Cocaine Dependence
Conditions
Keywords
substance abuse, cocaine, impulsivity, serotonin, Remeron, Mirtzapine, Lexapro, Escatilopram
Brief summary
The purpose of this study is to examine the relationship between 5-HT2R function, impulsivity and cue reactivity in cocaine dependent subjects and healthy controls and examine specific effects of escitalopram and mirtazapine on impulsivity and cue reactivity in human cocaine users.
Detailed description
Specific Aim 1: We will test the hypothesis that cocaine-dependent subjects will exhibit greater impulsivity than controls as determined by a battery of impulsivity measures and that impulsivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce impulsivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression. Specific Aim 2: We will test the hypothesis that cocaine-dependent subjects will exhibit greater cue reactivity than controls as determined by a modified Stroop task, and that cue reactivity will be associated with specific profiles of 5-HT2AR and/or 5-HT2CR expression in platelets. We predict that treatment of cocaine-dependent subjects with escitalopram and/or mirtazapine will reduce cue reactivity and cocaine-positive urines, in concert with a normalized balance of platelet 5-HT2AR and/or 5-HT2CR expression. Specific Aim 3: We will test the hypothesis that specific polymorphisms in the 5-HT2AR and/or 5-HT2CR will predict baseline impulsivity and/or cue reactivity as well as treatment response to serotonergic medications in cocaine-dependent subjects.
Interventions
DRUGEscitalopram
Escitalopram: once daily 10 mg on days 1-3, 20 mg on days 4-24 and 10 mg on days 25-28
DRUGPlacebo
Once daily days 1-28
Sponsors
National Institute on Drug Abuse (NIDA)
The University of Texas Health Science Center, Houston
Virginia Commonwealth University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 55 Years
Healthy volunteers
Yes
Inclusion criteria
* Non-Drug Abusing Control Subjects: Male and female subjects age 18 to 55 who do not meet current or past DSM-IV criteria for any Axis I disorder including substance abuse or dependence. * Cocaine Dependent Subjects: Male and female subjects age 18 to 55 who meet current DSM-IV criteria for cocaine dependence. * Female subjects: a negative pregnancy test.
Exclusion criteria
* Non-Drug Abusing Control Subjects: 1. Current or past DSM-IV Axis I disorder 2. Any serious non-psychiatric medical illness requiring ongoing medical treatment or which could affect the central nervous system. 3. Positive HIV test. 4. For female subjects: a positive pregnancy test or breast feeding. 5. Concomitant use of prescription medications that could affect the central nervous system. 6. Active suicidal ideation. 7. Hamilton Depression or Anxiety Scale score greater than 15 * Cocaine Dependent Subjects: 1. Current DSM-IV Axis I disorder other than substance abuse/dependence 2. Current diagnosis of other substance dependence besides cocaine. 3. Any serious non-psychiatric medical illness requiring ongoing medical treatment or which could affect the central nervous system. 4. Positive HIV test. 5. For female subjects: a positive pregnancy test or breast feeding. 6. Concomitant use of prescription medications that could affect the central nervous system. 7. Active suicidal ideation. 8. Subjects within 14 days of discontinuing a monoamine oxidase inhibitor. 9. Subjects with cardiac arrythmias. 10. Subjects with known hypersensitivity to escitalopram or citalopram, or mirtazapine 11. Hamilton Depression or Anxiety Scale score greater than 15. 12. Current alcohol abuse or dependence.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Immediate Memory Task | after acute dose and after chronic administration | The IMT was used to measure impulsivity. The IMT is a continuous performance test. Subjects were instructed to respond on the computer's left mouse button when a five-digit number the target stimulus appeared that was exactly like the preceding stimulus. A catch stimulus was a number that differed only slightly from the preceding number. Only one of the five digits was changed its position and value was determined randomly. Responses errors made to catch stimuli were considered commission errors or 'false alarms'. Immediate Memory Task Commission Errors to catch stimuli were the primary measure of impulsivity in this study. Scale is percentage of overall responses to a catch stimulus that were commission errors, ranging from 0 to 100. Zero would equate to no impulsivity and 100 would equate to 100% impulsive responses. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Attentional Bias as Measured by the Cocaine Stroop Task. | 5 weeks of treatment | Attentional bias is the difference in reaction time to cocaine related words and neutral words. A slower reaction time indicates greater attentional bias. |
| Cocaine Positive Urines | 5 weeks of treatment | Number of urine drug screens positive for cocaine metabolite benzoylecgonine. |
Countries
United States
Participant flow
Pre-assignment details
The enrollment number was the number of participants who signed the informed consent. The Participants who Started in the Participant flow module were number of participants who completed the screening and met inclusion criteria to start medication.
