhibitionD(3) dopamine receptorHomo sapiens (human)
positive regulation of dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
negative regulation of adenylate cyclase activityD(3) dopamine receptorHomo sapiens (human)
adenylate cyclase-activating adrenergic receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
negative regulation of voltage-gated calcium channel activityD(3) dopamine receptorHomo sapiens (human)
regulation of potassium ion transportD(3) dopamine receptorHomo sapiens (human)
phospholipase C-activating dopamine receptor signaling pathwayD(3) dopamine receptorHomo sapiens (human)
positive regulation of MAPK cascadeD(3) dopamine receptorHomo sapiens (human)
negative regulation of cytosolic calcium ion concentrationD(3) dopamine receptorHomo sapiens (human)
negative regulation of synaptic transmission, glutamatergicD(3) dopamine receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Molecular Functions (20)

Processvia Protein(s)Taxonomy
outward rectifier potassium channel activityPotassium channel subfamily K member 2Homo sapiens (human)
potassium ion leak channel activityPotassium channel subfamily K member 2Homo sapiens (human)
dopamine neurotransmitter receptor activity, coupled via Gi/GoD(2) dopamine receptorHomo sapiens (human)
G-protein alpha-subunit bindingD(2) dopamine receptorHomo sapiens (human)
protein bindingD(2) dopamine receptorHomo sapiens (human)
heterotrimeric G-protein bindingD(2) dopamine receptorHomo sapiens (human)
dopamine bindingD(2) dopamine receptorHomo sapiens (human)
ionotropic glutamate receptor bindingD(2) dopamine receptorHomo sapiens (human)
identical protein bindingD(2) dopamine receptorHomo sapiens (human)
heterocyclic compound bindingD(2) dopamine receptorHomo sapiens (human)
G protein-coupled receptor activityD(2) dopamine receptorHomo sapiens (human)
dopamine neurotransmitter receptor activity, coupled via Gi/GoD(4) dopamine receptorHomo sapiens (human)
dopamine neurotransmitter receptor activityD(4) dopamine receptorHomo sapiens (human)
protein bindingD(4) dopamine receptorHomo sapiens (human)
potassium channel regulator activityD(4) dopamine receptorHomo sapiens (human)
SH3 domain bindingD(4) dopamine receptorHomo sapiens (human)
dopamine bindingD(4) dopamine receptorHomo sapiens (human)
identical protein bindingD(4) dopamine receptorHomo sapiens (human)
metal ion bindingD(4) dopamine receptorHomo sapiens (human)
epinephrine bindingD(4) dopamine receptorHomo sapiens (human)
norepinephrine bindingD(4) dopamine receptorHomo sapiens (human)
G protein-coupled serotonin receptor activityD(4) dopamine receptorHomo sapiens (human)
neurotransmitter receptor activityD(4) dopamine receptorHomo sapiens (human)
serotonin bindingD(4) dopamine receptorHomo sapiens (human)
dopamine neurotransmitter receptor activity, coupled via Gi/GoD(3) dopamine receptorHomo sapiens (human)
protein bindingD(3) dopamine receptorHomo sapiens (human)
G protein-coupled receptor activityD(3) dopamine receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Ceullar Components (32)

Processvia Protein(s)Taxonomy
endoplasmic reticulum membranePotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
cell surfacePotassium channel subfamily K member 2Homo sapiens (human)
apical plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
neuronal cell bodyPotassium channel subfamily K member 2Homo sapiens (human)
calyx of HeldPotassium channel subfamily K member 2Homo sapiens (human)
astrocyte projectionPotassium channel subfamily K member 2Homo sapiens (human)
voltage-gated potassium channel complexPotassium channel subfamily K member 2Homo sapiens (human)
plasma membranePotassium channel subfamily K member 2Homo sapiens (human)
Golgi membraneD(2) dopamine receptorHomo sapiens (human)
acrosomal vesicleD(2) dopamine receptorHomo sapiens (human)
plasma membraneD(2) dopamine receptorHomo sapiens (human)
ciliumD(2) dopamine receptorHomo sapiens (human)
lateral plasma membraneD(2) dopamine receptorHomo sapiens (human)
endocytic vesicleD(2) dopamine receptorHomo sapiens (human)
axonD(2) dopamine receptorHomo sapiens (human)
dendriteD(2) dopamine receptorHomo sapiens (human)
synaptic vesicle membraneD(2) dopamine receptorHomo sapiens (human)
sperm flagellumD(2) dopamine receptorHomo sapiens (human)
dendritic spineD(2) dopamine receptorHomo sapiens (human)
perikaryonD(2) dopamine receptorHomo sapiens (human)
axon terminusD(2) dopamine receptorHomo sapiens (human)
postsynaptic membraneD(2) dopamine receptorHomo sapiens (human)
ciliary membraneD(2) dopamine receptorHomo sapiens (human)
non-motile ciliumD(2) dopamine receptorHomo sapiens (human)
dopaminergic synapseD(2) dopamine receptorHomo sapiens (human)
GABA-ergic synapseD(2) dopamine receptorHomo sapiens (human)
G protein-coupled receptor complexD(2) dopamine receptorHomo sapiens (human)
glutamatergic synapseD(2) dopamine receptorHomo sapiens (human)
presynaptic membraneD(2) dopamine receptorHomo sapiens (human)
plasma membraneD(2) dopamine receptorHomo sapiens (human)
centrosomeD(4) dopamine receptorHomo sapiens (human)
plasma membraneD(4) dopamine receptorHomo sapiens (human)
membraneD(4) dopamine receptorHomo sapiens (human)
postsynapseD(4) dopamine receptorHomo sapiens (human)
glutamatergic synapseD(4) dopamine receptorHomo sapiens (human)
plasma membraneD(4) dopamine receptorHomo sapiens (human)
dendriteD(4) dopamine receptorHomo sapiens (human)
plasma membraneD(3) dopamine receptorHomo sapiens (human)
synapseD(3) dopamine receptorHomo sapiens (human)
plasma membraneD(3) dopamine receptorHomo sapiens (human)
[Information is prepared from geneontology information from the June-17-2024 release]

Bioassays (8)

Assay IDTitleYearJournalArticle
AID1474166Liver toxicity in human assessed as induction of drug-induced liver injury by measuring severity class index2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1184608Displacement of [3H]spiperone from human D2short receptor stably expressed in CHO cell membranes by competitive binding assay2014Bioorganic & medicinal chemistry letters, Aug-15, Volume: 24, Issue:16
Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.
AID1184609Displacement of [3H]spiperone from human D3 receptor stably expressed in CHO cell membranes by competitive binding assay2014Bioorganic & medicinal chemistry letters, Aug-15, Volume: 24, Issue:16
Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.
AID1184607Displacement of [3H]spiperone from human D2long receptor stably expressed in CHO cell membranes by competitive binding assay2014Bioorganic & medicinal chemistry letters, Aug-15, Volume: 24, Issue:16
Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.
AID1474167Liver toxicity in human assessed as induction of drug-induced liver injury by measuring verified drug-induced liver injury concern status2016Drug discovery today, Apr, Volume: 21, Issue:4
DILIrank: the largest reference drug list ranked by the risk for developing drug-induced liver injury in humans.
AID1184611Displacement of [3H]SCH23390 from porcine striatal membranes D1 receptor by competitive binding assay2014Bioorganic & medicinal chemistry letters, Aug-15, Volume: 24, Issue:16
Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.
AID1184610Displacement of [3H]spiperone from human D4.4 receptor stably expressed in CHO cell membranes by competitive binding assay2014Bioorganic & medicinal chemistry letters, Aug-15, Volume: 24, Issue:16
Synthesis and binding profile of haloperidol-based bivalent ligands targeting dopamine D(2)-like receptors.
AID1802150TREK1 Assay from Article 10.1111/cbdd.12810: \\Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently.\\2016Chemical biology & drug design, Dec, Volume: 88, Issue:6
Identification of the first in silico-designed TREK1 antagonists that block channel currents dose dependently.
[information is prepared from bioassay data collected from National Library of Medicine (NLM), extracted Dec-2023]

Research

Studies (179)

TimeframeStudies, This Drug (%)All Drugs %
pre-199052 (29.05)18.7374
1990's65 (36.31)18.2507
2000's25 (13.97)29.6817
2010's35 (19.55)24.3611
2020's2 (1.12)2.80
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Market Indicators

Research Demand Index: 61.23

According to the monthly volume, diversity, and competition of internet searches for this compound, as well the volume and growth of publications, there is estimated to be very strong demand-to-supply ratio for research on this compound.

MetricThis Compound (vs All)
Research Demand Index61.23 (24.57)
Research Supply Index5.47 (2.92)
Research Growth Index4.50 (4.65)
Search Engine Demand Index102.71 (26.88)
Search Engine Supply Index2.00 (0.95)

This Compound (61.23)

All Compounds (24.57)

Study Types

Publication TypeThis drug (%)All Drugs (%)
Trials40 (20.41%)5.53%
Reviews13 (6.63%)6.00%
Case Studies32 (16.33%)4.05%
Observational1 (0.51%)0.25%
Other110 (56.12%)84.16%
[information is prepared from research data collected from National Library of Medicine (NLM), extracted Dec-2023]

Clinical Trials (124)

