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

Enhancing Adherence and Outcomes in Bipolar Disorder With Abilify Maintena + a Targeted Behavioral Approach to Promote Sustained Adherence and Behavioral Change

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.

Study Overview

• Status: Completed
• Conditions: Bipolar Disorder; Medication Adherence; Medication Non Adherence
• Intervention / Treatment: Drug: Abilify Maintena; Behavioral: Customized Adherence Enhancement (CAE)

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 Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • Ohio
    • Cleveland, Ohio, United States, 44106
      • University Hospitals Cleveland Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: NA
• Interventional Model: SINGLE_GROUP
• Masking: NONE

Number of Arms

1

Arms and Interventions

Participant Group / 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).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Tablets Routine Questionnaire (TRQ, Past Week)	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.	Screen to Week 24
Change in Tablets Routine Questionnaire (TRQ, Past Month)	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.	Screen to Week 24
LAI Injection Adherence	LAI injection adherence will be determined as a proportion of LAI injections received at the appropriate time (within 7 days of scheduled time).	Baseline to Week 24

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in the Brief Psychiatric Rating Scale (BPRS) Score	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.	Baseline to Week 24
Change in Young Mania Rating Scale (YMRS) Score	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.	Screen to Week 24
Change in Montgomery Asberg Rating Scale (MADRS) Score	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.	Screen to Week 24
Change in Clinical Global Impressions (CGI) Score	The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition.	Screen to Week 24
Change in Drug Attitude Inventory (DAI) Score	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	Screen to Week 24
Change in Attitude Towards Medication Questionnaire (AMSQ) Score	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.	Screen to Week 24
Change in Social and Occupational Functioning Assessment Scale (SOFAS) Score	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.	Baseline to Week 24
Change in Global Assessment of Functioning (GAF) Score	The minimum score is 1 and the maximum score is 100. A higher score implies higher functioning.	Baseline to Week 24
Change in Oxford Bipolar Knowledge Questionnaires (OBQ) Score	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.	Screen to Week 24
Change in The Self-Report Habit Index (SRHI) Score	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.	Screen to Week 24
Change in Communication Styles Scale Score	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.	Screen to Week 24
Change in Stages of Change Readiness and Treatment Eagerness Scale (SOCRATES 8A) Score	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.	Screen to Week 24

Collaborators and Investigators

• Sponsor: Martha Sajatovic
• Collaborators: Otsuka Pharmaceutical Development & Commercialization, Inc.

Publications and helpful links

General Publications

• Sajatovic M, Levin JB, Ramirez LF, Cassidy KA, McNamara N, Fuentes-Casiano E, Wilson B, Appling D, S FB. Long-Acting Injectable Antipsychotic Medication Plus Customized Adherence Enhancement in Poor Adherence Patients With Bipolar Disorder. Prim Care Companion CNS Disord. 2021 Sep 16;23(5):20m02888. doi: 10.4088/PCC.20m02888.

Study record dates

Study Major Dates

• Study Start (ACTUAL): April 1, 2018
• Primary Completion (ACTUAL): May 6, 2020
• Study Completion (ACTUAL): May 6, 2020

Study Registration Dates

• First Submitted: January 16, 2018
• First Submitted That Met QC Criteria: January 16, 2018
• First Posted (ACTUAL): January 24, 2018

Study Record Updates

• Last Update Posted (ACTUAL): February 17, 2022
• Last Update Submitted That Met QC Criteria: January 26, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Bipolar Disorder; Medication Adherence; Antipsychotics; Medication Non-Adherence; Antipsychotic Drugs; Injectables; Long Acting Injectable Antipsychotic
• Additional Relevant MeSH Terms: Mental Disorders; Pathologic Processes; Bipolar and Related Disorders; Disease; Bipolar Disorder; Physiological Effects of Drugs; Neurotransmitter Agents; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Antipsychotic Agents; Tranquilizing Agents; Psychotropic Drugs; Serotonin Agents; Antidepressive Agents; Dopamine Agonists; Dopamine Agents; Serotonin 5-HT1 Receptor Agonists; Serotonin Receptor Agonists; Serotonin 5-HT2 Receptor Antagonists; Serotonin Antagonists; Dopamine D2 Receptor Antagonists; Dopamine Antagonists; Aripiprazole
• Other Study ID Numbers: I0113

Drug and device information, study documents

• 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