Abstract
Objective
To compare the efficacy of motivational enhancement therapy coupled with cognitive behavioral therapy (MET-CBT) to brief advice for treatment of substance use in pregnancy.
Method
This was a randomized, parallel, controlled trial that was yoked to prenatal care and delivered at hospital outpatient clinics. We enrolled 168 substance using women who had not yet completed an estimated 28 weeks of pregnancy. Obstetrical clinicians provided brief advice and study nurses administered manualized MET-CBT. The primary outcome was percentage of days in the prior 28 days, that alcohol and/or drugs were used immediately before and three months post delivery.
Results
There were no significant differences across groups in terms of self-reported percentage of days that drugs or alcohol were used prior to and three months post delivery. Biological measures showed similar results. There was a trend (p=0.08) for lower risk of preterm birth among those who received MET-CBT.
Conclusions
The tested interventions had similar therapeutic effects. Hence, both treatments may be suitable for pregnant substance users, depending on the population, setting, and provider availability. Interventions that are intensified after delivery may decrease postpartum ‘rebound’ effects in substance misuse.
Introduction
Among women aged 15–44, about 5% use illicit drugs, 24% have at least one episode of binge drinking (≥ 5 drinks on one occasion) and 7% qualify for heavy drinking (≥ 5 occasions) in the past month. Pregnant women are half as likely to use illicit drugs as compared to non-pregnant women while past month episodes of binge drinking and heavy drinking drop to about 4% and less than 1%, respectively. Despite this, over a million offspring are exposed to a drugs or alcohol in pregnancy. Moreover, by one to two years post-delivery, use approximates pre-pregnancy rates.
There is limited controlled research on behavioral interventions that promote drug abstinence in pregnancy and immediately after delivery. Among women enrolled in substance abuse treatment programs, voucher incentives for drug abstinence have shown success in reduction of cocaine, and opiate use. However, other studies show that only treatment attendance is enhanced by vouchers incentives. In pregnant smokers, vouchers increase abstinence and improve birth outcomes.
Manual based interventions, such as cognitive behavioral therapy (CBT), motivational interviewing (MI) and motivational enhancement therapy (MET) are more limited and show mixed results. CBT for pregnant injection drug users coupled with methadone does not diminish drug use to a greater extent than methadone alone. Motivational interventions for pregnant alcohol and illicit drug users have shown varied success with either no group differences or a reduction in drug or alcohol use.
The majority referenced studies included women participating in comprehensive substance abuse treatment programs that include an array of services, including integrated prenatal care, childcare, parenting classes and vocational training. Few studies have evaluated interventions that are randomized, controlled and implemented in outpatient settings among non-treatment seeking pregnant women. Brief interventions, such as simple health recommendations, patient education and self-help manuals provided by physicians or nurses, can motivate pregnant women to reduce alcohol and illicit drug use and obviate the need for more intensive and complex behavioral interventions. Outpatient behavioral treatment that is integrated into prenatal care also shows promise in the promotion of drug and alcohol abstinence, although such interventions have not been tested in randomized, controlled studies. Well-controlled studies are needed to test attention effects, as women often decrease alcohol and drug use during pregnancy even without treatment.
In this population, attention to the dependent variable (substances used) is critical. Pregnant women sometimes continue one drug and discontinue another that they feel is more harmful to their fetus, or replace one substance with another that is perceived to be less harmful. Thus, to accurately assess harm reduction, it is important to assess whether an intervention is effective for a range of drugs that may be used in pregnancy or after delivery. Accordingly, the goal of this study was to evaluate changes in the use of a range of substances immediately prior to delivery and at three months postpartum, between groups who received one of two behavioral treatments that were yoked to prenatal and post-natal care. A secondary aim was to assess the impact of the interventions on birth outcomes. The behavioral interventions were (1) motivational enhancement therapy (MET) integrated with CBT for substance misuse and administered by a nurse and (2) brief advice from an obstetrical provider. We hypothesized that the MET-CBT group would show greater reductions in illicit drug and alcohol use and better birth outcomes as compared to women who received brief advice.
Method
This was a randomized, controlled, parallel-group study conducted in two hospital-based reproductive health clinics in New Haven and Bridgeport, Connecticut, between June 2006 and July 2010. We drew from work on alcohol and poly-substance use, marijuana and cocaine to estimate effect size. Cocaine had the lowest effect size and was used to determine the target sample size. This conservative estimate suggested 110 women per group would provide more than 80% power. No interim analyses or predefined stopping criteria were stipulated.
Participants
Women were eligible if they were age ≥ 16 years, fluent in English or Spanish, had not yet completed 28 estimated weeks of pregnancy at screening, were planning to deliver at a collaborating hospital and were using alcohol or an illicit drug (other than opiates), during the 28 days prior to screening or scored at least a “3” on the modified TWEAK. Although the latter group may not have been actively using during the latter portion of pregnancy, they were at high risk of relapse immediately after delivery.
Women were ineligible if they were already engaged in substance use treatment, endorsed nicotine or opiates as their only substance, had plans to relocate, were not willing to provide consent, were an imminent danger to themselves or their fetus or required inpatient general medical or psychiatric treatment. Opiate users were given a referral to a local methadone maintenance treatment facility. A Certificate of Confidentiality was obtained from National Institute of Drug Abuse and the human subjects’ board at participating hospitals approved the study.
Treatments
Individual behavioral therapy that combined MET and CBT (MET-CBT) was adapted from existing manuals but was formatted into six sessions that could be delivered in conjunction with prenatal and immediate postnatal care visits. The content included motivational enhancement, functional analysis, safe sexual behavior, communication skills, relapse prevention and problem solving skills. Research nurse therapists had the flexibility to offer additional sessions or repeat topics if there was time and need. Each session lasted approximately 30 minutes.
Brief advice was a manualized version of standard interventions offered by obstetrical doctors and nurses. The manual provided guidance on the risks of substance use, the importance of abstinence, and the benefit of seeking drug and alcohol treatment outside of the prenatal setting. Brief advice was administered by the participant’s obstetrical provider and typically lasted around 1 minute.
Training and Fidelity Measures
MET-CBT research nurses attended a two-day workshop where the training manual was reviewed by the supervising psychologist and psychiatrist. They reviewed tapes of at least four training cases and completed at least two pilot training cases and were intensely supervised on a session-by-session basis until they were proficient and able to see randomized participants. Afterward, sessions were randomly checked by the project director, senior psychiatrist or psychologist and supervision was provided as needed.
For the brief advice intervention, obstetrical practitioners attended seminars that included a review of the manual and practice sessions. Training sessions were repeated at least annually to capture clinicians who were new to rotations at the hospital clinics.