Trial Overview

TrialPhaseEnrollmentStudy TypeStart DateStatus
Preventing ICU Subsyndromal Delirium Conversion to Delirium With Low Dose IV Haloperidol: A Double-Blind, Placebo-Controlled Pilot Study [NCT01174290]Phase 468 participants (Actual)Interventional2010-09-30Completed
Pharmacological Modulation of Belief Salience [NCT03754062]Phase 130 participants (Actual)Interventional2017-06-01Completed
Blood Lactate Levels in Patients Treated With Typical or Atypical Antipsychotics [NCT01139463]60 participants (Actual)Observational2008-06-30Completed
Phase I Clinical Trial. Study of the Impact of Pharmacogenetic Markers in Predicting the Appearance of Extrapyramidal Symptomatology After the Treatment With Typical vs. Atypical Antipsychotics, in Healthy Volunteers [NCT01259973]Phase 124 participants (Anticipated)Interventional2011-02-28Enrolling by invitation
"Efficacy of the Combination of Z-track and Airlock Techniques During Intramuscular Injection of Haloperidol Decanoate in Adult Patients With Schizophrenic or Related Disorder : A Multicenter Randomized Controlled Trial" [NCT05995457]84 participants (Anticipated)Interventional2023-09-01Not yet recruiting
TREC-Lebanon Trial: A Randomised Controlled Trial for Rapid Tranquilisation for Agitated Patients in the Emergency Setting [NCT03639558]Phase 4100 participants (Actual)Interventional2018-08-28Completed
Randomized Double-Blind Clinical Trial to Compare Haloperidol and Non-Pharmacologic Treatment Versus Non-Pharmacologic Treatment and Placebo, in Elderly Hospitalized Patients With Hypoactive Delirium [NCT02345902]Phase 360 participants (Anticipated)Interventional2016-01-31Recruiting
Investigating the Efficacy of Using Haloperidol vs. Metoclopramide for Treatment of Acute Headaches and Migraines in the Emergency Department: A Prospective Randomized Clinical Trial [NCT02972502]Phase 466 participants (Actual)Interventional2014-02-28Terminated(stopped due to PI lapsed institutional training)
Strategies for Persistent Agitated Delirium in Palliative Care [NCT03743649]Phase 2/Phase 3206 participants (Anticipated)Interventional2019-07-17Recruiting
A Comparison of Haloperidol 5mg IM vs Droperidol 2.5mg and Ondansetron for the Treatment of Hyperemesis in Cannabis Hyperemesis Syndrome [NCT05065567]Phase 238 participants (Actual)Interventional2021-08-30Terminated(stopped due to Lost too many patients to follow up, unable to enroll enough patients)
Evaluation of Negative Symptoms and Cognitive Function After Administration of Antipsychotics in Healthy Volunteer: a Double-blind, Randomized Trial of a Single Dose of Placebo, Haloperidol, Amisulpride, Risperidone and Aripiprazole [NCT01185418]80 participants (Actual)Observational2009-03-31Completed
Intramuscular Olanzapine Versus Haloperidol or Midazolam for the Management of Acute Agitation in the Emergency Department - a Multicentre Randomised Clinical Trial [NCT02380118]Phase 4167 participants (Actual)Interventional2014-12-31Terminated(stopped due to Primary endpoint reached based on data projection from interim analysis.)
Risk of QT-prolongation and Torsade de Pointes in Patients Treated With Acute Medication in a University Hospital [NCT02068170]178 participants (Actual)Observational2014-02-28Completed
A Single Center, Randomized Controlled Prospective Double-blinded Trial Comparing Haloperidol to Standard Ondansetron Therapy for Control of Nausea and Vomiting in the Emergency Department [NCT04764344]Phase 460 participants (Actual)Interventional2021-04-01Completed
Haloperidol Versus Ondansetron for Cannabis Hyperemesis Syndrome (HaVOC): A Randomized Controlled Trial [NCT03056482]Phase 433 participants (Actual)Interventional2017-05-21Completed
Clozapine and Olanzapine in the Treatment of Violence in Schizophrenic Patients [NCT01123408]110 participants (Actual)Interventional1999-06-30Completed
A Prospective, Multi-centre, Randomised, Double-blind, Placebo-controlled Comparison of Intravenous Dexmedetomidine and Haloperidol in Treatment of Psychomotor Confusion After Heart Surgery [NCT01140529]Phase 33 participants (Actual)Interventional2010-05-31Terminated(stopped due to Slow recruitment)
A Prospective, Matched-Control, Randomized, Open-Label, Flexible-Dose, Study in Subjects With Recent-Onset Schizophrenia or Schizophreniform Disorder to Compare Disease Progression and Disease Modification Following Treatment With Paliperidone Palmitate L [NCT02431702]Phase 3337 participants (Actual)Interventional2015-07-08Completed
A Randomized Double-blind Multicenter Double-dummy Non-inferiority Trial of Inhaled Loxapine and Intramuscular Haloperidol + Lorazepam for the Reduction of Agitation [NCT03110900]Phase 42 participants (Actual)Interventional2017-09-30Terminated(stopped due to Sponsor Withdrawal)
Effects of Aripiprazole and Haloperidol on Mesolimbic System Functioning: A Pharmacological fMRI Study [NCT01161277]Phase 454 participants (Actual)Interventional2010-08-31Completed
Clinical Effectiveness Of The Newer Antipsychotic Compounds Olanzapine, Quetiapine And Aripiprazole In Comparison With Low Dose Conventional Antipsychotics (Haloperidol And Flupentixol) In Patients With Schizophrenia [NCT01164059]Phase 4149 participants (Actual)Interventional2010-02-28Completed
Early Clinical Evaluation of the Pharmacokinetics and Mechanism Based Pharmacodynamics of Haloperidol Using Positron Emission Tomography in Healthy Volunteers [NCT01193621]Phase 112 participants (Actual)Interventional2008-01-31Completed
A Multicenter, Randomized, Double-Blind, Fixed-Dose, 6-Week Trial of the Efficacy and Safety of Asenapine Compared With Placebo Using Haloperidol Positive Control in Subjects With an Acute Exacerbation of Schizophrenia [NCT00156104]Phase 3460 participants (Actual)Interventional2005-07-01Completed
Intravenous Haloperidol Versus Ondansetron for Treatment of Established Nausea and Vomiting in Patients Undergoing Surgery With General Anesthesia: A Randomized Clinical Trial [NCT02143531]Phase 4120 participants (Actual)Interventional2008-09-30Completed
Haldol/Diphenhydramine Versus Metoclopramide/Diphenhydramine for Treatment of Acute Headache in the Emergency Department: A Randomized Controlled Trial [NCT02098499]Phase 468 participants (Actual)Interventional2013-06-30Completed
A Double Blinded Randomized Trial of Ketamine Versus Haloperidol for Severe Prehospital Agitation [NCT02103881]Phase 40 participants (Actual)Interventional2014-04-30Withdrawn
Meth-OD: A Phase 2a Study of IXT-m200 in Patients With Toxicity From Methamphetamine Overdose [NCT04715230]Phase 220 participants (Actual)Interventional2021-06-30Terminated(stopped due to Sponsor decision based on slower than anticipated enrollment leading to fund exhaustion.)
A Randomized Blind Parallel Intramuscular Haloperidol-Controlled Multicenter Clinical Trial to Evaluate the Efficacy and Safety of Intramuscular Levosulpiride in the Treatment of Chinese Patients With Agitation Of Schizophrenia [NCT00866645]Phase 2/Phase 3240 participants (Anticipated)Interventional2009-02-28Completed
How Does the Brain Learn About Positive and Negative Things? [NCT06014606]150 participants (Actual)Interventional2021-03-01Completed
The Effect of Lamictal TM Augmentation of Haloperidol Decanoate in the Treatment of Resistant Schizophrenia Predominantly by Verbal Resistant Hallucinosis: Randomized, Double-blind, Placebo-controlled, Study [NCT00947375]Phase 4335 participants (Actual)Interventional2005-01-31Terminated(stopped due to All of the mentioned aim and objectives were achieved before the February 2007)
Efficacy of SCH 420814 to Reduce the Frequency or Severity of Neuroleptic Induced Akathisia [NCT00693472]Phase 246 participants (Actual)Interventional2007-08-15Terminated
A Randomized, Open Label, Rater Blind, Flexible Dose Multi-Center Study Comparing The Efficacy And Safety Of Intramuscular Ziprasidone With Haloperidol For Three Days In Patients With Agitation Of Schizophrenia [NCT00723606]Phase 3376 participants (Actual)Interventional2008-09-30Completed
Non-randomized Control Clinical Trial to Evaluate the Efficacy and Safety of Symptomatic Drug Therapy for Mild to Moderate Huntington's Disease Patients [NCT04071639]Phase 160 participants (Anticipated)Interventional2020-03-12Recruiting
Treatment of Clozapine-resistant Schizophrenia : Comparison Between Augmentation With Haloperidol and Electroconvulsive Therapy [NCT00753051]18 participants (Actual)Interventional2008-06-30Completed
A Randomized Open Label Study on the Efficacy, Tolerability, and Total Costs of Olanzapine Versus Conventional Antipsychotics in the Treatment of Acute Mania in Sweden [NCT00767715]Phase 411 participants (Actual)Interventional2004-10-31Terminated(stopped due to Trial discontinued due to low enrollment)
Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Haloperidol in Healthy Humans [NCT00625014]8 participants (Actual)Interventional2005-03-31Completed
Metabolic Effects of Subchronic Dopamine D2 Receptor Blockade by Antipsychotic Drugs in Healthy Humans [NCT00625170]11 participants (Actual)Interventional2004-05-31Completed
A Comparison of Long-Acting Injectable Medications for Schizophrenia [NCT01136772]Phase 4311 participants (Actual)Interventional2011-03-31Completed
MIND-USA Study: Modifying the Impact of ICU-Associated Neurological Dysfunction [NCT01211522]Phase 3566 participants (Actual)Interventional2011-12-14Completed
Study of Evaluating Quetiapine in Improving Sleep Quality of Schizophrenia [NCT00642369]60 participants (Actual)Interventional2008-03-31Completed
GiSAS Trial: Aripiprazole, Olanzapine, and Haloperidol in the Long Term Treatment of Schizophrenia. [NCT01052389]Phase 4300 participants (Actual)Interventional2007-07-31Completed
[NCT00631722]80 participants (Actual)Interventional2007-05-31Completed
Intravenous Haloperidol for the Treatment of Headache in the Emergency Department [NCT02747511]Phase 4118 participants (Actual)Interventional2015-10-31Completed
An Open-Label, Single-Dose, Crossover Study to Determine the Bioequivalency of Generic Haloperidol Tablets vs. Haldol in Normal Volunteers. [NCT00946491]Phase 130 participants (Actual)Interventional1987-04-30Completed
Stroke Risk Among Users of Typical vs. Atypical Antipsychotics Stratified by Broad Age Group, a Post-authorization Safety Study [NCT04002700]1,234,412 participants (Actual)Observational2019-05-06Completed
[NCT00838032]Phase 470 participants (Anticipated)Interventional2008-08-31Recruiting
Compare Efficacy and Safety Between Quetiapine and Haloperidol in Treatment Delirium [NCT00954603]Phase 352 participants (Actual)Interventional2009-06-30Terminated(stopped due to few delirious patients were enrolled.)
Efficacy and Safety of Risperidone Oral Solution Combination Clonazepam Versus Haloperidol IM Injection for Treatment of Acute Psychotic Agitation in Schizophrenia [NCT00859872]Phase 4198 participants (Actual)Interventional2008-08-31Completed
Treatment of Behavioral Symptoms in Alzheimer's Disease [NCT00009217]Phase 444 participants (Actual)Interventional1999-01-31Completed
Placebo- and Haloperidol-Controlled Double-Blind Trial of Olanzapine in Patients With Manic or Mixed Episode of Bipolar I Disorder [NCT00129220]Phase 3224 participants (Actual)Interventional2005-07-31Completed
Combination of Haloperidol and Magnesium for Delirium Prevention in Critically Ill Elderly Patients After Elective Major Surgery [NCT06168773]Phase 2/Phase 3135 participants (Actual)Interventional2022-11-01Completed
A Single Center, Single Dose, Open-label, Randomized, Two Period Crossover Pivotal Study to Determine the Bioequivalence of Two Formulations Containing Haloperidol 2 mg in Healthy Males and Females Under Fed Conditions [NCT04411953]Phase 132 participants (Actual)Interventional2019-11-15Completed
A Single Center, Single Dose, Open-label, Randomized, Two Period Crossover Pivotal Study to Determine the Bioequivalence of Two Formulations Containing Haloperidol 2 mg in Healthy Males and Females Under Fasting Conditions [NCT04411940]Phase 132 participants (Actual)Interventional2019-11-15Completed
A Comparison of Risperidone and Haloperidol for Prevention of Relapse in Subjects With Schizophrenia and Schizoaffective Disorders [NCT00253110]Phase 4396 participants (Actual)Interventional1996-05-31Completed
Drug Interactions With Risk of QT-prolongation in a General Hospital: an Epidemiological Point Prevalence Study [NCT02043912]222 participants (Actual)Observational2013-07-31Completed
CSP #451 - The Clinical and Economic Impact of Olanzapine in the Treatment of Schizophrenia [NCT00007774]Phase 4600 participants (Anticipated)Interventional1998-03-31Completed
A Randomized, Multicenter Clinical Trial to Assess the Efficacy and Safety of Clozapine vs Treatment as Usual for Treatment-resistant Psychosis in Adolescents and Young Adults With Intellectual Disability. [NCT04529226]Phase 2114 participants (Anticipated)Interventional2020-11-26Recruiting
Haloperidol vs Olanzapine for the Management of ICU Delirium: A Randomized Clinical Trial [NCT00833300]200 participants (Anticipated)Interventional2008-06-30Terminated
Intravenous Immunoglobulins as Effective Treatment in Sydenham's Chorea [NCT00615797]20 participants (Actual)Interventional2002-05-31Completed
A Multicenter, Randomized, Double-blind, Parallel-controlled Injection of Olanzapine in the Treatment of Acute Agitation Associated With Schizophrenia and Bipolar I Disorder. [NCT05803642]Phase 3318 participants (Anticipated)Interventional2023-03-28Not yet recruiting
Intramuscular Clozapine in the Management of Aggression in Schizophrenic Patients [NCT00189995]Phase 30 participants (Actual)InterventionalWithdrawn
Double-Blind Long-term Study Comparing the Efficacy and Safety of Olanzapine Versus Haloperidol in Patients With Schizophrenia Previously Stabilized With Conventional Antipsychotic Treatment [NCT00191555]Phase 4360 participants Interventional2003-08-31Completed
Haloperidol Prophylaxis in Cardiac Surgery for Patients at Risk for Delirium: A Randomized Placebo-Controlled Pilot Study [NCT01862302]Phase 325 participants (Actual)Interventional2013-08-31Completed
A Comparison of Midazolam or Haloperidol Premedication Versus Placebo for Reducing Ketamine Induced Agitation After Adult Procedural Sedation in the Emergency Department [NCT02909465]Phase 4185 participants (Actual)Interventional2016-07-31Completed
An Open-label, Randomized Trial of Intramuscular (IM) Olanzapine Versus Intramuscular Combination of Haloperidol and Lorazepam in the Treatment of Acute Agitation in Schizophrenia [NCT00797277]Phase 367 participants (Actual)Interventional2006-07-31Completed
Rapid Tranquilization of Violent or Agitated People in Psychiatric Emergency Settings- A Pragmatic Randomized Controlled Trial of Intramuscular Olanzepine Vs. Intramuscular Haloperidol + Promethazine. [NCT00455234]Phase 3300 participants Interventional2005-09-30Completed
Methylphenidate, Rivastigmine or Haloperidol in Hypoactive Delirium in Intensive Care Patients: a Randomized, Mono-blind Pilot Trial [NCT00599287]Phase 380 participants (Anticipated)Interventional2008-02-29Terminated(stopped due to Inclusion rate too low due to a lack of eligible patients and difficulties obtaining informed consent.)
A Double-Blind Randomized Comparison of the Efficacy and Safety of Intramuscular Olanzapine and Intramuscular Haloperidol in Acutely Agitated Patients With Schizophrenia [NCT00485901]Phase 350 participants (Actual)Interventional2004-07-31Completed
Metabolic Profile and Anthropometric Changes in Schizophrenia [NCT00534183]2,006 participants (Actual)Interventional2006-06-30Completed
Safety and Efficacy of Four Intramuscular Interventions for the Management of Acute Psychomotor Agitation [NCT01485692]120 participants (Actual)Interventional2009-02-28Completed
A Multicenter, Randomized, Double-Blind, Placebo Controlled Study of Aripiprazole Monotherapy in the Treatment of Acutely Manic Patients With Bipolar I Disorder [NCT00097266]Phase 3615 participants Interventional2004-12-31Completed
Randomised Double-blind Placebo-controlled Study of Post-operative Haloperidol Versus Placebo for Prevention of Post-operative Delirium After Acute Hip Surgery [NCT00250237]Phase 3220 participants (Actual)Interventional2005-11-30Completed
Modulation of Regional Brain Activation in Schizophrenic Patients by Pharmacological Therapy With Amisulpride, Olanzapine or Haloperidol. A Study With Functional Magnetic Resonance Imaging (fMRI) and Diffusion Tensor Imaging (DTI) [NCT00419653]Phase 419 participants (Actual)Interventional2003-01-31Terminated(stopped due to Recruitment issues)
A Randomized Prospective Pilot Study Of Haloperidol In Addition To Standard Sedation In Mechanically Ventilated Patients With Delirium [NCT00429676]Phase 220 participants (Anticipated)Interventional2005-12-31Completed
Delirium in the ICU: a Prospective, Randomized, Trial of Placebo vs. Haloperidol vs. Ziprasidone [NCT00096863]Phase 2102 participants (Actual)Interventional2004-12-31Completed
One Year Maintenance Treatment With Low Dose Haloperidol vs. Risperidone in First-Episode Schizophrenia [NCT00159081]Phase 4159 participants (Actual)Interventional2000-11-30Completed
A Randomised Open Label Pilot Study of the Efficacy of Dexmedetomidine and Haloperidol in Ventilated Patients With ICU-associated Agitation and Delirium [NCT00505804]Phase 220 participants (Actual)Interventional2005-01-31Completed
Clozapine or Haloperidol in First Episode Schizophrenia [NCT00169091]Phase 432 participants (Actual)Interventional1996-03-31Terminated
Early Pharmacological Intervention to Prevent Delirium: Haloperidol Prophylaxis in Older Emergency Department Patients [NCT01530308]Phase 4242 participants (Actual)Interventional2012-11-30Completed
Early Recognition and Optimal Treatment of Delirium in Patients With Advanced Cancer [NCT01539733]101 participants (Actual)Interventional2010-03-31Completed
5HT3 Antagonism and Auditory Gating in Schizophrenia [NCT00018850]0 participants Interventional1998-06-30Completed
[NCT00000179]Phase 30 participants InterventionalCompleted
Predicting the Optimal Pharmacotherapy for Outpatients With Schizophrenia [NCT00018642]0 participants Interventional1997-04-30Completed
Optimization of Acute Treatment in First Episode Schizophrenic Patients by New Pharmacological Treatments [NCT00157378]Phase 4300 participants Interventional2000-11-30Active, not recruiting
A Comparison of Two Different Treatments for Major Depression With Psychotic Features: Ziprasidone vs. Combined Sertraline and Haloperidol [NCT00340379]Phase 2/Phase 372 participants (Actual)Interventional2003-04-30Completed
Prospective Observational Investigation of Olanzapine Versus Haloperidol Versus Ziprasidone Versus Midazolam for the Treatment of Acute Undifferentiated Agitation in the Emergency Department [NCT03211897]737 participants (Actual)Observational2017-06-15Completed
Topical Haloperidol: Evidence of Absorption After Topical Administration [NCT01684969]Early Phase 10 participants (Actual)Interventional2012-03-31Withdrawn(stopped due to lack of accrual and funding is about to expire.)
Re-hospital Agitation and Sedation Trial: A Randomized Controlled Trial of Haloperidol Versus Midazolam for the Sedation of the Agitated Patient [NCT01501123]10 participants (Actual)Interventional2011-11-30Completed
Oro-dispersible Olanzapine (Wafer) Versus Conventional Oral Haloperidol or Diazepam Tablets for the Management of Acute Agitation in the Accident and Emergency Department - a Multicentre Randomised Clinical Trial [NCT03246620]Phase 412 participants (Actual)Interventional2017-09-01Terminated(stopped due to The study was terminated prematurely due to difficulties in patient recruitment and associated potential for selection bias.)
Haloperidol vs. Valproate in the Management of Agitated Patients Presenting to the Emergency Department: A Randomized Clinical Trial [NCT01750541]Phase 356 participants (Actual)Interventional2012-12-31Completed
Prophylactic Haloperidol Use for Delirium in ICU Patients; a Randomized Placebo-controlled Double-blind Multicentre Trial [NCT01785290]Phase 41,800 participants (Actual)Interventional2013-06-30Completed
Randomized Controlled Trial Comparing Haloperidol, Quetiapine and Placebo in the Pharmacological Treatment of Delirium : The Haloquet Trial [NCT01811459]Phase 3107 participants (Actual)Interventional2013-02-28Completed
Preventing Post-Operative Delirium in Pneumonectomy, Esophagectomy and Thoracotomy Patients [NCT02213900]Phase 4135 participants (Actual)Interventional2013-09-30Completed
Correlation Between Cognitive Function and Relapse of Schizophrenia Regarding Dose Reduction in Patients Undergoing High-dose Antipsychotic Therapy [NCT03019887]139 participants (Actual)Interventional2011-04-30Completed
Valproic Acid for Treatment of Hyperactive or Mixed Delirium in ICU [NCT02343575]Phase 43 participants (Actual)Interventional2015-01-31Terminated(stopped due to We did not recruit the research assistant and terminated the study)
Open-label Randomized Controlled Trial of Oral Transmucosal Haloperidol and Olanzapine in the Treatment of Terminal Delirium [NCT04750395]Phase 280 participants (Anticipated)Interventional2021-09-01Recruiting
Managing Agitated Delirium With Neuroleptics and Anti-Epileptics as a Neuroleptic Sparing Strategy [NCT05431595]Phase 2/Phase 3150 participants (Anticipated)Interventional2022-07-19Enrolling by invitation
A Multicenter, Randomized, Double-Blind, Flexible-Dose, Long-Term Extension Trial of the Safety and Maintenance of Effect of Asenapine Using Haloperidol Positive Control in Subjects Who Complete Protocol 041023 [NCT00156104] [NCT00156065]Phase 3187 participants (Actual)Interventional2005-09-30Completed
A Prospective Trial of Customized Adherence Enhancement Plus Long-acting Injectable Antipsychotic (CAE-L) in Individuals With Schizophrenia or Schizoaffective Disorder at Risk for Treatment Non-adherence and for Homelessness [NCT01152697]30 participants (Actual)Interventional2010-06-30Completed
"Absorption of ABH Gel (Ativan®, Lorazepam; Benadryl®, Diphenhydramine; and Haldol®, Haloperidol Gel) From the Skin of Normal Volunteers" [NCT01204255]11 participants (Actual)Interventional2010-11-15Completed
Phase 4 Study of Optimal Dose of Haloperidol [NCT01639599]150 participants (Actual)Interventional2012-03-31Completed
ORIC-I: Optimizing Recovery From Intensive Care: Mechanical Ventilation and Delirium [NCT00300391]Phase 340 participants (Actual)Interventional2006-03-31Terminated(stopped due to Insufficient recruitment to meet aims.)
Phase 2 Study of the Antipsychotic Effects of Sorghum Bicolor (JOBELYN) in the Treatment of Schizophrenia. [NCT02240173]Phase 1/Phase 2100 participants (Anticipated)Interventional2017-06-30Not yet recruiting
Agents Intervening Against Delirium in Intensive Care Unit (AID-ICU) A Randomized, Blinded, Placebo-controlled Trial [NCT03392376]Phase 41,000 participants (Anticipated)Interventional2018-06-13Active, not recruiting
Comparative Effects of a D2 and Mixed D1-D2 Dopamine Antagonist on Gambling and Amphetamine Reinforcement in Pathological Gamblers and Healthy Controls [NCT02203786]Phase 260 participants (Actual)Interventional2009-09-30Completed
A Preliminary Double-Blind Randomized Controlled Trial of Haloperidol and Lorazepam for Delirium in Patients With Advanced Cancer Admitted to a Palliative Care Unit [NCT01949662]Phase 293 participants (Actual)Interventional2014-01-31Active, not recruiting
Reducing the Burden of Chronic Psychotic Disorders in Tanzania [NCT04327843]Phase 322 participants (Actual)Interventional2019-11-05Completed
Study of add-on Ramelteon Therapy on Sleep and Circadian Rhythm Disruption in Patients With Schizophrenia [NCT03075657]Phase 4120 participants (Actual)Interventional2017-05-01Completed
Baden PRIDe Trial - Baden Prevention and Reduction of Incidence of Postoperative Delirium Trial [NCT02433041]Phase 4200 participants (Actual)Interventional2013-07-31Completed
Haloperidol Compared to Dexamethasone in Lowering Postoperative Nausea and Vomiting and Pain in Adult After Laparoscopy [NCT05246631]Phase 480 participants (Actual)Interventional2020-01-01Completed
The Impact of Genetic Variation In Nicotinic Cholinergic Receptors on Functional Brain Networks Underlying Addiction Susceptibility [NCT01924468]Phase 176 participants (Actual)Interventional2013-08-14Completed
A 6-Week, Double-Blind, Randomized, Fixed-Dose, Parallel-Group Study of the Efficacy and Safety of Three Dose Levels of SM-13496 Compared to Placebo and Haloperidol in Patients With Schizophrenia Who Are Experiencing an Acute Exacerbation of Symptoms [NCT00044044]Phase 2356 participants (Actual)Interventional2002-07-31Completed
Haloperidol and/or Chlorpromazine for Refractory Agitated Delirium in the Palliative Care Unit [NCT03021486]Phase 2/Phase 370 participants (Actual)Interventional2017-06-05Active, not recruiting
Quetiapine Versus Haloperidol in the Management of Hyperactive Delirium [NCT05690698]Phase 3100 participants (Actual)Interventional2023-04-09Completed
A Comparison Study of the Efficacy of a Rapid Titration of Quetiapine and Haloperidol in Agitated Adults in an Emergency Setting. [NCT00457366]Phase 472 participants (Actual)Interventional2006-05-31Completed
Pharmacological Management of Delirium [NCT00842608]551 participants (Actual)Interventional2009-02-28Completed
Lurasidone Effects on Tissue Glutamate in Schizophrenia [NCT02199743]Phase 435 participants (Actual)Interventional2013-02-28Completed
Haloperidol vs Conventional Therapy for Gastroparesis [NCT02057549]Phase 436 participants (Actual)Interventional2012-11-30Terminated(stopped due to PI left institution)
Prospective Evaluation of Symptoms and Open Label Haloperidol in Cannabinoid Hyperemesis Syndrome (HALO) [NCT04176055]Phase 44 participants (Actual)Interventional2020-10-13Completed
[NCT02493192]Phase 4110 participants (Anticipated)Interventional2015-07-31Not yet recruiting
A Concierge Model of Customized Adherence Enhancement Plus Long-acting Injectable Antipsychotic (CAL-C) in Individuals With Schizophrenia at Risk for Treatment Non-adherence and for Homelessness [NCT02085447]30 participants (Actual)Interventional2014-05-31Completed
Rapid Agitation Control With Ketamine in the Emergency Department (RACKED): a Randomized Controlled Trial [NCT03375671]Phase 281 participants (Actual)Interventional2018-05-29Completed
Delirium: Is Prophylactic Drug Therapy Useful in High Risk Patients as Defined by the Delirium Risk Prediction Model? [NCT03199950]Phase 41,366 participants (Anticipated)Interventional2017-06-23Recruiting
Efficacy of Haloperidol to Decrease the Burden of Delirium in Adult Critically Ill Patients (EuRIDICE): a Prospective Randomised Multi-center Double-blind Placebo-controlled Clinical Trial [NCT03628391]Phase 3142 participants (Actual)Interventional2018-02-22Terminated(stopped due to The study was stopped because of futility of being able to reach a one-day difference between treatment groups in the primary outcome of DCFD in the intended sample size.)
[information is prepared from clinicaltrials.gov, extracted Sep-2024]

