Treatment to Enhance Cognition in Bipolar Disorder

Not Applicable

Completed

Conditions: Psychosis
Bipolar Disorder

Interventions: Behavioral: BrainWorks
Behavioral: Computer Control

Registration Number: NCT01470781

Lead Sponsor: Mclean Hospital

Brief Summary: The purpose of the present study is to evaluate a neuroplasticity-oriented, computer-based cognitive remediation treatment program in patients with bipolar disorder and its effects on cognitive deficits and community functioning compared to an active, computer-based control.

Detailed Description: Cognitive dysfunction is increasingly recognized as a major feature of bipolar disorder (BD), present by illness onset, persistent into euthymia, and associated with functional outcome. Deficits are qualitatively similar to those seen in schizophrenia (SZ), and may be quantitatively similar in some patient groups, e.g. in patients with a history of psychosis. Despite strong associations between cognitive impairment and functional outcomes in BD, treatment for these symptoms at present is inadequate. Pharmacotherapies do little to address cognitive symptoms, and may even worsen them. Psychosocial cognitive remediation (CR) treatments have been developed to target these symptoms and their functional correlates, and have shown early promise in patients with SZ in improving both neurocognition and community functioning. However, despite the overlap of neurocognitive deficits between patients with SZ and BD, no studies to date have extended neuroscience-based CR to patients with BD. The present study aims to assess the efficacy of CR treatment in patients with BD with a history of psychosis using a 70-hour CR paradigm compared to a dose-matched computer-based control. It is hypothesized that patients in the CR group will exhibit improvements in cognitive and community functioning compared to controls, which will persist during a 6-month durability phase. Additionally, putative mechanisms of functional change will be examined, including mediator effects of cognitive and clinical change on community functioning. 130 patients with BD with a history of psychosis recruited from the Psychotic Disorders Programs at McLean Hospital will be randomized into either the CR or computer control group. CR will be administered using the BrainWorks program, neuroscience-based training programs that have shown early promise in patients with SZ. Participants will be assessed on measures of clinical, cognitive, and community functioning at baseline, following the 70-hour treatment or control phase, and again 6 months later. Participants may opt to participate in an functional magnetic resonance imaging (fMRI) study at pre- and post-treatment; resting state, task-based and functional connectivity, and diffusion tensor imaging data will be collected to evaluate preliminary evidence of neurobiological changes after training versus control. Additionally, participants may opt in to participation in two tasks of reward sensitivity including the Probabilistic Reward task and Richard's Delay Discounting. These tasks are administered pre- and post-treatment to evaluate the role of reward in treatment response as well as the potential for CR to modulate reward processing. This project is in keeping with the NIH's stated strategic priorities for improving mental health outcomes in patients and strengthening the impact of National Institute of Mental Health (NIMH)-supported research on public health, with specific recommendations for broad implementation of effective psychosocial interventions.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 72

Inclusion Criteria

Clinical diagnosis of BD with psychosis
Positive and Negative syndrome Scale (PANSS) < 75; PANSS Psychosis item scores = 3 or under; Young Mania Rating Scale (YMRS) = 6 or under
Age between 18 and 50
Within 10 years of illness onset
Legal and mental competency of the participant

Exclusion Criteria

Age under 18 or over 50
PANSS >75; PANSS Psychosis item scores >3; YMRS > 6
Legal or mental incompetence (legal incompetence defined by any guardianship (including of person or treatment guardianship); mental incompetence defined by failure of the informed consent survey)
Psychiatric inpatient status at time of enrollment
Delirium secondary to medical illness
Psychotic or mood disorder due to general medical or neurological illness
History of head trauma
History of seizure disorder or photo-sensitive seizures
Use of anticholinergic medication, clozapine or olanzapine at baseline
Rapid-cycling bipolar disorder
Diagnosis of current substance abuse (past month) or substance dependence within the past year.

