CAE Plus LAI in Individuals With Bipolar Disorder at Risk for Treatment Non-adherence (BD-CAEL)

• Sponsor: Martha Sajatovic (Other)
• Overall Status: Completed
• CT.gov ID: NCT03408873
• Collaborator: Otsuka Pharmaceutical Development & Commercialization, Inc. (Industry)
• Enrollment: 30
• Location: 1
• Arm: 1
• Actual Duration (Months): 25.2
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This is a prospective study using customized adherence enhancement (CAE) and long-acting injectable (LAI) antipsychotic in 30 individuals with bipolar disorder (BD) at risk for treatment non-adherence. The CAE approach is expected to improve treatment adherence, as well as improve BD symptoms, functioning and treatment attitudes among subjects with bipolar disorder.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Medication Adherence; Medication Non Adherence	Drug: Abilify Maintena; Behavioral: Customized Adherence Enhancement (CAE)	Phase 4

Detailed Description

Oral Abilify (aripiprazole) is effective in the treatment of patients with BD when prescribed as an acute anti-manic agent and for the maintenance treatment of bipolar disorder. Abilify Maintena is an intramuscular (IM) depot formulation of oral aripiprazole (Abilify). Abilify Maintena appears to be as effective as standard oral Abilify and may maximize patient adherence. Recent clinical trials suggest that Abilify Maintena is effective for the treatment of patients with BD.

Customized Adherence Enhancement (CAE) is a brief behavioral intervention that improves adherence approximately 30% more than an educational control in adults with BD. The CAE program is a brief, practical intervention consisting of a series of up to four psychosocial treatment modules based upon an adult's unique adherence barriers: 1) Psychoeducation on BD Medications; 2) Communication with Providers; 3) Strategies to Enhance Medication Routines; and 4) Targeting Substance Use Problems with Modified Motivational Enhancement Therapy. Multiple studies conducted by these investigators has shown that CAE is effective in in treating poorly adherent BD adults.

In addition, studies by these investigators have shown that combining LAI + CAE dramatically improves adherence, symptoms and functional outcomes in people with schizophrenia and schizoaffective disorder. In summary, LAI can maximize medication adherence, while CAE addresses individual barriers to sustained adherence and behavioral change. Combining LAI + CAE improves adherence, symptoms and functioning in high-risk people with primary psychotic disorders. The proposed project will test the efficacy of combining Abilify Maintena with CAE to help improve outcomes in poorly adherent patients with BD. Pilot data suggest that adherence with concomitantly prescribed psychotropic drugs improves with LAI + CAE. The findings have particular relevance to BD because many BD patients are on concomitant oral psychotropic drugs in addition to antipsychotic. Thus, it is expected that combining CAE with LAI will lead to a "halo effect" in that these BD patients will engage in their own care more broadly.

Study Design

• Study Type: Interventional
• Actual Enrollment: 30 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Enhancing Adherence and Outcomes in Bipolar Disorder With Abilify Maintena + a Targeted Behavioral Approach to Promote Sustained Adherence and Behavioral Change
• Actual Study Start Date: Apr 1, 2018
• Actual Primary Completion Date: May 6, 2020
• Actual Study Completion Date: May 6, 2020

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Patient Noncompliance Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention

Drug: Abilify Maintena; Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist.; Behavioral: Customized Adherence Enhancement (CAE); CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).

Outcome Measures

Primary Outcome Measures

1. Change in Tablets Routine Questionnaire (TRQ, Past Week) [Screen to Week 24]

   Treatment non-adherence is measured as a percentage of medications not taken within the past week at time of assessment. The minimum score is 0% and the maximum score is 100%. A higher score implies poorer treatment adherence.

2. Change in Tablets Routine Questionnaire (TRQ, Past Month) [Screen to Week 24]

   Treatment non-adherence is measured as a percentage of medications not taken within the past month at time of assessment. The minimum score is 0 and the maximum score is 100. A higher score implies poorer treatment adherence.