Trial Outcomes

TrialOutcome
NCT00044044 (4) [back to overview]Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score
NCT00044044 (4) [back to overview]Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores
NCT00044044 (4) [back to overview]Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores
NCT00044044 (4) [back to overview]Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores
NCT00129220 (11) [back to overview]Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)
NCT00129220 (11) [back to overview]Percentage of Participants Who Switched to Symptomatic Depression
NCT00129220 (11) [back to overview]Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score
NCT00129220 (11) [back to overview]Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)
NCT00129220 (11) [back to overview]Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score
NCT00129220 (11) [back to overview]Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness
NCT00129220 (11) [back to overview]Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale
NCT00129220 (11) [back to overview]Percentage of Participants Who Switched to Syndromic Depression
NCT00129220 (11) [back to overview]Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks
NCT00129220 (11) [back to overview]Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)
NCT00129220 (11) [back to overview]Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks
NCT00156065 (2) [back to overview]Median Survival Time of Effect
NCT00156065 (2) [back to overview]Loss of Effect Over Time
NCT00300391 (4) [back to overview]ICU Length of Stay
NCT00300391 (4) [back to overview]Duration of Mechanical Ventilation
NCT00300391 (4) [back to overview]90-day All-cause Mortality
NCT00300391 (4) [back to overview]28-day All-cause Mortality
NCT00340379 (3) [back to overview]21 Item Hamilton Depression Rating Scale
NCT00340379 (3) [back to overview]Brief Psychiatric Rating Scale at 12 Weeks
NCT00340379 (3) [back to overview]Clinical Global Impression Improvement Scale
NCT00457366 (1) [back to overview]Change in the PANSS-EC Score Among Participants From Baseline to 2 Hours After Administration of the Medication.
NCT00642369 (2) [back to overview]Percentage of Slow Wave Sleep
NCT00642369 (2) [back to overview]Percentage of Rapid Eye Movement Sleep
NCT00693472 (6) [back to overview]Part 2: PANSS Total Score at Day 14
NCT00693472 (6) [back to overview]Part 2: Number of Participants Who Were Treatment Failures
NCT00693472 (6) [back to overview]Part 2: Mean GCI at Day 14
NCT00693472 (6) [back to overview]Part 1: Mean Global Clinical Impression at Day 14
NCT00693472 (6) [back to overview]Part 1: Number of Participants With Akathisia
NCT00693472 (6) [back to overview]Part 1: Mean Positive and Negative Symptom Scale for Schizophrenia (PANSS) Total Score at Day 14
NCT00723606 (6) [back to overview]Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours
NCT00723606 (6) [back to overview]Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours
NCT00723606 (6) [back to overview]Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours
NCT00723606 (6) [back to overview]BPRS Agitation Subscale Response at 72 Hours
NCT00723606 (6) [back to overview]Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours
NCT00723606 (6) [back to overview]Change From Baseline in BPRS Agitation Subscale Score at 72 Hours
NCT00797277 (2) [back to overview]The Change of the Positive and Negative Symptom Scale Excited Component (PANSS-EC) Score From Baseline to 120 Minutes After First Injection
NCT00797277 (2) [back to overview]Change of the Agitation-Calmness Evaluation Scale (ACES) Score From Baseline to 120 Minutes After 1st Injection
NCT00842608 (3) [back to overview]Mortality
NCT00842608 (3) [back to overview]Hospital Length of Stay Post Randomization
NCT00842608 (3) [back to overview]Days Free of Delirium and Coma
NCT01136772 (2) [back to overview]Changes in Psychiatric Symptoms
NCT01136772 (2) [back to overview]Efficacy Failure
NCT01152697 (20) [back to overview]Treatment Satisfaction as Measured by the Participant Acceptability and Satisfaction Questionnaire at 25 Weeks
NCT01152697 (20) [back to overview]Treatment Satisfaction as Measured by the Participant Acceptability and Satisfaction Questionnaire at 12 Months
NCT01152697 (20) [back to overview]Treatment Adherence Behavior Score as Measured by the Morisky Medication Rating Scale at 12 Months
NCT01152697 (20) [back to overview]Frequency of Health Resource Use in the Past 3 Months as Measured at 25 Weeks
NCT01152697 (20) [back to overview]Global Psychopathology as Measured by the Clinical Global Impressions (CGI) at 12 Months
NCT01152697 (20) [back to overview]Treatment Adherence Score as Measured at 12 Months
NCT01152697 (20) [back to overview]Change in Social and Occupational Functioning Scale (SOFAS) as Measured at 12 Months
NCT01152697 (20) [back to overview]Days Homeless Out of the Previous 6 Months as Measured at 12 Months
NCT01152697 (20) [back to overview]Adherence Attitude Score as Measured by the Attitude Toward Medication Questionnaire (AMQ) at 12 Months
NCT01152697 (20) [back to overview]Change in Social and Occupational Functioning Scale (SOFAS) as Measured at 25 Weeks
NCT01152697 (20) [back to overview]Change From Baseline in Adherence Attitude Score as Measured by the Attitude Toward Medication Questionnaire (AMQ) at 25 Weeks
NCT01152697 (20) [back to overview]Change in Schizophrenia and Schizoaffective Disorder Symptom Severity Scale as Measured by the Positive and Negative Syndrome Scale (PANSS) at 25 Weeks
NCT01152697 (20) [back to overview]Adherence Attitude Score as Measured by the Drug Attitude Inventory (DAI) at 12 Months
NCT01152697 (20) [back to overview]Frequency of Health Resource Use Throughout Months 10, 11, and 12
NCT01152697 (20) [back to overview]Change in Serious Mental Illness Severity Score as Measured by the Brief Psychiatric Rating Scale (BPRS) at 25 Weeks
NCT01152697 (20) [back to overview]Change in Global Psychopathology as Measured by the Clinical Global Impressions (CGI) at 25 Weeks
NCT01152697 (20) [back to overview]Change From Baseline in Treatment Adherence Score as Measured at 25 Weeks
NCT01152697 (20) [back to overview]Change From Baseline in Treatment Adherence Behavior Score as Measured by the Morisky Medication Rating Scale at 25 Weeks
NCT01152697 (20) [back to overview]Change From Baseline in Days Homeless Out of the Previous 6 Months as Measured at 25 Weeks
NCT01152697 (20) [back to overview]Change From Baseline in Adherence Attitude Score as Measured by the Drug Attitude Inventory (DAI) at 25 Weeks
NCT01204255 (2) [back to overview]Side Effects
NCT01204255 (2) [back to overview]Lorazepam, Diphenyhydramine, Haloperidol Absorption
NCT01211522 (10) [back to overview]Time to Hospital Discharge
NCT01211522 (10) [back to overview]Time to ICU Readmission
NCT01211522 (10) [back to overview]Time to Liberation From Mechanical Ventilation
NCT01211522 (10) [back to overview]Delirium Duration
NCT01211522 (10) [back to overview]Mortality
NCT01211522 (10) [back to overview]Delirium/Coma-free Days (DCFDs)
NCT01211522 (10) [back to overview]Number of Participants With Extrapyramidal Symptoms
NCT01211522 (10) [back to overview]Number of Participants With Neuroleptic Malignant Syndrome
NCT01211522 (10) [back to overview]Number of Participants With Torsades de Pointes
NCT01211522 (10) [back to overview]Time to Final ICU Discharge
NCT01639599 (4) [back to overview]Sedation Change in Recovery Room
NCT01639599 (4) [back to overview]Incidence of Postoperative Nausea and Vomiting
NCT01639599 (4) [back to overview]Incidence of Extrapyramidal Symptoms
NCT01639599 (4) [back to overview]Incidence of Cardiac Arrhythmia
NCT01949662 (4) [back to overview]Absolute Richmond Agitation-Sedation Scale Score at 8 Hour, Points
NCT01949662 (4) [back to overview]Number of Participants With Richmond Agitation-Sedation Scale Score >=1 Within 8 hr
NCT01949662 (4) [back to overview]Change in Richmond Agitation-Sedation Scale Score From Baseline to 30 Min
NCT01949662 (4) [back to overview]Change in Richmond Agitation-Sedation Scale Score (Baseline to 8 hr), Points
NCT02057549 (8) [back to overview]Number of Participants Admitted to the Hospital After Emergency Department Visit
NCT02057549 (8) [back to overview]Pain Relief as Indicated by Number of Participants Not Requesting Additional Pain Medication
NCT02057549 (8) [back to overview]Pain Score as Measured by a Visual Analogue Scale (VAS)
NCT02057549 (8) [back to overview]Nausea Score as Measured by a Visual Analogue Scale (VAS)
NCT02057549 (8) [back to overview]Emergency Department Length of Stay (EDLOS)
NCT02057549 (8) [back to overview]Nausea Relief as Indicated by Number of Participants Not Requesting Additional Antiemetic Medication
NCT02057549 (8) [back to overview]Nausea Score as Measured by a Visual Analogue Scale (VAS)
NCT02057549 (8) [back to overview]Pain Score as Measured by a Visual Analogue Scale (VAS)
NCT02085447 (22) [back to overview]Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Dyskinesia) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Dystonia) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Parkinsonism) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in Hospitalizations (Medical) in the Past 6 Months From Screen and Week 25
NCT02085447 (22) [back to overview]Change in Hospitalizations (Psychiatric) in the Past 6 Months From Screen and Week 25
NCT02085447 (22) [back to overview]Change in PANSS (Positive and Negative Syndrome Scale; Composite Scale) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in PANSS (Positive and Negative Syndrome Scale; General Psychopathology) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in PANSS (Positive and Negative Syndrome Scale; Negative Symptoms Scale) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in PANSS (Positive and Negative Syndrome Scale; Positive Symptoms Scale) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in SAS (Simpson Angus Scale) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in SOFAS (Social and Occupational Functioning Assessment Scale) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in Tablets Routine Questionnaire (TRQ, Past Week) From Screen to Week 25 Visit
NCT02085447 (22) [back to overview]Change in Tablets Routine Questionnaire (TRQ) (Past Month) From Screen to Week 25
NCT02085447 (22) [back to overview]Long-acting Injection (LAI) Adherence
NCT02085447 (22) [back to overview]Percentage Change of Days of Sub-optimal Housing in the Past Six Months; Change From Screen to Week 25
NCT02085447 (22) [back to overview]Change in AIMS (Abnormal Involuntary Movement Scale) From Baseline to Week 25
NCT02085447 (22) [back to overview]Change in AMSQ (Attitudes Toward Mood Stabilizers Questionnaire) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in ASSIST GRS (Alcohol, Smoking and Substance Involvement Screening Test ) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in BARS (Barnes Akathisia Rating Scale) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in CGI (Clinical Global Impression) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in DAI (Drug Attitudes Index) From Screen to Week 25
NCT02085447 (22) [back to overview]Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Akathisia)
NCT02199743 (2) [back to overview]Cerebral Glutamate Levels
NCT02199743 (2) [back to overview]Brief Assessments of Cognition in Schizophrenia Scores (BACS)
NCT02203786 (6) [back to overview]Betting Behaviour in Laboratory-based Slot Machine Game
NCT02203786 (6) [back to overview]Diastolic Blood Pressure (DBP)
NCT02203786 (6) [back to overview]Cognitive Task Performance
NCT02203786 (6) [back to overview]Winnings on Slot Machine Upon Completion of Game
NCT02203786 (6) [back to overview]Subjective Reinforcement Self-report Scales
NCT02203786 (6) [back to overview]Speed of Play on Slot Machine Game
NCT02213900 (4) [back to overview]Efficacy of Low-dose Haloperidol in Reducing Days With Delirium
NCT02213900 (4) [back to overview]Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay
NCT02213900 (4) [back to overview]Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up
NCT02213900 (4) [back to overview]Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence
NCT02343575 (5) [back to overview]Time to Delirium Resolution
NCT02343575 (5) [back to overview]Use of as Needed Anti-psychotic Agent
NCT02343575 (5) [back to overview]Length of Hospital Stay
NCT02343575 (5) [back to overview]Side Effects From Medications
NCT02343575 (5) [back to overview]Intensity of Delirium as Measured by the Intensive Care Delirium Screening Checklist (ICDSC) Delirium Severity Scale
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
NCT02431702 (31) [back to overview]Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by Clinician-Rated Dimensions of Psychosis Symptom Severity Scale (CRDPSS)
NCT02431702 (31) [back to overview]Part-2 (Disease Progression): Time to First Treatment Failure
NCT02431702 (31) [back to overview]Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Time to First Treatment Failure
NCT02431702 (31) [back to overview]Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score
NCT02431702 (31) [back to overview]Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score
NCT02431702 (31) [back to overview]Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI)
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Adjusted Intracortical Myelin (ICM) Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)
NCT02431702 (31) [back to overview]Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain
NCT02972502 (1) [back to overview]Change in Pain Score According to the Numeric Pain Intensity Scale
NCT03019887 (1) [back to overview]Number of Participants With Relapse
NCT03021486 (11) [back to overview]Perceived Comfort Level as Assessed by Caregiver
NCT03021486 (11) [back to overview]Edmonton Expression Assessment System, ESAS
NCT03021486 (11) [back to overview]Change in Delirium Experience Questionnaire
NCT03021486 (11) [back to overview]Percentage of Participants With RASS Score -2 to 0
NCT03021486 (11) [back to overview]Number of Participants With RASS Score of >=1
NCT03021486 (11) [back to overview]Memorial Delirium Assessment Scale (MDAS)
NCT03021486 (11) [back to overview]Change in Richmond Agitation Sedation Score (RASS) (0-24h)
NCT03021486 (11) [back to overview]Udvalg for Kliniske Undersogelser, UKU
NCT03021486 (11) [back to overview]Perceived Comfort Level as Assessed by Nurse
NCT03021486 (11) [back to overview]Pattern of Medication Use
NCT03021486 (11) [back to overview]Change in RASS Score (0-30 Minutes)
NCT03639558 (4) [back to overview]Time Noted Where Important Adverse Effects Occurred Post Intervention
NCT03639558 (4) [back to overview]Number of Participants According to the Time Taken for Aggressive Behaviour to Change to Calm and Tranquil
NCT03639558 (4) [back to overview]Time Patient Was Placed in Straitjacket/Restraint Post Intervention Treatment
NCT03639558 (4) [back to overview]Time Taken for Patient to Fall Asleep Post Intervention
NCT04327843 (11) [back to overview]ESRS-A Parkinsonism
NCT04327843 (11) [back to overview]ESRS-A Dyskinesia
NCT04327843 (11) [back to overview]ESRS-A Akathisia
NCT04327843 (11) [back to overview]Drug Attitude Inventory (DAI)
NCT04327843 (11) [back to overview]Clinical Global Impressions (CGI)
NCT04327843 (11) [back to overview]Brief Psychiatric Rating Scale (BPRS)
NCT04327843 (11) [back to overview]Body Mass Index
NCT04327843 (11) [back to overview]Tablets Routine Questionnaire (TRQ)
NCT04327843 (11) [back to overview]Social and Occupational Functioning Scale (SOFAS)
NCT04327843 (11) [back to overview]Long-Acting Injectable Adherence (LAI Adherence): Count of Participants Who Received All LAI Injections:
NCT04327843 (11) [back to overview]ESRS-A Dystonia
NCT04411940 (6) [back to overview]Time to Maximum Concentration (Tmax)
NCT04411940 (6) [back to overview]Terminal Elimination Rate Constant (λz)
NCT04411940 (6) [back to overview]Concentration Maximum (Cmax)
NCT04411940 (6) [back to overview]Area Under the Curve(0-∞) (AUC(0-∞))
NCT04411940 (6) [back to overview]Area Under the Curve (0-t) (AUC(0-t))
NCT04411940 (6) [back to overview]Apparent Terminal Elimination Half-Life (t½)
NCT04411953 (6) [back to overview]Time to Maximum Concentration (Tmax)
NCT04411953 (6) [back to overview]Terminal Elimination Rate Constant (λz)
NCT04411953 (6) [back to overview]Terminal Elimination Half-life (t½)
NCT04411953 (6) [back to overview]Concentration Maximum (Cmax)
NCT04411953 (6) [back to overview]Area Under the Curve(0-∞) (AUC(0-∞))
NCT04411953 (6) [back to overview]Area Under the Curve (0-t) (AUC(0-t))
NCT04715230 (12) [back to overview]Time Course and Degree of Normalization of Agitation
NCT04715230 (12) [back to overview]Time Course and Degree of Normalization of Temperature
NCT04715230 (12) [back to overview]Time Course and Degree of Normalization of Temperature
NCT04715230 (12) [back to overview]Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time
NCT04715230 (12) [back to overview]Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time
NCT04715230 (12) [back to overview]Number of Patients With Treatment-related AEs as Measured by Physical Examinations
NCT04715230 (12) [back to overview]Number of Patients With Treatment-related Adverse Events (AEs) as Measured by Vital Signs
NCT04715230 (12) [back to overview]Time Course and Degree of Normalization of Agitation
NCT04715230 (12) [back to overview]Number of Patients With Treatment-related AEs as Measured by Clinical Laboratory Testing
NCT04715230 (12) [back to overview]Number of Patients With Treatment-related AEs as Measured by Electrocardiogram
NCT04715230 (12) [back to overview]Time Course and Degree of Normalization of Agitation
NCT04715230 (12) [back to overview]Length of Patient Stay in the ED

Change From Baseline to the End of the Double-blind Treatment in the BPRS (Brief Psychiatric Rating Scale)Total Score

"The BPRS consists of 18 ordered categorical items (from not present to extremely severe, on a 1- to 7-point scale), each developed to assess patient symptomatology in a relatively discrete symptom area. The BPRS will be extracted from the PANSS by adding the scores of the 18 items (P2 to P7, N1, N2, and G1 to G10) of the PANSS and will not be assessed separately. The minimum score on the BPRS is 18 and the maximum is 126. The higher number indicates a worsening of schizophrenia." (NCT00044044)
Timeframe: Baseline and 6 weeks

Interventionunits on a scale (Least Squares Mean)
20 mg-5.0
40 mg-5.2
80 mg-8.0
10 mg Haloperidol-9.8
Placebo-7.9

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Change From Baseline to the End of the Double-blind Treatment in the CGI-S (Clinical Global Impression of Severity) Scores

The CGI Severity (CGI-S) assesses the severity of illness of the patient relative to the particular population on a 7-point scale ranging from 1 (normal, not at all ill) to 7 (among the most extremely ill patients). (NCT00044044)
Timeframe: Baseline and 6 weeks

Interventionunits on a scale (Least Squares Mean)
20 mg-0.5
40 mg-0.4
80 mg-0.8
10 mg Haloperidol-0.8
Placebo-0.7

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Change From Baseline to the End of the Double-blind Treatment in the PANSS (Positive and Negative Syndrome Scale) Scores

The PANSS Positive and Negative Syndrome Scale)is a 30-item scale that evaluates positive, negative, and other symptoms in patients with schizophrenia. Each item is rated on a 7-point scale that ranges from 1 (absent) to 7 (extreme). Scores range from 30-210 with higher scores representing a worsening of schizophrenia. (NCT00044044)
Timeframe: Baseline and 6 weeks

Interventionunits on a scale (Least Squares Mean)
20 mg-7.1
40 mg-7.2
80 mg-13.6
10 mg Haloperidol-16.0
Placebo-12.3

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Change From Baseline to the End of the Double-blind Treatment in the MADRS (Montgomery Asberg-Depression Scale) Scores

The MADRS is a 10-item rating scale that assesses apparent and reported sadness, lassitude, pessimism, inner tension, suicidality, reduced sleep or appetite, difficulty in concentration, and lack of interest. Each item is scored on a 7-point scale with a score of 0 reflecting no symptoms and a score of 6 reflecting symptoms of maximum severity. (NCT00044044)
Timeframe: Baseline and 6 weeks

Interventionunits on scale (Least Squares Mean)
20 mg-1.3
40 mg-1.1
80 mg-2.5
10 mg Haloperidol-2.7
Placebo-1.9

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Change From Baseline to 6 Week Endpoint in Young Mania Rating Scale (YMRS)

The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. (NCT00129220)
Timeframe: Baseline, 6 weeks

Interventionunits on a scale (Mean)
Olanzapine-16.0
Haloperidol-14.7
Placebo-10.1

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Percentage of Participants Who Switched to Symptomatic Depression

Switch to symptomatic depression was defined as HAMD-17 total score ≥13 at any time in the participants with HAMD-17 total scores ≤7 at baseline. The 17-item HAMD measures depression severity. Each item was evaluated and scored using either a 5-point scale (e.g. absent, mild, moderate, severe, very severe) or a 3-point scale (e.g. absent, mild, marked). The total score of HAMD-17 may range from 0 (normal) to 52 (severe). (NCT00129220)
Timeframe: 3 weeks, 6 weeks

,,
Interventionpercentage of participants (Number)
3-Week Symptomatic Depression Rate6-Week Symptomatic Depression Rate
Haloperidol16.716.7
Olanzapine2.42.4
Placebo1.32.7

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Maximum Change From Baseline During 6-Week Period in Drug-Induced Extrapyramidal Symptoms Scale (DIEPSS) Total Score

Drug Induced Extra-Pyramidal Symptoms Scale (DIEPSS) is a scale used to evaluate the severity of drug induced extra-pyramidal symptoms occurring during antipsychotic drug treatment. Scale consists of 8 individual symptom scales with scores ranging from 0 (none/normal) to 4 (severe). The total score is the sum of the 8 item scores, for a total range of 0 (normal) to 32 (severe). (NCT00129220)
Timeframe: Baseline to 6 weeks

,,
Interventionunits on a scale (Mean)
BaselineMaximum Change from Baseline
Haloperidol0.502.70
Olanzapine0.200.70
Placebo0.300.09

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Change From Baseline to 3 Week and 6 Week Endpoints in the Positive Subscore of Positive and Negative Syndrome Scale (PANSS)

Assesses positive symptoms associated with schizophrenia. 7 items make up the Positive scale (ex. delusions, conceptual disorganization, and hallucinatory behavior). Each item is rated on a scale from 1 (symptom not present) to 7 (symptoms extremely severe). Total Positive Subscale scores range from 7 to 49. For this study, the score was converted to 0 to 6 for each item range; hence, the total positive subscale score ranges from 0 to 42. (NCT00129220)
Timeframe: Baseline, 3 weeks, 6 weeks

,,
Interventionunits on a scale (Mean)
3-Week Change6-Week Change
Haloperidol-1.8-1.6
Olanzapine-1.8-2.2
Placebo-0.0-0.3

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Change From Baseline to 3 Week Endpoint in Young Mania Rating Scale (YMRS) Total Score

The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. (NCT00129220)
Timeframe: Baseline, 3 weeks

Interventionunits on a scale (Mean)
Olanzapine-12.6
Haloperidol-14.3
Placebo-6.8

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Change From Baseline to 6 Week Endpoint in Clinical Global Impressions - Bipolar Version (CGI-BP), Overall Severity of Illness

