Ketamine interactions with gut-microbiota in rats: relevance to its antidepressant and anti-inflammatory properties.

BACKGROUND: Appreciable evidence suggest that dysbiosis in microbiota, reflected in gut microbial imbalance plays a key role in the pathogenesis of neuropsychiatric disorders including depression and inflammatory diseases. Recently, the antidepressant properties of ketamine have gained prominence due to its fast and long lasting effects. Additional uses for ketamine in inflammatory disorders such as irritable bowel syndrome have been suggested. However, ketamine's exact mechanism of action and potential effects on microbiome is not known. Here, we examined the effects of low dose ketamine, known to induce antidepressant effects, on stool microbiome profile in adult male Wistar rats. Animals (5/group) were injected intraperitoneally with ketamine (2.5 mg/kg) or saline, daily for 7 days and sacrificed on day 8 when intestinal stools were collected and stored at - 80 °C. DNA was extracted from the samples and the 16 S rRNA gene-based microbiota analysis was performed using 16S Metagenomics application. RESULTS: At genus-level, ketamine strikingly amplified Lactobacillus, Turicibacter and Sarcina by 3.3, 26 and 42 fold, respectively. Conversely, opportunistic pathogens Mucispirillum and Ruminococcus were reduced by approximately 2.6 and 26 fold, respectively, in ketamine group. Low levels of Lactobacillus and Turicibacter are associated with various disorders including depression and administration of certain species of Lactobacillus ameliorates depressive-like behavior in animal models. Hence, some of the antidepressant effects of ketamine might be mediated through its interaction with these gut bacteria. Additionally, high level of Ruminococcus is positively associated with the severity of irritable bowel syndrome (IBS), and some species of Mucispirillum have been associated with intestinal inflammation. Indirect evidence of anti-inflammatory role of Sarcina has been documented. Hence, some of the anti-inflammatory effects of ketamine and its usefulness in specific inflammatory diseases including IBS may be mediated through its interaction with these latter bacteria. CONCLUSION: Our data suggest that at least some of the antidepressant and anti-inflammatory effects of daily ketamine treatment for 7 days may be mediated via its interaction with specific gut bacteria. These findings further validate the usefulness of microbiome as a target for therapeutic intervention and call for more detailed investigation of microbiome interaction with central mediators of mood and/or inflammatory disorders.

Physical activity, psychiatric distress, and interest in exercise group participation among individuals seeking methadone maintenance treatment with and without chronic pain.

BACKGROUND AND OBJECTIVES: Physical activity may improve chronic pain, anxiety, and depression, which are prevalent among patients in methadone maintenance treatment (MMT), but relatively little is known about the physical activity levels or interest in exercise of patients in MMT. METHODS: We used a brief self-report instrument to assess physical activity levels, chronic pain, psychiatric distress, and interest in exercise group participation among 303 adults seeking MMT. RESULTS: Most (73%) reported no moderate or vigorous intensity physical activity in the past week; 27% met recommended physical activity levels, and 24% reported interest in exercise group participation. Participants with (compared to those without) chronic pain had higher levels of psychiatric distress and were less likely to meet recommended levels of physical activity (p < .05), but did not differ significantly in their interest in participating in an exercise group. Participants who met recommended levels of physical activity in the past week were more likely to be men and had lower levels of depression than others (p < .05). CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Low levels of physical activity and low interest in exercise group participation among patients entering MMT point to the need for and likely challenges of implementing exercise interventions in MMT.

Pain and associated substance use among opioid dependent individuals seeking office-based treatment with buprenorphine-naloxone: a needs assessment study.

