Bipolar Disorder, Mood Disorders, Substance Use Disorders
Conditions
Keywords
youth, adolescent, young adult, substance use disorder, bipolar disorder, quetiapine, mood dysregulation
Brief summary
This study proposes to use quetiapine as an adjunct treatment to treatment as usual to improve both substance use disorder (SUD) and mood symptoms in youth with SUD and severe mood dysregulation (SMD). This is a randomized, double blind placebo controlled parallel design study. Youth with symptoms of mood dysregulation and active substance use that meets criteria for a SUD will be randomized to adjunct treatment with quetiapine or placebo. The investigators hypothesize that treatment with quetiapine will lead to a reduction in substance use, improvement in mood, and lead to greater engagement in outpatient treatment.
Interventions
DRUGQuetiapine
Participants will be randomly assigned Quetiapine and will be titrated to the maximum daily dose over three weeks and then enter a dose maintenance phase for weeks 4 through 8 of the study.
OTHERPlacebo
Participants will be randomly assigned to placebo and will be titrated to the maximum daily dose over three weeks and then enter a dose maintenance phase for weeks 4 through 8 of the study.
Sponsors
National Institute on Drug Abuse (NIDA)
Boston Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
15 Years to 24 Years
Healthy volunteers
No
Inclusion criteria
* Male or female age 15 to 24 * Meet DSM-5 criteria for a substance use disorder * Substance use ≥ 14 days of past 28 days (i.e. use ≥ 50% of days in the past 28 days) * If subject in restricted setting/care (e.g. inpatient detox unit or residential treatment) for ≤ 2 weeks, then use ≥ 50% of days while outside of restricted setting (e.g. 7 days of substance use out of 14 days in unrestricted setting) * Subjects need to have been in an unrestricted setting for at least 2 weeks prior to screening * Meets DSM-5 criteria for bipolar disorder or disruptive mood dysregulation disorder or DSM IV criteria for mood disorder not otherwise specified * Symptoms of SMD: Youth Self Report (YSR) or Adult Self Report (ASR) AAA ≥180 * Stable to be treated in outpatient level of care
Exclusion criteria
* Current methamphetamine use disorder * Current unstable opioid use disorder (i.e. \< 3 months on medication assisted treatment for an opioid use disorder) * Pregnant or breastfeeding * Placement in a restricted setting (e.g. detox or residential treatment) for ≥ 2 weeks out of past 28 days prior to screening visit, or placement in a restricted setting at anytime during study participation * Unwilling or unable to use effective birth control * Unwilling or unable to sign release of information for the treatment program providing behavioral treatment * For participants \>17 years-unable or unwilling to identify emergency contact
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Timeline Followback of Substance Use (TLFB) | baseline, 8 weeks | The TLFB is used to quantify self-reported drug of choice use during the past month. Counts the number of days with substance use in the past 28 days. |
| Change in Symptoms of Mania | baseline, 8 weeks | Symptoms of mania will be assessed using the Young Mania Rating Scale (YMRS). The YMRS consists of 11 items rated on a scale. Each item is composed of 5 explicitly defined levels of severity. Severity ratings for 7 items are scored on a scale of 0 -4. The remaining 4 items are double weighted to account for poor cooperation of client when unwell and are scored on a scale of 0 - 8. Item ratings are sum to produce a total YMRS score between 0 -60. Higher scores on the YMRS indicate greater symptoms of mania. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in the Number of Negative Urine Toxicology Specimens | baseline, 8 weeks | Urine toxicology specimens for the participant's drug of choice assessed as positive or negative. For each participant, the proportion of urine toxicology specimens that are negative over the course of the trial are calculated as the number of negative specimens divided by the total number of specimens collected from week 1 until study endpoint. |
| Change in Craving for the Substance That the Participant Identifies as Most Problematic | baseline, 8 weeks | Craving will be measured by the Weiss Craving Scale. This scale consists of 3 items rated on a scale from 0 (no desire/likelihood of use) to 9 (strong desire/likelihood of use). The total Weiss Craving Scale score ranges from 0 to 27. Higher scores on the Weiss Craving Scale indicate greater cravings for a substance. |
| Change in Symptoms of Depression | baseline, 8 weeks | Symptoms of depression will be assessed using the Beck Depression Inventory II (BDI-II) scale. The BDI-II consists of 21 items rated on a scale from 0 (symptoms not present) to 3 (symptoms extremely severe). Total scores on the BDI-II range from 0 to 63. Higher scores indicate greater symptoms of depression. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Quetiapine Quetiapine
Quetiapine: Participants will be randomly assigned Quetiapine and will be titrated to the maximum daily dose over three weeks and then enter a dose maintenance phase for weeks 4 through 8 of the study. | 13 |
| Placebo Placebo
Placebo: Participants will be randomly assigned to placebo and will be titrated to the maximum daily dose over three weeks and then enter a dose maintenance phase for weeks 4 through 8 of the study. | 11 |
| Total | 24 |
Baseline characteristics
| Characteristic | Quetiapine | Total | Placebo |
|---|---|---|---|
| Age, Categorical <=18 years | 1 Participants | 1 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 12 Participants | 23 Participants | 11 Participants |
| Age, Continuous | 21.2 years STANDARD_DEVIATION 2.1 | 20.8 years STANDARD_DEVIATION 1.9 | 20.5 years STANDARD_DEVIATION 1.8 |