A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of overall mood symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients). (NCT00129220)
Timeframe: Baseline, 6 weeks

Interventionunits on a scale (Mean)
Olanzapine-1.6
Haloperidol-1.3
Placebo-0.9

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Change From Baseline to 3 Week and 6 Week Endpoints in Clinical Global Impression - Bipolar Version (CGI-BP) Mania Subscale

A global rating scale for severity of patients adapted to bipolar disorder. Measures severity of the patient's overall severity of manic symptoms on a scale of 1 (normal, not at all ill) to 7 (among the most extremely ill patients). (NCT00129220)
Timeframe: Baseline, 3 weeks, 6 weeks

,,
Interventionunits on a scale (Mean)
3-Week Change6-Week Change
Haloperidol-1.7-1.9
Olanzapine-1.2-1.7
Placebo-0.6-1.0

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Percentage of Participants Who Switched to Syndromic Depression

Switch to syndromic depression was operationally defined by meeting both of the following criteria: At baseline, the symptoms did not meet the criteria for a mixed episode based on the Diagnostic and Statistical Manual of Mental Disorders Fourth Edition, Text Revision (DSM-IV-TR). The critiera were met for a Major Depressive Episode (MDE), at any point after randomization, based on DSM-IV-TR. Rather than the 2-week period required for an MDE in the DSM-IV-TR, the patient had to meet the criteria of an MDE for at least 7 consecutive days (during Weeks 1 through 6). (NCT00129220)
Timeframe: 3 weeks, 6 weeks

,,
Interventionpercentage of participants (Number)
3-Week Syndromic Depression Rate6-Week Syndromic Depression Rate
Haloperidol5.35.3
Olanzapine0.01.1
Placebo0.00.0

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Response Rate of Manic Symptoms at 3 Weeks and 6 Weeks

Participants who had 50 percent or more decrease from the baseline in YMRS total scores were defined as a responder. The YMRS is an 11-item scale that measures the severity of manic episodes. Four items are rated on a scale from 0 (symptom not present) to 8 (symptom extremely severe). The remaining items are rated on a scale from 0 (symptom not present) to 4 (symptom extremely severe). The YMRS total score ranges from 0 to 60. Response Rate (percent) = number of patients meeting response criterion for manic symptom divided by number of patients in treatment arm, multiplied by 100. (NCT00129220)
Timeframe: Baseline, 3 weeks, 6 weeks

,,
Interventionpercentage of participants (Number)
3 Week Response Rate6 Week Response Rate
Haloperidol65.065.0
Olanzapine51.067.3
Placebo44.355.7

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Remission Rate of Bipolar Disorder (Olanzapine Versus Haloperidol)

Remission of bipolar disorder was defined as completing the 6-week period with meeting the criteria for Young Mania Rating Scale (YMRS) total score of 12 or less and 17-Item Hamilton Depression Rating Scale (HAMD-17) total scores of 7 or less at Week 6. YMRS is an 11-item scale measuring severity of manic episodes; total score ranges = 0 (normal) to 60 (severe). The 17-item HAMD measures depression severity; total score ranges = 0 (normal) to 52 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100. (NCT00129220)
Timeframe: 6 weeks

Interventionpercentage of participants (Number)
Olanzapine44.2
Haloperidol20.0

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Remission Rate of Manic Symptoms at 3 Weeks and 6 Weeks

Participants who had a YMRS total score of 12 or less were considered to be in remission of manic symptoms. YMRS is an 11-item scale that measures severity of manic episodes; total score ranges from 0 (normal) to 60 (severe). Remission Rate (percent) = number of patients meeting remission criteria divided by number of patients in treatment arm, multiplied by 100. (NCT00129220)
Timeframe: 3 weeks, 6 weeks

,,
Interventionpercentage of participants (Number)
3-Week Remission Rate6-Week Remission Rate
Haloperidol65.060.0
Olanzapine47.163.5
Placebo41.252.6

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Median Survival Time of Effect

"Kaplan-Meier estimate of median time to loss of effect in subjects who had >=30% decrease from baseline in PANSS score at the end of the original trial (NCT00156104) preceding the long-term extension.~PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity.~Loss of effect = increase in total PANSS >=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score >=6; discontinuation for lack of efficacy." (NCT00156065)
Timeframe: 52 Weeks

InterventionDays (Median)
Placebo/Asenapine57
Asenapine/Asenapine31
Haloperidol/Haloperidol85

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Loss of Effect Over Time

"Loss of effect in subjects who had >=30% decrease from baseline in Positive and Negative Syndrome Scale (PANSS) score at the end of the original trial (NCT00156104) preceding the long-term extension.~PANSS is a 30-item clinician-rated instrument for assessing symptoms of schizophrenia. Scores range from 30-210; higher scores indicate greater severity.~Loss of effect = increase in total PANSS >=30% from start of current study; subjective worsening of schizophrenia/request for dose increase; Clinical Global Impressions of Severity of Illness score >=6; discontinuation for lack of efficacy." (NCT00156065)
Timeframe: Throughout the 52 weeks of the trial.

,,
InterventionParticipants (Number)
<=Week 1>Week 1 to Week 2>Week 2 to Week 4>Week 4 to Week 8>Week 8 to Week 12>Week 12 to Week 16>Week 16 to Week 20>Week 20 to Week 24>Week 24 to Week 28>Week 28 to Week 32>Week 32 to Week 36>Week 36 to Week 40>Week 40 to Week 44>Week 44 to Week 48>Week 48 to Week 52
Asenapine/Asenapine15414311131300005
Haloperidol/Haloperidol643114100101002
Placebo/Asenapine731323000100002

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ICU Length of Stay

(NCT00300391)
Timeframe: Daily

Interventionday (Median)
Delirium9
Persistent Coma6
No Delirium7

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Duration of Mechanical Ventilation

(NCT00300391)
Timeframe: daily

Interventionday (Median)
Delirium4.5
Persistent Coma6
No Delirium4

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90-day All-cause Mortality

(NCT00300391)
Timeframe: 90 Days from enrollment in study

InterventionParticipants (Count of Participants)
Delirium4
Persistent Coma2
No Delirium1

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28-day All-cause Mortality

(NCT00300391)
Timeframe: Daily

InterventionParticipants (Count of Participants)
Delirium4
Persistent Coma2
No Delirium1

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21 Item Hamilton Depression Rating Scale

The scale rates 21 symptoms related to major depression. A total score of 0-7 is considered to be normal, scores of 20 or higher indicate moderately severe depression. Total scores range from a minimum of 0(not ill) to a maximum of 64 (severely ill). (NCT00340379)
Timeframe: 12 week

InterventionUnits on Hamilton Depression Scale (Mean)
Ziprasidone13.6
Sertraline/Haloperidol11.0

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Brief Psychiatric Rating Scale at 12 Weeks

A rating scale used to measure psychiatric symptoms such as depression, anxiety, hallucinations and unusual behaviour. Each symptom is rated 1-7 and in this version a total of 24 symptoms are scored. Thus the total range of scores is from a minimum of 24 to a maximum of 168. Lower scores are considered better, so the minimum total score of 24 indicates someone with no psychiatric symptoms, while any score over 40 is considered at least moderately severe, with only the most severely ill patients scoring over 60. (NCT00340379)
Timeframe: 12 weeks

Interventionunits on a Psychiatric Rating scale (Mean)
Ziprasidone28.7
Sertraline/Haloperidol25.8

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Clinical Global Impression Improvement Scale

A 7 point scale that requires the clinician to assess how much the patient's illness has improved or worsened relative to a baseline state at the beginning of the intervention. and rated as: 1, very much improved; 2, much improved; 3, minimally improved; 4, no change; 5, minimally worse; 6, much worse; or 7, very much worse. Overall the scale goes from a minimum of 1(very much improved) to a maximum of 7(very much worse). (NCT00340379)
Timeframe: 12 weeks

Interventionunits on a Clinical Impressions Scale (Mean)
Ziprasidone3.1
Sertraline/Haloperidol2.5

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Change in the PANSS-EC Score Among Participants From Baseline to 2 Hours After Administration of the Medication.

The PANSS-EC is the Positive and Negative Syndrome Score - Excited Component, which includes 5 items (excitement, hostility, tension, uncooperative, poor impulse control), which are rated from 1 (not present) to 7 (extremely severe); scores range from 5 to 35; mean scores ≥ 20 clinically correspond to severe agitation. This set of items detects differences between drug and placebo when evaluating acute agitation and aggression in psychiatric patients with different psychiatric pathologies (Montoya, A; Villadares, A; Lizan, L, et al., 2011). (NCT00457366)
Timeframe: Two hours

Interventionscore on a scale (Least Squares Mean)
Cocktail-11.0
Quetiapine-11.5

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Percentage of Slow Wave Sleep

The primary variable is the change of percentage of slow wave sleep (SWS) from baseline to the 28th day (LOCF). (NCT00642369)
Timeframe: 28 days

,
Interventionpercentage of slow wave sleep (Mean)
percentage at baselinepercentage on the 28th daypercentage change from baseline to the 28th day
Haloperidol8.66.3-2.3
Quetiapine Fumarate10.59.2-1.4

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Percentage of Rapid Eye Movement Sleep

The primary variable is the change of the percentage of rapid eye movement (REM)sleep from baseline to the 28th day (LOCF). (NCT00642369)
Timeframe: 28 days

,
Interventionpercentage of rapid eye movement sleep (Mean)
percentage at baselinepercentage on the 28th daypercentage change from baseline to the 28th day
Haloperidol13.210.4-2.7
Quetiapine Fumarate12.616.43.9

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Part 2: PANSS Total Score at Day 14

The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal). For each item, symptom severity was rated on a 7-point scale, from 0=absent to 6=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 0 to 180 with a higher score indicating greater severity of symptoms. Although the PANSS is traditionally scored with a range of 30-210, with a score of absent = 1 (for each item), for this analysis the range was set from 0-180, with a score of absent = 0 (for each item). (NCT00693472)
Timeframe: Day 14 of Part 2

InterventionScore on a scale (Mean)
Part 2: Preladenant43.5000
Part 2: Standard of Care27.75

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Part 2: Number of Participants Who Were Treatment Failures

Incidence of treatment failure is reported as the number of participants who were treatment failures. A treatment failure is defined as the failure to achieve at least a 1 point reduction from baseline in BAS score at 24 to 26 hours following study treatment. The BAS is scored as follows: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness are rated on a 4-point scale from 0 - 3 and are summed yielding a total score ranging from 0 (no akathisia) to 9 (severe akathisia). (NCT00693472)
Timeframe: Up to 14 days

InterventionParticipants (Number)
Part 2: Preladenant4
Part 2: Standard of Care1

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Part 2: Mean GCI at Day 14

The GCI was administered to assess whether any deterioration is due to akathisia or uncontrolled psychoses. Score on a scale +2 to -2 (+2 represents much improvement, +1 some improvement, 0 no change, -1 some worsening, and -2 much worsening). (NCT00693472)
Timeframe: Day 14 of Part 2

InterventionScore on a scale (Mean)
Part 2: Preladenant0.6667
Part 2: Standard of Care2.0000

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Part 1: Mean Global Clinical Impression at Day 14

Global clinical impression (GCI) was administered to assess whether any deterioration is due to akathisia or uncontrolled psychoses. Score on a scale +2 to -2 (+2 represents much improvement, +1 some improvement, 0 no change, -1 some worsening, and -2 much worsening). (NCT00693472)
Timeframe: Day 14 of Part 1

InterventionScore on a scale (Mean)
Part 1: Preladenant0.9231
Part 1: Placebo1.7778

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Part 1: Number of Participants With Akathisia

Incidence of akathisia is reported as the number of participants who experienced akathisia. Akathisia is defined as a score of 3 on the Barnes akathisia scale (BAS) for 3 consecutive intervals or an akathisia score (BAS) of ≥4 for any single day, or the use of a rescue medication within 13 days of initiating treatment with haloperidol and preladenant. The BAS is scored as follows: objective akathisia, subjective awareness of restlessness and subjective distress related to restlessness are rated on a 4-point scale from 0 - 3 and are summed yielding a total score ranging from 0 (no akathisia) to 9 (severe akathisia). (NCT00693472)
Timeframe: Up to 13 days

InterventionParticipants (Number)
Part 1: Preladenant0
Part 1: Placebo0

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Part 1: Mean Positive and Negative Symptom Scale for Schizophrenia (PANSS) Total Score at Day 14

"The PANSS is a 30-item clinician-rated instrument for assessing the symptoms of schizophrenia. It consists of 3 subscales: positive subscale (7 items), negative subscale (7 items), and general psychopathology subscale (16 items). Positive symptoms refer to an excess or distortion of normal mental status (e.g., delusions). Negative symptoms represent a diminution or loss of normal functions (e.g., emotional withdrawal).~For each item, symptom severity was rated on a 7-point scale, from 0=absent to 6=extreme. The PANSS total score for each participant was calculated as the sum of the rating assigned to each of the 30 PANSS items, and ranged from 0 to 180 with a higher score indicating greater severity of symptoms. Although the PANSS is traditionally scored with a range of 30-210, with a score of absent = 1 (for each item), for this analysis the range was set from 0-180, with a score of absent = 0 (for each item)." (NCT00693472)
Timeframe: Day 14 of Part 1

InterventionScore on a scale (Mean)
Part 1: Preladenant38.4615
Part 1: Placebo36.3333

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Change From Baseline in Brief Psychiatric Rating Scale (BPRS) Total Scores at 72 Hours

BPRS is an 18-item clinician rated scale with 11 general symptom items, 5 positive-symptom items, and 2 negative symptom items scored on a 7-point scale (1=not present and 7=extremely severe), with higher score indicating greater severity of symptom. Total possible score range=18 to 126. Change: score at final visit minus score at baseline. (NCT00723606)
Timeframe: Baseline, 72 hours

Interventionscores on a scale (Least Squares Mean)
Ziprasidone-17.32
Haloperidol-18.44

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Clinical Global Impression-Improvement (CGI-I) Score at 72 Hours

CGI-I: 7-point clinician rated scale ranging from 1 (very much improved) to 7 (very much worse). Improvement is defined as a score of 1 (very much improved), 2 (much improved), or 3 (minimally improved) on the scale. Higher score = more affected. (NCT00723606)
Timeframe: 72 hours

Interventionscores on a scale (Least Squares Mean)
Ziprasidone2.52
Haloperidol2.55

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Change From Baseline in Behavioral Activity Rating Scale (BARS) at 72 Hours

BARS measures the degree of agitated behavior using a 7-point scale describing increasing levels of activity (1 =difficult or unable to rouse; 2 = asleep but responds normally to verbal or physical contact; 3 = drowsy, appears sedated; 4 = quiet and awake [normal level of activity]; 5 = signs of overt [physical or verbal] activity, calms down with instructions; 6 = extremely or continuously active, not requiring restraint; 7 = violent, requires restraint. (NCT00723606)
Timeframe: Baseline, 72 hours

Interventionscores on a scale (Least Squares Mean)
Ziprasidone-0.93
Haloperidol-1.06

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BPRS Agitation Subscale Response at 72 Hours

The BPRS agitation subscale score was composed of 4 questions (questions 2, 6, 10, 17). The BPRS agitation subscale score was obtained by summing the relevant individual items. Total possible score range=4 to 28. A response was defined as a > 30 percent reduction from baseline in BPRS agitation subscale score. (NCT00723606)
Timeframe: 72 hours

,
Interventionparticipants (Number)
ResponseNo Response
Haloperidol15529
Ziprasidone14939

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Change From Baseline in Clinical Global Impressions Severity (CGI-S) Score at 72 Hours

CGI-S: 7-point clinician rated scale to assess severity of subject's current illness state; range: 1 (normal - not ill at all) to 7 (among the most extremely ill patients). Higher score = more affected. Change: score at observation minus score at baseline. (NCT00723606)
Timeframe: Baseline, 72 hours

Interventionscores on a scale (Least Squares Mean)
Ziprasidone-1.18
Haloperidol-1.21

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Change From Baseline in BPRS Agitation Subscale Score at 72 Hours

The BPRS agitation subscale score was composed of 4 questions (questions 2, 6, 10, 17). The BPRS agitation subscale score was obtained by summing the relevant individual items. Total possible score range=4 to 28. Change: score at final visit minus score at baseline. (NCT00723606)
Timeframe: Baseline, 72 hours

Interventionscores on a scale (Least Squares Mean)
Ziprasidone-6.97
Haloperidol-7.45

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The Change of the Positive and Negative Symptom Scale Excited Component (PANSS-EC) Score From Baseline to 120 Minutes After First Injection

The primary efficacy measure was PANSS-EC, which was derived from the PANSS by its originators using a principal-components factor analysis, and includes the items of tension, uncooperativeness, hostility, poor impulse control and excitement.22 The score of each item ranges from 1 (normal) to 7 (most severe), with a total sum score ranging from 5 to 35. The changes in PANSS-EC from baseline to 2 hours after the first injection were compared. (NCT00797277)
Timeframe: from baseline to 120 minutes after first injection

Interventionunits on a scale (Mean)
1. IM Olanzapine-10.2
2. IM Haloperidol Plus Lorazepam-9.9

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Change of the Agitation-Calmness Evaluation Scale (ACES) Score From Baseline to 120 Minutes After 1st Injection

Agitation was further assessed by the Agitation Calmness Evaluation Scale (ACES) (Copyright 1998, Eli Lilly and Company), a single-item scale developed by Eli Lilly and Company on which 1 indicates marked agitation; 2, moderate agitation; 3, mild agitation; 4, normal; 5, mild calmness; 6, moderate calmness; 7, marked calmness; 8, deep sleep; and 9, unable to be aroused. (NCT00797277)
Timeframe: from baseline to 120 minutes after first injection

Interventionunits on a scale (Mean)
1. IM Olanzapine2.14
2. IM Haloperidol Pus Lorazepam2.23

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Mortality

(NCT00842608)
Timeframe: ICU, in-hospital, 30-days post hospitalization

InterventionParticipants (Count of Participants)
Haloperidol Eligible Intervention20
Haloperidol Eligible Usual Care32
Haldol-Ineligible Arm11
Haldol Ineligible Usual Care8

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Hospital Length of Stay Post Randomization

(NCT00842608)
Timeframe: Participants were followed for the duration of hospital stay, an average of 11 days

Interventiondays (Mean)
Haloperidol Eligible Intervention20.2
Haloperidol Eligible Usual Care18.6
Haldol-Ineligible Arm18.8
Haldol Ineligible Usual Care14.9

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Days Free of Delirium and Coma

(NCT00842608)
Timeframe: Admission through day 8 of stay

Interventiondays (Median)
Haloperidol Eligible Intervention4
Haloperidol Eligible Usual Care5
Haldol-Ineligible Arm4
Haldol Ineligible Usual Care5

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Changes in Psychiatric Symptoms

The Positive and Negative Syndrome Scale measures the core symptoms associated with schizophrenia. The measure includes 30 items rated from 1=absent to 7=extremely severe. Full range of scores is 30-210 with higher scores representing more severe illness. Reductions in symptoms over time represent improvement. (NCT01136772)
Timeframe: Baseline to 6 months

InterventionUnits on a scale (Mean)
Paliperidone Palmitate-6.87
Haloperidol Decanoate-6.40

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Efficacy Failure

Efficacy failure as indicated by psychiatric hospitalization, need for crisis intervention, clinical decision that oral antipsychotic medication cannot be discontinued in less than eight weeks, a clinical decision to discontinue the medication due to inadequate benefit, or the ongoing or repeated need for adjunctive antipsychotic medication. (NCT01136772)
Timeframe: 24 months

Interventionparticipants (Number)
Paliperidone Palmitate49
Haloperidol Decanoate47

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Treatment Satisfaction as Measured by the Participant Acceptability and Satisfaction Questionnaire at 25 Weeks

"Satisfaction will be measured by a seven item inventory taken by the participant.~Scale ranges from 1 (Strongly Agree) to 5 (Strongly Disagree). Lower scores indicate better outcomes, while higher scores indicate worse outcomes. The highest possible score is 35." (NCT01152697)
Timeframe: 25 weeks

