Geri-BD SAD: Lamotrigine for Symptoms of Geriatric Bipolar Depression

• Sponsor: University Hospitals Cleveland Medical Center (Other)
• Overall Status: Completed
• CT.gov ID: NCT00621842
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 57
• Locations: 5
• Arm: 1
• Duration (Months): 26
• Patients Per Site: 11.4
• Patients Per Site Per Month: 0.4

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Bipolar Disorder; Depression, Bipolar	Drug: Lamotrigine regular tablet formulation; Drug: Lamotrigine novel formulation	Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 57 participants
• Allocation: Non-Randomized
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Open-label, Prospective Trial of Lamotrigine for Symptoms of Geriatric Bipolar Depression
• Study Start Date: Jan 1, 2008
• Actual Primary Completion Date: Mar 1, 2010
• Actual Study Completion Date: Mar 1, 2010

Arms and Interventions

Arm

Intervention/Treatment

Experimental: Open-Label Lamotrigine Treatment

Drug: Lamotrigine 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.; Other Names: Lamictal ; Drug: Lamotrigine 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.; Other Names: Lamictal

Outcome Measures

Primary Outcome Measures

1. 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 Outcome Measures

1. 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.

2. 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.

3. 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.

4. 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.

5. 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.

6. Change in Body Weight From Baseline [12 weeks]

7. Number of Participants Who Fell at Least Once During the Study [12 weeks]

8. 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.

9. 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.

10. Number of Participants Who Had a Fall That Required Medical Attention [12 weeks]

11. Number of Participants Who Had a Fall That Required Medical Attention and Was Related to Lamotrigine [12 weeks]

Eligibility Criteria

Criteria

• Ages Eligible for Study: 60 Years and Older
• Sexes Eligible for Study: All
• Accepts 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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Weill Medical College of Cornell University	White Plains	New York	United States	10605
2	University Hospitals Case Medical Center/ Case Western Reserve University	Cleveland	Ohio	United States	44106
3	University of Pennsylvania	Philadelphia	Pennsylvania	United States	19104
4	University of Pittsburgh School of Medicine, Western Psychiatric Institute and Clinic	Pittsburgh	Pennsylvania	United States	15213
5	Baylor College of Medicine/Michael E. DeBakey VAMC	Houston	Texas	United States	77030

Sponsors and Collaborators

• University Hospitals Cleveland Medical Center
• GlaxoSmithKline

Investigators

• Principal Investigator: Martha Sajatovic, MD, Case Western Reserve University School of Medicine

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Martha Sajatovic, Professor of Psychiatry, University Hospitals Cleveland Medical Center
• ClinicalTrials.gov Identifier: NCT00621842
• Other Study ID Numbers: L0971; GSK110720; IND 78,081
• First Posted: Feb 22, 2008
• Last Update Posted: Dec 30, 2014
• Last Verified: Dec 1, 2014

• Keywords provided by Martha Sajatovic, Professor of Psychiatry, University Hospitals Cleveland Medical Center: Geriatric Psychiatry; Aged; lamotrigine
• Additional relevant MeSH terms: Depression; Depressive Disorder; Bipolar Disorder; Lamotrigine; Anticonvulsants

Study Results

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 Detail	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.

Arm/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Period Title: Overall Study
STARTED	57
COMPLETED	38
NOT COMPLETED	19

Baseline Characteristics

Arm/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Overall Participants	57
Age (Count of Participants)
<=18 years	0 0%
Between 18 and 65 years	27 47.4%
>=65 years	30 52.6%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	66.5 (6.7)
Sex: Female, Male (Count of Participants)
Female	23 40.4%
Male	34 59.6%
Region of Enrollment (participants) [Number]
United States	57 100%

Outcome Measures

1. Primary Outcome

Title	Assessment of Change in Depressive Symptoms From Baseline on the Montgomery Asberg Depression Rating Scale (MADRS)
Description	The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	54
Mean (95% Confidence Interval) [units on a scale]	-15.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference score between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.01
	Comments
	Method	t-test, 2 sided
	Comments	df=53
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.5
	Confidence Interval	(2-Sided) 95%; -18.0 to -12.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

Title	Assessment of Adverse Effects With the Udvalg Fur Kliniske Undersogelser (UKU)
Description	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

Outcome Measure Data

Analysis Population Description

The number of participants was chosen from the number who received at least one dose of lamotrigine.