| Beck Depression Inventory-II (BDI-II) | 25 Score on a scale STANDARD_DEVIATION 9.5 | 25.4 Score on a scale STANDARD_DEVIATION 9 | 25.9 Score on a scale STANDARD_DEVIATION 9 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 3 Participants | 4 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 20 Participants | 10 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Number of Participants with a Negative Urine Screen at Baseline | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 3 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 2 Participants | 3 Participants | 1 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 9 Participants | 15 Participants | 6 Participants |
| Region of Enrollment United States | 13 participants | 24 participants | 11 participants |
| Sex: Female, Male Female | 8 Participants | 15 Participants | 7 Participants |
| Sex: Female, Male Male | 5 Participants | 9 Participants | 4 Participants |
| Timeline Followback of Substance Use (TLFB) | 19.5 days STANDARD_DEVIATION 9.3 | 17.4 days STANDARD_DEVIATION 8.8 | 15.4 days STANDARD_DEVIATION 8.2 |
| Weiss Craving Scale | 17.1 Score on a scale STANDARD_DEVIATION 5.7 | 16.8 Score on a scale STANDARD_DEVIATION 5.8 | 16.4 Score on a scale STANDARD_DEVIATION 6.3 |
| Young Mania Rating Scale | 18.8 Score on a scale STANDARD_DEVIATION 4.9 | 16.9 Score on a scale STANDARD_DEVIATION 5.4 | 14.6 Score on a scale STANDARD_DEVIATION 5.4 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 11 | 0 / 10 |
| other Total, other adverse events | 11 / 11 | 10 / 10 |
| serious Total, serious adverse events | 0 / 11 | 0 / 10 |
Outcome results
Primary
Change in Symptoms of Mania
Symptoms of mania will be assessed using the Young Mania Rating Scale (YMRS). The YMRS consists of 11 items rated on a scale. Each item is composed of 5 explicitly defined levels of severity. Severity ratings for 7 items are scored on a scale of 0 -4. The remaining 4 items are double weighted to account for poor cooperation of client when unwell and are scored on a scale of 0 - 8. Item ratings are sum to produce a total YMRS score between 0 -60. Higher scores on the YMRS indicate greater symptoms of mania.
Time frame: baseline, 8 weeks
Population: Participants who took at least one week of study medication and completed the YMRS at baseline and at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change in Symptoms of Mania | -8.8 score on a scale | Standard Deviation 8.1 |
| Placebo | Change in Symptoms of Mania | -0.4 score on a scale | Standard Deviation 7.5 |
Primary
Change in Timeline Followback of Substance Use (TLFB)
The TLFB is used to quantify self-reported drug of choice use during the past month. Counts the number of days with substance use in the past 28 days.
Time frame: baseline, 8 weeks
Population: Participants who completed at least one week of study medication and had 28 days-worth of past substance use data at baseline and study endpoint.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change in Timeline Followback of Substance Use (TLFB) | 2.3 Days | Standard Deviation 6.9 |
| Placebo | Change in Timeline Followback of Substance Use (TLFB) | 3.3 Days | Standard Deviation 6 |
Secondary
Change in Craving for the Substance That the Participant Identifies as Most Problematic
Craving will be measured by the Weiss Craving Scale. This scale consists of 3 items rated on a scale from 0 (no desire/likelihood of use) to 9 (strong desire/likelihood of use). The total Weiss Craving Scale score ranges from 0 to 27. Higher scores on the Weiss Craving Scale indicate greater cravings for a substance.
Time frame: baseline, 8 weeks
Population: Participants who took at least one week of study medication and completed the Weiss Craving Scale at baseline and at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change in Craving for the Substance That the Participant Identifies as Most Problematic | -1.8 score on a scale | Standard Deviation 4.5 |
| Placebo | Change in Craving for the Substance That the Participant Identifies as Most Problematic | 0.4 score on a scale | Standard Deviation 4.8 |
Secondary
Change in Symptoms of Depression
Symptoms of depression will be assessed using the Beck Depression Inventory II (BDI-II) scale. The BDI-II consists of 21 items rated on a scale from 0 (symptoms not present) to 3 (symptoms extremely severe). Total scores on the BDI-II range from 0 to 63. Higher scores indicate greater symptoms of depression.
Time frame: baseline, 8 weeks
Population: Participants who took at least one week of study medication and completed the BDI-II at baseline and at least one follow-up visit.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Quetiapine | Change in Symptoms of Depression | -9.1 score on a scale | Standard Deviation 13.5 |
| Placebo | Change in Symptoms of Depression | -6.2 score on a scale | Standard Deviation 10.6 |
Secondary
Change in the Number of Negative Urine Toxicology Specimens
Urine toxicology specimens for the participant's drug of choice assessed as positive or negative. For each participant, the proportion of urine toxicology specimens that are negative over the course of the trial are calculated as the number of negative specimens divided by the total number of specimens collected from week 1 until study endpoint.
Time frame: baseline, 8 weeks
Population: Participants who took at least one week of study medication, completed at least one post-baseline urine toxicology screen, and whose drug of choice could be assessed with urine toxicology testing.
| Arm | Measure | Value (MEDIAN) |
|---|---|---|
| Quetiapine | Change in the Number of Negative Urine Toxicology Specimens | 0 Proportion of Specimens |
| Placebo | Change in the Number of Negative Urine Toxicology Specimens | 0 Proportion of Specimens |