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Cognitive Remediation	BrainWorks	This arm will receive computer-based cognitive remediation treatment 3 times per week for 24 weeks, for a total of 70 hours of treatment
Computer Control	Computer Control	Group will receive 70 hours of computer time playing pre-selected computer games administered in a similar format as the Cognitive Remediation condition

Primary Outcome Measures

Name	Time	Method
MATRICS Consensus Cognitive Battery (MCCB)	within 1 week prior to initiating intervention; midpoint - on average 8 weeks after initiation; post-treatment - on average 24 weeks after initiation; after 6 months no active intervention	The Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) battery includes 10 tasks that are designed to measure seven key cognitive domains: processing speed, attention, working memory, verbal learning, visual learning, problem solving and social cognition. These scores are also combined to yield a cognitive Composite. All subtest, domain, and composite scores are reported in standardized T scores with a mean of 50 and a standard deviation of 10; higher scores reflect better performance. For example, a score of 60 on any subtest, domain, or the Composite would represent a score 1 standard deviation above than the mean. All standardized scores are computed by the MCCB scoring software included in the testing battery, and are normed by age and sex. Total administration time is 60-90 minutes.

Secondary Outcome Measures

Name	Time	Method
Positive and Negative Syndrome Scale (PANSS)	within 1 week prior to initiating intervention; midpoint - on average after 8 weeks of initiation; post-treatment - on average 24 weeks after initiation; after 6 months of no active study intervention	The PANSS is an interview-administered measure assessing positive and negative symptoms of psychosis, and general psychiatric symptoms. The PANSS consists of 30 total items scored 1-7 (least to most severe). Both Positive and Negative sub scales consist of 7 items each for a total possible score of 49 for each sub scale; the General sub scale consists of 16 items for a total possible score of 112. As the lowest possible score is 1, the lower bound of PANSS total score is 30. Higher scores reflect greater symptom severity. Based on the authors' original publication Kay and colleagues reported mean score in a sample of people with schizophrenia as follows: Positive scale = 18.20 Negative scale = 21.01 General psychopathology = 37.74 Administration = approximately 40 minutes
Social and Occupational Functioning Assessment Scale	within 1 week prior to initiating intervention; midpoint - on average after 8 weeks of initiation; post-treatment - on average 24 weeks after initiation; after 6 months of no active study intervention	The SOFAS is a 100-point scale similar to the Global Assessment of Functioning designed to evaluate social and occupational functioning not directly influenced by psychological symptom severity. Assessment is based on rater impression and includes a single assigned number. Scores may range from 0-100, with higher scores reflecting better functioning.
Young Mania Rating Scale (YMRS)	within 1 week prior to initiating intervention; midpoint - on average after 8 weeks of initiation; post-treatment - on average 24 weeks after initiation; after 6 months of no active study intervention	The YMRS is an interview style measure asking about hallmark symptoms of mania. Total score ranges from 0 to 60 where higher scores indicate more severe symptoms of mania. Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania). Administration time = approximately 10 minutes
Montgomery-Asberg Depression Rating Scale (MADRS)	within 1 week prior to initiating intervention; midpoint - on average after 8 weeks of initiation; post-treatment - on average 24 weeks after initiation; after 6 months of no active study intervention	The MADRS is an interview-style rating scale to assess severity of symptoms of depression. The MADRS consists of 10 items scored 0-6. Total MADRS scores range from 0-60, with higher score indicates more severe depression. Typical clinical cutoff points are: 0 to 6 - normal/symptom absent; 7 to 19 - mild depression; 20 to 34 - moderate depression; 34 - severe depression. Administration time = 10 minutes
Multnomah Community Ability Scale (MCAS)	within 1 week prior to initiating intervention; midpoint - on average after 8 weeks of initiation; post-treatment - on average 24 weeks after initiation; after 6 months of no active study intervention	The MCAS is an interview-based assessment that measures functioning in psychiatric patients in multiple domains including social interest and effectiveness, independence in daily living, and instrumental role functioning. The present study uses an abbreviated version of the form consisting of 11 total items scored 1-5, with higher scores reflecting better community functioning. The abbreviated version (Lewandowski et al., 2013) was selected because it assesses community functioning independent of cognition or clinical symptoms, which would represent a confound in the present study. Total possible scores range from 11-55, with higher scores reflecting better community functioning.