Interventionunits on a scale (Mean)
Patient Noncompliance12.12

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Treatment Satisfaction as Measured by the Participant Acceptability and Satisfaction Questionnaire at 12 Months

"Satisfaction will be measured by a seven item inventory taken by the participant.~Scale ranges from 1 (Strongly Agree) to 5 (Strongly Disagree). Lower scores indicate better outcomes, while higher scores indicate worse outcomes. The highest possible score is 35." (NCT01152697)
Timeframe: 12 months

Interventionunits on a scale (Mean)
Patient Noncompliance12.33

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Treatment Adherence Behavior Score as Measured by the Morisky Medication Rating Scale at 12 Months

Four item inventory taken by participant with Scale Range: 0-4. Lower scores indicate better outcomes. (NCT01152697)
Timeframe: 12 months

Interventionunits on a scale (Mean)
Patient Noncompliance1.33

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Frequency of Health Resource Use in the Past 3 Months as Measured at 25 Weeks

The frequency of health resource use will be measured through interview of the participant. (NCT01152697)
Timeframe: 25 weeks

Interventiondays (Mean)
Patient Noncompliance20.18

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Global Psychopathology as Measured by the Clinical Global Impressions (CGI) at 12 Months

"Global psychopathology will be measured with the Clinical Global Impressions (CGI) (Guy 1976) a widely used scale which evaluates illness severity on a 1 to 7 point continuum. Severity of illness ratings on the CGI have reported reliability scores ranging from 0.41-0.66 (Guy 1976) Lower scores indicate improved outcomes. Higher scores indicate worse outcomes.~Illness scale: 1 - 7 (1 = Normal/not at all ill ; 7 = Among the most extremely ill patients) Global improvement scale: 1 - 7 (1 = Very much improved ; 7 = Very much worse)" (NCT01152697)
Timeframe: 12 months

Interventionunits on a scale (Mean)
SeverityGlobal Improvement
Patient Noncompliance3.172.42

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Treatment Adherence Score as Measured at 12 Months

A total treatment adherence score will calculated as a proportion of medications taken as reported from the participant, and evidenced by pill counts and documented medication injections. (NCT01152697)
Timeframe: 12 months

InterventionPercentage of doses (Mean)
Past WeekPast Month
Patient Noncompliance28.656

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Change in Social and Occupational Functioning Scale (SOFAS) as Measured at 12 Months

Life and Work Functional status will be evaluated using the Social and Occupational Functioning Scale (SOFAS), which is derived from the GAF. The GAF is a 100-point single-item scale which measures global functioning of psychiatric patients and is widely utilized in clinical studies involving Seriously Mentally Ill patients (Jones 1995). The reliability of the GAF ranges from 0.62-0.82. Higher scores indicate improved outcomes. (NCT01152697)
Timeframe: Baseline-12 months

Interventionunits on a scale (Mean)
Baseline12 months
Patient Noncompliance45.3363.83

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Adherence Attitude Score as Measured by the Attitude Toward Medication Questionnaire (AMQ) at 12 Months

Nineteen item inventory taken by the participant with Scale Range:0-19. Lower scores indicate improved outcomes. (NCT01152697)
Timeframe: 12 months

Interventionunits on a scale (Mean)
Patient Noncompliance2.43

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Change in Social and Occupational Functioning Scale (SOFAS) as Measured at 25 Weeks

Life and Work Functional status will be evaluated using the Social and Occupational Functioning Scale (SOFAS), which is derived from the GAF (Global Assessment of Functioning). The GAF is a 100-point single-item scale which measures global functioning of psychiatric patients and is widely utilized in clinical studies involving Seriously Mentally Ill patients (Jones 1995). The reliability of the GAF ranges from 0.62-0.82. Higher scores indicate improved outcomes. (NCT01152697)
Timeframe: Baseline-25 weeks

Interventionunits on a scale (Mean)
BaselineWeek 25
Patient Noncompliance47.3558.65

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Change From Baseline in Adherence Attitude Score as Measured by the Attitude Toward Medication Questionnaire (AMQ) at 25 Weeks

Nineteen item inventory taken by the participant with Scale Range:0-19. Lower scores indicate improved outcomes. (NCT01152697)
Timeframe: Baseline-25 weeks

Interventionunits on a scale (Mean)
BaselineWeek 25
Patient Noncompliance6.634.47

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Change in Schizophrenia and Schizoaffective Disorder Symptom Severity Scale as Measured by the Positive and Negative Syndrome Scale (PANSS) at 25 Weeks

"The PANSS (Kay, Fiszbein, & Opler 1987) was created to assess both the positive and negative symptoms of schizophrenia such as hallucinations and emotional withdrawal, respectively. The scale rates 30 symptoms on a scale from 1 (absent) to 7 (extreme) and has been shown to limit bias between the assessment of positive and negative symptoms, providing a broad but balanced spectrum of the illness.~There are three subscales: positive symptoms, negative symptoms, general psychopathology. Potential responses to Items on all subscales range from 1 (absent) to 7 (extreme). Lower scores indicate lower symptoms and, therefore, better outcomes. Higher scores indicate more presence of symptoms and, therefore, worse outcomes.~Subscales are combined to produce a total score, which is summed from all of the subscales. Lower total scores indicate lower symptoms and, therefore, better outcomes. Higher total scores indicate more presence of symptoms and, therefore, worse outcomes." (NCT01152697)
Timeframe: Baseline-25 weeks

Interventionunits on a scale (Mean)
BaselineWeek 25
Patient Noncompliance46.3732.84

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Adherence Attitude Score as Measured by the Drug Attitude Inventory (DAI) at 12 Months

Ten item inventory taken by the participant with a Scale Range: 0-10. Higher scores indicate improved outcomes. (NCT01152697)
Timeframe: 12 months

Interventionunits on a scale (Mean)
Patient Noncompliance7.00

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Frequency of Health Resource Use Throughout Months 10, 11, and 12

The frequency of health resource use will be measured through interview of the participant. (NCT01152697)
Timeframe: Month 1-3, Month 10-12

Interventiondays (Mean)
3 Month12 Month
Patient Noncompliance19.3315.50

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Change in Serious Mental Illness Severity Score as Measured by the Brief Psychiatric Rating Scale (BPRS) at 25 Weeks

"The BPRS, developed by Overall and Gorham (1962), is a widely used, relatively brief scale that measures major psychotic and non-psychotic symptoms in individuals with SMI. The 18-item BPRS is well-validated and is perhaps the most researched instrument in psychiatry. Reliability coefficients are reported to be in the range of 0.56-0.87.~Scale Range: 18-126 Lower scores represent improved outcomes." (NCT01152697)
Timeframe: Baseline-25 weeks

Interventionunits on a scale (Mean)
BaselineWeek 25
Patient Noncompliance46.3732.84

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Change in Global Psychopathology as Measured by the Clinical Global Impressions (CGI) at 25 Weeks

"Global psychopathology will be measured with the Clinical Global Impressions (CGI) (Guy 1976) a widely used scale which evaluates illness severity on a 1 to 7 point continuum. Severity of illness ratings on the CGI have reported reliability scores ranging from 0.41-0.66 (Guy 1976) Lower scores indicate improved outcomes. Higher scores indicate worse outcomes.~Illness scale: 1 - 7 (1 = Normal/not at all ill ; 7 = Among the most extremely ill patients) Global improvement scale: 1 - 7 (1 = Very much improved ; 7 = Very much worse)" (NCT01152697)
Timeframe: Baseline-25 weeks

Interventionunits on a scale (Mean)
Baseline - SeverityWeek 25 - SeverityBaseline - Global ImprovementWeek 25 - Global Improvement
Patient Noncompliance4.763.243.432.14

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Change From Baseline in Treatment Adherence Score as Measured at 25 Weeks

A total treatment adherence score will calculated as a proportion of medications taken as reported from the participant, and evidenced by pill counts and documented medication injections. (NCT01152697)
Timeframe: Baseline-25 weeks

InterventionPercentage of doses (Mean)
Past weekPast month
Patient Noncompliance30.9110.10

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Change From Baseline in Treatment Adherence Behavior Score as Measured by the Morisky Medication Rating Scale at 25 Weeks

Four item inventory taken by participant with Scale Range: 0-4. Lower scores indicate improved outcomes. (NCT01152697)
Timeframe: Baseline-25 weeks

Interventionunits on a scale (Mean)
BaselineWeek 25
Patient Noncompliance2.311.19

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Change From Baseline in Adherence Attitude Score as Measured by the Drug Attitude Inventory (DAI) at 25 Weeks

Ten item inventory taken by the participant with a Scale Range: 0-10. Higher scores indicate improved outcomes. (NCT01152697)
Timeframe: Baseline-25 weeks

Interventionunits on a scale (Mean)
BaselineWeek 25
Patient Noncompliance7.478.07

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Side Effects

(NCT01204255)
Timeframe: 3 months

InterventionTotal number of side effects (Number)
Application of Lorazepam, Diphenhydramine, Haloperidol0

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Lorazepam, Diphenyhydramine, Haloperidol Absorption

Level of lorazepam absorption measured by the serum concentration of the drug (NCT01204255)
Timeframe: 4 hours

Interventionng/ml (Mean)
lorazepam absorptiondiphenhydramine absorptionhaloperidol absorption
Application of Lorazepam, Diphenhydramine, Haloperidol0.080

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Time to Hospital Discharge

"Days from randomization to successful hospital discharge, where successful indicates that discharge was followed by at least 48 hours alive." (NCT01211522)
Timeframe: 90 days

Interventiondays (Median)
Haloperidol13
Ziprasidone12
Placebo13

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Time to ICU Readmission

Days from first ICU discharge to next ICU readmission. (NCT01211522)
Timeframe: 90 days after first ICU discharge

Interventiondays (Median)
Haloperidol5
Ziprasidone5
Placebo4

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Time to Liberation From Mechanical Ventilation

"Days from randomization to successful liberation from mechanical ventilation, where successful indicates that liberation was followed by at least 48 hours alive and without reinitiation of invasive or noninvasive ventilation." (NCT01211522)
Timeframe: 30 days

Interventiondays (Median)
Haloperidol2
Ziprasidone3
Placebo3

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Delirium Duration

Duration of delirium during the intervention period (NCT01211522)
Timeframe: 14 days

Interventiondays (Median)
Haloperidol4
Ziprasidone4
Placebo4

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Mortality

Deaths within the specified timeframe (NCT01211522)
Timeframe: 30-day and 90-day

,,
InterventionParticipants (Count of Participants)
30-day mortality90-day mortality
Haloperidol5073
Placebo5063
Ziprasidone5365

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Delirium/Coma-free Days (DCFDs)

Defined as the number of days during the 14-day intervention period (beginning on the day of randomization) that the patient was alive and experienced neither delirium nor coma. (NCT01211522)
Timeframe: 14 days

Interventiondays (Median)
Haloperidol8
Ziprasidone8
Placebo7

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Number of Participants With Extrapyramidal Symptoms

(NCT01211522)
Timeframe: 14 days plus 4-day post-study drug period (if longer than 14 days)

InterventionParticipants (Count of Participants)
Haloperidol1
Ziprasidone1
Placebo1

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Number of Participants With Neuroleptic Malignant Syndrome

(NCT01211522)
Timeframe: 14 days plus 4-day post-study drug period (if longer than 14 days)

InterventionParticipants (Count of Participants)
Haloperidol0
Ziprasidone0
Placebo0

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Number of Participants With Torsades de Pointes

(NCT01211522)
Timeframe: 14 days plus 4-day post-study drug period (if longer than 14 days)

InterventionParticipants (Count of Participants)
Haloperidol2
Ziprasidone0
Placebo0

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Time to Final ICU Discharge

"Days from randomization to final, successful ICU discharge, where successful indicates that discharge was followed by at least 48 hours alive. ICU discharge is represented by readiness for ICU discharge indicated by a physician order for transfer to a lower level of care even if a bed availability problems prevent actual discharge from the ICU." (NCT01211522)
Timeframe: 90 days

Interventiondays (Median)
Haloperidol5
Ziprasidone6
Placebo5

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Sedation Change in Recovery Room

measurement of sedation change using a visual analogue scale (visual analogue scale; the minimum: 0 = widely awake and the maximum: 10 = maximally asleep) (NCT01639599)
Timeframe: postoperative 30, 60, 90, and 120 min

,,
Interventionscore on a scale (Mean)
postoperative 30 minpostoperative 60 minpostoperative 90 minpostoperative 120 min
Dexamethasone4.64.43.53.0
Dexamethasone + Haloperidol 2mg5.55.04.74.3
Dexamethasone, Haloperiol 1mg4.74.44.03.2

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Incidence of Postoperative Nausea and Vomiting

incidence of nausea, vomiting and requirement for rescue antiemetics (NCT01639599)
Timeframe: postoperative 24 hours

Interventionparticipants (Number)
Dexamethasone21
Dexamethasone, Haloperiol 1mg11
Dexamethasone + Haloperidol 2mg10

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Incidence of Extrapyramidal Symptoms

(NCT01639599)
Timeframe: postoperative 24 hours

Interventionparticipants (Number)
Dexamethasone0
Dexamethasone, Haloperiol 1mg0
Dexamethasone + Haloperidol 2mg0

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Incidence of Cardiac Arrhythmia

cardiac arrhythmia on continuous standard lead EKG monitoring (NCT01639599)
Timeframe: postoperative 2 hours

InterventionParticipants (Count of Participants)
Dexamethasone0
Dexamethasone, Haloperiol 1mg0
Dexamethasone + Haloperidol 2mg0

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Absolute Richmond Agitation-Sedation Scale Score at 8 Hour, Points

Absolute score of Richmond Agitation-Sedation Scale at 8 hr, points. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient. (NCT01949662)
Timeframe: 8 hours

Interventionscore on a scale (Mean)
Intervention Group (Lorazepam & Haloperidol)-2.5
Control Group (Placebo & Haloperidol)-0.7

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Number of Participants With Richmond Agitation-Sedation Scale Score >=1 Within 8 hr

Number of participants with Richmond Agitation-Sedation Scale score >=1 within 8 hr. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient. (NCT01949662)
Timeframe: Baseline to 8 hours

InterventionParticipants (Count of Participants)
Intervention Group (Lorazepam & Haloperidol)8
Control Group (Placebo & Haloperidol)22

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Change in Richmond Agitation-Sedation Scale Score From Baseline to 30 Min

Change in Richmond Agitation-Sedation Scale score from baseline to 30 min. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient. (NCT01949662)
Timeframe: Baseline to 30 minutes

Interventionscore on a scale (Mean)
Intervention Group (Lorazepam & Haloperidol)-3.6
Control Group (Placebo & Haloperidol)-1.6

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Change in Richmond Agitation-Sedation Scale Score (Baseline to 8 hr), Points

The primary outcome was change in Richmond Agitation-Sedation Scale score from baseline to 8 hours after treatment administration. Richmond Agitation-Sedation Score ranged from -5 (unarousable) to +4 (very agitated) , where 0 denotes a calm and alert patient. (NCT01949662)
Timeframe: Baseline to 8 hours

Interventionscore on a scale (Mean)
Intervention Group (Lorazepam & Haloperidol)-4.1
Control Group (Placebo & Haloperidol)-2.3

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Number of Participants Admitted to the Hospital After Emergency Department Visit

(NCT02057549)
Timeframe: 2 hours after study medication given

InterventionParticipants (Count of Participants)
Haloperidol Plus Conventional Therapy4
Conventional Therapy13

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Pain Relief as Indicated by Number of Participants Not Requesting Additional Pain Medication

(NCT02057549)
Timeframe: 1 hour after study medication given

InterventionParticipants (Count of Participants)
Haloperidol Plus Conventional Therapy11
Conventional Therapy5

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Pain Score as Measured by a Visual Analogue Scale (VAS)

The Visual Analogue Scale (VAS) ranges from 0-10, with 0 being the absence of pain and 10 the worst imaginable pain. (NCT02057549)
Timeframe: 1 hour after study medication given

Interventionunits on a scale (Mean)
Haloperidol Plus Conventional Therapy3.13
Conventional Therapy7.17

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Nausea Score as Measured by a Visual Analogue Scale (VAS)

The Visual Analogue Scale (VAS) ranges from 1-5, with 1 being minimal nausea and 5 being severe nausea. (NCT02057549)
Timeframe: 1 hour after study medication given

Interventionunits on a scale (Mean)
Haloperidol Plus Conventional Therapy1.83
Conventional Therapy3.39

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Emergency Department Length of Stay (EDLOS)

"The time frame starts from the moment of receiving the study drug to the time when the decision for final disposition is made. Usually after symptoms are controlled, patients are given a PO challenge (food or drink) in order to establish if they are OK to go home. If symptoms return, additional medications are given, the treatment is consider failed and they are admitted to the Hospital.~Patients will not be followed up if admitted to any service. The study ends when final disposition is made.~Patients follow up after final disposition is not part of the study and will not be done." (NCT02057549)
Timeframe: at the time the decision for final disposition is made (about 8 hours)

Interventionhours (Median)
Haloperidol Plus Conventional Therapy4.8
Conventional Therapy9

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Nausea Relief as Indicated by Number of Participants Not Requesting Additional Antiemetic Medication

(NCT02057549)
Timeframe: 1 hour after study medication given

InterventionParticipants (Count of Participants)
Haloperidol Plus Conventional Therapy11
Conventional Therapy13

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Nausea Score as Measured by a Visual Analogue Scale (VAS)

The Visual Analogue Scale (VAS) ranges from 1-5, with 1 being minimal nausea and 5 being severe nausea. (NCT02057549)
Timeframe: before study medication given

Interventionunits on a scale (Mean)
Haloperidol Plus Conventional Therapy4.53
Conventional Therapy4.11

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Pain Score as Measured by a Visual Analogue Scale (VAS)

The Visual Analogue Scale (VAS) ranges from 0-10, with 0 being the absence of pain and 10 the worst imaginable pain. (NCT02057549)
Timeframe: before study medication given

Interventionunits on a scale (Mean)
Haloperidol Plus Conventional Therapy8.50
Conventional Therapy8.28

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Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Dyskinesia) From Screen to Week 25

For the subjective examination scoring is on a 4-point scale (0=Absent;1=Mild, 2=Moderate, 3=Severe). The evaluator takes into account the verbal report of the patient on: 1) the frequency and duration of the symptom during the day; 2) the number of days the symptom was present during the last week; and, 3) the subjective evaluation of the intensity of the symptom by the patient. Score for TD, ranging from 0 to 42, is based on the sum of all seven items in the TD objective examination. Higher scores indicate more severe symptomology. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L1.4

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Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Dystonia) From Screen to Week 25

For the subjective examination scoring is on a 4-point scale (0=Absent;1=Mild, 2=Moderate, 3=Severe). The evaluator takes into account the verbal report of the patient on: 1) the frequency and duration of the symptom during the day; 2) the number of days the symptom was present during the last week; and, 3) the subjective evaluation of the intensity of the symptom by the patient. The score for dystonia ranges from 0 to 60 (10 items), and is formed by including both acute and chronic dystonia, based on the dystonia examination. Higher scores indicate more severity. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L0.0

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Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Parkinsonism) From Screen to Week 25

For the subjective examination scoring is on a 4-point scale (0=Absent;1=Mild, 2=Moderate, 3=Severe). The evaluator takes into account the verbal report of the patient on: 1) the frequency and duration of the symptom during the day; 2) the number of days the symptom was present during the last week; and, 3) the subjective evaluation of the intensity of the symptom by the patient. The score for Parkinsonism (including akathisia), ranges from 0 to 102 (17 items), and is based on all items of the Parkinsonism examination: tremor (0-48), gait and posture (0-6), postural stability (0-6), rigidity (0-24), expressive automatic movements (0-6), bradykinesia (0-6), akathisia (0-6). Higher scores indicate more severity. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L0.0

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Change in Hospitalizations (Medical) in the Past 6 Months From Screen and Week 25

Change in number of psychiatric hospitalizations from the past 6 months from Screen and Week 25. This is calculated by subtracting the number of psychiatric hospitalizations at screen from the number of psychiatric hospitalizations at week 25. (NCT02085447)
Timeframe: Screen, Week 25

Interventionhospital visits (Mean)
CAE-L.2

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Change in Hospitalizations (Psychiatric) in the Past 6 Months From Screen and Week 25

