Risperidone Long-acting Versus Oral Risperidone in Patients With Schizophrenia and Alcohol Use Disorder

• Sponsor: Dartmouth-Hitchcock Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00130923
• Collaborator: Janssen, LP (Industry)
• Enrollment: 95
• Locations: 8
• Arms: 2
• Duration (Months): 58
• Patients Per Site: 11.9
• Patients Per Site Per Month: 0.2

Study Details

Study Description

Brief Summary

The purpose of this study is to compare the efficacy of oral risperidone (Risperdal) to risperidone long-acting (Consta) in reducing alcohol use in persons diagnosed with schizophrenia or schizoaffective disorder.

Condition or Disease	Intervention/Treatment	Phase
Schizophrenia; Psychotic Disorders; Substance Abuse; Alcohol Abuse	Drug: Risperidone Long Acting; Drug: oral risperidone	Phase 4

Detailed Description

Comorbid alcohol/substance use disorder (SUD) in people with schizophrenia is a major concern, both in view of the high frequency of SUD among patients with schizophrenia and the difficulty in managing such patients. Though antipsychotic medications are effective in reducing symptoms and impairment in persons with schizophrenia, the typical antipsychotic agents are of limited value in controlling alcohol/substance use in these patients. Extrapyramidal, dysphoric side effects of conventional neuroleptics may actually promote the use of substances in an attempt to counteract these effects. In addition, medication non-compliance is common among patients with schizophrenia.

Novel antipsychotics have altered treatment expectations and outcomes for patients with severe forms of schizophrenia. A growing number of studies have assessed the effects of oral risperidone in persons with dual disorders. Potential mechanisms of action by which risperidone and other atypical antipsychotics could decrease substance use include being less likely to cause extrapyramidal side effects than typical agents, improving negative symptoms and ameliorating a dysfunction of the brain reward system. Risperidone long-acting injectable medication addresses issues of noncompliance, while avoiding peak blood levels of oral preparations, thereby minimizing EPS and improving negative symptoms of schizophrenia. Risperidone may also facilitate dopamine neurotransmission in the prefrontal cortex and correct a hypothesized dysfunction of the brain reward system.

This study is an open, randomized, controlled study to compare intramuscular long-acting risperidone to oral risperidone with blinded ratings to determine whether the long-acting form of risperidone has greater efficacy in reducing substance use. Patients with schizophrenia or schizoaffective disorder, age 18 to 65, who are taking any single oral antipsychotic medication except clozapine or risperidone long-acting may be enrolled.

Study Design

• Study Type: Interventional
• Actual Enrollment: 95 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Risperidone Long-Acting for Alcohol and Schizophrenia Treatment (R-LAST)
• Study Start Date: Sep 1, 2005
• Actual Primary Completion Date: Jun 1, 2009
• Actual Study Completion Date: Jul 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Risperidone Long Acting Risperidone Long Acting; aka Risperdal Consta; injectable form	Drug: Risperidone Long Acting; Dose 25.00, 37.50 or 50.00 mg q two weeks; Other Names: Risperdal Consta
Active Comparator: Oral Risperidone Oral Risperidone; aka Risperdal; oral form	Drug: oral risperidone; 0.50-6.00 mg oral risperidone daily; Other Names: Risperdal

Outcome Measures

Primary Outcome Measures

1. Change Over Time in Frequency of Heavy Drinking Days (Used to Evaluate Treatment Efficacy) [6 months]

   Frequency of heavy drinking days is obtained each week retrospectively as the number of heavy drinking days during the prior week (assessed by the Timeline Followback Scale). A heavy drinking day is defined as 4 or more drinks per day for a female and 5 or more drinks per day for a male. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

Secondary Outcome Measures

1. Average Over Time of Frequency of Drinking Days (Used to Evaluate Treatment Efficacy) [6 months]

   Frequency of drinking days is obtained each week retrospectively as the number of drinking days during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