We audiotaped 830 (82%) of sessions with the permission of the subject; 20% were randomly selected and reviewed for fidelity as per the Yale Adherence and Competence System.
Procedures
We obtained screening consent and recruited women at a usual, not necessarily first, obstetrical visit. We obtained written, informed consent for the treatment phase of the study for those potentially eligible. Respondents completed an intake assessment at this or their next regularly scheduled prenatal visit. Data on obstetric and sexual history, substance use, substance use treatment and concurrent psychiatric conditions were collected via audio computer-assisted self-interview software. If there was concern for a participant’s decision-making capacity, a psychiatrist assessed capacity prior to consent.
Allocation was derived from a computer program that generated randomized assignment in blocks of two, and was stratified by primary substance of abuse categorized as alcohol, marijuana, cocaine or other. A statistician or project member, who had no direct contact with subjects, maintained allocation. This obviated any opportunity for staff to be biased by the allocation strategy. Similarly, staff that had contact with subjects had no knowledge of the allocation strategy. We stipulated primary drug by combining 1) self-reported recent use of substances and 2) preferred substance according to the subject. If the participant used only one substance in the past 28 days, it was designated as primary. If the woman used more than one or did not endorse use of a substance in the prior 28 days, we used patient- identified primary drug. Subjects who reported more than one drug as primary were classified as ‘other’, regardless of substances endorsed.
Appointments were coordinated by study staff in conjunction with regularly scheduled prenatal care visits. Subjects were seen in the prenatal clinic or hospital if they were an inpatient. Study staff obtained a urine sample for drugs, breath test for alcohol, and self-reports of recent substance use. Staff then guided the subject in completion of a brief computer assessment (see below). It was not possible to obtain urine tests during most inpatient visits since subjects had catheters in place; study staff were not hospital employees and did not have permission to remove urine from a foley catheter bag.
Study treatment sessions and assessment types were as follows. Intake, delivery and three-month post-delivery interviews were only assessments. The delivery assessment was performed within four weeks of delivery and was re-administered if the pregnancy endured beyond the four week window. The three-month post-delivery assessment was performed as close to three months postpartum as possible, +/− two months. At treatment sessions, therapy was offered after the assessment. Subjects could receive an unlimited number of treatment sessions in pregnancy and up to two booster sessions after delivery although the manual included six total planned sessions.
Measures
At screening, potential subjects were queried about lifetime and the prior 30 days use of substances (alcohol, marijuana, cocaine, opiates, other). They also completed the TWEAK, which was modified by adding “and drugs” to questions for alcohol For example, “In the past year did friends or family worry or complain about your use of alcohol or drugs? The addition of the TWEAK was intended to detect women who may not admit to current use or were not currently using but at risk for relapse postpartum. If a respondent endorsed either use in the last 30 days or a score of at least “3” on the modified TWEAK, they were further assessed for eligibility.
The intake battery included the MINI International Neuropsychiatric Interview, which included diagnostic criteria for substance abuse and dependence. At each visit, research staff collected the Timeline Followback (TLFB), a calendar method that collectis data on of individual substances on a daily basis. Although primarily opiate users were excluded, opiate use was measured to detect poly-drug use or substance substitution. The TLFB was collected for the previous 28 days; at follow-up visits data were collected dating back to the previous completed visit.
After delivery, medical records were reviewed by trained staff who abstracted data on birth outcomes, medical complications and prenatal care attendance. Attendance was rated according to the Kotelchuck Adequacy of Prenatal Care Index. Of interest was the percent of visits attended after prenatal care initiation, accounting for time of delivery. We included only the normally scheduled prenatal care visits. Guidelines set by the American College of Obstetricians and Gynecologists determined adequacy as: 1) Inadequate (0–49% attendance); 2) Intermediate (50–79% attendance); 3) Adequate (80–109% attendance) and 4) Adequate Plus (110+ %). Birth outcomes included preterm birth (PTB), defined as birth of less than 37 completed weeks gestation and low birth weight (LBW), operationalized as weight less than 2500 grams.
Urine Toxicology and Breath Tests
We used a commercially available immune-chromatographic test (one-step Status Stik®) to detect cannabinoids, cocaine, opiates and their major metabolites in urine. We used the Redwood Labs Breath Alcohol Test®, to monitor alcohol use. For biological measures, any detected amount was categorized as positive.
Data Analysis
The primary outcome was pre-specified as the percentage of days of any alcohol or drug use in the prior 28 days. Three non-overlapping intervals were constructed from the TLFB based on interview dates, delivery and three-month post-delivery assessment. If the interval contained fewer than 28 days, the calculation was based upon available days unless there were fewer than 14 days available, in which case the data point was considered missing. To determine the percentage of days using alcohol and/or illicit drugs, the number of days endorsing any drug or alcohol use were counted and divided by the total number of days in the interval. Secondary outcomes for the primary analysis included abstinence from substances according to self-report, urine toxicology, and combined self-report and urine. Self-reported abstinence from drugs and alcohol utilized the same intervals as percentage of days that substances were used, but data were categorized into abstinence or non-abstinence. An individual was considered abstinent according to urine if all drugs were negative. For combined self-report and urine analyses, we used only participants with data from both sources. We ran models for breathalyzer tests but they did not converge due to the preponderance of negative tests. Other than breathalyzer data and as per CONSORT guidelines, we present unadjusted data only.
To assess differences in treatment effects over time for percent days, we used negative binomial regression, a generalized linear mixed-effects (GEE) model. The analysis accounted for repeated measures and within-subject correlation and is more appropriate for zero-saturated and skewed outcomes than a normal mixed effects model. Our primary effect of interest was the time by group interaction for three time points (baseline, delivery, three months post-delivery) with two degrees of freedom, using a GEE score type 3 contrast. For the binary measures of abstinence, we used logistic GEE regression and similarly constructed tests of parameters.
For a secondary analysis that examined possible differences in treatment effects between women with and without a diagnosis of substance abuse dependence at intake, we used previously described models, with the addition of factors for a diagnosis of dependence or abuse, two-way interactions with group and time, and the three-way dependence/abuse-group-time interaction. To assess whether treatment effects differed between women with and without a baseline diagnosis, we used a joint test of the three-way interaction terms.
Fisher’s exact test was used to evaluate differences across groups in birth outcomes and in attendance of outside substance use treatment. We analyzed prenatal care attendance using the Mantel-Haenszel Chi-Square test for trend. Analyses were performed for both the intent to treat (n=168) as well as completer samples. Results were similar between the samples and thus we present only intention to treat analysis.
