Bipolar Disorder, Depression, Bipolar
Conditions
Keywords
Geriatric Psychiatry, Aged, lamotrigine
Brief summary
This is a 12-week, open label trial of lamotrigine for older adults (age 60 and older) with type I or type II Bipolar depression. Non-demented older adults with Bipolar I or II depression, confirmed via the Structured Clinical Interview for the Diagnostic and Statistical Manual for Mental Disorders (DSM) - Patient edition (SCID-I/P) and meeting inclusion criteria for depressive symptom severity (score of 18 or greater on the Hamilton Depression Rating Scale/HAM-D-24) will receive add-on lamotrigine dosed to a target of 200 mg/day.
Interventions
DRUGLamotrigine regular tablet formulation
Day 0 lamotrigine regular tablet formulation or lamotrigine novel formulation will be initiated at 25 mg/day and upward titrated as per package insert to targeted maximum dose of 200 mg/day. Dosing will be reduced for individuals who experience adverse effects. Dosing will be modified as per package insert for lamotrigine for individuals on anticonvulsant compounds.
DRUGLamotrigine novel formulation
Participants will have the option of trying a novel formulation of lamotrigine tablets instead of the lamotrigine regular formulation tablets. The dosing will remain the same regardless of which type of lamotrigine tablet is used. Day 0 lamotrigine regular tablet formulation or lamotrigine novel formulation will be initiated at 25 mg/day and upward titrated as per package insert to targeted maximum dose of 200 mg/day. Dosing will be reduced for individuals who experience adverse effects. Dosing will be modified as per package insert for lamotrigine for individuals on anticonvulsant compounds.
Sponsors
GlaxoSmithKline
University Hospitals Cleveland Medical Center
Study design
Allocation
NON_RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
60 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Age 60 Years or older * BP Disorder-I or II: Depressive episode (DSM -IV-TR; SCID-I/P) * HAM-D score \> 18 (GRID-HAM-D 24-item version) * Availability of an Informant is encouraged but not required for study participation
Exclusion criteria
* Chronic psychotic conditions, ie. schizophrenia, schizoaffective disorder, delusional disorder * Contraindication to lamotrigine (Physician interview, medical assessment) * Documented history of intolerance to lamotrigine * Patients who have previously failed to respond to at least 12 weeks of treatment with lamotrigine * Active substance dependence (SCID-I/P) or substance-related safety issues or PI concerns * Mood Disorder Due to a General Medical Condition or Treatment (Physician interview) * Rapid cycling (Physician interview): As defined in DSM-IV: At least 4 episodes of mood disturbance in the previous 12 months that meet criteria for a Major Depressive, Manic, Mixed or Hypomanic Episode. Episodes are distinguished either by partial or full remission for at least 2 months or by a switch to an episode of opposite polarity * Dementia (by DSM-IV or brain degenerative diseases; Physician interview); * Inability to communicate in English (i.e., interview cannot be conducted without an interpreter; subject largely unable to understand questions and cannot respond in English) * Clinically significant sensory impairment (i.e., cannot see well enough to read consent or visually-presented material; cannot hear well enough to cooperate with interview; Physician interview) * Recent history of cardiovascular, peripheral vascular events or stroke * High risk for suicide (e.g., active SI or current intent or plan) * Inpatient status
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Change in Depressive Symptoms From Baseline on the Montgomery Asberg Depression Rating Scale (MADRS) | 12 weeks | The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | 12 weeks | Frequency of adverse effects was measured using the UKU. The total number of adverse effects assessed by the UKU is 49 plus one open-ended question about any adverse effects not assessed. |
| Change in Depressive Symptoms From Baseline Using the Hamilton Depression Rating Scale (GRID-HAM-D) | 12 weeks | The minimum possible score is 0 and the maximum score is 78. A higher score implies a worse condition. |
| Change in Manic Symptoms From Baseline Using the Young Mania Rating Scale (YMRS) | 12 weeks | The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition. |
| Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Simpson Angus Scale (SAS) | 12 weeks | The minimum possible score is 0 and the maximum score is 4. A higher score implies a worse condition. |
| Change in Body Weight From Baseline | 12 weeks | — |
| Change From Baseline in Overall Clinical Diagnosis Using the CGI-BP | 12 weeks | The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition. |
| Change in Appearance of Extrapyramidal Symptoms From Baseline Using the Abnormal Involuntary Movement Scale (AIMS) | 12 weeks | The minimum possible score is 0 and the maximum score is 4. A higher score implies a worse condition. |
| Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Barnes Akathisia Scale (BAS) | 12 weeks | The minimum possible score is 0 and the maximum score is 5. A higher score implies a worse condition. |
| Number of Participants Who Had a Fall That Required Medical Attention | 12 weeks | — |
| Number of Participants Who Had a Fall That Required Medical Attention and Was Related to Lamotrigine | 12 weeks | — |
| Number of Participants Who Fell at Least Once During the Study | 12 weeks | — |
Countries
United States
Participant flow
Recruitment details
Recruitment began in January 2008 and ended in December 2009. The study screened and enrolled participants at five academic institutions in the United States.
Pre-assignment details
All subjects were required to have a score of 18 or higher on the Hamilton Rating Scale for Depression 24 to be included in the study.
