Trial Outcomes & Findings for Lamotrigine add-on Therapy for Bipolar Disorder and Cocaine Dependency (NCT NCT00280293)

NCT ID: NCT00280293

Last Updated: 2013-09-26

Results Overview

Number of days of cocaine use during the 7 days that comprise week 10 of the protocol, by self report, or at last assessment if participant withdrew early, as assessed by the Timeline Followback method.

• Recruitment status: COMPLETED
• Study phase: PHASE4
• Target enrollment: 112 participants
• Primary outcome timeframe: 10 weeks
• Results posted on: 2013-09-26

Participant Flow

112 participants with at least one post-baseline visit were recruited between 2006 and 2010 at our research clinic in Dallas, TX and included for analysis.

Participants with a diagnosis of bipolar I, II or NOS disorders currently depressed or mixed mood with current cocaine dependence and self-reported use within 14 days were included. The study drug was added to existing psychiatric medications or given as monotherapy when participants were not taking other medications at baseline.

Participant milestones

Measure	Lamotrigine Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Overall Study STARTED	55	57
Overall Study COMPLETED	29	34
Overall Study NOT COMPLETED	26	23

Reasons for withdrawal

Measure	Lamotrigine Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Overall Study Protocol Violation	3	0
Overall Study Physician Decision	5	4
Overall Study Lost to Follow-up	14	12
Overall Study Withdrawal by Subject	3	5
Overall Study Incarceration/Legal Reasons	1	1
Overall Study Adverse Event	0	1

Baseline Characteristics

Lamotrigine add-on Therapy for Bipolar Disorder and Cocaine Dependency

Baseline characteristics by cohort

Measure	Lamotrigine n=55 Participants Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo n=57 Participants Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Total n=112 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	55 Participants n=5 Participants	57 Participants n=7 Participants	112 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age Continuous	45.1 years STANDARD_DEVIATION 7.3 • n=5 Participants	43.5 years STANDARD_DEVIATION 10.0 • n=7 Participants	44.3 years STANDARD_DEVIATION 8.8 • n=5 Participants
Sex: Female, Male Female	23 Participants n=5 Participants	22 Participants n=7 Participants	45 Participants n=5 Participants
Sex: Female, Male Male	32 Participants n=5 Participants	35 Participants n=7 Participants	67 Participants n=5 Participants
Region of Enrollment United States	55 participants n=5 Participants	57 participants n=7 Participants	112 participants n=5 Participants

PRIMARY outcome

Timeframe: 10 weeks

Number of days of cocaine use during the 7 days that comprise week 10 of the protocol, by self report, or at last assessment if participant withdrew early, as assessed by the Timeline Followback method.

Outcome measures

Measure	Lamotrigine n=55 Participants Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo n=57 Participants Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Days of Cocaine Use	1.8 days Standard Deviation 2.0	2.8 days Standard Deviation 4.0

PRIMARY outcome

Timeframe: 10 weeks

Percentage of participants with a positive urine drug screen for cocaine at the week 10 visit or at last assessment if participant withdrew early.

Outcome measures

Measure	Lamotrigine n=55 Participants Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo n=57 Participants Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Positive Urine Drug Screens	67.3 percentage of participants	73.6 percentage of participants

SECONDARY outcome

Timeframe: 10 weeks

Total score on the Hamilton Rating Scale for Depression at week 10 visit or at last assessment if participant withdrew early(total score values range 0 - 52. A higher score indicates more severe depression.

Outcome measures

Measure	Lamotrigine n=55 Participants Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo n=57 Participants Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Depression Score on the Hamilton Rating Scale For Depression	13.4 units on a scale Standard Deviation 8.5	13.6 units on a scale Standard Deviation 8.2

SECONDARY outcome

Timeframe: 10 weeks

Dollars spent on cocaine during the 7 days of week 10, or at last assessment if participant withdrew early, based on self report.

Outcome measures

Measure	Lamotrigine n=55 Participants Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo n=57 Participants Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Dollars Spent	68.6 Dollars Standard Deviation 121.1	155.4 Dollars Standard Deviation 355.5

Adverse Events

Lamotrigine

Serious events: 5 serious events

Other events: 6 other events

Deaths: 0 deaths

Placebo

Serious events: 4 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Measure	Lamotrigine n=55 participants at risk Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo n=57 participants at risk Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Psychiatric disorders Inpatient psychiatric admittance	5.5% 3/55 • Number of events 3 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Congenital, familial and genetic disorders Inpatient admittance for blood transfusion	0.00% 0/55 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Renal and urinary disorders Inpatient admittance for urinary tract blockage	0.00% 0/55 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Infections and infestations Cellulitis	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Cardiac disorders Inpatient admittance due to hypertension	0.00% 0/55 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Injury, poisoning and procedural complications Fall related injury	3.6% 2/55 • Number of events 2 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Psychiatric disorders Expression of violent thoughts/ideation	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.

Other adverse events

Measure	Lamotrigine n=55 participants at risk Lamotrigine therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.	Placebo n=57 participants at risk Placebo group received medication in identical color/sizes as the lamotrigine group. Placebo therapy was initiated at 25 mg/day and increased to 200 mg/day using a slow upward titration over 5 weeks. After that time additional increases in 100 mg/day increments to a maximum of 400 mg/day were made if the medication was well tolerated and signs of poor response were noted.
Psychiatric disorders Admittance to psychiatric facility	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Respiratory, thoracic and mediastinal disorders Hemoptysis	0.00% 0/55 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Respiratory, thoracic and mediastinal disorders Asthma attack	1.8% 1/55 • Number of events 2 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Vascular disorders Nosebleed	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Vascular disorders Superficial Thrombophlebitis	0.00% 0/55 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Respiratory, thoracic and mediastinal disorders Pneumonia	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Skin and subcutaneous tissue disorders Skin rash	0.00% 0/55 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Injury, poisoning and procedural complications Cut related injury	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Injury, poisoning and procedural complications Fall related injury	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Infections and infestations Abscessed Tooth	0.00% 0/55 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	1.8% 1/57 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.
Skin and subcutaneous tissue disorders Dry skin	1.8% 1/55 • Number of events 1 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.	0.00% 0/57 • Adverse events were collected during the study between 2006 and 2010. Each participant was enrolled for 10 weeks. Adverse events were collected for the full 10 weeks, beginning after consent was signed. Adverse events were assessed by a weekly questionnaire at each appointment.

Additional Information

Dr. E. Sherwood Brown

UT Southwestern Medical Center

Phone: 214-645-6950

Email: sherwood.brown@utsouthwestern.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place

Restriction type: LTE60