BACKGROUND AND OBJECTIVES: A paucity of studies has examined the pain experiences of opioid dependent individuals seeking office-based buprenorphine-naloxone treatment (BNT). We set out to examine, among those seeking BNT: (a) the prevalence of pain types (i.e., recent pain, chronic pain), (b) the characteristics of pain (intensity, frequency, duration, interference, location, and genesis), and (c) substance use to alleviate pain. METHOD: We surveyed 244 consecutive individuals seeking office-based BNT for opioid dependence about physical pain and associated substance use. RESULTS: Thirty-six percent of respondents reported chronic pain (CP) (i.e., pain lasting at least 3 months) and 36% reported "some pain" (SP) (i.e., past week pain not meeting the threshold for CP). In comparison to SP respondents, those with CP were, on average, older; reported greater current pain intensity, pain frequency, typical pain duration, typical pain intensity, and typical pain interference; were more likely to report shoulder or pelvis and less likely to report stomach or arms as their most bothersome pain location; and were more likely to report accident or nerve damage and less likely to report opioid withdrawal as the genesis of their pain. Both pain subgroups reported similarly high rates of past-week substance use to alleviate pain. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The high rates of pain and self-reported substance use to manage pain suggest the importance of assessing and addressing pain in BNT patients.

Pain catastrophizing and pain coping among methadone-maintained patients.

OBJECTIVE: The aim of this study was to examine the association of pain catastrophizing and pain coping strategies with characteristic pain intensity (an average of worst, least, and typical pain intensity in the past week) and recent pain-related disability (an average of three measures of past week pain interference) in opioid-dependent patients enrolled in a methadone maintenance treatment program (MMTP) who reported recent pain. DESIGN: Cross-sectional survey. PATIENTS: One hundred and eight MMTP patients who reported recent pain. MEASURES: Participants completed measures of demographics, pain status (i.e., "chronic severe pain" [pain lasting at least 6 months with at least moderate pain intensity or significant pain interference in the past week] vs "some pain" [pain in the past week not meeting the threshold of chronic severe pain]), characteristic pain intensity, recent pain-related disability, somatization, depression, catastrophizing, and pain coping strategies. RESULTS: Catastrophizing explained a significant proportion of the variance in characteristic pain intensity (14%) and recent pain-related disability (11%) after controlling for demographics, pain status, somatization, and depression. Mirroring the findings of studies of non-opioid-dependent chronic pain patients, greater catastrophizing was associated with greater pain intensity and increases in recent pain-related disability. On average, the "chronic severe pain" group reported higher levels of catastrophizing than the "some pain" group. CONCLUSION: Consistent with studies of patients with chronic pain who are not opioid dependent, our findings emphasize the importance of assessing and addressing catastrophizing in MMTP patients with pain.

Conventional and unconventional treatments for stress among methadone-maintained patients: treatment willingness and perceived efficacy.

We surveyed 150 methadone maintenance treatment (MMT) program patients about willingness to use, and perceived efficacy of, conventional and unconventional nonpharmacological stress-related treatments. Although levels of treatment willingness and perceived efficacy for both conventional and unconventional treatments were high, ratings for conventional interventions were, on average, significantly higher than those for unconventional ones. Dimensions of psychiatric distress-but not demographic or MMT characteristics-predicted treatment willingness for conventional therapies and treatment willingness and perceived efficacy for unconventional therapies. These findings are likely to have implications for resource and program planning in MMT programs.

Behavioral counseling and abstinence-contingent take-home buprenorphine in general practitioners' offices in Malaysia: a randomized, open-label clinical trial.

BACKGROUND AND AIM: To address the widespread severe problems with opioid use disorder, buprenorphine-naloxone treatment provided by primary care physicians has greatly expanded treatment access; however, treatment is often provided with minimal or no behavioral interventions. Whether or which behavioral interventions are feasible to implement in various settings and improve treatment outcomes has not been established. This study aimed to evaluate two behavioral interventions to improve buprenorphine-naloxone treatment. DESIGN: A 2 × 2 factorial, repeated-measures, open-label, randomized clinical trial. SETTINGS: General medical practice offices in Muar, Malaysia. PARTICIPANTS: Opioid-dependent individuals (n = 234). INTERVENTIONS: Participants were randomly assigned to one of four treatment conditions and received study interventions for 24 weeks: (1) physician management with or without behavioral counseling and (2) physician management with or without abstinence-contingent buprenorphine-naloxone (ACB) take-home doses. MEASUREMENTS: The primary outcomes were proportions of opioid-negative urine tests and HIV risk behaviors [assessed by audio computer-assisted AIDS risk inventory (ACASI-ARI)]. FINDINGS: The rates of opioid-negative urine tests over 24 weeks of treatment were significantly higher with [68.2%, 95% confidence interval (CI) = 65-71] than without behavioral counseling (59.2%, 95% CI = 56-62, P < 0.001) and with (71.0%, 95% CI = 68-74) than without ACB (56.4%, 95% CI = 53-59, P < 0.001); interaction effects between and among behavioral interventions and time were not statistically significant. Scores on ACASI-ARI decreased significantly from baseline across all treatment groups (P < 0.001) and did not differ significantly with or without behavioral counseling (P = 0.099) or with or without ACB (P = 0.339). CONCLUSIONS: Providing opioid-dependent patients in Muar, Malaysia with buprenorphine-naloxone and physician management plus behavioral counseling or abstinence-contingent buprenorphine-naloxone (ACB) resulted in greater reductions of opioid use compared with providing buprenorphine-naloxone and physician management without behavioral counseling or ACB.

