Trial Outcomes & Findings for Lithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder (NCT NCT00194129)

NCT ID: NCT00194129

Last Updated: 2018-02-20

Results Overview

A relapse is a return to either a depressive, manic, hypomanic or mixed episode after a period of not have any symptoms.

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

31 participants

Primary outcome timeframe

Up to 6 months

Results posted on

2018-02-20

Participant Flow

The study was conducted at the outpatient Mood Disorders Program of Case Western Reserve University/University Hospitals Case Medical Center between October 1997 and October 2006.

Patients meeting stabilization criteria for a minimum of 4 consecutive weeks were eligible for random assignment to double-blind maintenance treatment. Patients not meeting these criteria by 24 weeks were discontinued from the study.

Participant milestones

Participant milestones
Measure
Lithium Plus Divalproex
Participants were given lithium monotherapy was initiated at 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L. If randomized to divalproex arm, divalproex was then initiated at 250 mg twice daily and increased over 3-6 weeks to minimum blood levels of 50 ug/ml.
Lithium Plus Placebo
Participants were given lithium monotherapy was initiated at 300 mg twice daily and titrated over 3-6 weeks to minimum blood levels of 0.8 meq/L. If randomized to placebo arm, placebo pills that looked exact to divaloproex were provided to subjects and take twice daily.
Overall Study
STARTED
15
16
Overall Study
COMPLETED
5
3
Overall Study
NOT COMPLETED
10
13

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Lithium and Divalproex for the Treatment of Comorbid Rapid Cycling Bipolar Disorder and Substance Abuse Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
Lithium Plus Divalproex
n=15 Participants
Lithium Plus Placebo
n=16 Participants
Total
n=31 Participants
Total of all reporting groups
Age, Continuous
37.1 years
STANDARD_DEVIATION 10.9 • n=99 Participants
40 years
STANDARD_DEVIATION 10.6 • n=107 Participants
38.4 years
STANDARD_DEVIATION 10.7 • n=206 Participants
Sex: Female, Male
Female
6 Participants
n=99 Participants
4 Participants
n=107 Participants
10 Participants
n=206 Participants
Sex: Female, Male
Male
9 Participants
n=99 Participants
12 Participants
n=107 Participants
21 Participants
n=206 Participants
Illness Type
Bipolar I disorder
13 participants
n=99 Participants
13 participants
n=107 Participants
26 participants
n=206 Participants
Illness Type
Bipolar II disorder
2 participants
n=99 Participants
3 participants
n=107 Participants
5 participants
n=206 Participants

PRIMARY outcome

Timeframe: Up to 6 months

A relapse is a return to either a depressive, manic, hypomanic or mixed episode after a period of not have any symptoms.

Outcome measures

Outcome measures
Measure
Lithium Plus Divalproex
n=15 Participants
Lithium Plus Placebo
n=16 Participants
Time to Treatment for Emerging Symptoms of a Mood Relapse
17.8 weeks
Interval 12.8 to 27.6
15.9 weeks
Interval 11.0 to 22.9

SECONDARY outcome

Timeframe: Up to 6 months

Population: Due to the heavily censored nature of this data, the median survival for time to treatment for emerging manic/hypomanic/mixed symptoms in both arms is not evaluable. Statistics software was unable to analyze the data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Up to 6 months

Population: Due to the heavily censored nature of this data, the median survival for time to treatment for emerging depression symptoms in both arms is not evaluable. Statistics software was unable to analyze the data.

Outcome measures

Outcome data not reported

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: This only includes subjects who had an alcohol use disorder at study entry. The purpose of this analysis was to see if treatment with both open-label lithium and divalproex during the first phase of study participation (i.e. prior to randomization to lithium monotherapy or continued dual therapy) lead to a change in rates of alcohol use disorders.

Number of subjects who no longer met criteria for active abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex

Outcome measures

Outcome measures
Measure
Lithium Plus Divalproex
n=19 Participants
Lithium Plus Placebo
Change in Rate of Alcohol Use Disorders After Open-label Treatment With Lithium and Divalproex
11 Participants

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: This only includes subjects who had a cannabis use disorder at study entry. The purpose of this analysis was to see if treatment with both open-label lithium and divalproex during the first phase of study participation (i.e. prior to randomization to lithium monotherapy or continued dual therapy) lead to a change in rates of cannabis use disorders.

Number of subjects who no longer met criteria for active cannabis abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex

Outcome measures

Outcome measures
Measure
Lithium Plus Divalproex
n=15 Participants
Lithium Plus Placebo
Change in Rate of Cannabis Use Disorders After Open-label Treatment With Lithium and Divalproex
8 Participants

SECONDARY outcome

Timeframe: Baseline to Month 6

Population: This only includes subjects who were using cocaine at the time of study entry. The purpose of this analysis was to see if treatment with both open-label lithium \& divalproex during the first phase of study participation (i.e. prior to randomization to lithium monotherapy or continued dual therapy) lead to a change in rates of cocaine use disorders.

Number of subjects who no longer met criteria for active cocaine abuse or had entered into early full remission after receiving up to 6 months of open-label treatment with lithium and divalproex

Outcome measures

Outcome measures
Measure
Lithium Plus Divalproex
n=9 Participants
Lithium Plus Placebo
Change in Rate of Cocaine Use Disorders After Open-label Treatment With Lithium and Divalproex
7 Participants

Adverse Events

Lithium Plus Divalproex

Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths

Lithium Plus Placebo

Serious events: 0 serious events
Other events: 13 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
Lithium Plus Divalproex
n=15 participants at risk
Lithium Plus Placebo
n=16 participants at risk
Nervous system disorders
Tremors
66.7%
10/15 • Number of events 10
62.5%
10/16 • Number of events 10
Renal and urinary disorders
Polyuria/Polydipsia
40.0%
6/15 • Number of events 6
31.2%
5/16 • Number of events 5
Gastrointestinal disorders
Diarrhea
26.7%
4/15 • Number of events 4
37.5%
6/16 • Number of events 6
General disorders
Weight Gain
13.3%
2/15 • Number of events 2
31.2%
5/16 • Number of events 5
General disorders
Fatigue
33.3%
5/15 • Number of events 5
6.2%
1/16 • Number of events 1
Gastrointestinal disorders
Nausea
13.3%
2/15 • Number of events 2
18.8%
3/16 • Number of events 3
General disorders
Alopecia
20.0%
3/15 • Number of events 3
6.2%
1/16 • Number of events 1
General disorders
Dry Mouth
20.0%
3/15 • Number of events 3
0.00%
0/16
Social circumstances
Sexual Dysfunction
13.3%
2/15 • Number of events 2
12.5%
2/16 • Number of events 2
Social circumstances
Cognitive Dysfunction
13.3%
2/15 • Number of events 2
12.5%
2/16 • Number of events 2
Eye disorders
Blurred Vision
13.3%
2/15 • Number of events 2
6.2%
1/16 • Number of events 1
General disorders
Increased Appetite
0.00%
0/15
12.5%
2/16 • Number of events 2
Skin and subcutaneous tissue disorders
Acne
0.00%
0/15
12.5%
2/16 • Number of events 2

Additional Information

David Kemp, MD

UHCMC Mood Disorders Program

Phone: 216-844-2865

Results disclosure agreements

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