Bipolar Youth Treated With Second-generation Antipsychotics
Conditions
Keywords
Bipolar disorder, Second-generation antipsychotics, Obesity, Cardiometabolic risk
Brief summary
The investigators tested the hypothesis that long-chain omega-3 (LCn-3) fatty acid supplementation will attenuate the adverse cardiometabolic effects of second-generation antipsychotics exposure in first-episode adolescent manic patients.
Detailed description
Following acute (6-week) open-label treatment with quetiapine, first-episode adolescent manic patients (ages 10-17 years) were randomized to double-blind adjunctive treatment with long-chain omega-3 (LCn-3) fatty acids or placebo for 24 weeks to investigate protective effects on the of adverse cardiometabolic events and weight gain during quetiapine maintenance therapy. They will have 6 visits over a 24-week period.
Interventions
DRUGOmega
Omega-3 supplements
DRUGPlacebo
Similar in shape and color to Omega supplements
DRUGQuetiapine fumarate
Prior to randomization to Omega/placebo, patients were started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg.
Sponsors
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
University of Cincinnati
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
10 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
* DSM-IV-TR criteria for bipolar disorder, type I, manic or mixed episode * Baseline YMRS score \> 20 * Ages 10-17 years * Tanner scale stages III-V * No prior exposure to SGA medications * Fluent in English * Provision of written informed consent by a legal guardian and written assent by the subject * Manic or depressive symptoms do not result entirely from acute medical illness or acute intoxication or withdrawal from drugs or alcohol as determined by medical evaluation and rapid symptom resolution * If female and of child bearing potential, agrees to use one of the following method of birth control: complete abstinence from sexual intercourse, barrier (diaphragm or condom), or oral/injectable contraceptive. For Phase II, additional Inclusion criteria are * Receiving a stable therapeutic dose of quetiapine for a minimum of 1 week (i.e., patients who achieved remission (YMRS total score 7 during Phase I) * Not requiring concomitant use of antidepressant or mood-stabilizer medications (see Section C.4.c. Concomitant Medications).
Exclusion criteria
* IQ \< 70, as determined by The Wechsler Abbreviated Scale of Intelligence * Positive pregnancy test (to avoid teratogenesis) * A history of major cardiovascular or neurological illness * Any lifetime DSM-IV-TR substance use disorder (nicotine dependence is permitted) * A lifetime DSM-IV-TR diagnosis of any pervasive developmental disorder * Any history of a hematological disorder in themselves or a first-degree relative will be excluded (since omega-3 fatty acids may be associated with anti-thrombotic effects). Similarly, concomitant use of medications with anticoagulant effects (e.g. aspirin) will be prohibited * Allergy to fish/seafood; 8) Currently taking omega-3 fatty acid supplements
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Body Mass Index (BMI) | 24 weeks | Body Mass Index (BMI) is a measure of body fat calculated as weight in kilograms divided by height in meters squared (kg/m\^2). BMI Categories are: Underweight = \<18.5; Normal weight = 18.5-24.9; Overweight = 25-29.9; Obesity = BMI of 30 or greater. Greater decreases in BMI are a better outcome. |
| Fasting Blood Triglycerides Levels | 24 weeks | Triglycerides are the chemical form in which most fat exists in food as well as in the body. They're also present in blood plasma and, in association with cholesterol, form the plasma lipids. Levels are categorized as follows: Normal - Less than 150 milligrams per deciliter (mg/dL); Borderline high - 150 to 199 mg/dL; High - 200 to 499 mg/dL; Very high - 500 mg/dL or above. Greater reductions blood triglyceride levels are a better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Manic Symptom Severity | 24 weeks | Manic symptom ratings will be obtained using the Young Mania Rating Scale (YMRS). The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania: Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania). Greater reductions from baseline indicates a greater improvement in manic symptoms. |
Countries
United States
Participant flow
Pre-assignment details
All patients received 6-week open-label quetiapine prior to entering the trial.