Results
Recruitment occurred between June 2006 and September 2009, with follow-up concluding in July 2010. Figure 1 summarizes recruitment, randomization (n=183) and treatment receipt (n=168). Baseline characteristics of participants are shown in Table 1.
Figure 1.
PRIDE Study Flow Diagram
* Randomization occurred between signing consent and the intake visit. Allocation was not disclosed to the participant until after intake was completed and eligibility confirmed
Table 1.
Demographics and Baseline Drug Use by Randomized Group
| Characteristic | BA (N=86) % (N) | MET-CBT (N=82) % (N) | Total (N=168) % (N) |
|---|---|---|---|
| Age | |||
| <20 | 15% (13) | 20% (16) | 17% (29) |
| 20–34 | 76% (65) | 74% (61) | 75% (126) |
| 35+ | 9% (8) | 6% (5) | 8% (13) |
| Race/Ethnicity | |||
| White | 20% (17) | 23% (19) | 22% (36) |
| Black | 55% (47) | 51% (42) | 53% (89) |
| Hispanic | 20% (24) | 23% (19) | 23% (39) |
| Other | 1% (1) | 2% (2) | 2% (3) |
| Education (years) | |||
| <12 | 30% (26) | 38% (31) | 34% (57) |
| 12 | 36% (31) | 43% (35) | 40% (66) |
| 13–15 | 27% (23) | 17% (14) | 22% (37) |
| 16+ | 7% (6) | 1% (1) | 4% (7) |
| Parity | |||
| 0 | 41% (35) | 38% (31) | 39% (66) |
| 1 | 31% (27) | 30% (25) | 31% (52) |
| 2+ | 28% (24) | 32% (26) | 30% (50) |
| Gestational Age at Intake | |||
| Weeks 1–8 | 6% (5) | 4% (3) | 5% (8) |
| Weeks 9–16 | 29% (25) | 34% (28) | 32% (53) |
| Weeks 17–24 | 36% (31) | 33% (27) | 35% (58) |
| Week 25 or later | 29% (25) | 29% (24) | 29% (49) |
| Prenatal care initiation1 | |||
| Weeks 1–8 | 24% (21) | 29% (23) | 27% (44) |
| Weeks 9–16 | 55% (47) | 51% (40) | 53% (87) |
| Weeks 17–24 | 15% (13) | 13% (10) | 14% (23) |
| Week 25 or later | 5% (4) | 6% (5) | 6% (9) |
| Site | |||
| 1 | 26% (22) | 30% (25) | 28% (47) |
| 2 | 74% (64) | 70% (57) | 72% (121) |
| MINI Drug or alcohol abuse or dependence | 33% (28) | 23% (19) | 28% (47) |
| Past month use | |||
| Alcohol (any) | 39% (33) | 23% (19) | 31% (52) |
| Alcohol (intoxication)2 | 8% (7) | 11% (9) | 10% (16) |
| Heroin | 1% (1) | 4% (3) | 2% (4) |
| Methadone | 6% (5) | 10% (8) | 8% (13) |
| Opiates (excl methadone) | 7% (6) | 5% (4) | 6% (10) |
| Barbituates | 0% (0) | 0% (0) | 0% (0) |
| Sedatives | 6% (5) | 1% (1) | 4% (6) |
| Cocaine | 13% (11) | 9% (7) | 11% (18) |
| Amphetamines | 1% (1) | 0% (0) | 1% (1) |
| Marijuana | 47% (40) | 41% (34) | 44% (74) |
| Hallucinogens | 2% (2) | 1% (1) | 2% (3) |
| Inhalants | 0% (0) | 0% (0) | 0% (0) |
| Primary Drug | |||
| Alcohol | 29% (25) | 32% (26) | 30% (51) |
| Cocaine | 17% (15) | 17% (14) | 17% (29) |
| Marijuana | 47% (40) | 45% (37) | 46% (77) |
| Other | 7% (6) | 6% (5) | 7% (11) |
BA= Brief Advice; MET-CBT= Motivational Enhancement Therapy-Cognitive Behavioral Therapy
Not found in medical record (n=5)
Felt the effects of alcohol or 3+ drinks in one sitting or 5+ drinks in one day
Treatment and Prenatal Care Attendance
Women in the brief advice group attended an average of 7 treatment visits while MET-CBT subjects attended an average of 5 visits. Based on an average session length of 1 minute for brief advice and 30 minutes for MET-CBT, the average time in treatment is 7.12 (SD 3.57) minutes for brief advice participants and 148.17 (SD 97.34) minutes for MET-CBT participants. An average of 5.88 sessions and 3.89 sessions were received in pregnancy by the brief advice and MET-CBT groups, respectively. Although initiation of prenatal care was similar in both groups, participants in the brief advice group attended more prenatal care after initiation than those in the MET-CBT group. Adequacy of Received Services for the brief advice group was as follows: 2 (2%) subjects had inadequate, 7 (9%) had intermediate, 24 (29%) had adequate, and 51 (61%) had adequate plus attendance. In the MET-CBT group, 2 (3%) subjects had inadequate, 13 (17%) had intermediate, 33 (42%) had adequate, and 30 (38%) had adequate plus attendance. Six women had unknown attendance. Adequacy of Received Services differed significantly between groups (p=0.01).
Treatment Implementation and Fidelity
Both conditions showed good content adherence. MET-CBT sessions were rated significantly higher on MET and CBT adherence as compared with brief advice (for MET, the MET-CBT group mean = 3.89, brief advice mean = 1.26, p < .001; for CBT the MET-CBT mean = 2.53, brief advice mean = 1.01, p < .001). Similarly, brief advice sessions were rated significantly higher on brief advice scales as compared with MET-CBT sessions (brief advice mean = 2.01, MET-CBT mean = 1.42, p < .001).
Other Substance Use Treatment Received After Intake
Attendance of treatment outside the study did not differ substantially between groups. In the 30 days prior to delivery, 4 (5%) of brief advice subjects as compared to 6 (9%) of MET-CBT subjects, attended additional treatment. In the 30 days prior to the three-month post-delivery assessment, outside treatment was obtained by 9 (13%) of brief advice subjects and 6 (9%) of those assigned to MET-CBT.
Treatment Outcomes
Analysis of treatment efficacy is presented in Table 2. Substance use decreased in both groups between intake and delivery but increased again after delivery. Treatment effects did not differ between groups with regard to self-reported percentage of days of substance use and analyses of biologic (urine) data.
Table 2.
