Adherence, Depression, Heroin Dependence, Methadone, Motivational Interviewing, Substance-Related Disorders
Conditions
Brief summary
Patients with HIV, depression, and opioid-dependence are at high risk for poor health outcomes. This is a two-arm randomized controlled trial of cognitive-behavioral therapy for depression and HIV medication adherence in patients with opioid dependence who are receiving methadone maintenance treatment. The project is based on our pilot work with close attention to NIDA guidelines for a staged approach to treatment development and testing (Rounsaville et al., 2001). Depression is highly comorbid with both HIV infection and with opioid dependence. Depression and substance abuse are both associated with poor adherence to antiretroviral medications. Patients with HIV, depression, and opioid dependence are at high risk for poor health outcomes. Cognitive-behavioral therapy is the most widely studied and efficacious psychosocial intervention for depression; and research by the PI and others has shown that cognitive-behavioral interventions have been successful in promoting adherence to HIV medications.
Detailed description
Symptoms of depression (i.e. low motivation, poor concentration, loss of interest, sad mood, suicidal ideation) that occur in the context of substance abuse or dependence can interfere with self-care behaviors necessary for maintaining HIV care, as well as interfere with potential benefit from an intervention that focuses on adherence alone. We hypothesize that teaching skills to cope with depression will improve the outcome from an adherence intervention to promote healthier living with HIV, in HIV+ opioid dependent individuals in methadone maintenance treatment. Overview of Research Plan. Patients who are HIV positive and who are receiving methadone maintenance for opioid dependence will be randomized to treatment with either: (1) CBT, a combination of CBT for depression and HIV medication adherence, including a single session intervention for HIV medication adherence (Life-Steps, Safren et al., 2001) in conjunction with physician feedback regarding baseline study assessments or (2) the single session intervention for HIV medication adherence (Life-Steps, Safren et al., 2001) in conjunction with physician feedback regarding baseline study assessments. Participants will be followed for one-year post-randomization.
Interventions
BEHAVIORALCBT-AD
Cognitive behavioral therapy for adherence and depression consisting of 1 session focusing on adherence and 8 sessions consisting of cognitive behavioral therapy for medication adherence and depression.
BEHAVIORALETAU
Enhanced treatment as usual consisting of 1 session focused on adherence (the same session as the CBT-AD intervention) and 8 sessions for participants to complete self-reports and collect adherence data.
Sponsors
National Institute on Drug Abuse (NIDA)
Massachusetts General Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* HIV seropositive * Currently enrolled in methadone maintenance treatment for at least one month * Current major or subsyndromal depression (subsyndromal depression is defined by major depression that does not meet full diagnostic criteria but with a clinical global impression of severity (CGI-S) of 2 (mildly ill)) * Is prescribed antiretroviral therapy for HIV and therefore under the care of a primary care provider. * Between the ages of 18 and 65.
Exclusion criteria
* Active untreated, unstable, major mental illness (i.e., untreated psychosis or mania), or other Axis I psychiatric disorders (other than depression) that would interfere with the ability to participate (i.e. CGI-S \>6) * Unable or unwilling to provide informed consent. * Currently in cognitive behavioral therapy for depression.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percent Medication Adherence at 3-month Follow-up Assessment | 3-month assessment | Post-treatment assessment in adherence to HIV medication. Doses taken were assessed by downloading information from the electronic pill cap and corroborated by participant self-report. Adherence was calculated as the number of doses taken over the time period divided by the number of doses prescribed. |
| Percent Medication Adherence at 12-month Follow-up Assessment | 12-month follow-up assessment | Follow-up assessment in adherence to HIV medication. Doses taken were assessed by downloading information from the electronic pill cap and corroborated by participant self-report. Adherence was calculated as the number of doses taken over the time period divided by the number of doses prescribed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| CD4+ Lymphocyte Count at 12-month Follow-up Assessment. | 12-month follow-up assessment | CD4+ lymphocyte cell count at 12-month follow-up assessment. |
| Clinician-assessed Depression at 12-month Follow-up Assessment | 12-month follow-up assessment | Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) by a clinical interviewer blind to participants' study condition. The scale ranges from 0 to 60 with 7-19 indicating mild depression and 20-34 indicating moderate depression. |
| Clinician-assessed Depression Rating at 3 Month Follow-up Assessment | 3 month follow-up | Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) by a clinical interviewer blind to participants' study condition. The scale ranges from 0 to 60 with 7-19 indicating mild depression and 20-34 indicating moderate depression. |
| CD4+ Lymphocyte Count at 3-month Follow-up Assessment. | 3-month assessment | CD4+ lymphocyte cell count at 3-month follow-up assessment. |
| HIV Viral Load at 3-month Follow-up Assessment | 3-month assessment | HIV plasma RNA (log HIV viral load)at the 3-month follow-up assessment. |
| HIV Viral Load at 12-month Follow-up Assessment | 12-month follow-up assessment | HIV plasma RNA (log HIV viral load)at the 12-month follow-up assessment. |
Countries
United States
Participant flow
Recruitment details
First participants from methadone clinics, remainder from MGH or RIH clinics.
Pre-assignment details
Participants had to screen for study inclusion/exclusion criteria before randomization.