3. LAI Injection Adherence [Baseline to Week 24]

   LAI injection adherence will be determined as a proportion of LAI injections received at the appropriate time (within 7 days of scheduled time).

Secondary Outcome Measures

1. Change in the Brief Psychiatric Rating Scale (BPRS) Score [Baseline to Week 24]

   The BPRS measure psychiatric symptoms such as depression, anxiety, hallucinations and unusual behavior. The minimum score is 18 and the maximum score is 126. A higher score implies a worse condition.

2. Change in Young Mania Rating Scale (YMRS) Score [Screen to Week 24]

   The YMRS measures symptoms of mania. The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.

3. Change in Montgomery Asberg Rating Scale (MADRS) Score [Screen to Week 24]

   The MADRS measures symptoms of depression. The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.

4. Change in Clinical Global Impressions (CGI) Score [Screen to Week 24]

   The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition.

5. Change in Drug Attitude Inventory (DAI) Score [Screen to Week 24]

   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

6. Change in Attitude Towards Medication Questionnaire (AMSQ) Score [Screen to Week 24]

   A modification of the Lithium Attitudes Questionnaire (Harvey 1991) which evaluates an individual's attitudes towards mood stabilizers. The AMSQ is used to measure attitudes towards medications. The scale contains 19 items grouped into 7 subscales: general opposition to prophylaxis (4 items), denial of therapeutic effectiveness (2 items), fear of side effects (2 items), difficulty with medication routines (4 items), denial of illness severity (3 items), negative attitudes toward drugs in general (3 items), and lack of information about psychiatric medication (1 item). 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 which is reported, with the minimum total score of 0 and maximum total score of 19. Higher scores on each subscale represent more negative attitudes toward mood stabilizers.

7. Change in Social and Occupational Functioning Assessment Scale (SOFAS) Score [Baseline to Week 24]

   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.

8. Change in Global Assessment of Functioning (GAF) Score [Baseline to Week 24]

   The minimum score is 1 and the maximum score is 100. A higher score implies higher functioning.

9. Change in Oxford Bipolar Knowledge Questionnaires (OBQ) Score [Screen to Week 24]

   The OBQ assess knowledge of BD management. Total score rangers from 0-80, with a higher score indicative of better knowledge of bipolar mood management.

10. Change in The Self-Report Habit Index (SRHI) Score [Screen to Week 24]

    The SRHI is a measure of habit strength. The minimum score is 12 and the maximum score is 84. A higher score implies stronger habits.

11. Change in Communication Styles Scale Score [Screen to Week 24]

    The Communication Styles Scale is a measure of the impact of physician communication style on medication beliefs and adherence behavior. Total scores range from 0-27 where the higher score indicates a more initial collaborative communication style.

12. Change in Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Score [Screen to Week 24]

    The SOCRATES measures motivation to reduce the use of substances. The minimum score is 10 and the maximum score is 50. A higher score indicates a higher desire to reduce drinking.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. Individuals age 18 and older with BD Type 1 or 2 as confirmed by the Mini International Psychiatric Inventory (MINI).

2. Known to have medication treatment adherence problems as identified by the Treatment Routines Questionnaire (TRQ, 20% or more missed medications in past week or past month)

3. Screening the Brief Psychiatric Rating Scale (BPRS) score of ≥ 36

4. Ability to be rated on psychiatric rating scales.

5. Willingness to take long-acting injectable antipsychotic medication (LAI)

6. Currently in treatment or scheduled to receive treatment at a Community Mental Health Clinic (CMHC) or other clinical setting able to provide mental health care during and after study participation

7. Able to provide written, informed consent to study participation.

Exclusion Criteria:

1. Individuals on LAI immediately prior to study enrollment.

2. Individuals with known intolerance or resistance to either oral aripiprazole or LAI formulation of aripiprazole

3. Prior or current treatment with clozapine

4. Medical condition or illness, which in the opinion of the research psychiatrist, would interfere with the patient's ability to participate in the trial

5. Physical dependence on substances (alcohol or illicit drugs) likely to lead to withdrawal reaction during the course of the study in the clinical opinion of the treated research psychiatrist

6. Immediate risk of harm to self or others

7. Female who is currently pregnant or breastfeeding

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University Hospitals Cleveland Medical Center	Cleveland	Ohio	United States	44106

Sponsors and Collaborators

• Martha Sajatovic
• Otsuka Pharmaceutical Development & Commercialization, Inc.