Treatment Effects by Outcome
| Outcome/group | Intake | Delivery | 3 months post delivery | Treatment effect | |||
|---|---|---|---|---|---|---|---|
| Continuous outcome | Mean±SD (N) | Mean±SD (N) | Mean±SD (N) | Effect | B | 95% CI | P-value1 |
| Percentage of days used drugs or alcohol (primary outcome) | 0.88 | ||||||
| BA group | 18±27 (86) | 6±17 (83) | 14±25 (72) | MET-CBT vs. BA: intake to delivery | 0.08 | (−0.76, 0.92) | |
| MET-CBT group | 21±34 (82) | 7±22 (80) | 13±24 (71) | MET-CBT vs. BA: delivery to 3 months post delivery | −0.21 | (−1.11, 0.69) | |
| Binary outcome | % (n/N) | % (n/N) | % (n/N) | Effect | OR CI | 95% | P-value2 |
| Percent abstinent from both drugs and alcohol (28 days prior to assessment) according to self report | 0.79 | ||||||
| BA group | 41% (35/86) | 75% (62/83) | 38% (27/72) | MET-CBT vs. BA: intake to delivery | 0.77 | (0.36, 1.67) | |
| MET-CBT group | 49% (40/82) | 76% (61/80) | 41% (29/71) | MET-CBT vs. BA: delivery to 3 months post delivery | 1.05 | (0.42, 2.62) | |
| Percent abstinent from drugs according to urine3 | 0.88 | ||||||
| BA group | 54% (43/80) | 84% (43/51) | 52% (33/64) | MET-CBT vs. BA: intake to delivery | 0.96 | (0.34, 2.72) | |
| MET-CBT group | 56% (45/81) | 84% (46/55) | 59% (38/64) | MET-CBT vs. BA: delivery to 3 months post delivery | 1.21 | (0.57, 2.57) | |
| Percent abstinent from both drugs and alcohol according to combined self report and urine3 | 0.50 | ||||||
| BA group | 33% (26/80) | 76% (39/51) | 34% (22/64) | MET-CBT vs. BA: intake to delivery | 0.77 | (0.32, 1.84) | |
| MET-CBT group | 43% (35/81) | 75% (41/55) | 33% (21/64) | MET-CBT vs. BA: delivery to 3 months post delivery | 0.76 | (0.27, 2.11) | |
| Percent abstinent from alcohol according to breathalyzer | N/A4 | ||||||
| BA group | 97% (57/59) | 100% (49/49) | 97% (56/58) | MET-CBT vs. BA: intake to delivery | |||
| MET-CBT group | 96% (48/50) | 100% (45/45) | 95s% (52/55) | MET-CBT vs. BA: delivery to 3 months post delivery | |||
BA= Brief Advice; MET-CBT= Motivational Enhancement Therapy-Cognitive Behavioral Therapy
Mixed effects negative binomial regression, type 3 GEE score test for the group by time interaction (2 df)
Mixed effects logistic regression, type 3 GEE score test for the group by time interaction (2 df)
Based on urine tests for marijuana, cocaine, or opioids
GEE model did not converge
Differential Treatment Effects
Evaluation of outcomes as a function of presence or absence of a baseline diagnosis of substance abuse/dependence is presented in Table 3 and Figure 2. Among women with a diagnosis of abuse or dependence, those in the MET-CBT group markedly decreased the percentage of days that substances were used but also showed a decrease in aggregate abstinence (according to combined self-report and urine), compared to the brief advice group.
Table 3.
Differential Treatment Effects for Women With and Without a Baseline Diagnosis of Drug Abuse or Dependence
| Outcome/abuse or dependence/group | Intake | Delivery | 3 months post delivery | Differential treatment effect1 | |||
|---|---|---|---|---|---|---|---|
| Continuous outcome | Mean±SD (N) | Mean±SD (N) | Mean±SD (N) | Effect | B | 95% CI | P-value |
| Percentage of days used drugs or alcohol (primary outcome) | 0.10 | ||||||
| No abuse or dependence | |||||||
| BA group | 14±25 (58) | 4±11 (55) | 11±20 (46) | MET-CBT vs. BA: intake to delivery | 0.34 | (−0.84, 1.52) | |
| MET-CBT group | 15±27 (63) | 6±20 (62) | 14±27 (55) | MET-CBT vs. BA: delivery to 3 months post delivery | −0.08 | (−1.19, 1.03) | |
| Abuse or dependence | |||||||
| BA | 27±29 (28) | 10±25 (28) | 18±32 (26) | MET-CBT vs. BA: intake to delivery | −0.14 | (−1.28, 0.99) | |
| MET-CBT | 40±45 (19) | 13±28 (18) | 8±8 (16) | MET-CBT vs. BA: delivery to 3 months post delivery | −1.12 | (−2.61, 0.37) | |
| Binary outcome | % (n/N) | % (n/N) | % (n/N) | Effect | OR | 95% CI | P-value2 |
| Percent abstinent from both drugs and alcohol (28 days prior to assessment) according to self report | 0.07 | ||||||
| No abuse or dependence | |||||||
| BA group | 50% (29/58) | 76% (42/55) | 28% (13/46) | MET-CBT vs. BA:intake to delivery | 1.18 | (0.44, 3.14) | |
| MET-CBT group | 52% (33/63) | 81% (50/62) | 44% (24/55) | MET-CBT vs. BA: delivery to 3 months post delivery | 1.46 | (0.47, 4.52) | |
| Abuse or dependence | |||||||
| BA | 21% (6/28) | 71% (20/28) | 54% (14/26) | MET-CBT vs. BA: intake to delivery | 0.28 | (0.08, 1.02) | |
| MET-CBT | 37% (7/19) | 61% (11/18) | 31% (5/16) | MET-CBT vs. BA: delivery to 3 months post delivery | 0.62 | (0.10, 3.90) | |
| Percent abstinent from drugs according to urine3 | 0.91 | ||||||
| No abuse or dependence | |||||||
| BA group | 56% (29/52) | 82% (27/33) | 46% (18/39) | MET-CBT vs. BA:intake to delivery | 1.15 | (0.32, 4.20) | |
| MET-CBT group | 60% (37/62) | 85% (39/46) | 58% (28/48) | MET-CBT vs. BA: delivery to 3 months post delivery | 1.33 | (0.35, 5.07) | |
| Abuse or dependence | |||||||
| BA | 50% (14/28) | 89% (16/18) | 60% (15/25) | MET-CBT vs. BA:intake to delivery | 0.85 | (0.14, 5.23) | |
| MET-CBT | 42% (8/19) | 78% (7/9) | 63% (10/16) | MET-CBT vs. BA: delivery to 3 months post delivery | 1.23 | (0.21, 7.12) | |
| Percent abstinent from both drugs and alcohol according to combined self report and urine3 | 0.04 | ||||||
| No abuse or dependence | |||||||
| BA group | 42% (22/52) | 76% (25/33) | 23% (9/39) | MET-CBT vs. BA: intake to delivery | 1.28 | (0.46, 3.55) | |
| MET-CBT group | 47% (29/62) | 76% (35/46) | 35% (17/48) | MET-CBT vs. BA: delivery to 3 months post delivery | 1.21 | (0.35, 4.17) | |
| Abuse or dependence | |||||||
| BA | 14% (4/28) | 78% (14/18) | 52% (13/25) | MET-CBT vs. BA: intake to delivery | 0.25 | (0.04, 1.63) | |
| MET-CBT | 32% (6/19) | 67% (6/9) | 25% (4/16) | MET-CBT vs. BA: delivery to 3 months post delivery | 0.40 | (0.04, 3.74) | |
BA= Brief Advice; MET-CBT= Motivational Enhancement Therapy-Cognitive Behavioral Therapy
Type 3 GEE score chi-square test statistic for the abuse/dependence-group-time interaction
Based on urine tests for marijuana, cocaine, or opioids
Figure 2.