Psychiatric comorbidity and order of condition onset among patients seeking treatment for chronic pain and opioid use disorder.

BACKGROUND: The study objective was to compare psychiatric comorbidity among patients seeking treatment for chronic pain and opioid use disorder (OUD) by order of condition onset (i.e., "Pain First," "OUD First," "Same Time"). METHODS: Data from 170 patients entering two clinical trials of treatments for current comorbid chronic pain and OUD conducted between March 2009 and July 2013 were compared by order of condition onset. The Structured Clinical Interview for DSM-IV-TR Axis I Disorders and the Diagnostic Interview for DSM-IV Personality Disorders (Axis II) were performed by doctoral-level providers using a standardized training protocol. Age of onset group differences on specific diagnostic variables were examined using multinomial logistic regression. RESULTS: Fifty-two percent were in the "Pain First" group (n = 89), 35 % in the "OUD First" group (n = 59), and 13 % in the "Same Time" group (n = 22). Compared with the Pain First group, the Same Time group was less likely to report heroin (vs. prescription opioids) as the primary drug used (OR = 0.20, 95 % CI = 0.06-0.72) or meet criteria for an Axis II disorder (OR = 0.24, 95 % CI = 0.07-0.83). Compared with the Pain First group, the OUD First group was more likely to meet criteria for a current nonopioid substance use disorder (OR = 3.20, 95 % CI = 1.22-8.40). CONCLUSIONS: Our findings regarding differences in psychiatric comorbidity associated with order of condition onset indicate that varying pathways may exist for the emergence of chronic pain and OUD; further research should investigate potential treatment implications.

The association between cocaine use and treatment outcomes in patients receiving office-based buprenorphine/naloxone for the treatment of opioid dependence.

Cocaine use in patients receiving methadone is associated with worse treatment outcomes. The association between cocaine use and office-based buprenorphine/naloxone treatment outcomes is not known. We evaluated the association between baseline and in-treatment cocaine use, treatment retention, and urine toxicology results in 162 patients enrolled in a 24-week trial of primary care office-based buprenorphine/naloxone maintenance. Patients with baseline cocaine metabolite-negative urine toxicology tests compared with those with cocaine metabolite-positive tests had more mean weeks of treatment retention (18.3 vs. 15.8, p = .04), a greater percentage completed 24 weeks of treatment (50% vs. 33%, p = .04) and had a greater percentage of opioid-negative urines (47% vs. 34%, p = .02). Patients with in-treatment cocaine metabolite-negative urine toxicology tests compared with cocaine metabolite-positive patients had more mean weeks of treatment retention (19.0 vs. 16.5, p = .003), a greater percentage completed 24 weeks of treatment (60% vs. 30%, p < .001), and had a greater percentage of opioid-negative urines (51% vs. 35%, p = .001). We conclude that both baseline and in-treatment cocaine use is associated with worse treatment outcomes in patients receiving office-based buprenorphine/naloxone and may benefit from targeted interventions.

Impact of 12 step mutual help groups on drug use disorder patients across six clinical trials.

