Bipolar Disorder, Mania
Conditions
Keywords
bipolar disorder, lamotrigine, children, mania
Brief summary
The main objective of this study is to assess the effectiveness and safety of lamotrigine in the treatment of youth with bipolar and bipolar spectrum disorder. This is an exploratory, 12-week, open-label treatment period, pilot study, of youth ages 6-17, who meet the DSM-IV diagnostic criteria for bipolar I, bipolar II, or bipolar spectrum disorder. The study results will be used to generate hypotheses for a larger randomized controlled clinical trial. Based on the available literature in adults with bipolar disorder, we hypothesized that lamotrigine will be efficacious and well tolerated in youth with pediatric bipolar and bipolar spectrum disorders.
Detailed description
Lamotrigine is a new generation antiepileptic drug, approved by the FDA in 2003 for the maintenance treatment of adults with Bipolar I disorder to delay the time to occurrence of mood episodes (depression, mania, hypomania,& mixed episodes) in patients treated for acute mood episodes with standard therapy. Recent studies have shown that Lamotrigine maintenance treatment was more robust in bipolar depression. The study includes 1) use of a 12-week design to document the response rate 2) assessment of the impact of Lamotrigine on functional capacities and cognition, 3) careful assessment of safety and tolerability.
Interventions
DRUGlamotrigine
Open-label, flexible-dose, BID treatment of lamotrigine (Lamictal). For children \<12 years, dosing began at 0.35 mg/kg/day, divided in 2 doses, rounded down to nearest 5mg, to be increased weekly depending on response and tolerability to maintenance dose of 5-15 mg/kg/day (maximum 400 mg/day in 2 divided doses). For children ≥12 years, dose began at 25 mg/day in 1 dose, to be increased weekly depending on response and tolerability to maintenance dose of 300-500 mg/day in 2 divided doses.
Sponsors
Massachusetts General Hospital
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
6 Years to 17 Years
Healthy volunteers
No
Inclusion criteria
1. Male or female subjects, 6-17 years of age. 2. Subjects must have a DSM-IV diagnosis of bipolar I, bipolar II disorder or bipolar spectrum disorder and currently displaying manic, hypomanic, or mixed symptoms (with or without psychotic features) according to the DSM-IV based on clinical assessment and confirmed by structured diagnostic interview (Kiddie Schedule of Affective Disorders and Schizophrenia Epidemiological Version. Bipolar Spectrum Disorder (or sub-threshold bipolar disorder) is operationalized as having severe mood disturbance, which meets DSM-IV Criteria A for bipolar disorder but meet fewer elements in criteria B (only require 2 items for elation category and 3 for irritability). 3. Subjects and their legal representative must have a level of understanding sufficient to communicate intelligently with the investigator and study coordinator, and to cooperate with all tests and examinations required by the protocol. 4. Subjects and their legal representative must be considered reliable. 5. Each subject and his/her authorized legal representative must understand the nature of the study. The subject's authorized legal representative must sign an informed consent document and the subject must sign an informed assent document. 6. Subjects must have an initial score on the Y-MRS total score of at least 20. 7. Subject must be able to participate in mandatory blood draws. 8. Subject must be able to swallow pills. 9. Subjects with comorbid ADHD, ODD, CD, anxiety and depressive disorders will be allowed to participate in the study provided they do not meet for any of the exclusionary criteria. 10. For concomitant stimulant therapy used to treat ADHD, subjects must have been on a stable dose of the medication for 1 month prior to study enrollment. The dose of the stimulant therapy will not change throughout the duration of the study.
Exclusion criteria
1. Investigator and his/her immediate family; defined as the investigator's spouse, parent, child, grandparent, or grandchild. 2. Subjects unable to swallow pills. 3. Serious, unstable illness including hepatic, renal, gastroenterological, respiratory, cardiovascular (including ischemic heart disease), endocrinologic, neurologic, immunologic, or hematologic disease. 4. History of sensitivity to lamotrigine or known, severe allergies or multiple adverse drug reactions. 5. History of previous bone marrow depression. 6. History of serious rashes. 7. DSM-IV substance (except nicotine or caffeine) dependence within past 3 months. 8. Judged clinically to be at serious suicidal risk. 9. Any other concomitant medication with primarily central nervous system activity other than specified in Concomitant Medication portion of the protocol. 10. A non-responder or a history of intolerance to lamotrigine in an adequate trial (2 months or more at an adequate dose) as determined by the clinician. 11. Current diagnosis of schizophrenia. 12. Pregnant or nursing females.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of Mania Symptoms Assessed by Young Mania Rating Scale (YMRS) | baseline to 12 weeks | Mean reduction in YMRS score at endpoint/LOCF. This is a scale to measure symptoms of mania in children and adolescents. 11 items are rated from 0-4 (7 items) or 0-8 (4 items). The minimum (least severe) total score is 0, and maximum (most severe) total score is 60. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Lamotrigine | 39 |
| Total | 39 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Exposed to Study Medication | Adverse Event | 10 |
| Exposed to Study Medication | Difficulty meeting study schedule | 2 |
| Exposed to Study Medication | Lack of Efficacy | 2 |
| Exposed to Study Medication | Non-compliance | 2 |
| Exposed to Study Medication | Withdrawal by Subject | 1 |
| Signed Consent | Did not meet entrance criteria | 7 |
| Signed Consent | Withdrawal by Subject | 5 |
Baseline characteristics
| Characteristic | Lamotrigine |
|---|---|
| Age, Categorical <=18 years | 39 Participants |
| Age, Categorical >=65 years | 0 Participants |
| Age, Categorical Between 18 and 65 years | 0 Participants |
| Age Continuous | 10.8 years STANDARD_DEVIATION 2.9 |
| Region of Enrollment United States | 39 participants |
| Sex: Female, Male Female | 15 Participants |
| Sex: Female, Male Male | 24 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 34 / 39 |
| serious Total, serious adverse events | 0 / 39 |
Outcome results
Primary
Change of Mania Symptoms Assessed by Young Mania Rating Scale (YMRS)
Mean reduction in YMRS score at endpoint/LOCF. This is a scale to measure symptoms of mania in children and adolescents. 11 items are rated from 0-4 (7 items) or 0-8 (4 items). The minimum (least severe) total score is 0, and maximum (most severe) total score is 60.
Time frame: baseline to 12 weeks
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Lamotrigine | Change of Mania Symptoms Assessed by Young Mania Rating Scale (YMRS) | -14.9 Units on a scale | Standard Deviation 9.7 |