Participants by arm
| Arm | Count |
|---|---|
| Quitiapine Plus Omega Patients will be randomized to EPA+DHA supplements (OmegaRx) a fixed dose of 3.0 g/day (EPA: 2.0 g, DHA: 1.0 g; 5 capsules/d) for 24 weeks
Omega: Omega-3 supplements
Quetiapine fumarate: Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg. | 9 |
| Quetiapine Plus Placebo Patients will be randomized to similar in shape an color placebo supplements (corn oil)
Placebo: Similar in shape and color to Omega supplements
Quetiapine fumarate: Patients will be started on 100 mg BID of quetiapine, and the dose adjusted based on tolerability and response. The quetiapine target dose is 400-600 mg. | 10 |
| Total | 19 |
Baseline characteristics
| Characteristic | Quitiapine Plus Omega | Quetiapine Plus Placebo | Total |
|---|---|---|---|
| Age, Continuous | 15.4 years STANDARD_DEVIATION 2.2 | 14.1 years STANDARD_DEVIATION 1.8 | 14.7 years STANDARD_DEVIATION 2 |
| Body Mass Index (BMI) | 23.1 kg/m^2 STANDARD_DEVIATION 4.2 | 26.2 kg/m^2 STANDARD_DEVIATION 6.1 | 24.7 kg/m^2 STANDARD_DEVIATION 5.4 |
| Fasting blood triglyceride levels | 122.3 mg/dL STANDARD_DEVIATION 43.5 | 122.9 mg/dL STANDARD_DEVIATION 54.9 | 122.6 mg/dL STANDARD_DEVIATION 47.1 |
| Manic Symptom Severity | 26.2 units on a scale STANDARD_DEVIATION 6.6 | 21.1 units on a scale STANDARD_DEVIATION 7.6 | 23.5 units on a scale STANDARD_DEVIATION 7.4 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 2 Participants | 3 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) White | 8 Participants | 7 Participants | 15 Participants |
| Sex: Female, Male Female | 3 Participants | 8 Participants | 11 Participants |
| Sex: Female, Male Male | 6 Participants | 2 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 9 | 0 / 10 |
| other Total, other adverse events | 0 / 9 | 0 / 10 |
| serious Total, serious adverse events | 0 / 9 | 0 / 10 |
Outcome results
Primary
Body Mass Index (BMI)
Body Mass Index (BMI) is a measure of body fat calculated as weight in kilograms divided by height in meters squared (kg/m\^2). BMI Categories are: Underweight = \<18.5; Normal weight = 18.5-24.9; Overweight = 25-29.9; Obesity = BMI of 30 or greater. Greater decreases in BMI are a better outcome.
Time frame: 24 weeks
Population: First-episode adolescent manic patients treated with open-label quetiapine were randomized to adjunctive treatment with fish oil or placebo for 24-weeks.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quitiapine Plus Omega | Body Mass Index (BMI) | 24.4 kg/m^2 | Standard Deviation 4.7 |
| Quetiapine Plus Placebo | Body Mass Index (BMI) | 26.3 kg/m^2 | Standard Deviation 7.4 |
Primary
Fasting Blood Triglycerides Levels
Triglycerides are the chemical form in which most fat exists in food as well as in the body. They're also present in blood plasma and, in association with cholesterol, form the plasma lipids. Levels are categorized as follows: Normal - Less than 150 milligrams per deciliter (mg/dL); Borderline high - 150 to 199 mg/dL; High - 200 to 499 mg/dL; Very high - 500 mg/dL or above. Greater reductions blood triglyceride levels are a better outcome.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quitiapine Plus Omega | Fasting Blood Triglycerides Levels | 99.7 mg/dL | Standard Deviation 24.9 |
| Quetiapine Plus Placebo | Fasting Blood Triglycerides Levels | 88 mg/dL | Standard Deviation 39.3 |
Secondary
Manic Symptom Severity
Manic symptom ratings will be obtained using the Young Mania Rating Scale (YMRS). The YMRS total score ranges from 0 to 60 where higher scores indicate more severe mania: Total score ≤12 indicates remission (13-19=minimal symptoms; 20-25=mild mania, 26-37=moderate mania, 38-60=severe mania). Greater reductions from baseline indicates a greater improvement in manic symptoms.
Time frame: 24 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quitiapine Plus Omega | Manic Symptom Severity | 4.3 units on a scale | Standard Deviation 3.7 |
| Quetiapine Plus Placebo | Manic Symptom Severity | 7.2 units on a scale | Standard Deviation 5.1 |