Investigators

• Principal Investigator: Martha Sajatovic, MD, University Hospitals Cleveland Medical Center

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Dec 18, 2017

More Information

Publications

None provided.

• Responsible Party: Martha Sajatovic, Professor of Psychiatry, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT03408873
• Other Study ID Numbers: I0113
• First Posted: Jan 24, 2018
• Last Update Posted: Feb 17, 2022
• Last Verified: Jan 1, 2022

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Product Manufactured in and Exported from the U.S.: No
• Keywords provided by Martha Sajatovic, Professor of Psychiatry, University Hospitals Cleveland Medical Center: Antipsychotic Drugs; Antipsychotics; Injectables; Long Acting Injectable Antipsychotic; Bipolar Disorder; Medication Adherence; Medication Non-Adherence
• Additional relevant MeSH terms: Disease; Bipolar Disorder; Aripiprazole

Study Results

Participant Flow

Recruitment Details

. Individuals were recruited from an academic medical center and via outreach to community settings including community mental health clinics (CMHCs). Enrolled participants had self-reported adherence problems as identified by the TRQ (≥20% missed BD medications in past week or past month), a screening Brief Psychiatric Rating Scale15 score ≥36, willingness to take LAI, and were in treatment at a CMHC or other clinical setting. Participants were adults ≥ age 18 with Type 1 or Type 2 BD.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Period Title: Visit 1 Assessment (Baseline)
STARTED	30
COMPLETED	27
NOT COMPLETED	3
Period Title: Visit 1 Assessment (Baseline)
STARTED	27
COMPLETED	26
NOT COMPLETED	1
Period Title: Visit 1 Assessment (Baseline)
STARTED	26
COMPLETED	25
NOT COMPLETED	1
Period Title: Visit 1 Assessment (Baseline)
STARTED	25
COMPLETED	23
NOT COMPLETED	2
Period Title: Visit 1 Assessment (Baseline)
STARTED	23
COMPLETED	22
NOT COMPLETED	1
Period Title: Visit 1 Assessment (Baseline)
STARTED	22
COMPLETED	21
NOT COMPLETED	1
Period Title: Visit 1 Assessment (Baseline)
STARTED	21
COMPLETED	21
NOT COMPLETED	0

Baseline Characteristics

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Overall Participants	30
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	49.47 (9.28)
Sex: Female, Male (Count of Participants)
Female	13 43.3%
Male	17 56.7%
Race/Ethnicity, Customized (Count of Participants)
White	9 30%
Black or African American	17 56.7%
Other or Multiracial	4 13.3%
Race/Ethnicity, Customized (Count of Participants)
Hispanic	1 3.3%
Non Hispanic	29 96.7%
Marital Status (Count of Participants)
Single, never married	17 56.7%
Married	1 3.3%
Separated/Divorced/Widowed	12 40%
Mean Years of Education Attained (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	13.63 (2.85)
Occupation Status (Count of Participants)
Full time employment/homemaker	0 0%
Part time employment/ homemaker or student	4 13.3%
Unemployed or on disability	25 83.3%
Other	1 3.3%
Number of Participants Who Live Alone (Count of Participants)
Count of Participants [Participants]	16 53.3%
Age at Bipolar onset (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	27.63 (11.80)
Duration of bipolar illness (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	21.56 (11.74)
Number of Participants With Current Substance Use Problems (Count of Participants)
Count of Participants [Participants]	6 20%
Mean lifetime psychiatric hospitalizations (hospitalizations) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hospitalizations]	3.07 (3.43)
Mean lifetime substance abuse hospitalizations (hospitalizations) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [hospitalizations]	1.06 (2.00)
Number of Participants With History of Physical Abuse (Count of Participants)
Count of Participants [Participants]	16 53.3%
Number of Participants With History of Sexual Abuse (Count of Participants)
Count of Participants [Participants]	10 33.3%
Number of Participants With Family history of Mental Illness (Count of Participants)
Count of Participants [Participants]	28 93.3%
Number of Participants With Family history of Substance Abuse (Count of Participants)
Count of Participants [Participants]	23 76.7%