Change in Days of Drug Use and Abstinence Over Time
Birth Outcomes
A singleton live birth occurred in 163 subjects and 5 had twins. Of the brief advice women, 17 of 84 (20%) gave birth preterm, while 8 of 79 (10%) of the MET-CBT group were delivered preterm (p=0.08). Three women had an unknown birth weight, so the sample size for between groups comparison of LBW was 160 women. Of the 84 women who received brief advice, 17 (20%) delivered a LBW infant, compared to 11 (14%) of the 76 MET-CBT group (p=0.41).
Conclusions
In this randomized controlled trial of MET-CBT versus brief advice integrated with prenatal care visits, substance use decreased significantly across groups and rebounded after delivery, with no significant differences in abstinence rates or days of substance use between groups. For women with an abuse or dependence diagnosis, there was a trend toward cutting down in the MET-CBT group and quitting in the brief advice group. There was also a trend toward a reduction on preterm birth for MET-CBT participants as compared to those in the brief advice group.
Given the substantial reductions in substance use overall during pregnancy, both approaches evaluated here may be effective. Brief advice is efficient and well integrated with prenatal care while MET-CBT may be suitable for more chronic and severe substance use. It is also possible that the reduction in substance use was independent of behavioral intervention as naturalistic studies also show that pregnancy is associated with a meaningful reduction in the use of drugs and alcohol. Many women are motivated to adopt healthy habits in pregnancy and there may be additional hormonal or other biological changes that contribute to this effect. The decrease in use did not endure after delivery and the use of drugs and alcohol increased equally in both treatment groups.
Differences in administration of the treatments may have led to the differences in attendance. Since brief advice was administered by an obstetrical provider employed at the clinic and typically lasted about 1 minute, treatment was difficult to avoid. Attendance in the MET-CBT group required greater time and effort, which may have led to lower attendance and an inadequate “dose” of treatment for some women. However, these differences may not be a limitation of the study so much as an illustration of the convenience and efficiency of brief advice.
We did not expect to find that the brief advice group would receive more prenatal care than the MET-CBT group. Given the higher rate of preterm birth in the brief advice group, this may partly be a function of a greater obstetrical risk. On the other hand, integrating MET-CBT with prenatal care may have caused some women to avoid prenatal care if MET-CBT treatment was uncomfortable or required too much time. Although we had intended to enhance exposure to substance abuse treatment, we need to bear in mind our population was seeking prenatal care primarily.
The lack of superiority of MET-CBT relative to brief advice may be surprising given evidence in support of the efficacy of both MET and CBT. A few factors may explain our results. First, treatment effects for MET or CBT are small to moderate and tend to be less when compared to other active treatments. Second, advice from an obstetrical provider, especially if given repetitively, may carry more weight than treatment offered by a research nurse. Third, our use of a comprehensive outcome measure may have avoided interpreting substance substitution as evidence of treatment efficacy. Even aside from pregnancy, studies that measure use of a single substance may falsely conclude that a treatment is effective rather than consider the possible effect of substance substitution. Finally, targeted enrollment was not reached. We had originally planned to recruit 220 women per group but only enrolled 183. While this was unfortunate, based on the data collected it is unlikely that the overall conclusions would have been affected if we had met recruitment goals.
Although it seems clear that the treatments had similar effect in our population overall, we had limited ability to study women with abuse and dependence diagnoses (28% of overall sample). It remains possible that the MET-CBT treatment is more appropriate for these women with more serious substance use problems. For example, contingent vouchers, coupled with intensive behavioral treatment, decreased the days of cocaine use in pregnant and parenting women but all women met criteria for cocaine dependence in this study.
We found a trend in the data suggesting MET-CBT may protect against preterm birth. It is possible that this effect was driven by decreases in amount of substance use, without changes in frequency, among women who had an abuse or dependence diagnosis at intake. We were not able to detect this because our outcome was days of use. There are a number of potential alternative explanations, including greater obstetrical risk in the brief advice group or other chance factors. This trend needs replication in other studies before it can be accepted as a benefit of MET-CBT.
Our design attempted to balance the need for a controlled trial with that of a pragmatic design that included a diverse group of substance using pregnant women. The fact that it was “yoked” to prenatal care has benefits and limitations. We posited that linkage of behavioral treatment with prenatal care would enhance exposure to substance use treatment but it may also have limited its intensity. For example, some women with severe substance use problems may not seek prenatal care if providers focus on substance use treatment. We need to bear in mind our population was seeking prenatal care and not, primarily, substance use treatment.
We allowed women to enter relatively late in pregnancy (before 28 completed weeks) in order to allow participation from users who enter prenatal care late. However, late entry in conjunction with a high rate of preterm delivery[60] meant that participants had few prenatal visits in this interval and we had less opportunity to provide behavioral treatment before delivery. Follow-up work may need to consider a mixture of visits that coincide with prenatal care but also offer additional visits for those who would like more intense treatment.
The unavailability of some urine samples is a limitation. For hospitalized subjects, even if we had obtained urine, they had less access to drugs and alcohol. On the other hand, we used a self-report measure of substance utilization in the last 30 days that would have included days prior to hospitalization. In other analyses we found that the rate of non-disclosure of substance use was low among women randomized to treatment in our cohort, although women often reported that use occurred far earlier than urine tests would suggest.
In summary, it appears that MET-CBT was similar to brief advice in reducing use of illicit drugs and alcohol among a cohort of perinatal women who were recruited from prenatal care sites and reported a range of severity of substance use. Whether the use of more intensive services can benefit a more severe subset of this group, particularly after delivery, remains to be established.