BACKGROUND: 12 step mutual help groups are widely accessed by people with drug use disorder but infrequently subjected to rigorous evaluation. Pooling randomized trials containing a condition in which mutual help group attendance is actively facilitated presents an opportunity to assess the effectiveness of 12 step groups in large, diverse samples of drug use disorder patients. METHODS: Data from six federally-funded randomized trials were pooled (n = 1730) and subjected to two-stage instrumental variables modelling, and, fixed and random effects regression models. All trials included a 12 step group facilitation condition and employed the Addiction Severity Index as a core measure. RESULTS: The ability of 12 step facilitation to increase mutual help group participation among drug use disorder patients was minimal, limiting ability to employ two-stage instrumental variable models that correct for selection bias. However, traditional fixed and random effect regression models found that greater 12 step mutual help group attendance by drug use disorder patients predicted reduced use of and problems with illicit drugs and also with alcohol. CONCLUSION: Facilitating significant and lasting involvement in 12 step groups may be more challenging for drug use disorder patients than for alcohol use disorder patients, which has important implications for clinical work and for effectiveness evaluations. Though selection bias could explain part of the results of traditional regression models, the finding that participation in 12 step mutual help groups predicts lower illicit drug and alcohol use and problems in a large, diverse, sample of drug use disorder patients is encouraging.

Maintenance treatment with buprenorphine and naltrexone for heroin dependence in Malaysia: a randomised, double-blind, placebo-controlled trial.

BACKGROUND: Expansion of access to effective treatments for heroin dependence is a worldwide health priority that will also reduce HIV transmission. We compared the efficacy of naltrexone, buprenorphine, and no additional treatment, in patients receiving detoxification and subsequent drug counselling, for maintenance of heroin abstinence, prevention of relapse, and reduction of HIV risk behaviours. METHODS: 126 detoxified heroin-dependent patients, from an outpatient research clinic and detoxification programme in Malaysia, were randomly assigned by a computer-generated randomisation sequence to 24 weeks of manual-guided drug counselling and maintenance with naltrexone (n=43), buprenorphine (n=44), or placebo (n=39). Medications were administered on a double-blind and double-dummy basis. Primary outcomes, assessed by urine testing three times per week, were days to first heroin use, days to heroin relapse (three consecutive opioid-positive urine tests), maximum consecutive days of heroin abstinence, and reductions in HIV risk behaviours over 6 months. The study was terminated after 22 months of enrolment because buprenorphine was shown to have greater efficacy in an interim safety analysis. Analysis was by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00383045. FINDINGS: We observed consistent, linear contrasts in days to first heroin use (p=0.0009), days to heroin relapse (p=0.009), and maximum consecutive days abstinent (p=0.0007), with all results best for buprenorphine and worst for placebo. Buprenorphine was associated with greater time to first heroin use than were naltrexone (hazard ratio 1.87 [95% CI 1.21-2.88]) or placebo (2.02 [1.29-3.16]). With buprenorphine, we also recorded significantly greater time to heroin relapse (2.17 [1.38-3.42]), and maximum consecutive days abstinent than with placebo (mean days 59 [95% CI 43-76] vs 24 [13-35]; p=0.003); however, for these outcomes, differences between buprenorphine and naltrexone were not significant. Differences between naltrexone and placebo were not significant for any outcomes. HIV risk behaviours were significantly reduced from baseline across all three treatments (p=0.003), but the reductions did not differ significantly between the three groups. INTERPRETATION: Our findings lend support to the widespread dissemination of maintenance treatment with buprenorphine as an effective public-health approach to reduce problems associated with heroin dependence.

Counseling plus buprenorphine-naloxone maintenance therapy for opioid dependence.