Outcome Measures

1. Primary Outcome

Title	Change in Tablets Routine Questionnaire (TRQ, Past Week)
Description	Treatment non-adherence is measured as a percentage of medications not taken within the past week at time of assessment. The minimum score is 0% and the maximum score is 100%. A higher score implies poorer treatment adherence.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	29
Screen	50.1 (24.8)
Baseline	37.5 (30.0)
Week 24	16.9 (26.97)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 29 participants with screen data only 11 had Week 24 data. Statistical Analysis was conducted for 11 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-31.4
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between baseline & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 28 participants with baseline data only 11 had Week 24 data. Statistical Analysis was conducted for 11 participants with data at the 2 timepoints. The mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.12
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-11.7
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Primary Outcome

Title	Change in Tablets Routine Questionnaire (TRQ, Past Month)
Description	Treatment non-adherence is measured as a percentage of medications not taken within the past month at time of assessment. The minimum score is 0 and the maximum score is 100. A higher score implies poorer treatment adherence.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	29
Screen	40.6 (23.7)
Baseline	29.4 (21.6)
Week 24	19.2 (24.5)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 29 participants with screen data only 11 had Week 24 data. Statistical Analysis was conducted for 11 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0599
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-19.6
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between baseline & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 28 participants with baseline data only 11 had Week 24 data. Statistical Analysis was conducted for 11 participants with data at the 2 timepoints. The mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.63
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.2
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

3. Primary Outcome

Title	LAI Injection Adherence
Description	LAI injection adherence will be determined as a proportion of LAI injections received at the appropriate time (within 7 days of scheduled time).
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	20
Mean (Standard Deviation) [percentage of adherence]	100 (0)

4. Secondary Outcome

Title	Change in the Brief Psychiatric Rating Scale (BPRS) Score
Description	The BPRS measure psychiatric symptoms such as depression, anxiety, hallucinations and unusual behavior. The minimum score is 18 and the maximum score is 126. A higher score implies a worse condition.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Baseline	36.4 (7.4)
Week 24	24.9 (5.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between baseline & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with baseline data only 19 had Week 24 data. Statistical Analysis was conducted for 19 participants with data at the 2 timepoints. The mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.7
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change in Young Mania Rating Scale (YMRS) Score
Description	The YMRS measures symptoms of mania. The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	13.2 (6.2)
Baseline	10.4 (5.6)
Week 24	5.6 (4.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with screen data, only 19 had Week 24 data. Statistical Analysis was conducted for 19 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.4
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared for the primary and secondary outcomes across two sets of time-points: 1) difference between screen and week 24, and 2) between baseline and week 24. A non-parametric Wilcoxon signed-rank test compared these repeated measurements (matched on participant) between these time-points to determine whether the population medians differed.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-5.8
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change in Montgomery Asberg Rating Scale (MADRS) Score
Description	The MADRS measures symptoms of depression. The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	24.5 (5.7)
Baseline	18.1 (9.4)
Week 24	7.95 (8.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with screen data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-16.6
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared for the primary and secondary outcomes across two sets of time-points: 1) difference between screen and week 24, and 2) between baseline and week 24. A non-parametric Wilcoxon signed-rank test compared these repeated measurements (matched on participant) between these time-points to determine whether the population medians differed.
	Type of Statistical Test	Other
	Comments	We compared the repeated measure outcome across 2 time-points (difference between baseline & week 24) to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with baseline data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. The mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
Statistical Test of Hypothesis	p-Value	0.003
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-8.1
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in Clinical Global Impressions (CGI) Score
Description	The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	4.6 (0.5)
Baseline	4.1 (0.6)
Week 24	2.8 (0.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments
	Type of Statistical Test	Other
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data.
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.8
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Statistical Analysis 2