Acknowledgments
This research was supported by Grant R01 DA 019135 from the National Institute on Drug Abuse to Drs. Yonkers, Kershaw, Carroll and Rounsaville. Other support was provided by NIDA P50 DA09241. Clinical trial Registry Number: NCT00227903
Footnotes
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Contributor Information
Kimberly A. Yonkers, Departments of Psychiatry and, Obstetrics, Gynecology and Reproductive Sciences and the School of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA 06510
Ariadna Forray, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA 06510
Heather B. Howell, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA 06510
Nathan Gotman, Department of Psychiatry, Yale University School of Medicine New Haven, CT, USA 06510
Trace Kershaw, School of Epidemiology and Public Health, Yale University School of Medicine, New Haven, CT, USA 06510
Bruce J. Rounsaville, Department of Psychiatry, Yale University School of Medicine.
Kathleen M. Carroll, Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA 06510
References
- 1.SAMHSA. Results from the 2007 National Survey on Drug Use and Health: National Findings. Rockville, MD: Office of Applied Studies; 2007. pp. 1–290. [Google Scholar]
- 2.Ebrahim SH, Gfroerer J. Pregnancy-related substance use in the United States during 1996–1998. Obstetrics and Gynecology. 2003;101(2):374–9. doi: 10.1016/s0029-7844(02)02588-7. [DOI] [PubMed] [Google Scholar]
- 3.Lui S, Terplan M, Smith EJ. Psychosocial interventions for women enrolled in alcohol treatment during pregnancy. Cochrane Database of Systematic Reviews. 2008;(3):CD006753. doi: 10.1002/14651858.CD006753.pub2. [DOI] [PubMed] [Google Scholar]
- 4.Terplan M, Lui S. Psychosocial interventions for pregnant women in outpatient illicit drug treatment programs compared to other interventions. Cochrane Database of Systematic Reviews. 2008;(4):CD006037. doi: 10.1002/14651858.CD006037.pub2. [DOI] [PubMed] [Google Scholar]
- 5.Jones HE, O’Grady KE, Tuten M. Reinforcement-based treatment improves the maternal treatment and neonatal outcomes of pregnant patients enrolled in comprehensive care treatment. Am J Addictions. 2011;20(3):196–204. doi: 10.1111/j.1521-0391.2011.00119.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Schottenfeld RS, Moore B, Pantalon MV. Contingency management with community reinforcement approach or twelve-step facilitation drug counseling for cocaine dependent pregnant women or women with young children. Drug Alcohol Depend. 2011;118(1):48–55. doi: 10.1016/j.drugalcdep.2011.02.019. [DOI] [PubMed] [Google Scholar]
- 7.Silverman K, Svikis D, Robles E, Stitzer ML, Bigelow GE. A reinforcement-based therapeutic workplace for the treatment of drug abuse: Six-month abstinence outcomes. Exp Clin Psychopharmacol. 2001;9(1):14–23. doi: 10.1037/1064-1297.9.1.14. [DOI] [PubMed] [Google Scholar]
- 8.Svikis DS, Lee JH, Haug NA, Stitzer ML. Attendance incentives for outpatient treatment: Effects in methadone and nonmethadone-maintained pregnant drug dependent women. Drug Alcohol Depend. 1997;48:33–41. doi: 10.1016/s0376-8716(97)00101-4. [DOI] [PubMed] [Google Scholar]
- 9.Jones HE, Haug NA, Stitzer ML, Svikis DS. Improving treatment outcomes for pregnant drug-dependent women using low-magnitude voucher incentives. Addictive Behaviors. 2000;25(2):263–7. doi: 10.1016/s0306-4603(98)00119-1. [DOI] [PubMed] [Google Scholar]
- 10.Jones HE, Haug N, Silverman K, Stitzer M, Svikis D. The effectiveness of incentives in enhancing treatment attendance and drug abstinence in methadone-maintained pregnant women. Drug Alcohol Depend. 2001;61:297–306. doi: 10.1016/s0376-8716(00)00152-6. [DOI] [PubMed] [Google Scholar]
- 11.Elk R, Schmitz J, Manfredi L, Rhoades H, Andres R, Grabowski J. Cessation of cocaine use during pregnancy: A preliminary comparison. Addictive Behaviors. 1994;19(6):697–702. doi: 10.1016/0306-4603(94)90024-8. [DOI] [PubMed] [Google Scholar]
- 12.Carroll KM, Chang G, Behr H, Clinton B, Kosten TR. Improving Treatment Outcome in Pregnant, Methadone-Maintained Women: Results From a Randomized Clinical Trial. Am J Addictions. 1995;4(1):56–9. [Google Scholar]
- 13.Heil SH, Higgins ST, Bernstein IM, Solomon LJ, Rogers RE, Thomas CS, Badger GJ, Lynch ME. Effects of voucher-based incentives on abstinence from cigarette smoking and fetal growth among pregnant women. Addiction. 2008;103(6):1009–18. doi: 10.1111/j.1360-0443.2008.02237.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 14.Higgins ST, Bernstein IM, Washio Y, Heil SH, Badger GJ, Skelly JM, Higgins TM, Solomon LJ. Effects of smoking cessation with voucher-based contingency management on birth outcomes. Addiction. 2010;105(11):2023–30. doi: 10.1111/j.1360-0443.2010.03073.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15.O’Neil K, Baker A, Cooke M, Collins E, Heather N, Wodak A. Evaluation of a cognitive-behavioral intervention for pregnant injecting drug users at risk of HIV infection. Addiction. 1996;91(8):115–1125. doi: 10.1046/j.1360-0443.1996.91811154.x. [DOI] [PubMed] [Google Scholar]
- 16.Winhusen T, Kropp F, Babcock D, Hague D, Erickson SJ, Renz C, Rau L, Lewis D, Leimberger J, Somoza E. Motivational enhancement therapy to improve treatment utilization and outcome in pregnant substance users. J Sub Abuse Treat. 2008;35(2):161–73. doi: 10.1016/j.jsat.2007.09.006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17.Haug NA, Svikis DS, Diclemente C. Motivational enhancement therapy for nicotine dependence in methadone-maintained pregnant women. Psychol Addict Behav. 2004;18(3):289–92. doi: 10.1037/0893-164X.18.3.289. [DOI] [PubMed] [Google Scholar]
