Marc Fishman

Screening for Psychiatric Morbidity in a Medical Outpatient Clinic for HIV Infection: The Need for a Psychiatric Presence

Objective: To ascertain the prevalence and type of psychiatric morbidity present in HIV infected patients presenting for the first time to a specialty HIV medical clinic. Also, to develop a way of screening for psychiatric cases in this setting using established self-report questionnaires. Method: Fifty patients who presented consecutively for medical care at the Johns Hopkins Hospital General HIV Clinic participated in this study. These patients were first screened using the General Health Questionnaire and the Beck Depression Inventory and subsequently underwent a comprehensive neuropsychiatric evaluation. Results: Fifty-four percent were found to suffer from a psychiatric disorder with an additional 22 percent from an active substance use disorder. These rates are one-and-one-half to two times higher than those reported from other medical clinics. The GHQ and BDI used together as screens could identify psychiatric “cases” with a sensitivity of 81 percent and a specificity of 61 percent, an efficacy similar to that found in other clinics. Conclusions: Given the high prevalence of psychiatric disorders in HIV infected patients presenting for medical care, screening, evaluating, and treating for these disorders is crucial and should be pursued systematically. This is best done through the presence of a psychiatric team within HIV medical clinics rather than in affiliation with such clinics.

Extended-Release Naltrexone to Prevent Opioid Relapse in Criminal Justice Offenders

BACKGROUND Extended-release naltrexone, a sustained-release monthly injectable formulation of the full mu-opioid receptor antagonist, is effective for the prevention of relapse to opioid dependence. Data supporting its effectiveness in U.S. criminal justice populations are limited. METHODS In this five-site, open-label, randomized trial, we compared a 24-week course of extended-release naltrexone (Vivitrol) with usual treatment, consisting of brief counseling and referrals for community treatment programs, for the prevention of opioid relapse among adult criminal justice offenders (i.e., persons involved in the U.S. criminal justice system) who had a history of opioid dependence and a preference for opioid-free rather than opioid maintenance treatments and who were abstinent from opioids at the time of randomization. The primary outcome was the time to an opioid-relapse event, which was defined as 10 or more days of opioid use in a 28-day period as assessed by self-report or by testing of urine samples obtained every 2 weeks; a positive or missing sample was computed as 5 days of opioid use. Post-treatment follow-up occurred at weeks 27, 52, and 78. RESULTS A total of 153 participants were assigned to extended-release naltrexone and 155 to usual treatment. During the 24-week treatment phase, participants assigned to extended-release naltrexone had a longer median time to relapse than did those assigned to usual treatment (10.5 vs. 5.0 weeks, P<0.001; hazard ratio, 0.49; 95% confidence interval [CI], 0.36 to 0.68), a lower rate of relapse (43% vs. 64% of participants, P<0.001; odds ratio, 0.43; 95% CI, 0.28 to 0.65), and a higher rate of opioid-negative urine samples (74% vs. 56%, P<0.001; odds ratio, 2.30; 95% CI, 1.48 to 3.54). At week 78 (approximately 1 year after the end of the treatment phase), rates of opioid-negative urine samples were equal (46% in each group, P=0.91). The rates of other prespecified secondary outcome measures--self-reported cocaine, alcohol, and intravenous drug use, unsafe sex, and reincarceration--were not significantly lower with extended-release naltrexone than with usual treatment. Over the total 78 weeks observed, there were no overdose events in the extended-release naltrexone group and seven in the usual-treatment group (P=0.02). CONCLUSIONS In this trial involving criminal justice offenders, extended-release naltrexone was associated with a rate of opioid relapse that was lower than that with usual treatment. Opioid-use prevention effects waned after treatment discontinuation. (Funded by the National Institute on Drug Abuse; ClinicalTrials.gov number, NCT00781898.).

Psychiatric morbidity on entry to an HIV primary care clinic

Objective:To ascertain the prevalence and predictors of psychiatric distress in an inner-city HIV primary care clinic. Design:Cross-sectional study. Setting:Inner-city adult HIV clinic. Participants:A series of 222 HIV-infected patients newly presenting to the medical clinic for evaluation over a 1-year period. Outcome measures:A screening method, based on the General Health Questionnaire (GHQ) and the Beck Depression Inventory (BDI), whose sensitivity, specificity and positive predictive value for psychiatric diagnosis were previously established in this clinic. Results:Fifty-two per cent of participants scored above the screening threshold (i.e., scored > 14 on the BDI or > 6 on the GHQ). A comorbid substance use condition was the most powerful and consistent predictor of psychiatric distress (P < 0.05). Limited education and current unemployment contributed to higher scores on the BDI or the GHQ (P < 0.05). However, HIV illness variables and psychiatric personal or family histories were not significant predictors of psychiatric distress (P > 0.05 in all cases). Conclusions:Rates of psychiatric distress in inner-city adult HIV clinics are much higher than in the general population or than in other outpatient medical clinics. They are also not associated with what most clinicians perceive as traditional risk groups such as psychiatric histories and social disadvantage. These findings support the position that easy access to psychiatric care is essential to HIV clinics.