BACKGROUND: The optimal level of counseling and frequency of attendance for medication distribution has not been established for the primary care, office-based buprenorphine-naloxone treatment of opioid dependence. METHODS: We conducted a 24-week randomized, controlled clinical trial with 166 patients assigned to one of three treatments: standard medical management and either once-weekly or thrice-weekly medication dispensing or enhanced medical management and thrice-weekly medication dispensing. Standard medical management was brief, manual-guided, medically focused counseling; enhanced management was similar, but each session was extended. The primary outcomes were the self-reported frequency of illicit opioid use, the percentage of opioid-negative urine specimens, and the maximum number of consecutive weeks of abstinence from illicit opioids. RESULTS: The three treatments had similar efficacies with respect to the mean percentage of opioid-negative urine specimens (standard medical management and once-weekly medication dispensing, 44 percent; standard medical management and thrice-weekly medication dispensing, 40 percent; and enhanced medical management and thrice-weekly medication dispensing, 40 percent; P=0.82) and the maximum number of consecutive weeks during which patients were abstinent from illicit opioids. All three treatments were associated with significant reductions from baseline in the frequency of illicit opioid use, but there were no significant differences among the treatments. The proportion of patients remaining in the study at 24 weeks did not differ significantly among the patients receiving standard medical management and once-weekly medication dispensing (48 percent) or thrice-weekly medication dispensing (43 percent) or enhanced medical management and thrice-weekly medication dispensing (39 percent) (P=0.64). Adherence to buprenorphine-naloxone treatment varied; increased adherence was associated with improved treatment outcomes. CONCLUSIONS: Among patients receiving buprenorphine-naloxone in primary care for opioid dependence, the efficacy of brief weekly counseling and once-weekly medication dispensing did not differ significantly from that of extended weekly counseling and thrice-weekly dispensing. Strategies to improve buprenorphine-naloxone adherence are needed. (ClinicalTrials.gov number, NCT00023283 [ClinicalTrials.gov].).

Integrating buprenorphine treatment into office-based practice: a qualitative study.

BACKGROUND: Despite the availability and demonstrated effectiveness of office-based buprenorphine maintenance treatment (BMT), the systematic examination of physicians' attitudes towards this new medical practice has been largely neglected. OBJECTIVE: To identify facilitators and barriers to the potential or actual implementation of BMT by office-based medical providers. DESIGN: Qualitative study using individual and group semi-structured interviews. PARTICIPANTS: Twenty-three practicing office-based physicians in New England. APPROACH: Interviews were audiotaped, transcribed, and entered into a qualitative software program. The transcripts were thematically coded using the constant comparative method by a multidisciplinary team. RESULTS: Eighty percent of the physicians were white; 55% were women. The mean number of years since graduating medical school was 14 (SD = 10). The primary areas of clinical specialization were internal medicine (50%), infectious disease (20%), and addiction medicine (15%). Physicians identified physician, patient, and logistical factors that would either facilitate or serve as a barrier to their integration of BMT into clinical practice. Physician facilitators included promoting continuity of patient care, positive perceptions of BMT, and viewing BMT as a positive alternative to methadone maintenance. Physician barriers included competing activities, lack of interest, and lack of expertise in addiction treatment. Physicians' perceptions of patient-related barriers included concerns about confidentiality and cost, and low motivation for treatment. Perceived logistical barriers included lack of remuneration for BMT, limited ancillary support for physicians, not enough time, and a perceived low prevalence of opioid dependence in physicians' practices. CONCLUSIONS: Addressing physicians' perceptions of facilitators and barriers to BMT is crucial to supporting the further expansion of BMT into primary care and office-based practices.

Pain and substance-related pain-reduction behaviors among opioid dependent individuals seeking methadone maintenance treatment.

We surveyed 293 opioid dependent individuals seeking methadone maintenance treatment about their pain experiences and their substance-related pain reduction behaviors. Among the 213 respondents reporting recent pain of at least moderate typical pain intensity, two-thirds had a lifetime history of chronic pain. In comparison to those without a lifetime history of chronic pain, those with a lifetime history were older, reported higher pain frequency, were more likely to endorse accident or surgery and less likely to endorse "don't know" as the genesis of their recent pain, and endorsed comparable levels of substance-related pain reduction behaviors. These findings may have implications for resource and program planning in MMT programs.

Allopathic, complementary, and alternative medical treatment utilization for pain among methadone-maintained patients.