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared for the primary and secondary outcomes across two time-points: difference between baseline and week 24. A non-parametric Wilcoxon signed-rank test compared these repeated measurements (matched on participant with complete data) between these time-points to determine whether the population medians differed.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-1.3
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Change in Drug Attitude Inventory (DAI) Score
Description	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
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	7.2 (1.9)
Week 24	8.1 (1.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared for the primary and secondary outcomes across two sets of time-points: 1) difference between screen and week 24, and 2) between baseline and week 24. A non-parametric Wilcoxon signed-rank test compared these repeated measurements (matched on participant) between these time-points to determine whether the population medians differed.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.0566
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	0.8
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

9. Secondary Outcome

Title	Change in Attitude Towards Medication Questionnaire (AMSQ) Score
Description	A modification of the Lithium Attitudes Questionnaire (Harvey 1991) which evaluates an individual's attitudes towards mood stabilizers. The AMSQ is used to measure attitudes towards medications. The scale contains 19 items grouped into 7 subscales: general opposition to prophylaxis (4 items), denial of therapeutic effectiveness (2 items), fear of side effects (2 items), difficulty with medication routines (4 items), denial of illness severity (3 items), negative attitudes toward drugs in general (3 items), and lack of information about psychiatric medication (1 item). 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 which is reported, with the minimum total score of 0 and maximum total score of 19. Higher scores on each subscale represent more negative attitudes toward mood stabilizers.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	7.9 (3.3)
Week 24	4.0 (3.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared for the primary and secondary outcomes across two time-points: difference between screen and week 24. A non-parametric Wilcoxon signed-rank test compared these repeated measurements (matched on participant with complete data) between these time-points to determine whether the population medians differed.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-3.4
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in Social and Occupational Functioning Assessment Scale (SOFAS) Score
Description	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.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Baseline	51.9 (8.1)
Week 24	70.8 (8.1)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with screen data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	17.7
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Change in Global Assessment of Functioning (GAF) Score
Description	The minimum score is 1 and the maximum score is 100. A higher score implies higher functioning.
Time Frame	Baseline to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Baseline	53.5 (8.1)
Week 24	70.7 (7.9)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between baseline & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with baseline data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. The mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	16.9
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

12. Secondary Outcome

Title	Change in Oxford Bipolar Knowledge Questionnaires (OBQ) Score
Description	The OBQ assess knowledge of BD management. Total score rangers from 0-80, with a higher score indicative of better knowledge of bipolar mood management.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	29
Screen	52.9 (16.1)
Week 24	70.7 (8.4)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 29 participants with screen data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	14.7
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

13. Secondary Outcome

Title	Change in The Self-Report Habit Index (SRHI) Score
Description	The SRHI is a measure of habit strength. The minimum score is 12 and the maximum score is 84. A higher score implies stronger habits.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	47.3 (12.4)
Week 24	68.5 (13.8)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with screen data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	<0.001
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	19.2
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

14. Secondary Outcome

Title	Change in Communication Styles Scale Score
Description	The Communication Styles Scale is a measure of the impact of physician communication style on medication beliefs and adherence behavior. Total scores range from 0-27 where the higher score indicates a more initial collaborative communication style.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	22.4 (4.2)
Week 24	22.1 (6.3)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with screen data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.73
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-0.5
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

15. Secondary Outcome

Title	Change in Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Score
Description	The SOCRATES measures motivation to reduce the use of substances. The minimum score is 10 and the maximum score is 50. A higher score indicates a higher desire to reduce drinking.
Time Frame	Screen to Week 24

Outcome Measure Data

Analysis Population Description

Poorly adherent patients with bipolar disorder who received long-acting injectable antipsychotic medication and a customized adherence enhancement intervention (CAE). Descriptive statistics (means and standard deviations or counts and percentages) were generated for all outcomes measures using complete cases.

Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
Measure Participants	30
Screen	46.8 (16.8)
Week 24	34.8 (18.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	CAE-L
	Comments	We compared the repeated measure outcome across 2 time-points (difference between screen & week 24 to determine whether the population medians differed matched on participant with complete data. Of the 30 participants with screen data, only 21 had Week 24 data. Statistical Analysis was conducted for 21 participants with data at the 2 timepoints. Thus, the mean difference reported is not consistent with the mean values reported because only those with complete data were included in the analysis.
	Type of Statistical Test	Other
	Comments
Statistical Test of Hypothesis	p-Value	0.02
	Comments
	Method	Wilcoxon (Mann-Whitney)
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-10.7
	Confidence Interval	(2-Sided) 95%; to
	Parameter Dispersion	Type: Value:
	Estimation Comments

Adverse Events

Time Frame	Safety evaluations at baseline & Week 24 included basic laboratory evaluations (comprehensive metabolic panel, lipid profile, complete blood count (CBC) with differential & pregnancy testing).EKGs at baseline & Weeks 4 & 24. Side effects, vital signs & weight assessed at each clinical visit &standardized measures of extrapyramidal symptoms i.e.Simpson Angus Scale (SAS)Barnes Akathisia Scale(BAS) Abnormal Involuntary Movement Scale(AIMS) &Extrapyramidal Symptoms Scale-Abbreviated version(ESRS-A).
Arm/Group Title	CAE-L
Arm/Group Description	Subjects enrolled in the study will receive both Abilify Miantena and the Customized Adherence Enhancement (CAE) intervention Abilify Maintena: Drug is in an injectable form and will be administered approximately every four weeks through Week 24 of the study. Dosage is per package insert or at the discretion of the psychiatrist. Customized Adherence Enhancement (CAE): CAE targets key areas relevant to non-adherent populations with schizophrenia or schizoaffective disorder: 1) inadequate or incorrect understanding of mental disorder; 2) lack of medication-taking routines; 3) poor communication with care providers; and 4) substance use which interferes with adherence and healthy behaviors that promote recovery. CAE is delivered based upon initial assessment of reasons for non-adherence and only those components of CAE that are determined to be indicated for that individual are delivered (psychoeducation, modified motivational interviewing, assistance with medication routines, coaching in communication with providers).
All Cause Mortality
	CAE-L
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Serious Adverse Events
	CAE-L
	Affected / at Risk (%)	# Events
Total	0/30 (0%)
Other (Not Including Serious) Adverse Events
	CAE-L
	Affected / at Risk (%)	# Events
Total	23/30 (76.7%)
General disorders
Drooling	2/23 (8.7%)
Metabolism and nutrition disorders
Weight gain	2/23 (8.7%)
Musculoskeletal and connective tissue disorders
Muscle Movement complaints	2/23 (8.7%)
Nervous system disorders
Drowsiness	7/23 (30.4%)
Tremor	6/23 (26.1%)
Reproductive system and breast disorders
Sexual dysfunction	3/23 (13%)
Skin and subcutaneous tissue disorders
Injection site pain or reaction	7/23 (30.4%)

Limitations/Caveats

This study had a number of limitations including small sample, non-controlled design, and single-site setting. An additional limitation is that adherence was based upon self-report, which has potential to under-count missed medication. The improvement in adherence behaviors immediately after screen (and before CAE was administered) may possibly reflect a Hawthorne effect which could have obscured improvement in CAE-related change.

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.