2. Average Over Time of Severity of Illness and Global Improvement (Used to Evaluate Treatment Efficacy) [6 months]

   A rater assesses the severity of illness and global impression using a scale from 1 to 7 (Clinical Global Impression), where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

3. Average Over Time of Positive and Negative Symptoms (Used to Evaluate Treatment Efficacy) [6 months]

   A rater assesses positive and negative symptoms of schizophrenia using a 30-item scale (Positive and Negative Symptom Score) Scores range from 30 to 210, where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

4. Average Over Time of Global Functioning (Used to Evaluate Treatment Efficacy) [6 months]

   A rater assesses social, occupational and psychological functioning on a hypothetical continuum of mental health - illness (using Global Assessment of Functioning); scores range from 100 to 1, where higher values represent a better outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.

5. Number of Participants With Medication Adherence [6 months]

   Number of participants with medication adherence (defined as taking medication at least 75% of the days in the treatment period).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years to 65 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Ages 18-65

• Schizophrenia or schizoaffective disorder

• Meets the Structured Clinical Interview for DSM-IV (SCID) criteria for an alcohol use disorder

• Alcohol use on at least 5 days during the 4 weeks prior to randomization

• Patient is medically stable to start either form of risperidone.

Exclusion Criteria:

• Current treatment with clozapine.

• Current treatment with injectable risperidone long-acting.

• Currently pregnant, planning to become pregnant, or unwilling to use an acceptable form of birth control.

• Change in medications (dose of current medication, discontinuation of medication, or new medication) in past 30 days.

• History of or current breast cancer.

• History of intolerance of or allergy to risperidone or risperidone long-acting.

• Currently residing in a residential program designed to treat substance use disorders.

• Current treatment with long-acting, injectable antipsychotic medication will require a review by the medication adjustment group before entering the client into the study.

• Past treatment with risperidone long-acting will require a review by the medication adjustment group before entering the client into the study.

• Treatment at baseline with a second antipsychotic medication will require a review by the medication adjustment group before entering the client into the study.

• Treatment at baseline with a psychotropic agent proposed to curtail substance use will require a review by the medication adjustment group before entering the client into the study.

• Patients who, in the opinion of the investigator, are judged unsuitable to participate in the study.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	JMH Mental Health Center, University of Miami	Miami	Florida	United States	33136
2	School of Pharmacy, Univ. of Missouri Kansas City	Kansas City	Missouri	United States	64108
3	Washington University School of Medicine	Saint Louis	Missouri	United States	63110
4	West Central Behavioral Health	Lebanon	New Hampshire	United States	03766
5	Mental Health Center of Greater Manchester	Manchester	New Hampshire	United States	03101
6	Center for Psychiatric Advancement	Nashua	New Hampshire	United States	03060
7	University of South Carolina	Columbia	South Carolina	United States	29203
8	White River Junction Veterans Admininistration Medical Center	White River Junction	Vermont	United States	05009

Sponsors and Collaborators

• Dartmouth-Hitchcock Medical Center
• Janssen, LP

Investigators

• Principal Investigator: Alan I. Green, MD, Dartmouth Medical School, Dartmouth College

Study Documents (Full-Text)

None provided.