Change in number of psychiatric hospitalizations from the past 6 months from Screen and Week 25. This is calculated by subtracting the number of psychiatric hospitalizations at screen from the number of psychiatric hospitalizations at week 25. (NCT02085447)
Timeframe: Screen, Week 25

Interventionhospital visits (Mean)
CAE-L.2

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Change in PANSS (Positive and Negative Syndrome Scale; Composite Scale) From Screen to Week 25

The PANSS is used to assess patients for positive and negative symptoms of schizophrenia or schizoaffective disorder. The Composite Scale is scored by subtracting the negative score from the positive score. This yields a bipolar index that ranges from -42 to +42. The bipolar composite scale simply expresses the direction and magnitude of difference between positive and negative syndromes. Scores >0 indicate there are more positive symptoms of schizophrenia endorsed, and scores <0 indicate there are more negative symptoms of schizophrenia endorsed. There is no aggregate score for this measure, as the subscales are to be scored separately. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L.8

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Change in PANSS (Positive and Negative Syndrome Scale; General Psychopathology) From Screen to Week 25

The PANSS is used to assess patients for positive and negative symptoms of schizophrenia or schizoaffective disorder. The General Psychopathology Subscale consists of 16 questions. Each item is rated on a scale of 1 (Absent) to 7 (Extreme). Total scores range from 16-112 on the General Psychopathology scale. Higher scores indicate more symptoms of psychopathology. There is no aggregate score for this measure, as the subscales are to be scored separately. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L24.7

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Change in PANSS (Positive and Negative Syndrome Scale; Negative Symptoms Scale) From Screen to Week 25

The PANSS is used to assess patients for positive and negative symptoms of schizophrenia or schizoaffective disorder. The Negative Symptoms Subscale consists of 7 questions. Each item is rated on a scale of 1 (Absent) to 7 (Extreme). Total scores for the Negative Symptoms Subscale range from 7-49. Higher scores indicate more symptoms of psychopathology. There is no aggregate score for this measure, as the subscales are to be scored separately. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L12.1

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Change in PANSS (Positive and Negative Syndrome Scale; Positive Symptoms Scale) From Screen to Week 25

The PANSS is used to assess patients for positive and negative symptoms of schizophrenia or schizoaffective disorder. The Positive Symptoms Subscale consists of 7 questions. Each item is rated on a scale of 1 (Absent) to 7 (Extreme). Total scores for the Positive Symptoms Subscale range from 7-49. Higher scores indicate more symptoms of psychopathology. There is no aggregate score for this measure, as the subscales are to be scored separately. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L21.2

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Change in SAS (Simpson Angus Scale) From Screen to Week 25

The Simpson-Angus Scale is used to monitor for neurological and musculoskeletal side effects that may be a result of certain psychotropic medications. The scale consists of 10 questions which each can be rated on a scale of 0 to 4. Scores for each item are added to produce a total score. Total scores range from 0 to 40. Higher scores indicate more adverse outcomes. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L0.0

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Change in SOFAS (Social and Occupational Functioning Assessment Scale) From Screen to Week 25

Evaluates social and occupational functioning on a scale of 0 (Inadequate information) to 100 (Superior functioning). It is a one-item measure. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L63.1

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Change in Tablets Routine Questionnaire (TRQ, Past Week) From Screen to Week 25 Visit

The Tablets Routine Questionnaire (TRQ) determines the proportion of prescribed medication taken and is not dependent upon timing of medication provided that medication is consumed within the required day/24 hour period. This rating has demonstrated statistically significant association with past non-adherence, repeated past non-adherence, any non-adherence in the past month, and non-adherence in the past week. The TRQ format will be modified slightly to document all adherence values (an exact proportion) for each item. TRQ scores ranges from perfect adherence (0% missed) to missing all medication (100% missed). An average TRQ was calculated for individuals on more than one BD medication. (NCT02085447)
Timeframe: Screen, Week 25

Interventionpercentage of adherence (Mean)
CAE-L56.2

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Change in Tablets Routine Questionnaire (TRQ) (Past Month) From Screen to Week 25

The Tablets Routine Questionnaire (TRQ) determines the proportion of prescribed medication taken and is not dependent upon timing of medication provided that medication is consumed within the required day/24 hour period. This rating has demonstrated statistically significant association with past non-adherence, repeated past non-adherence, any non-adherence in the past month, and non-adherence in the past week. The TRQ format will be modified slightly to document all adherence values (an exact proportion) for each item. TRQ scores ranges from perfect adherence (0% missed) to missing all medication (100% missed). An average TRQ was calculated for individuals on more than one BD medication. (NCT02085447)
Timeframe: Screen, Week 25

Interventionpercentage of adherence (Mean)
CAE-L15.2

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Long-acting Injection (LAI) Adherence

Long-acting injection (LAI) adherence will be determined as a proportion of LAI (paliperidone palmitate or haloperidol decanoate) injections received at the appropriate time (within 7 days of scheduled time). (NCT02085447)
Timeframe: Week 25

Interventionpercentage of adherence (Mean)
CAE-L90.5

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Percentage Change of Days of Sub-optimal Housing in the Past Six Months; Change From Screen to Week 25

Change in number of sub-optimal housing from the past 6 months from Screen and Week 25. This is calculated by subtracting the percent of sub-optimal housing at screen from the number of sub-optimal housing at week 25. (NCT02085447)
Timeframe: Screen, Week 25

Interventionpercentage of days (Mean)
CAE-L29.0

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Change in AIMS (Abnormal Involuntary Movement Scale) From Baseline to Week 25

"The AIMS is used to monitor for the development of involuntary movements that may occur as a result of certain psychotropic medication. It contains 14 items, 10 of which are rated on a scale of 0 (None) to 4 (Severe). The remaining four items are yes or no questions. Items 1 thru 7 are added for a total score, while item 8 is used as an overall severity index. Total scores range from 0 to 28. Higher scores indicate more adverse outcomes.Items 9 thru 12 provide additional information that may be useful in determining lip, jaw, and tongue movements." (NCT02085447)
Timeframe: Baseline, Week 25

Interventionunits on a scale (Mean)
CAE-L1.5

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Change in AMSQ (Attitudes Toward Mood Stabilizers Questionnaire) From Screen to Week 25

"The AMSQ/AMQ is used to measure attitudes towards medications. The scale contains 19 items. Responses which suggest positive attitudes towards medications are scored 0, while responses which suggest negative attitudes towards medications are scored 1. The items scores are added for a total score. Total scores range from 0 to 19. Lower total scores suggest more positive attitudes, while higher scores suggest more negative attitudes." (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L4.0

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Change in ASSIST GRS (Alcohol, Smoking and Substance Involvement Screening Test ) From Screen to Week 25

The ASSIST was used to measure drug use. A total score is derived by combining item scores (minimum score = 0; maximum score = 382). Higher scores indicate higher risk of lifestyle problems, including health. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L2.0

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Change in BARS (Barnes Akathisia Rating Scale) From Screen to Week 25

This scale is used to measure the presence of akathisia, as may result from use of certain psychotropic medications. The scale contains four items and the score for each item is added to produce the total score. Total scores range from 0 to 14. Higher scores indicate more adverse outcomes. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L.3

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Change in CGI (Clinical Global Impression) From Screen to Week 25

The CGI evaluates global psychopathology illness severity on a 7 point Likert Scale (minimum score = 1; maximum score = 7) with higher scores indicating worse pathology. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L2.9

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Change in DAI (Drug Attitudes Index) From Screen to Week 25

The DAI contains ten true-false items. Correct responses are scored as +1, while incorrect responses are scored as 0. The highest possible score is 10, while the lowest possible score is 0. Higher scores indicate better drug attitudes, while lower scores indicate worse drug attitudes. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L8.5

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Change in ESRS-A (Extrapyramidal Symptoms Scale-Abbreviated; Akathisia)

For the subjective examination scoring is on a 4-point scale (0=Absent;1=Mild, 2=Moderate, 3=Severe). The evaluator takes into account the verbal report of the patient on: 1) the frequency and duration of the symptom during the day; 2) the number of days the symptom was present during the last week; and, 3) the subjective evaluation of the intensity of the symptom by the patient. The score for akathisia is separated from the Parkinsonism score and is based on the combined score of subjective akathisia (item 6 of the questionnaire) and objective akathisia (item 7 of the Parkinsonism/Akathisia objective examination). This subscore total ranges from 0 to 6. Higher scores indicate more severity. (NCT02085447)
Timeframe: Screen, Week 25

Interventionunits on a scale (Mean)
CAE-L.2

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Cerebral Glutamate Levels

"Mean values of cerebral glutamate levels was measured by high resolution 3T magnetic resonance spectroscopy (MRS) in the anterior cingulate cortex (ACC). Data were acquired from the dorsal anterior cingulate cortex (ACC) using single voxel localized PRESS (TE1, TE2) = (32, 65) ms with an 8-channel head coil in a 3T whole-body scanner (Philips Medical Systems). Voxel size was 30x20x15 mm3 (9 mL) and were placed over the bilateral anterior cingulate cortex (ACC). All values are normalized to water.~More negative values represent less cerebral glutamate levels." (NCT02199743)
Timeframe: Baseline and 4 weeks

,
Interventionrelative unit (RU as compared to water) (Mean)
Baseline (week 0)week 4
Lurasidone-1.434662171-1.412294235
Non-Lurasidone-1.933853656-1.838991525

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Brief Assessments of Cognition in Schizophrenia Scores (BACS)

"Mean of cognition was assessed by BACS, which measures neurocognitive function in schizophrenia. BACs is a validated, composite measure of cognition which is used in schizophrenia. It is composed of Verbal memory (range: 0-75), Working memory (range: 0-28), Motor speed (range: 0-100), Verbal Fluency (number of words generated), Information processing (range: 0-110) and Executive functions (range: 0-22).~Higher z-scores indicate a better performance and outcome. BACS composite score are represented as z-scores which can be positive or negative. There is no minimum or maximum as this is a continuous measure." (NCT02199743)
Timeframe: Baseline and 4 weeks

,
InterventionBACS composite score (z score) (Mean)
Baseline (week 0)week 4
Lurasidone-1.596573107-2.002433521
Non-Lurasidone-1.933853656-1.500292967

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Betting Behaviour in Laboratory-based Slot Machine Game

Risk taking was operationally defined as credits wagered per spin (mean computed for total spins) (NCT02203786)
Timeframe: 1x per test session (total of 4 test sessions) for duration of the study: 4 weeks (1 session/week)

,,,
Interventioncredits/spin on slot machine (Mean)
Mean bet under drugMean bet under placebo
Fluphenazine - Controls14.412.2
Fluphenazine - Pathological Gamblers16.016.1
Haloperidol - Controls11.69.5
Haloperidol - Pathological Gamblers12.810.4

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Diastolic Blood Pressure (DBP)

Measure changes from baseline, especially physiologic reactivity to the slot machine and amphetamine. (NCT02203786)
Timeframe: At key points in testing: immediately after the slot machine game (change from session baseline), and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)(change from session baseline).

,,,
Interventionmm Hg (Mean)
Drug-Change in DBP pre-to-post slot machinePlacebo-Change in DBP pre-to-post slot machineDrug-Change in DBP pre-amphetamine to peak amphPlacebo-Change in DBP pre-amphetamine to peak amp
Fluphenazine - Controls23.61932.736.3
Fluphenazine - Pathological Gamblers2221.632.135.2
Haloperidol - Controls15.119.128.526.6
Haloperidol - Pathological Gamblers20.222.527.233.6

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Cognitive Task Performance

Response time to words (gambling, alcohol, positive affect, negative affect) as a percentage of neutral categorized words (parts of a building). This provides an index of the relative salience of stimuli from these four categories against a baseline of reaction to words with no clinical relevance or emotional valence. Smaller scores indicate faster relative response time to the test stimuli vs. neutral stimuli (i.e., greater salience) (NCT02203786)
Timeframe: At key points during testing: immediately after the slot machine, at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration)

,,,
Interventionpercentage of neutral categorized words (Mean)
post-slots-GAM words under drugpost-slots-ALC words under drugpost-slots POS words under drugpost-slots NEG words under drugpost-slots GAM words under placebopost-slots ALC words under placebopost-slots POS words under placebopost-slots NEG words under placebopeak AMPH GAM words under drugpeak AMPH ALC words under drugpeak AMPH POS words under drugpeak AMPH NEG words under drugpeak AMPH GAM words under placebopeak AMPH ALC words under placebopeak AMPH POS words under placebopeak AMPH NEG words under placebo
Fluphenazine - Controls91.093.188.387.992.193.386.884.797.0100.396.398.796.997.595.196.7
Fluphenazine - Pathological Gamblers94.098.195.396.595.099.094.997.295.899.598.799.497.999.997.7100.0
Haloperidol - Controls94.896.593.789.697.297.093.792.398.199.197.296.896.8100.297.898.1
Haloperidol - Pathological Gamblers91.695.591.389.191.694.892.793.096.7101.298.299.595.099.998.499.0

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Winnings on Slot Machine Upon Completion of Game

Credits (NCT02203786)
Timeframe: 15-minutes

,,,
Interventioncredits (Mean)
Winnings (Final Credit Tally) under drugWinnings (Final Credit Tally) under Placebo
Fluphenazine - Controls544.3215
Fluphenazine - Pathological Gamblers277.8140.8
Haloperidol - Controls449.1339.2
Haloperidol - Pathological Gamblers239562.4

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Subjective Reinforcement Self-report Scales

Self-reported Confidence to Refrain from Gambling (0 - 10) was assessed at test session baseline, before the slot machine and after the slot machine (Phase 1); and before amphetamine and at peak amphetamine (Phase 2). The maximum score (10) denotes complete confidence to refrain from gambling (i.e., NO urge or compulsion to gamble); the minimum score (0) denotes complete lack of confidence to refrain from gambling (i.e., overwhelming urge to gamble). Scores between 10 and 0 denote intermediate confidence to refrain from gambling with LOWER scores denoting less confidence to refrain from gambling -- i.e., GREATER urge or compulsive motivation to gamble. Scores shown are based on single item visual analogue ratings 0-10 from each participant at the specified time point. The mean (SD) of these single item ratings is presented for each sub-group. (NCT02203786)
Timeframe: At key points in testing: immediately after the slot machine game, and at expected peak subjective-behavioral effects for amphetamine (90-minutes post-capsule administration).

,,,
Interventionunits on a scale (Mean)
Drug - Confidence not to gamble after slot machinePlacebo - Confidence not to gamble after slot machDrug - Confidence not to gamble at peak amphetaminPlac -Confidence not to gamble at peak amphetamine
Fluphenazine - Controls9.38.29.89.3
Fluphenazine - Pathological Gamblers4.84.86.45.7
Haloperidol - Controls9.599.89.4
Haloperidol - Pathological Gamblers4.84.25.25.5

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Speed of Play on Slot Machine Game

Number of individual spins in a 15-minute slot machine game. Each spin corresponds to one wager. (NCT02203786)
Timeframe: 15-minutes

,,,
Interventionindividual spins/15-minutes (Mean)
Spins/15-minutes under DrugSpins/15-minutes under Placebo
Fluphenazine - Controls71.866.7
Fluphenazine - Pathological Gamblers78.568.4
Haloperidol - Controls66.472.2
Haloperidol - Pathological Gamblers76.988.6

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Efficacy of Low-dose Haloperidol in Reducing Days With Delirium

Test the efficacy of low dose haloperidol in reducing the number of days with delirium among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. (NCT02213900)
Timeframe: Up to 30 days

InterventionDays with Delirium (Mean)
Haloperidol0.3
Placebo0.5

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Efficacy of Low-dose Haloperidol in Reducing ICU and Hospital Length of Stay

Test the efficacy of low dose haloperidol in reducing ICU and hospital length of stay among patients who are status post esophagectomy or pneumonectomy compared to placebo. (NCT02213900)
Timeframe: Date of hospital admission through date of hospital discharge, up to 3 weeks on average.

,
InterventionDays (Mean)
ICU Length of StayOverall Length of Stay
Haloperidol2.59.3
Placebo2.810.2

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Efficacy of Low-dose Haloperidol in Reducing Cognitive Impairment at Post-operative Follow-up

Test the efficacy of low dose haloperidol in reducing cognitive impairment at post-operative follow-up among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. Cognitive status is assessed using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). The RBANS measures attention, language, visuospatial/constructional abilities, and memory. It is made up of 12 subtests. The subtests produce 5 index scores and a total scale score. All the subtest scores are summed to calculate a Total Index score. The Total Index score is presented. The Total Index score scale is from 0-100 with higher scores indicating less cognitive impairment. (NCT02213900)
Timeframe: Up to 3 months after hospital discharge on average.

,
InterventionUnits on a scale (Mean)
Baseline RBANS Total Score3 Month RBANS Total Score
Haloperidol31.731.8
Placebo30.122.7

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Efficacy of Low-dose Haloperidol in Reducing Delirium Incidence

Test the efficacy of low dose haloperidol in reducing delirium incidence among patients who are status post esophagectomy, pneumonectomy or thoracotomy compared to placebo. (NCT02213900)
Timeframe: Up to 30 days

InterventionParticipants (Count of Participants)
Haloperidol15
Placebo19

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Time to Delirium Resolution

Delirium resolution was defined as three negative Confusion Assessment Method (CAM) assessments, performed by nurses every 12 hours. (NCT02343575)
Timeframe: Up to 5 days

Interventiondays (Mean)
Valproic Acid2
Placebo1.5

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Use of as Needed Anti-psychotic Agent

Amount of Haldol administered. (NCT02343575)
Timeframe: Up to 5 days

Interventionmg (Mean)
Valproic Acid0
Placebo1

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Length of Hospital Stay

Participation in the study ended once delirium was resolved and the patient was off study drug. This outcome presents the total length of hospital stay, which may have been longer than participation in the study. (NCT02343575)
Timeframe: During expected average hospitalization (of 1 month)

Interventiondays (Mean)
Valproic Acid4
Placebo8

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Side Effects From Medications

Side effects may have included liver function test (LFT) increase, platelet decrease, bleeding, or QTc prolongation. (NCT02343575)
Timeframe: Up to 5 days

,
InterventionParticipants (Count of Participants)
LFT increasePlatelet decreaseBleedingQTc prolongation
Placebo0001
Valproic Acid0000

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Intensity of Delirium as Measured by the Intensive Care Delirium Screening Checklist (ICDSC) Delirium Severity Scale

The items include the assessment of: (1) consciousness ( deep sedation/coma, agitation, normal wakefulness, or light sedation); (2) inattention; (3) disorientation; (4) hallucination, delusion, or psychosis; (5) psychomotor agitation or retardation; (6) inappropriate speech or mood; (7) sleep-wake cycle disturbances; and (8) fluctuation of symptomatology. The maximum score is eight; scores of ≥4 indicate the presence of delirium and score zero is indicate not in delirium. Each item is scored 0-8. (NCT02343575)
Timeframe: Up to 5 days

Interventionscore on a scale (Mean)
Valproic Acid5
Placebo4

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Part 2 (Disease Progression): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score

"The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The score ranges from 1 to 7, where 1 is equivalent to Normal, not at all ill and a rating of 7 is equivalent to Among the most extremely ill participants. Higher scores indicate worsening." (NCT02431702)
Timeframe: Baseline, up to 9 Months of Part 2

Interventionunits on a scale (Mean)
Part-2: Paliperidone Palmitate (PP)-0.2
Part-2: OAP-0.3

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Part 2 (Disease Progression): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Higher score indicate better performance. (NCT02431702)
Timeframe: Baseline and Month 9

Interventionunits on a scale (Mean)
Part-2: Paliperidone Palmitate (PP)2.5
Part-2: OAP2.9

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Part 2 (Disease Progression): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Total Score

The Medication Satisfaction Questionnaire (MSQ) is a 7-point, verbally administered, Likert-type scale rated as follows: 1=Extremely Dissatisfied, 2=Very Dissatisfied, 3=Somewhat Dissatisfied, 4=Neither Satisfied Nor Dissatisfied, 5=Somewhat Satisfied, 6=Very Satisfied, 7=Extremely Satisfied. Worst value is 1 (Extremely Dissatisfied) and best value is 7 (Extremely Satisfied). Total score ranges from 1 to 7. Higher score indicate improvement. (NCT02431702)
Timeframe: Baseline and endpoint Part 2 (up to 9 Months)

