News Release

Study finds long-term injectable medications combined with counseling improves adherence and symptoms in patients with bipolar disorder

Researchers from University Hospitals Cleveland Medical Center and Case Western Reserve University School of Medicine see potential for substantial outcome improvements

Peer-Reviewed Publication

University Hospitals Cleveland Medical Center

CLEVELAND -- Researchers have found that adherence to taking medications improved in people with bipolar disorder with the use of long-term injectable meds combined with psychosocial intervention.

The research results from University Hospitals (UH) Cleveland Medical Center and Case Western Reserve University (CWRU) School of Medicine appear in the September 16, 2021 issue of the journal the Primary Care Companion for CNS Disorders. 

“Poor medication adherence is widely prevalent in people with bipolar disorder and is often associated with negative outcomes,” said lead author Martha Sajatovic, MD, Director of the Neurological and Behavioral Outcomes Center, CWRU School of Medicine and UH Cleveland Medical Center.  “A growing body of literature focuses on clinical approaches to address poor adherence that may lead to substantial outcome improvements for this group of people.”

Bipolar disorder is a mental health condition that causes extreme mood swings that include emotional highs (mania or hypomania) and lows (depression).

The study enrolled 30 people with bipolar disorder who had adherence problems.  More than 20 percent of them reported missing their bipolar medication in the past week or month when initially screened.  

For the study, the participants were given the long-acting injectable (LAI) antipsychotic medication aripiprazole, approved by the US Food and Drug Administration (FDA) for the treatment of bipolar disorder.

“However, in spite of the adherence advantages for long-acting injectable meds, simply switching individuals to them may not be enough to sustain long-term behavioral change,” said Dr. Sajatovic.  “Our pilot trial combined the LAI with a brief behavioral approach called customized adherence enhancement (CAE). Together we called them CAE-L to assess the effects on adherence, bipolar disorder symptoms, and functional status,” she said.

CAE was delivered by a trained social worker following a detailed curriculum and delivered in the same clinical visit when the patients came in for their medication.  According to Dr. Sajatovic, barriers to adherence could consist of multiple components, including a lack of education about the medications; communication issues with providers; strategies to enhance medication routines, and substance abuse issues.  

The CAE is a brief, practical intervention program designed to address an individual’s specific adherence barriers. Each module could be combined with other modules as determined by a screening assessment.  For this study, CAE was delivered in seven sessions (an initial baseline session, followed by one each month for the six months of the study).

The medication was also administered once a month for six months.  Participants also continued other maintenance treatments such as mood-stabilizing drugs (lithium, valproate, or lamotrigine), or antidepressants, and hypnotic drugs for sleep prescribed for at least one month prior to enrollment.

“Overall, our findings suggest that a personalized intervention to address adherence barriers combined with LAI can significantly improve outcomes in high-risk individuals with bipolar disorder,” said Dr. Sajatovic.  

At the end of the six months, self-reported adherence behaviors improved.  Adherence remained steady and bipolar symptoms improved.

CAE-L was associated with excellent adherence to LAI (100 percent of individuals received injection within one week of the scheduled time), compared with initial screening where individuals missed a mean of 50.1 percent of prescribed oral medication in the past week and 40.6 percent of medication in the past month.

The proportion of missed medications in the past week from screen to 24 weeks significantly improved from 50.1 percent to 16.9 percent, and past month improved from 40.6 percent to 19.2 percent.

From baseline to week 24, there were significant decreases in bipolar disorder symptoms and global psychopathology. Functioning was significantly improved from baseline to week 24.  Participants also found CAE intervention was highly acceptable.

The study’s limitations include small sample size, no control group for comparison, and all patients coming from a single hospital site.  An additional limitation is that adherence was based on self-report, which has potential to undercount missed medication.  Twenty-one completed the trial out of the initial 30 who started (nine participants dropped out of the study early for various reasons). 

In addition to Dr. Sajatovic, MD, the other authors are Jennifer B. Levin, PhD; Luis F. Ramirez, MD; Kristin A. Cassidy, MA; Nora McNamara, MD; Edna Fuentes-Casiano, MSSA, LSW;

Deionte Appling, BA, all with CWRU and UH; Farren B. S. Briggs, PhD, with CWRU, and Betsy Wilson, MPH, who was with CWRU and UH at the time of the study.


About Case Western Reserve University

Case Western Reserve University is one of the country's leading private research institutions. Located in Cleveland, we offer a unique combination of forward-thinking educational opportunities in an inspiring cultural setting. Our leading-edge faculty engage in teaching and research in a collaborative, hands-on environment. Our nationally recognized programs include arts and sciences, dental medicine, engineering, law, management, medicine, nursing and social work. About 5,100 undergraduate and 6,700 graduate students comprise our student body. Visit to see how Case Western Reserve thinks beyond the possible.

About University Hospitals / Cleveland, Ohio
Founded in 1866, University Hospitals serves the needs of patients through an integrated network of 23 hospitals (including 5 joint ventures), more than 50 health centers and outpatient facilities, and over 200 physician offices in 16 counties throughout northern Ohio. The system’s flagship quaternary care, academic medical center, University Hospitals Cleveland Medical Center, is affiliated with Case Western Reserve University School of Medicine, Oxford University and the Technion Israel Institute of Technology. The main campus also includes the UH Rainbow Babies & Children's Hospital, ranked among the top children’s hospitals in the nation; UH MacDonald Women's Hospital, Ohio's only hospital for women; and UH Seidman Cancer Center, part of the NCI-designated Case Comprehensive Cancer Center. UH is home to some of the most prestigious clinical and research programs in the nation, with more than 3,000 active clinical trials and research studies underway. UH Cleveland Medical Center is perennially among the highest performers in national ranking surveys, including “America’s Best Hospitals” from U.S. News & World Report. UH is also home to 19 Clinical Care Delivery and Research Institutes. UH is one of the largest employers in Northeast Ohio with more than 30,000 employees. Follow UH on LinkedIn, Facebook and Twitter. For more information, visit

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