More Information

Publications

• Akaike, H, Information theory and an extension of the maximum likelihood principle., in 2nd International Symposium on Information Theory and Control., EBN Petrovand & C. Csaki, Editors. 1973, Akademia Kiado: Budapest, p. 267-281.
• Albanese M. Risperidone in substance abusers with bipolar disorder. Presented at the 39th Annual Meeting of the American College of Neuropsychopharmacology. Sa Juan, PR, 2000.
• Albanese MJ, Khantzian EJ, Murphy SL, Green AI. Decreased substance use in chronically psychotic patients treated with clozapine. Am J Psychiatry. 1994 May;151(5):780-1.
• Bartels SJ, Teague GB, Drake RE, Clark RE, Bush PW, Noordsy DL. Substance abuse in schizophrenia: service utilization and costs. J Nerv Ment Dis. 1993 Apr;181(4):227-32.
• Birkett MA, Day SJ. Internal pilot studies for estimating sample size. Stat Med. 1994 Dec 15-30;13(23-24):2455-63.
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• Buckley P, McCarthy M, Chapman P, Richman C, Yamamoto B. Clozapine treatment of comorbid substance abuse in patients with schizophrenia. Schizophr Res 1999, 36:272.
• Buckley P, Thompson P, Way L, Meltzer HY. Substance abuse among patients with treatment-resistant schizophrenia: characteristics and implications for clozapine therapy. Am J Psychiatry. 1994 Mar;151(3):385-9.
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• Buckley PF. Substance abuse in schizophrenia: a review. J Clin Psychiatry. 1998;59 Suppl 3:26-30. Review.
• Coldham EL, Addington J, Addington D. Medication adherence of individuals with a first episode of psychosis. Acta Psychiatr Scand. 2002 Oct;106(4):286-90.
• Drake RE, Xie H, McHugo GJ, Green AI. The effects of clozapine on alcohol and drug use disorders among patients with schizophrenia. Schizophr Bull. 2000;26(2):441-9.
• Frison L, Pocock SJ. Repeated measures in clinical trials: analysis using mean summary statistics and its implications for design. Stat Med. 1992 Sep 30;11(13):1685-704.
• Green AI, Burgess ES, Dawson R, Zimmet SV, Strous RD. Alcohol and cannabis use in schizophrenia: effects of clozapine vs. risperidone. Schizophr Res. 2003 Mar 1;60(1):81-5.
• Green AI, Salomon MS, Brenner MJ, Rawlins K. Treatment of schizophrenia and comorbid substance use disorder. Curr Drug Targets CNS Neurol Disord. 2002 Apr;1(2):129-39. Review.
• Green AI, Zimmet SV, Strous RD, Schildkraut JJ. Clozapine for comorbid substance use disorder and schizophrenia: do patients with schizophrenia have a reward-deficiency syndrome that can be ameliorated by clozapine? Harv Rev Psychiatry. 1999 Mar-Apr;6(6):287-96. Review.
• Hunt GE, Bergen J, Bashir M. Medication compliance and comorbid substance abuse in schizophrenia: impact on community survival 4 years after a relapse. Schizophr Res. 2002 Apr 1;54(3):253-64.
• Khantzian EJ. The self-medication hypothesis of addictive disorders: focus on heroin and cocaine dependence. Am J Psychiatry. 1985 Nov;142(11):1259-64. Review.
• Khantzian EJ. The self-medication hypothesis of substance use disorders: a reconsideration and recent applications. Harv Rev Psychiatry. 1997 Jan-Feb;4(5):231-44. Review.
• Lacro JP, Dunn LB, Dolder CR, Leckband SG, Jeste DV. Prevalence of and risk factors for medication nonadherence in patients with schizophrenia: a comprehensive review of recent literature. J Clin Psychiatry. 2002 Oct;63(10):892-909. Review.
• Laird NM, Ware JH. Random-effects models for longitudinal data. Biometrics. 1982 Dec;38(4):963-74.
• Lee, ET. Statistical Methods for Survival Analysis. 1992, New York: John Wiley & Sons.
• Newton TF, Ling W, Kalechstein AD, Uslaner J, Tervo K. Risperidone pre-treatment reduces the euphoric effects of experimentally administered cocaine. Psychiatry Res. 2001 Jul 24;102(3):227-33.
• Salyers MP, Mueser KT. Social functioning, psychopathology, and medication side effects in relation to substance use and abuse in schizophrenia. Schizophr Res. 2001 Mar 1;48(1):109-23.
• Siris SG. Pharmacological treatment of substance-abusing schizophrenic patients. Schizophr Bull. 1990;16(1):111-22. Review.
• Smelson DA, Losonczy MF, Davis CW, Kaune M, Williams J, Ziedonis D. Risperidone decreases craving and relapses in individuals with schizophrenia and cocaine dependence. Can J Psychiatry. 2002 Sep;47(7):671-5.
• Tukey, JW. Exploratory Data Analysis. 1977, Reading, MA: Addison Wesley Publ. Co.
• Waternaux, C, Laird, N, Ware, J. Methods for the analysis of longitudinal data: Blood concentrations and cognitive development. J.Amer. Stat. Assoc. 1989: 84, p.33-41.
• Weiss RE, Lazaro CG. Residual plots for repeated measures. Stat Med. 1992 Jan 15;11(1):115-24.
• Zimmet SV, Strous RD, Burgess ES, Kohnstamm S, Green AI. Effects of clozapine on substance use in patients with schizophrenia and schizoaffective disorder: a retrospective survey. J Clin Psychopharmacol. 2000 Feb;20(1):94-8.