Interventionunits on a scale (Mean)
Part-2: Paliperidone Palmitate (PP)-0.2
Part-2: OAP0.1

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Part 2 (Disease Progression): Change From Baseline in Reasoning and Problem Solving: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving of participants. The range of reasoning and problem solving T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part-2: Paliperidone Palmitate (PP)0.2
Part-2: OAP2.8

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Part 2 (Disease Progression): Change From Baseline in Social Cognition Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part-2: Paliperidone Palmitate (PP)0.3
Part-2: OAP1.6

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Part 2 (Disease Progression): Change From Baseline in Verbal Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part-2: Paliperidone Palmitate (PP)1.3
Part-2: OAP1.0

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Part 3 (EDP): Change From Baseline in Working Memory Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. The range of working memory score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP-1.7
Part 3-OAP to OAP0.7

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Part 3 (EDP): Change From Baseline in Speed of Processing Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP2.5
Part 3-OAP to OAP4.9

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Part 3 (EDP): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)

"The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of IR volume minus PD volume. 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression." (NCT02431702)
Timeframe: Baseline and 18 Months

Interventionratio (Mean)
Part 3-PP to PP-0.001
Part 3-OAP to OAP-0.003

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Part 3 (EDP): Change From Baseline in Attention/Vigilance Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP2.4
Part 3-OAP to OAP0.7

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Part 3 (EDP): Change From Baseline in Clinical Global Impression Severity (CGI-S) Score

"The Clinical Global Impression Severity (CGI-S) rating scale is used to rate the severity of a participant's overall clinical condition on a 7 point scale. The total score ranges from 1 to 7, where 1 is equivalent to Normal, not at all ill and a rating of 7 is equivalent to Among the most extremely ill participants. Higher scores indicate worsening." (NCT02431702)
Timeframe: Baseline, up to 18 Months

Interventionunits on a scale (Mean)
Part 3-PP to PP-0.7
Part 3-OAP to OAP-0.7

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Part 3 (EDP): Change From Baseline in Functioning as Measured by the Personal and Social Performance (PSP) Total Score

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Each domain was assessed on a 6-point scale, from 1 (absent) to 6 (very severe) (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe). PSP total score was calculated as sum of all the domain scores and ranges from 1 to 100. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. Higher score indicate better performance. (NCT02431702)
Timeframe: Baseline and 18 Months

Interventionunits on a scale (Mean)
Part 3-PP to PP7.5
Part 3-OAP to OAP7.0

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Part 3 (EDP): Change From Baseline in Reasoning and Problem Solving: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess reasoning and problem solving score of participants. The range of reasoning and problem solving T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP3.4
Part 3-OAP to OAP4.7

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Part 2 (Disease Progression): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Month 9

InterventionT-score (Least Squares Mean)
Part-2: Paliperidone Palmitate (PP)2.0
Part-2: OAP2.8

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Part 3 (EDP): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by CRDPSS

The CRDPSS is an 8-item measure that assesses the severity of mental health symptoms that are important across psychotic disorders, including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, negative symptoms. Each item on the measure is rated on a 5-point scale (0=none; 1=equivocal; 2=present, but mild; 3=present and moderate; and 4=present and severe). Total Score is taken as summation. A higher score indicates a more severe condition. Worsened or improved is defined as increase or decrease compared to baseline. (NCT02431702)
Timeframe: Baseline, up to 18 Months

InterventionParticipants (Count of Participants)
Hallucinations72513609Hallucinations72513610Delusions72513609Delusions72513610Disorganized Speech72513609Disorganized Speech72513610Abnormal Psychomotor Behavior72513609Abnormal Psychomotor Behavior72513610Negative Symptoms72513609Negative Symptoms72513610Impaired Cognition72513609Impaired Cognition72513610Mania72513609Mania72513610Depression72513609Depression72513610
WorsenedUnchangedImproved
Part 3-PP to PP3
Part 3-OAP to OAP8
Part 3-PP to PP27
Part 3-OAP to OAP29
Part 3-PP to PP11
Part 3-OAP to OAP10
Part 3-PP to PP6
Part 3-PP to PP21
Part 3-OAP to OAP20
Part 3-PP to PP14
Part 3-OAP to OAP17
Part 3-PP to PP2
Part 3-OAP to OAP36
Part 3-PP to PP12
Part 3-PP to PP4
Part 3-OAP to OAP2
Part 3-PP to PP32
Part 3-OAP to OAP37
Part 3-PP to PP5
Part 3-OAP to OAP4
Part 3-OAP to OAP22
Part 3-PP to PP19
Part 3-OAP to OAP21
Part 3-PP to PP10
Part 3-OAP to OAP9
Part 3-OAP to OAP23
Part 3-PP to PP17
Part 3-OAP to OAP15
Part 3-PP to PP0
Part 3-OAP to OAP3
Part 3-PP to PP40
Part 3-OAP to OAP39
Part 3-PP to PP1
Part 3-OAP to OAP5
Part 3-PP to PP7
Part 3-OAP to OAP6
Part 3-PP to PP26
Part 3-PP to PP8
Part 3-OAP to OAP12

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Part 2 (Disease Progression): Number of Participants With Change From Baseline in Severity of Psychotic Symptoms, as Measured by Clinician-Rated Dimensions of Psychosis Symptom Severity Scale (CRDPSS)

The CRDPSS is an 8-item measure that assesses the severity of mental health symptoms that are important across psychotic disorders, including delusions, hallucinations, disorganized speech, abnormal psychomotor behavior, negative symptoms. Each item on the measure is rated on a 5-point scale (0=none; 1=equivocal; 2=present, but mild; 3=present and moderate; and 4=present and severe). Total Score is taken as summation. A higher score indicates a more severe condition. Worsened or improved is defined as increase or decrease compared to baseline. (NCT02431702)
Timeframe: Baseline, up to 9 Months

InterventionParticipants (Count of Participants)
Hallucinations72513608Hallucinations72513614Delusions72513614Delusions72513608Disorganized Speech72513614Disorganized Speech72513608Abnormal Psychomotor Behavior72513614Abnormal Psychomotor Behavior72513608Negative Symptoms72513608Negative Symptoms72513614Impaired Cognition72513614Impaired Cognition72513608Mania72513608Mania72513614Depression72513608Depression72513614
UnchangedImprovedWorsened
Part-2: OAP19
Part-2: Paliperidone Palmitate (PP)29
Part-2: OAP73
Part-2: Paliperidone Palmitate (PP)14
Part-2: OAP33
Part-2: Paliperidone Palmitate (PP)10
Part-2: OAP20
Part-2: Paliperidone Palmitate (PP)23
Part-2: OAP70
Part-2: OAP35
Part-2: OAP13
Part-2: Paliperidone Palmitate (PP)36
Part-2: OAP85
Part-2: Paliperidone Palmitate (PP)12
Part-2: OAP27
Part-2: Paliperidone Palmitate (PP)9
Part-2: OAP14
Part-2: Paliperidone Palmitate (PP)37
Part-2: OAP86
Part-2: Paliperidone Palmitate (PP)4
Part-2: OAP25
Part-2: Paliperidone Palmitate (PP)16
Part-2: OAP61
Part-2: Paliperidone Palmitate (PP)17
Part-2: OAP39
Part-2: Paliperidone Palmitate (PP)13
Part-2: OAP29
Part-2: Paliperidone Palmitate (PP)22
Part-2: OAP52
Part-2: Paliperidone Palmitate (PP)15
Part-2: OAP44
Part-2: Paliperidone Palmitate (PP)1
Part-2: OAP7
Part-2: Paliperidone Palmitate (PP)47
Part-2: OAP107
Part-2: Paliperidone Palmitate (PP)2
Part-2: OAP11
Part-2: Paliperidone Palmitate (PP)7
Part-2: OAP28
Part-2: Paliperidone Palmitate (PP)33
Part-2: OAP74
Part-2: OAP23

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Part-2 (Disease Progression): Time to First Treatment Failure

Treatment failure is defined as the time from participant's randomization to first treatment failure, which was a composite endpoint consisting of any of the following: 1) Psychiatric hospitalization due to worsening symptoms; 2) Any deliberate self-injury, suicidal ideation or behavior, homicidal ideation or violent behavior that is clinically significant and needs immediate intervention as determined by the study physician; 3) New arrest/incarceration; 4) Discontinuation of antipsychotic treatment due to inadequate efficacy as determined by the study physician; 5) Discontinuation of antipsychotic treatment due to safety or tolerability as determined by the study physician; 6) Treatment supplementation with another antipsychotic due to inadequate efficacy as determined by the study physician; 7) Increase in the level of psychiatric services in order to prevent imminent psychiatric hospitalization as determined by the study physician. (NCT02431702)
Timeframe: From Day 1 up to 9 Months

Interventiondays (Median)
Part-2: Paliperidone Palmitate (PP)NA
Part-2: OAPNA

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Part 3 (Extended Disease Progression [EDP]): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP1.6
Part 3-OAP to OAP3.2

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Part 3 (EDP): Change From Baseline in Visual Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP0.2
Part 3-OAP to OAP-0.2

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Part 3 (EDP): Time to First Treatment Failure

Treatment failure is defined as the time from participant's randomization to first treatment failure, which was a composite endpoint consisting of any of the following: 1) Psychiatric hospitalization due to worsening symptoms; 2) Any deliberate self-injury, suicidal ideation or behavior, homicidal ideation or violent behavior that is clinically significant and needs immediate intervention as determined by the study physician; 3) New arrest/incarceration; 4) Discontinuation of antipsychotic treatment due to inadequate efficacy as determined by the study physician; 5) Discontinuation of antipsychotic treatment due to safety or tolerability as determined by the study physician; 6) Treatment supplementation with another antipsychotic due to inadequate efficacy as determined by the study physician; 7) Increase in the level of psychiatric services in order to prevent imminent psychiatric hospitalization as determined by the study physician. (NCT02431702)
Timeframe: From Day 1 Up to 18 Months

Interventiondays (Median)
Part 3-PP to PPNA
Part 3-OAP to OAPNA

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Part 3 (Disease Modification): Personal and Social Performance (PSP) Total Observed Score

The Personal and Social Performance (PSP) scale assesses degree of a participant's dysfunction within 4 domains of behavior: 1) socially useful activities, 2) personal and social relationships, 3) self-care, and 4) disturbing and aggressive behavior. Score ranges from 1 to 100, divided into 10 equal intervals to rate degree of difficulty (1 = absent, 2 = mild, 3 = manifest, 4 = marked, 5 = severe, and 6 = very severe) in each of the 4 domains. Based on 4 domains there will be 1 transformed total score. Participants with score of 71 to 100 have mild degree of difficulty; from 31 to 70, varying degrees of disability; less than or equal to 30, functioning so poorly as to require intensive supervision. (NCT02431702)
Timeframe: Month 9 of Part 3

Interventionunits on a scale (Least Squares Mean)
Part 3-PP to PP67.6
Part 3- OAP to PP (or Delayed-Start PP)66.1
Part 3-OAP to OAP66.6

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Part 3 (Disease Modification): Change From Baseline in Cognition as Measured by the MATRICS Consensus Cognitive Battery (MCCB) Composite Score

The MATRICS Consensus Cognitive Battery is an instrument that contains 10 tests to measure cognitive performance in 7 cognitive domains: speed processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition. The composite score combines the individual scores of the 10 tests and scores them on a normative scale to derive a T-score and composites scores. The range of T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part 3- PP to PP-0.7
Part 3- OAP to PP (or Delayed-Start PP)-0.2
Part 3-OAP to OAP0.5

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Part 3 (Disease Modification): Change From Baseline in Adjusted Intracortical Myelin Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (SE MRI)

"The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of IR volume minus PD volume. 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression." (NCT02431702)
Timeframe: Baseline and Month 9 of Part 3

Interventionratio (Least Squares Mean)
Part 3-PP to PP-0.7
Part 3- OAP to PP (or Delayed-Start PP)-0.2
Part 3-OAP to OAP0.5

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Part 2 (Disease Progression): Change From Baseline in Working Memory Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess working memory of participants. The range of working memory score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part-2: Paliperidone Palmitate (PP)-0.2
Part-2: OAP-0.8

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Part 2 (Disease Progression): Change From Baseline in Visual Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess visual learning score of participants. The range of visual learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part-2: Paliperidone Palmitate (PP)1.3
Part-2: OAP1.4

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Part 3 (EDP): Change From Baseline in Medication Satisfaction Questionnaire (MSQ) Score

The Medication Satisfaction Questionnaire (MSQ) is a 7-point, verbally administered, Likert-type scale rated as follows: 1=Extremely Dissatisfied, 2=Very Dissatisfied, 3=Somewhat Dissatisfied, 4=Neither Satisfied Nor Dissatisfied, 5=Somewhat Satisfied, 6=Very Satisfied, 7=Extremely Satisfied. Worst value is 1 (Extremely Dissatisfied) and best value is 7 (Extremely Satisfied). Total score ranges from 1 to 7. Higher score indicate improvement. (NCT02431702)
Timeframe: Baseline, up to 18 Months

Interventionunits on a scale (Mean)
Part 3-PP to PP0.3
Part 3-OAP to OAP0.4

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Part 2 (Disease Progression): Change From Baseline in Speed of Processing Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess speed of processing score of participants. The range of speed of processing T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part-2: Paliperidone Palmitate (PP)1.8
Part-2: OAP3.5

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Part 3 (EDP): Change From Baseline in Social Cognition Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess social cognition score of participants. The range of social cognition score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP-0.2
Part 3-OAP to OAP1.4

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Part 3 (EDP): Change From Baseline in Verbal Learning Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess verbal learning score of participants. The range of verbal learning score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and 18 Months

InterventionT-score (Mean)
Part 3-PP to PP0.3
Part 3-OAP to OAP0.8

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Part 2 (Disease Progression): Change From Baseline in Adjusted Intracortical Myelin (ICM) Fraction Score as Measured by Inversion Recovery (IR) and Spin Echo Magnetic Resonance Imaging (MRI)

"The adjusted ICM fraction score is quantified as: 1. The volume of myelinated brain tissue is measured separately on co-localized IR and proton density (PD) MRI images, by outlining the boundary between gray matter and white matter on each image. 2. ICM is calculated from the difference of IR volume minus PD volume. 3. ICM is then expressed as a fraction of the total intracranial volume (ICM divided by intracranial volume). 4. The ICM fraction is then adjusted for effects of age, gender, and race/ethnicity in the sample of treated participants and healthy controls. A decrease in the adjusted ICM fraction score may be a sign of disease progression." (NCT02431702)
Timeframe: Baseline and Day 260

Interventionratio (Mean)
Part-2: Paliperidone Palmitate (PP)-0.001
Part-2: OAP-0.004

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Part 2 (Disease Progression): Change From Baseline in Attention/Vigilance Score: MCCB Domain

MCCB measures cognitive function across cognitive domains and is comprised of 10 independent tests assessing 7 cognitive domains (speed of processing, attention/vigilance, working memory, verbal learning, visual learning, reasoning and problem solving, and social cognition). A subset of the MCCB cognitive domain was used to assess attention/vigilance score of participants. The range of attention/vigilance score T-scores for a normal control population is between 0 to 100 with a mean of 50 and standard deviation of 10. Higher scores indicate better cognitive functioning. (NCT02431702)
Timeframe: Baseline and Day 260

InterventionT-score (Mean)
Part-2: Paliperidone Palmitate (PP)3.2
Part-2: OAP0.7

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Change in Pain Score According to the Numeric Pain Intensity Scale

Numeric Pain Intensity scale is a standard rating tool for pain, ranging from 0-10, with 0=no pain and 10=worst pain imaginable. (NCT02972502)
Timeframe: Change from baseline (prior to treatment) to 1 hour post treatment (1 hour)

Interventionunits on a scale (Mean)
Metoclopramide (Reglan)-2.86
Haloperidol (Haldol)-5.13

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Number of Participants With Relapse

The definition of relapse is as follows 1.50% or greater increase in total DIEPSS score, 2. an increase in the total PANSS score of 25% or more from baseline, 3. deliberate self-injury, 4. emergence of clinically significant suicidal ideation, 5. violent behavior resulting in clinically significant injury to another person or property damage. (NCT03019887)
Timeframe: One year after the baseline cognitive function test or three months after the end of dose reduction, whichever came first.

InterventionParticipants (Count of Participants)
Dose Reduction130

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Perceived Comfort Level as Assessed by Caregiver

"On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from strongly agree, agree, neutral, disagree, and strongly disagree. In this study, strongly agree and agree were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated)." (NCT03021486)
Timeframe: Baseline and 24 hour

,,
InterventionParticipants (Count of Participants)
Perceived To Have A High Level of Comfort (More Comfortable)Perceived To Have A Low Level of Agitation (Less Agitated)
Combination Group66
Escalation Group89
Rotation Group1010

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Edmonton Expression Assessment System, ESAS

Edmonton Symptom Assessment System (ESAS) has been validated and widely used in different clinical settings, including the acute palliative care unit. It assessed the average symptom intensity of 10 symptoms over the past 24 hours. Each symptom was assessed using an 11-point numeric rating scale, ranging from 0 (none) to 10 (worst). It was measured as change in ESAS as Perceived by Caregivers between baseline and day 1, mean. (NCT03021486)
Timeframe: Baseline and 24 hours

,,
Interventionscore on a scale (Mean)
PainFatigueNauseaDepressionAnxietyDrowsinessAppetiteFeeling of well being*Shortness of breathSleep
Combination Group-1.11-0.4-0.8-0.90.70.100-2.7
Escalation Group-1.3-0.50.1-1.4-1.5-0.2-0.30.20.8-2.7
Rotation Group-4.1-3-1.8-1.2-4.8-0.6-0.6-1.6-2.2-5.1

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Change in Delirium Experience Questionnaire

This 14-item questionnaire examines both the recalled frequency of 7 delirium symptoms and associated distress in the rater: disorientation to time, disorientation to place, visual hallucinations, tactile hallucinations, auditory hallucinations, delusional thoughts and psychomotor agitation. The score for recalled frequency ranges between 0 and 4, where 0=not present, 1=a little of the time, 2=some of the time, 3=good part of the time, and 4=most or all of the time. The score for distress in the rater related to each delirium symptom also ranges from 0 to 4, where 0=no distress, 1=a little, 2=a fair amount, 3=very much and 4=extremely distressed. Due to an error in the data collection form, the last category was omitted as a choice and thus the score only ranged from 0 to 3. (NCT03021486)
Timeframe: Baseline and Day 3

,,
Interventionscore on a scale (Mean)
Nursing assessment, disorientation to time - frequencyNursing assessment, disorientation to place - frequencyNursing assessment, visual hallucination - frequencyNursing assessment, tactile hallucination - frequencyNursing assessment, auditory hallucination - frequencyNursing assessment, delusional thoughts - frequencyNursing assessment, psychomotor agitation- frequencyNursing assessment, disorientation to time - distressNursing assessment, disorientation to place - distressNursing assessment, visual hallucination - distressNursing assessment, tactile hallucination - distressNursing assessment, auditory hallucination - distressNursing assessment, delusional thoughts - distressNursing assessment, psychomotor agitation - distress
Combination Group0.20.3-0.7-0.9-0.40.2-0.4-0.5-0.4-0.4-0.5-0.2-0.1-0.8
Escalation Group-0.8-0.9-1-0.4-0.1-0.8-1.2-0.3-0.3-0.6-0.5-0.3-0.6-0.8
Rotation Group-0.8-0.800.10.10-0.8-0.3-0.30.1000-0.5

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Percentage of Participants With RASS Score -2 to 0

RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The Secondary outcome was the percentage of participants with target RASS score of -2 to 0 within the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit. (NCT03021486)
Timeframe: Time 0 or Baseline and 24 hours later.