Arm/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	57
reduced sleep duration	14 24.6%
weight loss	12 21.1%
increased dream activity	12 21.1%
polyuria/polydipsia	11 19.3%
weight gain	9 15.8%
increased sleep	9 15.8%
lassitude/fatigue	8 14%
unsteady gait	8 14%

3. Secondary Outcome

Title	Change in Depressive Symptoms From Baseline Using the Hamilton Depression Rating Scale (GRID-HAM-D)
Description	The minimum possible score is 0 and the maximum score is 78. A higher score implies a worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	54
Mean (95% Confidence Interval) [units on a scale]	-15.2

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference score between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.01
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-15.2
	Confidence Interval	(2-Sided) 95%; -17.5 to -12.9
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

Title	Change in Manic Symptoms From Baseline Using the Young Mania Rating Scale (YMRS)
Description	The minimum possible score is 0 and the maximum score is 60. A higher score implies a worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	49
Mean (95% Confidence Interval) [units on a scale]	-.47

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference score between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.49
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-.47
	Confidence Interval	(2-Sided) 95%; -1.82 to .88
	Parameter Dispersion	Type: Value:
	Estimation Comments

5. Secondary Outcome

Title	Change From Baseline in Overall Clinical Diagnosis Using the CGI-BP
Description	The minimum possible score is 1 and the maximum score is 7. A higher score implies a worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	53
Mean (95% Confidence Interval) [units on a scale]	-2.06

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	<.01
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-2.06
	Confidence Interval	(2-Sided) 95%; -2.43 to -1.68
	Parameter Dispersion	Type: Value:
	Estimation Comments

6. Secondary Outcome

Title	Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Simpson Angus Scale (SAS)
Description	The minimum possible score is 0 and the maximum score is 4. A higher score implies a worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	48
Mean (95% Confidence Interval) [units on a scale]	-.04

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.80
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-.04
	Confidence Interval	(2-Sided) 95%; -.36 to .28
	Parameter Dispersion	Type: Value:
	Estimation Comments

7. Secondary Outcome

Title	Change in Body Weight From Baseline
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	52
Mean (95% Confidence Interval) [lbs.]	.83

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.36
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	.83
	Confidence Interval	() 95%; -.97 to 2.62
	Parameter Dispersion	Type: Value:
	Estimation Comments

8. Secondary Outcome

Title	Number of Participants Who Fell at Least Once During the Study
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The number of participants was chosen from the number who received at least one dose of lamotrigine.

Arm/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	57
Number [participants]	18 31.6%

9. Secondary Outcome

Title	Change in Appearance of Extrapyramidal Symptoms From Baseline Using the Abnormal Involuntary Movement Scale (AIMS)
Description	The minimum possible score is 0 and the maximum score is 4. A higher score implies a worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	48
Mean (95% Confidence Interval) [units on a scale]	-.79

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.08
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-.79
	Confidence Interval	(2-Sided) 95%; -1.67 to .09
	Parameter Dispersion	Type: Value:
	Estimation Comments

10. Secondary Outcome

Title	Change in or Appearance of Extrapyramidal Symptoms From Baseline Using the Barnes Akathisia Scale (BAS)
Description	The minimum possible score is 0 and the maximum score is 5. A higher score implies a worse condition.
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

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/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	47
Mean (95% Confidence Interval) [units on a scale]	-.53

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Open-label Lamotrigine Treatment
	Comments	The null hypothesis is that the mean difference between the 12 week time point or LOCF and baseline is zero.
	Type of Statistical Test	Superiority or Other
	Comments
Statistical Test of Hypothesis	p-Value	.04
	Comments
	Method	t-test, 2 sided
	Comments
Method of Estimation	Estimation Parameter	Mean Difference (Final Values)
	Estimated Value	-.53
	Confidence Interval	() 95%; -1.03 to -.04
	Parameter Dispersion	Type: Value:
	Estimation Comments

11. Secondary Outcome

Title	Number of Participants Who Had a Fall That Required Medical Attention
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The number of participants was chosen from the number who received at least one dose of lamotrigine.

Arm/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	57
Number [participants]	5 8.8%

12. Secondary Outcome

Title	Number of Participants Who Had a Fall That Required Medical Attention and Was Related to Lamotrigine
Time Frame	12 weeks

Outcome Measure Data

Analysis Population Description

The number of participants was chosen from the number who received at least one dose of lamotrigine.

Arm/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
Measure Participants	57
Number [participants]	1 1.8%

Adverse Events

Time Frame	Adverse event data was collected for the duration of the study (over two years) separate from any data collected using the UKU.
Arm/Group Title	Open-label Lamotrigine Treatment
Arm/Group Description	This solitary group received open-label lamotrigine treatment for bipolar depression.
All Cause Mortality
	Open-label Lamotrigine Treatment
	Affected / at Risk (%)	# Events
Total	/ (NaN)
Serious Adverse Events
	Open-label Lamotrigine Treatment
	Affected / at Risk (%)	# Events
Total	2/57 (3.5%)
Psychiatric disorders
Hospital Admission for Increased Anxiety	1/57 (1.8%)	1
Renal and urinary disorders
Hospital Admission for Urinary Tract Infection	1/57 (1.8%)	1
Other (Not Including Serious) Adverse Events
	Open-label Lamotrigine Treatment
	Affected / at Risk (%)	# Events
Total	22/57 (38.6%)
Gastrointestinal disorders
Vomiting	4/57 (7%)	9
Injury, poisoning and procedural complications
Fall	18/57 (31.6%)	28
Metabolism and nutrition disorders
Weight gain	4/57 (7%)	4
Weight Loss	4/57 (7%)	6
Renal and urinary disorders
Increased Urinary Frequency	3/57 (5.3%)	4
Skin and subcutaneous tissue disorders
Rash	4/57 (7%)	4

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.