Participants by arm
| Arm | Count |
|---|---|
| Open-label Lamotrigine Treatment This solitary group received open-label lamotrigine treatment for bipolar depression. | 57 |
| Total | 57 |
Withdrawals & dropouts
| Period | Reason | FG000 |
|---|---|---|
| Overall Study | Adverse Event | 6 |
| Overall Study | Lack of Efficacy | 2 |
| Overall Study | Protocol Violation | 4 |
| Overall Study | Withdrawal by Subject | 7 |
Baseline characteristics
| Characteristic | Open-label Lamotrigine Treatment |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 30 Participants |
| Age, Categorical Between 18 and 65 years | 27 Participants |
| Age, Continuous | 66.5 years STANDARD_DEVIATION 6.7 |
| Region of Enrollment United States | 57 participants |
| Sex: Female, Male Female | 23 Participants |
| Sex: Female, Male Male | 34 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | — / — |
| other Total, other adverse events | 22 / 57 |
| serious Total, serious adverse events | 2 / 57 |
Outcome results
Primary
Assessment of Change in Depressive Symptoms From Baseline on the Montgomery Asberg Depression Rating Scale (MADRS)
The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Assessment of Change in Depressive Symptoms From Baseline on the Montgomery Asberg Depression Rating Scale (MADRS) | -15.5 units on a scale |
Comparison: The null hypothesis is that the mean difference score between the 12 week time point or LOCF and baseline is zero.p-value: <0.0195% CI: [-18, -12.9]t-test, 2 sided
Secondary
Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU)
Frequency of adverse effects was measured using the UKU. The total number of adverse effects assessed by the UKU is 49 plus one open-ended question about any adverse effects not assessed.
Time frame: 12 weeks
Population: The number of participants was chosen from the number who received at least one dose of lamotrigine.
| Arm | Measure | Group | Value (NUMBER) |
|---|---|---|---|
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | reduced sleep duration | 14 participants |
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | weight loss | 12 participants |
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | increased dream activity | 12 participants |
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | polyuria/polydipsia | 11 participants |
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | weight gain | 9 participants |
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | increased sleep | 9 participants |
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | lassitude/fatigue | 8 participants |
| Open-label Lamotrigine Treatment | Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU) | unsteady gait | 8 participants |
Secondary
Change From Baseline in Overall Clinical Diagnosis Using the CGI-BP
The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition.
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Change From Baseline in Overall Clinical Diagnosis Using the CGI-BP | -2.06 units on a scale |
Comparison: The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.p-value: <0.0195% CI: [-2.43, -1.68]t-test, 2 sided
Secondary
Change in Appearance of Extrapyramidal Symptoms From Baseline Using the Abnormal Involuntary Movement Scale (AIMS)
The minimum possible score is 0 and the maximum score is 4. A higher score implies a worse condition.
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Change in Appearance of Extrapyramidal Symptoms From Baseline Using the Abnormal Involuntary Movement Scale (AIMS) | -.79 units on a scale |
Comparison: The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.p-value: 0.0895% CI: [-1.67, 0.09]t-test, 2 sided
Secondary
Change in Body Weight From Baseline
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Change in Body Weight From Baseline | .83 lbs. |
Comparison: The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.p-value: 0.3695% CI: [-0.97, 2.62]t-test, 2 sided
Secondary
Change in Depressive Symptoms From Baseline Using the Hamilton Depression Rating Scale (GRID-HAM-D)
The minimum possible score is 0 and the maximum score is 78. A higher score implies a worse condition.
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Change in Depressive Symptoms From Baseline Using the Hamilton Depression Rating Scale (GRID-HAM-D) | -15.2 units on a scale |
Comparison: The null hypothesis is that the mean difference score between the 12 week time point or LOCF and baseline is zero.p-value: <0.0195% CI: [-17.5, -12.9]t-test, 2 sided
Secondary
Change in Manic Symptoms From Baseline Using the Young Mania Rating Scale (YMRS)
The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Change in Manic Symptoms From Baseline Using the Young Mania Rating Scale (YMRS) | -.47 units on a scale |
Comparison: The null hypothesis is that the mean difference score between the 12 week time point or LOCF and baseline is zero.p-value: 0.4995% CI: [-1.82, 0.88]t-test, 2 sided
Secondary
Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Barnes Akathisia Scale (BAS)
The minimum possible score is 0 and the maximum score is 5. A higher score implies a worse condition.
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Barnes Akathisia Scale (BAS) | -.53 units on a scale |
Comparison: The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.p-value: 0.0495% CI: [-1.03, -0.04]t-test, 2 sided
Secondary
Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Simpson Angus Scale (SAS)
The minimum possible score is 0 and the maximum score is 4. A higher score implies a worse condition.
Time frame: 12 weeks
Population: The number of participants for analysis was determined by number of completers plus number of dropouts where the last known observation of a dropout taking lamotrigine was carried forward. Missing data and the lack of 3 participants completing more than the baseline assessment yielded a number for analysis that was less than total enrollment.
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Open-label Lamotrigine Treatment | Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Simpson Angus Scale (SAS) | -.04 units on a scale |
Comparison: The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.p-value: 0.895% CI: [-0.36, 0.28]t-test, 2 sided
Secondary
Number of Participants Who Fell at Least Once During the Study
Time frame: 12 weeks
Population: The number of participants was chosen from the number who received at least one dose of lamotrigine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Lamotrigine Treatment | Number of Participants Who Fell at Least Once During the Study | 18 participants |
Secondary
Number of Participants Who Had a Fall That Required Medical Attention
Time frame: 12 weeks
Population: The number of participants was chosen from the number who received at least one dose of lamotrigine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Lamotrigine Treatment | Number of Participants Who Had a Fall That Required Medical Attention | 5 participants |
Secondary
Number of Participants Who Had a Fall That Required Medical Attention and Was Related to Lamotrigine
Time frame: 12 weeks
Population: The number of participants was chosen from the number who received at least one dose of lamotrigine.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Open-label Lamotrigine Treatment | Number of Participants Who Had a Fall That Required Medical Attention and Was Related to Lamotrigine | 1 participants |