InterventionParticipants (Count of Participants)
Escalation Group2
Rotation Group3
Combination Group5

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Number of Participants With RASS Score of >=1

RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was the proportion of breakthrough restlessness participants with a RASS score of >=1 during the first 24 hours. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit. (NCT03021486)
Timeframe: 0 or Baseline and 24 hours later

InterventionParticipants (Count of Participants)
Escalation Group12
Rotation Group7
Combination Group9

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Memorial Delirium Assessment Scale (MDAS)

The Memorial Delirium Assessment Scale (MDAS) is a 10-item clinician-rated assessment scale validated for assessment of delirium in cancer patients. It examines the level of consciousness, disorientation, memory, recall, attention, disorganized thinking, perceptual disturbance, delusions, psychomotor activity and sleep, assigning a score between 0 to 3, for a total score between 0-30. A total score of 13 or higher indicates delirium. We measured the change in Memorial Delirium Rating scale between baseline and 24 hours. (NCT03021486)
Timeframe: Baseline and 24 hours

Interventionscore on a scale (Mean)
Escalation Group-2.7
Rotation Group1
Combination Group0.3

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Change in Richmond Agitation Sedation Score (RASS) (0-24h)

RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The primary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 24 h later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid oversedation in the Intensive Care Unit. (NCT03021486)
Timeframe: Time 0 or Baseline and 24 hours after study medication administration

Interventionscore on a scale (Mean)
Escalation Group-3.6
Rotation Group-3.3
Combination Group-3.0

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Udvalg for Kliniske Undersogelser, UKU

We also documented the selected adverse effects associated with neuroleptics using the Udvalg for Kliniske Undersogelser (UKU) side effects rating scale. Specifically, we assessed 8 neurologic symptoms (dystonia, rigidity, hypokinesia/akinesia, hyperkinesia, tremor, akathisia, epileptic seizures, paraesthesias). We are reporting only the neurologic symptoms (tremor and akathisia) that had changes during the study. Each item was assigned a score by the research coordinator 0 (absent) to 3 (most severe) based on symptom severity of the last 3 days. (NCT03021486)
Timeframe: Baseline and 3 days

,,
InterventionParticipants (Count of Participants)
Tremor (decreased)Akathisia (decreased)
Combination Group11
Escalation Group00
Rotation Group00

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Perceived Comfort Level as Assessed by Nurse

"On day 1 (after initiation of blinded treatment), we asked the blinded caregivers to provide their overall impression of change in patient comfort level and the agitation level. The response ranged from strongly agree, agree, neutral, disagree, and strongly disagree. In this study, strongly agree and agree were combined for analysis. The participants who reported 'Agree' and 'Strongly Agree' responses to perceived comfort level have a high level of comfort (more comfortable). And similarly, the participants who reported 'Agree' and 'Strongly Agree' responses to perceived agitation level have a low level of agitation (less agitated)." (NCT03021486)
Timeframe: Baseline and 24 hour

,,
InterventionParticipants (Count of Participants)
Perceived To Have A High Level of Comfort (More Comfortable)Perceived To Have A Low Level of Agitation (Less Agitated)
Combination Group77
Escalation Group98
Rotation Group98

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Pattern of Medication Use

Use of neuroleptics and benzodiazepines during the first 24 hours was retrieved from the Medication Administration Record. (NCT03021486)
Timeframe: Baseline and 24 hours

,,
InterventionParticipants (Count of Participants)
Need for study med dose escalation in first 24 hrsBenzodiazepine use in first 24 hrs (scheduled)Benzodiazepine use in first 24 hrs (as needed)
Combination Group704
Escalation Group410
Rotation Group100

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Change in RASS Score (0-30 Minutes)

RASS score is a 10-point scale with scores ranging from +4 (very combative, violent) to -5 (unarousable). The secondary outcome was mean change in RASS score between time 0 (immediately before initiation of masked treatment) and 30 minutes later. The Richmond Agitation-Sedation Scale (RASS) was developed by a multidisciplinary team at Virginia Commonwealth University in Richmond; it is a validated method used to avoid over sedation in the Intensive Care Unit. (NCT03021486)
Timeframe: Time 0 or Baseline and 30 minutes later.

Interventionscore on a scale (Mean)
Escalation Group-2.6
Rotation Group-2.4
Combination Group-2.1

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Time Noted Where Important Adverse Effects Occurred Post Intervention

If patient exhibits any adverse effects post intervention treatment, this will be noted within the time frames. (NCT03639558)
Timeframe: 20, 40, 60 and 120 minutes post intervention treatment

InterventionParticipants (Count of Participants)
Haloperidol + Promethazine + Chlorpromazine0
Haloperidol + Promethazine0

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Number of Participants According to the Time Taken for Aggressive Behaviour to Change to Calm and Tranquil

Patient no longer exhibiting aggressive behavior both verbal and physical post intervention treatment. A primary measure of outcome form will contain a Calm or Tranquil column followed by four rows: 20 mins, 40 mins, 60 mins and 120 mins post intervention medication. The boxes would be ticked depending if the patient meets the primary measure of outcome within the time frame provided. (NCT03639558)
Timeframe: 20, 40, 60 and 120 minutes post intervention treatment

,
Interventionparticipants (Number)
Calm or tranquil at 20 minutesCalm or tranquil at 40 minutesCalm or tranquil at 60 minutesCalm or tranquil at 120 minutes
Haloperidol + Promethazine14253535
Haloperidol + Promethazine + Chlorpromazine18414547

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Time Patient Was Placed in Straitjacket/Restraint Post Intervention Treatment

If patient was placed in a straitjacket post intervention due to aggression - this would be noted on the outcomes form which includes a checklist at certain time intervals 20,40,60 and 120 minutes post intervention treatment. (NCT03639558)
Timeframe: 20, 40, 60 and 120 minutes post intervention treatment

,
InterventionParticipants (Count of Participants)
Restraints at 20 minutesRestraints at 40 minutesRestraints at 60 minutesRestraints at 120 minutes
Haloperidol + Promethazine161395
Haloperidol + Promethazine + Chlorpromazine171086

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Time Taken for Patient to Fall Asleep Post Intervention

Patient has fallen asleep and is no longer aggressive post intervention treatment and will be noted on the outcomes form which includes a checklist of different time intervals: 20, 40, 60 and 120 minutes post intervention treatment. (NCT03639558)
Timeframe: 20, 40, 60 and 120 minutes post intervention treatment

,
InterventionParticipants (Count of Participants)
Asleep at 20 minutesAsleep at 40 minutesAsleep at 60 minutesAsleep at 120 minutes
Haloperidol + Promethazine291018
Haloperidol + Promethazine + Chlorpromazine092524

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ESRS-A Parkinsonism

Extrapyramidal Symptoms Scale-Abbreviated version for Parkinsonism. It looks at drug-induced Parkinsonism which is made up of motor disturbances. Rigidity, tremor, reduced facial expression/speech, impaired gait/posture, postural instability, and bradykinesia. Each item is rated on a 4 point scale: 0=absent, 3=severe. The higher the value the more severe the Parkinsonism and worst outcomes. (NCT04327843)
Timeframe: Baseline to 6 months(25 weeks)

Interventionscore on a scale (Mean)
Baseline25 Weeks
CAE + LAI Treatment0.060.06

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ESRS-A Dyskinesia

Extrapyramidal Symptoms Scale-Abbreviated version for Dyskinesia- drug-induced dyskinesia which is repetitive and involuntary movements. Each item is rated on a 4 point scale: 0=absent, 3=severe and higher values indicate greater severity of dyskinesia and worse outcomes. (NCT04327843)
Timeframe: Baseline to 6 months(25 weeks)

Interventionscore on a scale (Mean)
BaselineWeek 25
CAE + LAI Treatment0.170.11

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ESRS-A Akathisia

Extrapyramidal Symptoms Scale-Abbreviated version for akathisia- drug-induced akathisia consists of inner restlessness and urge to move. Items are measured on a 4 value scale: 0=absent, 3=severe, and higher values indicate more severe akathisia and worse outcomes. (NCT04327843)
Timeframe: Baseline to 6 months(25 weeks)

Interventionscore on a scale (Mean)
BaselineWeek 25
CAE + LAI Treatment0.280.00

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Drug Attitude Inventory (DAI)

DAI-10 scoring ranges from -10 to +10 with a total score >0 indicating a positive attitude toward psychiatric medications and a total score of <0 indicating a negative attitude toward psychiatric medications. (NCT04327843)
Timeframe: Baseline to 6 month visit

Interventionscore on a scale (Mean)
Baseline25 Weeks
CAE + LAI Treatment7.899.83

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Clinical Global Impressions (CGI)

The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition. (NCT04327843)
Timeframe: Baseline to 6 month visit

Interventionunits on a scale (Mean)
Baseline25 Weeks
CAE + LAI Treatment2.882.24

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Brief Psychiatric Rating Scale (BPRS)

The BPRS measures levels of mania. There are 24 items, scored on a 7-point scale ranging from 0 to 6. Total scores range from 0 to 42, with higher scores indicating higher levels of mania. (NCT04327843)
Timeframe: Baseline to 6 month visit

Interventionscore on a scale (Mean)
Baseline25-Weeks
CAE + LAI Treatment27.0025.06

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Body Mass Index

Body Mass Index kg/m^2 of participants (NCT04327843)
Timeframe: Baseline to Month 6(week 25)

Interventionkg/m^2 (Mean)
Baseline25 Weeks
CAE + LAI Treatment22.7922.92

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Tablets Routine Questionnaire (TRQ)

The TRQ evaluates adherence to medications via a brief self-report instrument that has been validated in populations with bipolar disorder medication adherence. The TRQ identifies nonadherent individuals, defined as those who miss 20-30% or more of their medication in the last week or month. Total scores are represented as a percentage and range from 0 to 100, with higher scores indicating a greater level of nonadherence (higher scores indicate worse adherence to medications). (NCT04327843)
Timeframe: Change from Baseline to 6 month visit

Interventionpercentage of change in adherence (Mean)
TRQ Week adherenceTRQ Month adherence
CAE + LAI Treatment-57-23

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Social and Occupational Functioning Scale (SOFAS)

The SOFAS measures social and occupational functioning independent of the overall severity of the individual's psychological symptoms. The minimum score is 0 and the maximum score is 100. A higher rating implies a higher level of functioning. (NCT04327843)
Timeframe: Baseline to 6 month visit

Interventionscore on a scale (Mean)
Baseline25 Weeks
CAE + LAI Treatment62.1768.39

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Long-Acting Injectable Adherence (LAI Adherence): Count of Participants Who Received All LAI Injections:

LAI injection adherence will be determined as a count of participants who received LAI injections at the appropriate time (within 7 days of scheduled time). (NCT04327843)
Timeframe: Baseline to 6 month visit

InterventionParticipants (Count of Participants)
CAE + LAI Treatment18

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ESRS-A Dystonia

Extrapyramidal Symptoms Scale-Abbreviated version for dystonia- drug-induced dystonia is a muscle disorder in which movements are jerky or twisting. Due to the 0.00 values at baseline and 25 weeks, unable to perform t-test and get a p value so no statistical analysis section is reported for this Outcome Measure. Each item is rated on a 4 point scale: 0=absent, 3=severe with the higher numbers indicating worse dystonia and worse outcomes. (NCT04327843)
Timeframe: Baseline to 6 months(25 weeks)

Interventionscore on a scale (Mean)
BaselineWeek 25
CAE + LAI Treatment0.000.00

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Time to Maximum Concentration (Tmax)

The timepoint at which the maximum concentration of haloperidol as measured by bioanalysis of the blood plasma is observed. (NCT04411940)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

InterventionHours (Mean)
Reference Product (Treatment A)4.394
Test Product (Treatment B)4.406

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Terminal Elimination Rate Constant (λz)

Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a blood plasma concentration versus time curve. (NCT04411940)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Intervention1/h (Mean)
Reference Product (Treatment A)0.01194
Test Product (Treatment B)0.01124

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Concentration Maximum (Cmax)

The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the Cmax. (NCT04411940)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Interventionng/ml (Mean)
Reference Product (Treatment A)0.9092
Test Product (Treatment B)0.8711

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Area Under the Curve(0-∞) (AUC(0-∞))

Area under the plasma concentration versus time curve from time zero to ∞, where ∞ is the timepoint of the last quantifiable concentration of haloperidol in the blood plasma, plus it's elimination rate constant. AUC(0-∞) = AUC(0-t) + AUC(t-∞). (NCT04411940)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Interventionh*ng/ml (Mean)
Reference Product (Treatment A)22.16
Test Product (Treatment B)22.28

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Area Under the Curve (0-t) (AUC(0-t))

Area under the plasma concentration versus time curve from time zero to t, where t is the time of the timepoint of the last quantifiable concentration of haloperidol in the blood plasma. The curve is constructed by plotting the concentration of haloperidol in the blood plasma against the time for each blood sample. (NCT04411940)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Interventionh*ng/ml (Mean)
Reference Product (Treatment A)20.10
Test Product (Treatment B)19.89

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Apparent Terminal Elimination Half-Life (t½)

The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by a factor of one-half in the terminal phase. (NCT04411940)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

InterventionHours (Mean)
Reference Product (Treatment A)62.31
Test Product (Treatment B)65.99

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Time to Maximum Concentration (Tmax)

The timepoint at which the maximum concentration of haloperidol as measured by bioanalysis of the blood plasma is observed. (NCT04411953)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

InterventionHours (Mean)
Reference Product (Treatment A)4.871
Test Product (Treatment B)3.839

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Terminal Elimination Rate Constant (λz)

Terminal elimination rate constant (λz) is a mathematical estimate calculated using log-linear regression of the terminal portions of a blood plasma concentration against time curve. (NCT04411953)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Intervention1/h (Mean)
Reference Product (Treatment A)0.01114
Test Product (Treatment B)0.01152

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Terminal Elimination Half-life (t½)

The apparent terminal elimination half-life (t½) is defined as the time necessary for the concentration of a drug to decrease by one-half in the terminal phase. (NCT04411953)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

InterventionHours (Mean)
Reference Product (Treatment A)69.12
Test Product (Treatment B)70.19

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Concentration Maximum (Cmax)

The maximum observed concentration of haloperidol as measured by bioanalysis of the blood plasma is referred to as the Cmax. (NCT04411953)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Interventionng/ml (Mean)
Reference Product (Treatment A)1.326
Test Product (Treatment B)1.293

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Area Under the Curve(0-∞) (AUC(0-∞))

Area under the plasma concentration versus time curve from time zero to ∞, where ∞ is the timepoint of the last quantifiable concentration of haloperidol in the blood plasma, plus it's elimination rate constant. AUC(0-∞) = AUC(0-t) + AUC(t-∞). (NCT04411953)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Interventionh*ng/ml (Mean)
Reference Product (Treatment A)30.61
Test Product (Treatment B)31.34

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Area Under the Curve (0-t) (AUC(0-t))

Area under the plasma concentration versus time curve from time zero to t, where t is the time of the timepoint of the last quantifiable concentration of haloperidol in the blood plasma. The curve is constructed by plotting the concentration of haloperidol in the blood plasma against the time for each blood sample. (NCT04411953)
Timeframe: pre-dose (0 hours), and at 0.5, 1, 1.5, 2, 2.5, 3, 3.5, 4, 4.5, 5, 5.5, 6, 8, 12, 16, 24, 30, 36, 48, 72, 96, 120, 144, 168, 192 hours post dose

Interventionh*ng/ml (Mean)
Reference Product (Treatment A)27.75
Test Product (Treatment B)28.46

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Time Course and Degree of Normalization of Agitation

Agitation/sedation scores over time as measured by Agitation/Calmness Evaluation Score (ACES). The minimum value is 1 (highly agitated) and the highest value is 9 (completely sedated). A score of 3-5 is considered normal. (NCT04715230)
Timeframe: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

Interventionscore on a scale (Mean)
Baseline0.5 hour1 hour2 hours3 hours4 hours
IXT-m200 High Dose (2 g)2.3.63.94.03.01.0

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Time Course and Degree of Normalization of Temperature

Temperature over time (NCT04715230)
Timeframe: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

Interventiondegrees Fahrenheit (Mean)
Baseline1 hour2 hoursDischarge
Treatment as Usual (TAU)98.1097.797.798.10

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Time Course and Degree of Normalization of Temperature

Temperature over time (NCT04715230)
Timeframe: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

,
Interventiondegrees Fahrenheit (Mean)
Baseline0.5 hour1 hour2 hours3 hoursDischarge
IXT-m200 High Dose (2 g)98.2598.5298.4898.3899.5098.0
IXT-m200 Low Dose (0.5 g)98.298.0598.4598.5099.1097.40

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Number of Participants at Certain Degrees of Normalization of Blood Pressure Over Time

Blood pressure over time; reported as the number of participants with blood pressure out of normal range (i.e., diastolic >110 or <50 mmHg, or systolic >180 or <90 mmHg)) (NCT04715230)
Timeframe: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

InterventionParticipants (Count of Participants)Participants (Count of Participants)
Baseline72425221Baseline72425222Baseline724252230.5 hour724252220.5 hour724252230.5 hour724252211 hour724252211 hour724252221 hour724252232 hours724252212 hours724252222 hours724252233 hours724252213 hours72425222Prior to discharge72425222Prior to discharge72425223
NormalLowHigh
Treatment as Usual (TAU)4
IXT-m200 High Dose (2 g)1
IXT-m200 Low Dose (0.5 g)0
Treatment as Usual (TAU)0
IXT-m200 Low Dose (0.5 g)8
Treatment as Usual (TAU)3
IXT-m200 High Dose (2 g)7
IXT-m200 High Dose (2 g)0
IXT-m200 Low Dose (0.5 g)7
IXT-m200 High Dose (2 g)5
IXT-m200 Low Dose (0.5 g)1
IXT-m200 High Dose (2 g)2
Treatment as Usual (TAU)1

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Number of Participants at Certain Degrees of Normalization of Heart Rate Over Time

Heart rate over time reported as number of participants with heart rate high (>120 beats/min), normal, or low (<40 beats/min). (NCT04715230)
Timeframe: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

InterventionParticipants (Count of Participants)Participants (Count of Participants)
Baseline72425221Baseline72425222Baseline724252230.5 hour724252220.5 hour724252230.5 hour724252211 hour724252211 hour724252221 hour724252232 hours724252222 hours724252212 hours724252233 hours724252213 hours72425222Prior to discharge72425222Prior to discharge72425223
HighNormalLow
IXT-m200 Low Dose (0.5 g)0
IXT-m200 Low Dose (0.5 g)8
Treatment as Usual (TAU)4
IXT-m200 High Dose (2 g)0
Treatment as Usual (TAU)0
IXT-m200 Low Dose (0.5 g)7
IXT-m200 High Dose (2 g)8
Treatment as Usual (TAU)3
IXT-m200 Low Dose (0.5 g)1
IXT-m200 Low Dose (0.5 g)6
IXT-m200 High Dose (2 g)5
Treatment as Usual (TAU)2
IXT-m200 High Dose (2 g)2
IXT-m200 High Dose (2 g)1
Treatment as Usual (TAU)1

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Time Course and Degree of Normalization of Agitation

Agitation/sedation scores over time as measured by Agitation/Calmness Evaluation Score (ACES). The minimum value is 1 (highly agitated) and the highest value is 9 (completely sedated). A score of 3-5 is considered normal. (NCT04715230)
Timeframe: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

Interventionscore on a scale (Mean)
Baseline0.5 hour1 hour2 hours
Treatment as Usual (TAU)2.83.95.84.8

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Time Course and Degree of Normalization of Agitation

Agitation/sedation scores over time as measured by Agitation/Calmness Evaluation Score (ACES). The minimum value is 1 (highly agitated) and the highest value is 9 (completely sedated). A score of 3-5 is considered normal. (NCT04715230)
Timeframe: Baseline and hours 0.5, 1, 2, 3, 4, and 8 post-dose or until discharge.

Interventionscore on a scale (Mean)
Baseline0.5 hour1 hour2 hours3 hours
IXT-m200 Low Dose (0.5 g)2.14.14.64.07.0

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Length of Patient Stay in the ED

ED length of stay as measured by discharge time minus start of treatment time (NCT04715230)
Timeframe: Start of treatment until discharge

Interventionhours (Mean)
IXT-m200 Low Dose (0.5 g)8.940
IXT-m200 High Dose (2 g)8.031
Treatment as Usual (TAU)10.196

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