• Responsible Party: Alan Green, Principal Investigator, Dartmouth-Hitchcock Medical Center
• ClinicalTrials.gov Identifier: NCT00130923
• Other Study ID Numbers: 17359; RIS-EMR-4032
• First Posted: Aug 16, 2005
• Last Update Posted: May 9, 2019
• Last Verified: Apr 1, 2019

• Keywords provided by Alan Green, Principal Investigator, Dartmouth-Hitchcock Medical Center: Risperidone; Schizophrenia; Substance Use Disorder; Alcohol Use Disorder; Treatment; Schizoaffective Disorder
• Additional relevant MeSH terms: Disease; Alcoholism; Substance-Related Disorders; Schizophrenia; Mental Disorders; Psychotic Disorders; Risperidone

Study Results

Participant Flow

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperdal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Period Title: Overall Study
STARTED	49	46
COMPLETED	36	32
NOT COMPLETED	13	14

Baseline Characteristics

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperal	Total
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.	Total of all reporting groups
Overall Participants	49	46	95
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	49 100%	46 100%	95 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	41.7 (10.1)	41.7 (11.5)	41.70 (10.7)
Sex: Female, Male (Count of Participants)
Female	12 24.5%	10 21.7%	22 23.2%
Male	37 75.5%	36 78.3%	73 76.8%
Region of Enrollment (Count of Participants)
United States	49 100%	46 100%	95 100%

Outcome Measures

1. Primary Outcome

Title	Change Over Time in Frequency of Heavy Drinking Days (Used to Evaluate Treatment Efficacy)
Description	Frequency of heavy drinking days is obtained each week retrospectively as the number of heavy drinking days during the prior week (assessed by the Timeline Followback Scale). A heavy drinking day is defined as 4 or more drinks per day for a female and 5 or more drinks per day for a male. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Measure Participants	49	46
Number (95% Confidence Interval) [heavy drinking days per week]	-.11	.68

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperidone Long Acting Injectable (LAI), Oral Risperidone Aka Risperal
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	0.054
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	difference in treatment slopes
	Estimated Value	-.043
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .021
	Estimation Comments	We report the estimated coefficient for difference in treatment slopes in a mixed model and its standard error.

2. Secondary Outcome

Title	Average Over Time of Frequency of Drinking Days (Used to Evaluate Treatment Efficacy)
Description	Frequency of drinking days is obtained each week retrospectively as the number of drinking days during the prior week (assessed using the Timeline Followback). Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperdal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Measure Participants	49	46
Number (95% Confidence Interval) [drinking days per week]	2.84	3.46

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperidone Long Acting Injectable (LAI), Oral Risperidone Aka Risperal
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.035
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	Difference in treatment means
	Estimated Value	-.62
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .29
	Estimation Comments	We report the estimated coefficient for difference in treatment means in a mixed model and its standard error.