Participants by arm
| Arm | Count |
|---|---|
| A (Escitalopram) Escitalopram: once daily 10 mg on days 1-3, 20 mg on days 4-24 and 10 mg on days 25-28 | 11 |
| B (Placebo) Placebo once daily for days 1-28 | 12 |
| Total | 23 |
Baseline characteristics
| Characteristic | Total | A (Escitalopram) | B (Placebo) |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 23 Participants | 11 Participants | 12 Participants |
| Age, Continuous | 40.01 years STANDARD_DEVIATION 7.3 | 38.4 years STANDARD_DEVIATION 7.88 | 41.75 years STANDARD_DEVIATION 6.65 |
| Region of Enrollment United States | 23 participants | 11 participants | 12 participants |
| Sex: Female, Male Female | 2 Participants | 1 Participants | 1 Participants |
| Sex: Female, Male Male | 21 Participants | 10 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 12 |
| serious Total, serious adverse events | 0 / 11 | 0 / 12 |
Outcome results
Primary
Immediate Memory Task
The IMT was used to measure impulsivity. The IMT is a continuous performance test. Subjects were instructed to respond on the computer's left mouse button when a five-digit number the target stimulus appeared that was exactly like the preceding stimulus. A catch stimulus was a number that differed only slightly from the preceding number. Only one of the five digits was changed its position and value was determined randomly. Responses errors made to catch stimuli were considered commission errors or 'false alarms'. Immediate Memory Task Commission Errors to catch stimuli were the primary measure of impulsivity in this study. Scale is percentage of overall responses to a catch stimulus that were commission errors, ranging from 0 to 100. Zero would equate to no impulsivity and 100 would equate to 100% impulsive responses.
Time frame: after acute dose and after chronic administration
Population: Numerical data values are not accessible because PI transferred institutions. See references.
Secondary
Attentional Bias as Measured by the Cocaine Stroop Task.
Attentional bias is the difference in reaction time to cocaine related words and neutral words. A slower reaction time indicates greater attentional bias.
Time frame: 5 weeks of treatment
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| A (Escitalopram) | Attentional Bias as Measured by the Cocaine Stroop Task. | Baseline | 90.2 milliseconds | Standard Deviation 107.8 |
| A (Escitalopram) | Attentional Bias as Measured by the Cocaine Stroop Task. | Acute | -8.6 milliseconds | Standard Deviation 21.6 |
| A (Escitalopram) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 1 | 56.4 milliseconds | Standard Deviation 58.7 |
| A (Escitalopram) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 2 | 45.0 milliseconds | Standard Deviation 68.6 |
| A (Escitalopram) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 3 | 23.4 milliseconds | Standard Deviation 33 |
| A (Escitalopram) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 4 | 63.6 milliseconds | Standard Deviation 82.5 |
| B (Placebo) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 3 | -11.3 milliseconds | Standard Deviation 68 |
| B (Placebo) | Attentional Bias as Measured by the Cocaine Stroop Task. | Baseline | 45.9 milliseconds | Standard Deviation 109.2 |
| B (Placebo) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 2 | 15.4 milliseconds | Standard Deviation 64.5 |
| B (Placebo) | Attentional Bias as Measured by the Cocaine Stroop Task. | Acute | 37.4 milliseconds | Standard Deviation 93.8 |
| B (Placebo) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 4 | 4.4 milliseconds | Standard Deviation 76.2 |
| B (Placebo) | Attentional Bias as Measured by the Cocaine Stroop Task. | Chronic Day 1 | 35.4 milliseconds | Standard Deviation 77.9 |
Secondary
Cocaine Positive Urines
Number of urine drug screens positive for cocaine metabolite benzoylecgonine.
Time frame: 5 weeks of treatment
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| A (Escitalopram) | Cocaine Positive Urines | 9 Positive urine drug screens |
| B (Placebo) | Cocaine Positive Urines | 8 Positive urine drug screens |