- 18.Mullins M, Suarez M, Ondersma S, Page M. The impact of motivational interviewing on substance abuse treatment retention: A randomized control trial of women involved with child welfare. J of Substance Abuse Treatment. 2004;27:51–8. doi: 10.1016/j.jsat.2004.03.010. [DOI] [PubMed] [Google Scholar]
- 19.Jones HE, Svikis DS, Tran G. Patient compliance and maternal/infant outcomes in pregnant drug-using women. Substance Use & Misuse. 2002;37(11):1411–22. doi: 10.1081/ja-120014084. [DOI] [PubMed] [Google Scholar]
- 20.Handmaker NS, Miller WR, Manicke M. Findings of a pilot study of motivational interviewing with pregnant drinkers. J Studies on Alcohol. 1999;60(2):285. doi: 10.15288/jsa.1999.60.285. [DOI] [PubMed] [Google Scholar]
- 21.Rosett HL, Weiner L, Edelin KC. Treatment experience with pregnant problem drinkers. JAMA. 1983;249(15):2029–33. [PubMed] [Google Scholar]
- 22.O’Connor MJ, Whaley SE. Brief Intervention for Alcohol Use by Pregnant Women. Am J Public Health. 2007;97(2):252–8. doi: 10.2105/AJPH.2005.077222. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 23.Chang G, Wilkins-Haug L, Berman S, Goetz MA. Brief intervention for alcohol use in pregnancy: A randomized trial. Addiction. 1999;94(10):1499–508. doi: 10.1046/j.1360-0443.1999.941014996.x. [DOI] [PubMed] [Google Scholar]
- 24.Chang G, Goetz MA, Wilkins-Haug L, Berman S. A brief intervention for prenatal alcohol use: an in-depth look. J Subst Abuse Treat. 2000;18(4):365–9. doi: 10.1016/s0740-5472(99)00105-1. [DOI] [PubMed] [Google Scholar]
- 25.Chang G, McNamara T, Orav J, Koby D, Lavigne A, Ludman B, Vincitorio N, Wilkins-Haug L. Brief intervention for prenatal alcohol use: a randomized trial. Obstetrics and Gynecologists. 2005;105(5):991–8. doi: 10.1097/01.AOG.0000157109.05453.84. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 26.Armstrong MA, Lieberman L, Carpenter DM, Gonzales VM, Usatin MS, Newman L, Escobar GJ. Early Start: An obstetric clinic-based, perinatal substance abuse intervention program. Quality Management in Health Care. 2001;9(2):6–15. doi: 10.1097/00019514-200109020-00004. [DOI] [PubMed] [Google Scholar]
- 27.Lejeune C, Floch-Tudal C, Crenn-Hebert C, Simonpoli AM Groupe d’Etudes Grossesse et A. [Perinatal drug abuse. Collaborative perinatal care for drug abusers and their infants] J Gynecol Obstet Biol Reprod (Paris) 2004;33(1 Suppl):S67–70. doi: 10.1016/s0368-2315(04)96668-9. [DOI] [PubMed] [Google Scholar]
- 28.Ebrahim SH, Diekman ST, Floyd RL, Decoufle P. Comparison of binge drinking among pregnant and nonpregnant women, United States, 1991–1995. Am J Obstet and Gynecol. 1999;181(1):1–7. doi: 10.1016/s0002-9378(99)70139-0. [DOI] [PubMed] [Google Scholar]
- 29.Moore DG, Turner JD, Parrott AC, Goodwin JE, Fulton SE, Min MO, Fox HC, Braddick FMB, Axelsson EL, Lynch S, Ribeiro H, Frostick CJ, Singer LT. During pregnancy, recreational drug-using women stop taking ecstasy (3,4-methylenedioxy-N-methylamphetamine) and reduce alcohol consumption, but continue to smoke tobacco and cannabis: initial findings from the Development and Infancy Study. J Psychopharmacolo. 2010;24(9):1403–10. doi: 10.1177/0269881109348165. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 30.Irvin JE, Bowers CA, Dunn ME, Wang MC. Efficacy of relapse prevention: A meta-analytic review. J Consult Clin Psychol. 1999;67(4):563–70. doi: 10.1037//0022-006x.67.4.563. [DOI] [PubMed] [Google Scholar]
- 31.Babor TF, Carroll K, Christiansen K, Kadden R, Litt M, McRee B, Miller M, Roffman R, Solowij N, Steinberg K, Stephens R, Vendetti J, Donaldson J, Herrell J. Brief treatments for cannabis dependence: Findings from a randomized multi-site trial. Consulting Psychol. 2004 [Google Scholar]
- 32.Carroll KM, Fenton LR, Ball SA, Nich C, Frankforter TL, Shi J, Rounsaville BJ. Efficacy of disulfiram and cognitive behavior therapy in cocaine-dependent outpatients: A randomized placebo-controlled trial. Arch Gen Psychiatry. 2004;61:264–72. doi: 10.1001/archpsyc.61.3.264. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 33.Chang G, Wilkins-Haug L, Berman S, Goetz M. The TWEAK: Application in a prenatal setting. Brigham and Women’s Hospital, Boston, & Department of Psychiatry. Harvard Medical School. 1999;60:306–9. doi: 10.15288/jsa.1999.60.306. [DOI] [PubMed] [Google Scholar]
- 34.Russell M. Detecting Risk Drinking during pregnancy: A comparison of Four Screening Questionnaires. Am J Public Health. 1996;86(10):1435–9. doi: 10.2105/ajph.86.10.1435. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 35.Yonkers Screening for Prenatal Substance Use: Development of the Substance Use Risk Profile-Pregnancy Scale. Obstet Gynecol. 2010;116(4):827–33. doi: 10.1097/AOG.0b013e3181ed8290. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 36.Miller W, Rolnick . Motivational interviewing: Preparing people to change addictive behavior. Guilford Press; 1991. [Google Scholar]
- 37.Miller WR, Zweben A, DiClemente CC, Rychtarik RG. Motivational enhancement therapy manual: A clinical research guide for therapists treating individuals with alcohol abuse and dependence. Rockville, MD: 1992. unpublished manuscript. [Google Scholar]
- 38.Carroll K, Ball S, Martino S. Cognitive, Behavioral, and Motivational Therapies. In: Galanter M, Kleber H, editors. The American Psychiatric Publishing Textbook of Substance Abuse Treatment. 3. Washington, DC: American Psychiatric Publishing; 2004. pp. 365–76. [Google Scholar]
- 39.Parsons J, Rosof E, Punzalan J, Di Maria L. Integration of Motivational Interviewing and Cognitive Behavioral Therapy to improve HIV medication adherence and reduce substance use among HIV-positive men and women: Results of a pilot project. AIDS Patient Care and STDs. 2005;19(1):31–9. doi: 10.1089/apc.2005.19.31. [DOI] [PubMed] [Google Scholar]
- 40.Monti PM, Kadden RM, Rohsenow DJ, Cooney NL, Abrams DB. Treating Alcohol Dependence: A Coping Skills Training Guide. 2. New York, NY: The Guilford Press; 2002. [Google Scholar]