We surveyed 150 methadone maintenance treatment program (MMTP) patients about pain, pain treatment utilization, perceived efficacy of prior pain treatment, and interest in pursuing pain treatment at the MMTP. Respondents with chronic severe pain (CSP) (ie, pain lasting at least six months with moderate to severe pain intensity or significant pain interference) and "some pain" (ie, pain reported in the previous week but not CSP) endorsed similar rates of past-week and lifetime allopathic or standard medical (with the exception of lifetime medical use of non-opiate medication) and complementary and alternative medicine (CAM) utilization for pain reduction. Prior pain treatments were perceived to be less effective by CSP than SP patients but both groups had equivalent high rates of interest in pain treatment associated with the MMTP. These findings may have implications for resource and program planning in MMTPs.

An evaluation of the feasibility, acceptability, and preliminary efficacy of cognitive-behavioral therapy for opioid use disorder and chronic pain.

AIMS: The primary study aim was to evaluate the feasibility and acceptability of cognitive-behavioral therapy (CBT) for opioid use disorder and chronic pain. The secondary aim was to examine its preliminary efficacy. METHODS: In a 12-week pilot randomized clinical trial, 40 methadone-maintained patients were assigned to receive weekly manualized CBT (n = 21) or Methadone Drug Counseling (MDC) to approximate usual drug counseling (n = 19). RESULTS: Twenty of 21 patients assigned to CBT and 18 of 19 assigned to MDC completed the pilot study. Mean (SD) sessions attended were 8.4 (2.9) for CBT (out of 12 possible) and 3.8 (1.1) for MDC (out of 4 possible); mean (SD) patient satisfaction ratings (scored on 1-7 Likert-type scales) were 6.6 (0.5) for CBT and 6.0 (0.4) for MDC (p < .001). The proportion of patients abstinent during the baseline and each successive 4-week interval was higher for patients assigned to CBT than for those assigned to MDC [Wald χ2 (1) = 5.47, p = .02]; time effects (p = .69) and interaction effects between treatment condition and time (p = .10) were not significant. Rates of clinically significant change from baseline to end of treatment on pain interference (42.9% vs. 42.1%, [χ2 (1, N = 40) = 0.002, p = 0.96]) did not differ significantly for patients assigned to CBT or MDC. CONCLUSIONS: We found support for the feasibility, acceptability, and preliminary efficacy of cognitive-behavioral therapy relative to standard drug counseling in promoting abstinence from nonmedical opioid use among patients with opioid use disorder and chronic pain. Overall, patients exhibited improved pain outcomes, but these improvements did not differ significantly by treatment condition.

Long-term treatment with buprenorphine/naloxone in primary care: results at 2-5 years.

To examine long-term outcomes with primary care office-based buprenorphine/naloxone treatment, we followed 53 opioid-dependent patients who had already demonstrated six months of documented clinical stability for 2-5 years. Primary outcomes were retention, illicit drug use, dose, satisfaction, serum transaminases, and adverse events. Thirty-eight percent of enrolled subjects were retained for two years. Ninety-one percent of urine samples had no evidence of opioid use, and patient satisfaction was high. Serum transaminases remained stable from baseline. No serious adverse events related to treatment occurred. We conclude that select opioid-dependent patients exhibit moderate levels of retention in primary care office-based treatment.

Research- and community-based clinicians' attitudes on treatment manuals.

We assessed the attitudes of 18 research- and 22 community-based substance abuse clinicians on treatment manuals. Research and community clinicians exhibited favorable attitudes toward manuals, and the majority (72% and 77%, respectively) reported an interest in learning more about substance use disorder (SUD) treatment manuals. Among community clinicians, greater years of experience was significantly associated with less favorable attitudes toward treatment manuals. Research clinicians endorsed significantly higher ratings for the importance attached to "theoretical rationale/overview" and "main session points to address" than community clinicians. Findings suggest that community SUD clinicians are already familiar with and have positive attitudes toward manuals, but specific subgroups have concerns that should be addressed.

Buprenorphine/naloxone treatment in primary care is associated with decreased human immunodeficiency virus risk behaviors.