3. Secondary Outcome

Title	Average Over Time of Severity of Illness and Global Improvement (Used to Evaluate Treatment Efficacy)
Description	A rater assesses the severity of illness and global impression using a scale from 1 to 7 (Clinical Global Impression), where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Measure Participants	49	46
Number (95% Confidence Interval) [ordinal unit of severity]	4.02	3.96

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperidone Long Acting Injectable (LAI), Oral Risperidone Aka Risperal
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.57
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	difference in treatment means
	Estimated Value	.056
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: .099
	Estimation Comments	We report the estimated coefficient for difference in treatment means in a mixed model and its standard error.

4. Secondary Outcome

Title	Average Over Time of Positive and Negative Symptoms (Used to Evaluate Treatment Efficacy)
Description	A rater assesses positive and negative symptoms of schizophrenia using a 30-item scale (Positive and Negative Symptom Score) Scores range from 30 to 210, where higher values represent a worse outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperdal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Measure Participants	49	46
Number (95% Confidence Interval) [ordinal severity of symptoms]	78.2	75.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperidone Long Acting Injectable (LAI), Oral Risperidone Aka Risperal
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.32
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	difference in treatment means
	Estimated Value	2.65
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 2.68
	Estimation Comments	We report the estimated coefficient difference in treatment means in a mixed model and its standard error.

5. Secondary Outcome

Title	Average Over Time of Global Functioning (Used to Evaluate Treatment Efficacy)
Description	A rater assesses social, occupational and psychological functioning on a hypothetical continuum of mental health - illness (using Global Assessment of Functioning); scores range from 100 to 1, where higher values represent a better outcome. Mixed models are used to obtain estimates of efficacy from the partial data provided by each subject while adherent to assigned treatment (under the 'missing at random' assumption). The 'explanatory' estimands (target of the mixed model estimation) are defined in terms of population quantities that would have occurred had all subjects remained on assigned treatment throughout the study. The point estimate for each arm is reported under Number.
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperdal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Measure Participants	49	46
Number (95% Confidence Interval) [ordinal severity of impairment]	50.8	49.9

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperidone Long Acting Injectable (LAI), Oral Risperidone Aka Risperal
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.44
	Comments
	Method	Mixed Models Analysis
	Comments
Method of Estimation	Estimation Parameter	difference in treatment means
	Estimated Value	.93
	Confidence Interval	(2-Sided) %; to
	Parameter Dispersion	Type: Standard Error of the Mean; Value: 1.19
	Estimation Comments	We report the estimated coefficient for difference in treatment means in a mixed model and its standard error.

6. Secondary Outcome

Title	Number of Participants With Medication Adherence
Description	Number of participants with medication adherence (defined as taking medication at least 75% of the days in the treatment period).
Time Frame	6 months

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Risperidone Long Acting Injectable (LAI)	Oral Risperidone Aka Risperdal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.	Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
Measure Participants	49	46
Count of Participants [Participants]	43 87.8%	28 60.9%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Risperidone Long Acting Injectable (LAI), Oral Risperidone Aka Risperal
	Comments
	Type of Statistical Test	Superiority
	Comments
Statistical Test of Hypothesis	p-Value	.003
	Comments
	Method	Chi-squared
	Comments	Statistical test of hypothesis. Value of the Chi-squared statistic is 9.08