Participants by arm
| Arm | Count |
|---|---|
| CBT-AD Cognitive behavioral therapy for adherence and depression | 44 |
| ETAU Enhanced Treatment as Usual | 45 |
| Total | 89 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Lost to Follow-up | 8 | 15 |
Baseline characteristics
| Characteristic | ETAU | CBT-AD | Total |
|---|---|---|---|
| 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 | 45 Participants | 44 Participants | 89 Participants |
| Age, Continuous | 46.67 years STANDARD_DEVIATION 7.05 | 47.05 years STANDARD_DEVIATION 7.34 | 46.85 years STANDARD_DEVIATION 7.15 |
| Region of Enrollment United States | 45 participants | 44 participants | 89 participants |
| Sex: Female, Male Female | 18 Participants | 17 Participants | 35 Participants |
| Sex: Female, Male Male | 27 Participants | 27 Participants | 54 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 44 | 0 / 45 |
| serious Total, serious adverse events | 0 / 44 | 0 / 45 |
Outcome results
Primary
Percent Medication Adherence at 12-month Follow-up Assessment
Follow-up assessment in adherence to HIV medication. Doses taken were assessed by downloading information from the electronic pill cap and corroborated by participant self-report. Adherence was calculated as the number of doses taken over the time period divided by the number of doses prescribed.
Time frame: 12-month follow-up assessment
Population: We used intent to treat for all data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | Percent Medication Adherence at 12-month Follow-up Assessment | 64.49 percent (doses taken/doses prescribed) | Standard Deviation 31.34 |
| ETAU | Percent Medication Adherence at 12-month Follow-up Assessment | 61.11 percent (doses taken/doses prescribed) | Standard Deviation 34.94 |
Primary
Percent Medication Adherence at 3-month Follow-up Assessment
Post-treatment assessment in adherence to HIV medication. Doses taken were assessed by downloading information from the electronic pill cap and corroborated by participant self-report. Adherence was calculated as the number of doses taken over the time period divided by the number of doses prescribed.
Time frame: 3-month assessment
Population: We used hierarchical linear modeling (HLM) methods and intent to treat for all randomized participants.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | Percent Medication Adherence at 3-month Follow-up Assessment | 79.02 percent (doses taken/doses prescribed) | Standard Deviation 23.23 |
| ETAU | Percent Medication Adherence at 3-month Follow-up Assessment | 73.66 percent (doses taken/doses prescribed) | Standard Deviation 25.15 |
Comparison: We used HLM with weekly visit data for the acute outcome. There were, therefore, 11 time points used.p-value: <0.05HLM
Secondary
CD4+ Lymphocyte Count at 12-month Follow-up Assessment.
CD4+ lymphocyte cell count at 12-month follow-up assessment.
Time frame: 12-month follow-up assessment
Population: We used intent to treat for all data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | CD4+ Lymphocyte Count at 12-month Follow-up Assessment. | 452.94 cells/mm^3 | Standard Deviation 235 |
| ETAU | CD4+ Lymphocyte Count at 12-month Follow-up Assessment. | 502.33 cells/mm^3 | Standard Deviation 314.19 |
Comparison: follow up analysis revealed that CD4, over time, significantly improved over control when covarying out baseline levels.p-value: <0.05HLM
Secondary
CD4+ Lymphocyte Count at 3-month Follow-up Assessment.
CD4+ lymphocyte cell count at 3-month follow-up assessment.
Time frame: 3-month assessment
Population: We used intent to treat for all analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | CD4+ Lymphocyte Count at 3-month Follow-up Assessment. | 380.97 cells/mm3 | Standard Deviation 266.62 |
| ETAU | CD4+ Lymphocyte Count at 3-month Follow-up Assessment. | 539.29 cells/mm3 | Standard Deviation 293.61 |
Secondary
Clinician-assessed Depression at 12-month Follow-up Assessment
Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) by a clinical interviewer blind to participants' study condition. The scale ranges from 0 to 60 with 7-19 indicating mild depression and 20-34 indicating moderate depression.
Time frame: 12-month follow-up assessment
Population: We used intent to treat for all data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | Clinician-assessed Depression at 12-month Follow-up Assessment | 15.28 Units on scale | Standard Deviation 9.22 |
| ETAU | Clinician-assessed Depression at 12-month Follow-up Assessment | 20.00 Units on scale | Standard Deviation 10.97 |
Secondary
Clinician-assessed Depression Rating at 3 Month Follow-up Assessment
Depression was assessed using the Montgomery-Asberg Depression Rating Scale (MADRS) by a clinical interviewer blind to participants' study condition. The scale ranges from 0 to 60 with 7-19 indicating mild depression and 20-34 indicating moderate depression.
Time frame: 3 month follow-up
Population: We used intent to treat for all data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | Clinician-assessed Depression Rating at 3 Month Follow-up Assessment | 17.02 Units on scale | Standard Deviation 10.62 |
| ETAU | Clinician-assessed Depression Rating at 3 Month Follow-up Assessment | 22.7 Units on scale | Standard Deviation 10.19 |
p-value: <0.05GLM and HLM
Secondary
HIV Viral Load at 12-month Follow-up Assessment
HIV plasma RNA (log HIV viral load)at the 12-month follow-up assessment.
Time frame: 12-month follow-up assessment
Population: We used intent to treat for all data analysis.
| Arm | Measure | Value (LOG_MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | HIV Viral Load at 12-month Follow-up Assessment | 2.203 log10 copies/mL | Standard Deviation 0.687 |
| ETAU | HIV Viral Load at 12-month Follow-up Assessment | 2.177 log10 copies/mL | Standard Deviation 0.82 |
Secondary
HIV Viral Load at 3-month Follow-up Assessment
HIV plasma RNA (log HIV viral load)at the 3-month follow-up assessment.
Time frame: 3-month assessment
Population: We used intent to treat for all data analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| CBT-AD | HIV Viral Load at 3-month Follow-up Assessment | 2.349 log10 copies/mL | Standard Deviation 0.928 |
| ETAU | HIV Viral Load at 3-month Follow-up Assessment | 2.044 log10 copies/mL | Standard Deviation 0.509 |