Methadone treatment reduces human immunodeficiency virus (HIV) risk, but the effects of primary-care-based buprenorphine/naloxone on HIV risk are unknown. The purpose of this study was to determine whether primary-care-based buprenorphine/naloxone was associated with decreased HIV risk behavior. We conducted a longitudinal analysis of 166 opioid-dependent persons (129 men and 37 women) receiving buprenorphine/naloxone treatment in a primary care clinic. We compared baseline and 12- and 24-week overall, drug-related, and sex-related HIV risk behaviors using the AIDS/HIV Risk Inventory (ARI). Buprenorphine/naloxone treatment was associated with significant reductions in overall and drug-related ARI scores from baseline to 12 and 24 weeks. Intravenous drug use in the past 3 months was endorsed by 37%, 12%, and 7% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Sex while you or your partner were "high" was endorsed by 64%, 13%, and 15% of patients at baseline and at 12 and 24 weeks, respectively (p< .001). Inconsistent condom use during sex with a steady partner was high at baseline and did not change over time. We conclude that primary-care-based buprenorphine/naloxone treatment is associated with decreased drug-related HIV risk, but additional efforts may be needed to address sex-related HIV risk when present.

Psychotherapy with American Indians: An exploration of therapist-rated techniques in three urban clinics.

The aim of the project was to conduct psychotherapy research in American Indian mental health clinics. To date, very little psychotherapy research has been conducted in this area. We report the findings from a multisite investigation of psychotherapy techniques used with American Indians. Psychotherapists, working in three American Indian clinics, were asked to self-report the therapeutic interventions that they used in sessions with 93 separate adult American Indian outpatients. Each therapist rated each client exactly once, and thus data on 93 sessions were collected. Therapists' self-reported technique use with the Multitheoretical List of Therapist Interventions (McCarthy & Barber, 2009). Ratings were made immediately following the delivery of a session. The common factors approach was the most reported approach, followed by person-centered and interpersonal approaches. However, the therapists reported using techniques from all of the main therapeutic approaches. Technique use was affected by client- (demographic and diagnostic), therapist-, and therapy-related variables. This project represents a promising start to systematic psychotherapy research in busy, urban American Indian clinics. Many psychotherapeutic techniques are utilized, and there are many avenues for future research. A replication with client and observer ratings will be an important next step. (PsycINFO Database Record

Atomoxetine for amphetamine-type stimulant dependence during buprenorphine treatment: A randomized controlled trial.

BACKGROUND: Amphetamine type stimulants (ATS) use is highly prevalent and frequently co-occurs with opioid dependence in Malaysia and Asian countries. No medications have established efficacy for treating ATS use disorder. This study evaluated the safety, tolerability, and potential efficacy of atomoxetine for treating ATS use disorder. METHODS: Participants with opioid and ATS dependence (N = 69) were enrolled in a pilot, double-blind, placebo-controlled randomized clinical trial; all received buprenorphine/naloxone and behavioral counseling and were randomized to atomoxetine 80 mg daily (n = 33) or placebo (n = 33). The effect size of the between-group difference on the primary outcome, proportion of ATS-negative urine tests, was estimated using Cohen's d for the intention-to-treat (ITT) sample and for higher adherence subsample (≥60 days of atomoxetine or placebo ingestion). RESULTS: Participants were all male with mean (SD) age 39.4 (6.8) years. The proportion of ATS-negative urine tests was higher in atomoxetine- compared to placebo-treated participants: 0.77 (0.63-0.91) vs. 0.67 (0.53-0.81, d = 0.26) in the ITT sample and 0.90 (0.75-1.00) vs. 0.64 (0.51-0.78, d = 0.56) in the higher adherence subsample. The proportion of days abstinent from ATS increased from baseline in both groups (p < 0.001) and did not differ significantly between atomoxetine- and placebo-treated participants (p = 0.42). Depressive symptoms were reduced from baseline in both groups (p < 0.02) with a greater reduction for atomoxetine- than placebo-treated participants (p < 0.02). There were no serious adverse events or adverse events leading to medication discontinuation. CONCLUSIONS: The findings support clinical tolerability and safety and suggest potential efficacy of atomoxetine for treating ATS use disorder in this population.