Adverse Events

Time Frame	6 months
Arm/Group Title	Risperidone Long Acting Injectable (LAI)		Oral Risperidone Aka Risperal
Arm/Group Description	Risperidone Long Acting Injectable (LAI), begun with 25 mg dose given intramuscularly(IM)every two weeks. The dose was titrated up to a target dose of 37.5 mg IM, with injections given every two weeks. The maximum dose of LAI risperidone was 50 mg every two weeks.		Oral Risperidone aka Risperdal. Participants who were randomized to take oral risperidone were titrated over two weeks up to a target dose of 4 mg per day. The maximum daily dose of oral risperidone was 6 mg.
All Cause Mortality
	Risperidone Long Acting Injectable (LAI)		Oral Risperidone Aka Risperal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Risperidone Long Acting Injectable (LAI)		Oral Risperidone Aka Risperal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	16/49 (32.7%)		12/46 (26.1%)
Cardiac disorders
Acute Coronary Syndrome	1/49 (2%)	1	0/46 (0%)	0
General disorders
Edema	0/49 (0%)	0	1/46 (2.2%)	1
Fever	1/49 (2%)	1	0/46 (0%)	0
Injury, poisoning and procedural complications
Fall	1/49 (2%)	1	0/46 (0%)	0
Hip fracture	0/49 (0%)	0	1/46 (2.2%)	1
Injury, poisongin and procedural complications - Other, specify - Gunshot wound	0/49 (0%)	0	1/46 (2.2%)	1
Injury, poisoning and procedural complications - Other, specify Laceration	1/49 (2%)	1	0/46 (0%)	0
Injury, poisoning and procedural complications - Other, specify Accidental overdose	0/49 (0%)	0	1/46 (2.2%)	1
Musculoskeletal and connective tissue disorders
Rhabdomyolysis	0/49 (0%)	0	1/46 (2.2%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Neoplasms benign, malignant and unspecified (incl cysts and polyps) - Other, specify Colon Cancer	1/49 (2%)	1	0/46 (0%)	0
Nervous system disorders
Somnolence	1/49 (2%)	1	0/46 (0%)	0
Psychiatric disorders
Agitation	1/49 (2%)	1	1/46 (2.2%)	4
Anxiety	1/49 (2%)	1	0/46 (0%)	0
Delerium	0/49 (0%)	0	1/46 (2.2%)	1
Depression	1/49 (2%)	1	0/46 (0%)	0
Psychiatric Disorders - Other, specify - unspecified	1/49 (2%)	1	1/46 (2.2%)	1
Psychiatric Disorders - Other, specify Substance Dependence	2/49 (4.1%)	2	1/46 (2.2%)	8
Psychosis	2/49 (4.1%)	2	5/46 (10.9%)	6
Suicidal Ideation	2/49 (4.1%)	2	2/46 (4.3%)	5
Suicide Attempt	1/49 (2%)	1	1/46 (2.2%)	1
Respiratory, thoracic and mediastinal disorders
Epitaxis	1/49 (2%)	1	0/46 (0%)	0
Vascular disorders
Hypertension	1/49 (2%)	2	0/46 (0%)	0
Other (Not Including Serious) Adverse Events
	Risperidone Long Acting Injectable (LAI)		Oral Risperidone Aka Risperal
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	27/49 (55.1%)		14/46 (30.4%)
Gastrointestinal disorders
Diarrhea	4/49 (8.2%)	6	2/46 (4.3%)	2
Gastrointestinal Disorder - Other, Hypersalivation	3/49 (6.1%)	4	0/46 (0%)	0
Vomiting	5/49 (10.2%)	6	1/46 (2.2%)	1
General disorders
Injection Site Reactions	3/49 (6.1%)	15	0/46 (0%)	0
Pain	5/49 (10.2%)	5	0/46 (0%)	0
Musculoskeletal and connective tissue disorders
Musculo-Skeletal Connective Tissue Disorder-Other, Muscle Stiffness	4/49 (8.2%)	6	0/46 (0%)	0
Nervous system disorders
Somnolence	4/49 (8.2%)	7	2/46 (4.3%)	2
Psychiatric disorders
Anxiety	4/49 (8.2%)	4	1/46 (2.2%)	1
Depression	4/49 (8.2%)	6	2/46 (4.3%)	3
Insomnia	5/49 (10.2%)	8	3/46 (6.5%)	3
Psychiatric Disorders - Other, Specify: Substance Dependence	1/49 (2%)	2	3/46 (6.5%)	5
Reproductive system and breast disorders
Erectile Disfunction	3/49 (6.1%)	3	1/46 (2.2%)	1

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.