- 41.Kadden R, Carrol K, Donovan D, Cooney N, Monti P, Abram D, Litt M, Hester R. Cognitive-behavioral coping skills therapy manual: A clinical research guide for therapits treating individuals with alscohol abuse and dependence. In: Mattson ME, editor. NIAAA Project MATCH monograph series (Vol3, DHHS Publication No ADM 92–1895) Washington, DC: U.S. Government Printing Office; 1992. [Google Scholar]
- 42.Yonkers KA, Howell HB, Allen AE, Ball SA, Pantalon MV, Rounsaville BJ. A treatment for substance abusing pregnant women. Arch Women’s Mental Health. 2009;12(4):221–7. doi: 10.1007/s00737-009-0069-2. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 43.Carroll KM, Nich C, Sifry RL, Nuro KF, Frankforter TL, Ball SA, Fenton L, Rounsaville BJ. A general system for evaluating therapist adherence and competence in psychotherapy research in the addictions. Drug Alcohol Depend. 2000;57:225–38. doi: 10.1016/s0376-8716(99)00049-6. [DOI] [PubMed] [Google Scholar]
- 44.Sheehan D, Lecrubier Y, Sheehan K, Amorim P, Janava J, Weiller E, Hergueta T, Baker R, Dunbar G. The Mini-International Neuropsychiatric Interview (M.I.N.I.): the development and validation of a structured diagnostic psychiatric interview for DSM-IV and ICD-10. J Clin Psychiatr. 1998;59(S20):22–33. [PubMed] [Google Scholar]
- 45.Falsetti S, Resnick H, Pesick P, Kilpatrick D. The modified PTSD symptom scale: A brief self-report measure of posttraumatic stress disorder. Behavior Therapist. 1993;16:161–2. [Google Scholar]
- 46.Rush AJ, Gullion CM, Basco MR, Jarrett RB, Trivedi MH. The Inventory of Depressive Symptomatology (IDS) Psychometric properties. Psychol Med. 1996;26:477–86. doi: 10.1017/s0033291700035558. [DOI] [PubMed] [Google Scholar]
- 47.Sobell L, Sobell M. Timeline Follow-Back: a technique for assessing self-reported alcohol consumption. In: Litten R, editor. Measuring Alcohol Consumption: Psychosocial and Biological Methods. Towota, NJ: Humana Press; 1992. pp. 41–72. [Google Scholar]
- 48.Fals-Stewart W, O’Farrell TJ, Freitas TT, McFarlin SK, Rutigliano P. The timeline followback reports of psychoactive substance use by drug-abusing patients: psychometric properties. J Consult Clin Psychol. 2000;68:134–44. doi: 10.1037//0022-006x.68.1.134. [DOI] [PubMed] [Google Scholar]
- 49.Kotelchuck M. The Adequacy of Prenatal Care Utilization Index: Its US distribution and association with low birthweight. Am J Public Health. 1994;84(9):1486–9. doi: 10.2105/ajph.84.9.1486. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 50.Anker JJ, Larson EB, Gliddon LA, Carroll ME, Anker JJ, Larson EB, Gliddon LA, Carroll ME. Effects of progesterone on the reinstatement of cocaine-seeking behavior in female rats. Exp Clin Psychopharmacol. 2007;15(5):472–80. doi: 10.1037/1064-1297.15.5.472. [DOI] [PubMed] [Google Scholar]
- 51.Feltenstein MW, Byrd EA, Henderson AR, See RE, Feltenstein MW, Byrd EA, Henderson AR, See RE. Attenuation of cocaine-seeking by progesterone treatment in female rats. Psychoneuroendocrinology. 2009;34(3):343–52. doi: 10.1016/j.psyneuen.2008.09.014. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 52.Larson EB, Anker JJ, Gliddon LA, Fons KS, Carroll ME. Effects of estrogen and progesterone on the escalation of cocaine self-administration in female rats during extended access. Exp Clin Psychopharmacol. 2007;15(5):461–71. doi: 10.1037/1064-1297.15.5.461. [DOI] [PubMed] [Google Scholar]
- 53.Evans SM, Foltin RW. Exogenous progesterone attenuates the subjective effects of smoked cocaine in women, but not in men. Neuropsychopharmacology. 2006;31(3):659. doi: 10.1038/sj.npp.1300887. [DOI] [PubMed] [Google Scholar]
- 54.Sofuoglu M, Babb DA, Hatsukami DK. Effects of progesterone treatment on smoked cocaine response in women. Pharmacology Biochemistry and Behavior. 2002;72(1–2):431. doi: 10.1016/s0091-3057(02)00716-5. [DOI] [PubMed] [Google Scholar]
- 55.Sofuoglu M, Mitchell E, Mooney M, Sofuoglu M, Mitchell E, Mooney M. Progesterone effects on subjective and physiological responses to intravenous nicotine in male and female smokers. Human Psychopharmacology. 2009;24(7):559–64. doi: 10.1002/hup.1055. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 56.Burke BL, Arkowitz H, Menchola M. The efficacy of motivational interviewing: a meta-analysis of controlled clinical trials.[see comment] J Consulting & Clin Psychol. 2003;71(5):843–61. doi: 10.1037/0022-006X.71.5.843. [DOI] [PubMed] [Google Scholar]
- 57.Magill M, Ray LA. Cognitive-behavioral treatment with adult alcohol and illicit drug users: a meta-analysis of randomized controlled trials. J Studies on Alcohol & Drugs. 2009;70(4):516–27. doi: 10.15288/jsad.2009.70.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 58.Lundahl B, Burke BL. The effectiveness and applicability of motivational interviewing: a practice-friendly review of four meta-analyses. J Clin Psychol. 2009;65(11):1232–45. doi: 10.1002/jclp.20638. [DOI] [PubMed] [Google Scholar]
- 59.McHugh RK, Hearon BA, Otto MW. Cognitive Behavioral Therapy for Substance Use Disorders. Psychiatric Clinics of North America. 2010;33(3):511–25. doi: 10.1016/j.psc.2010.04.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 60.Quesada O, Gotman N, Howell HB, Funai EF, Rounsaville BJ, Yonkers KA. Prenatal hazardous substance use and adverse birth outcomes. J Maternal-Fetal and Neonatal Medicine. 0(0):1–6. doi: 10.3109/14767058.2011.602143. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 61.Yonkers KA, Howell HB, Gotman N, Rounsaville BJ. Self-report of illicit substance use versus urine toxicology results from at-risk pregnant women. Journal of Substance Use. 2011;16(5):372–80. doi: 10.3109/14659891003721133. [DOI] [PMC free article] [PubMed] [Google Scholar]