Randomized Controlled Trial of Osmotic-Release Methylphenidate with Cognitive-Behavioral Therapy in Adolescents with Attention-Deficit/Hyperactivity Disorder and Substance Use Disorders.

OBJECTIVE To evaluate the efficacy and safety of osmotic-release methylphenidate (OROS-MPH) compared with placebo for attention-deficit/hyperactivity disorder (ADHD), and the impact on substance treatment outcomes in adolescents concurrently receiving cognitive-behavioral therapy (CBT) for substance use disorders (SUD). METHOD This was a 16-week, randomized, controlled, multi-site trial of OROS-MPH + CBT versus placebo + CBT in 303 adolescents (aged 13 through 18 years) meeting DSM-IV diagnostic criteria for ADHD and SUD. Primary outcome measures included the following: for ADHD, clinician-administered ADHD Rating Scale (ADHD-RS), adolescent informant; for substance use, adolescent-reported days of use in the past 28 days. Secondary outcome measures included parent ADHD-RS and weekly urine drug screens (UDS). RESULTS There were no group differences on reduction in ADHD-RS scores (OROS-MPH: -19.2, 95% confidence interval [CI], -17.1 to -21.2; placebo, -21.2, 95% CI, -19.1 to -23.2) or reduction in days of substance use (OROS-MPH: -5.7 days, 95% CI, 4.0-7.4; placebo: -5.2 days, 95% CI, 3.5-7.0). Some secondary outcomes favored OROS-MPH, including lower parent ADHD-RS scores at 8 (mean difference = 4.4, 95% CI, 0.8-7.9) and 16 weeks (mean difference =6.9; 95% CI, 2.9-10.9) and more negative UDS in OROS-MPH (mean = 3.8) compared with placebo (mean = 2.8; p = .04). CONCLUSIONS OROS-MPH did not show greater efficacy than placebo for ADHD or on reduction in substance use in adolescents concurrently receiving individual CBT for co-occurring SUD. However, OROS-MPH was relatively well tolerated and was associated with modestly greater clinical improvement on some secondary ADHD and substance outcome measures. Clinical Trial Registration Information-Attention Deficit Hyperactivity Disorder (ADHD) in Adolescents with Substance Use Disorders (SUD); http://www.clinicaltrials.gov; NCT00264797.

Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial

BACKGROUND Extended-release naltrexone (XR-NTX), an opioid antagonist, and sublingual buprenorphine-naloxone (BUP-NX), a partial opioid agonist, are pharmacologically and conceptually distinct interventions to prevent opioid relapse. We aimed to estimate the difference in opioid relapse-free survival between XR-NTX and BUP-NX. METHODS We initiated this 24 week, open-label, randomised controlled, comparative effectiveness trial at eight US community-based inpatient services and followed up participants as outpatients. Participants were 18 years or older, had Diagnostic and Statistical Manual of Mental Disorders-5 opioid use disorder, and had used non-prescribed opioids in the past 30 days. We stratified participants by treatment site and opioid use severity and used a web-based permuted block design with random equally weighted block sizes of four and six for randomisation (1:1) to receive XR-NTX or BUP-NX. XR-NTX was monthly intramuscular injections (Vivitrol; Alkermes) and BUP-NX was daily self-administered buprenorphine-naloxone sublingual film (Suboxone; Indivior). The primary outcome was opioid relapse-free survival during 24 weeks of outpatient treatment. Relapse was 4 consecutive weeks of any non-study opioid use by urine toxicology or self-report, or 7 consecutive days of self-reported use. This trial is registered with ClinicalTrials.gov, NCT02032433. FINDINGS Between Jan 30, 2014, and May 25, 2016, we randomly assigned 570 participants to receive XR-NTX (n=283) or BUP-NX (n=287). The last follow-up visit was Jan 31, 2017. As expected, XR-NTX had a substantial induction hurdle: fewer participants successfully initiated XR-NTX (204 [72%] of 283) than BUP-NX (270 [94%] of 287; p<0·0001). Among all participants who were randomly assigned (intention-to-treat population, n=570) 24 week relapse events were greater for XR-NTX (185 [65%] of 283) than for BUP-NX (163 [57%] of 287; hazard ratio [HR] 1·36, 95% CI 1·10-1·68), most or all of this difference accounted for by early relapse in nearly all (70 [89%] of 79) XR-NTX induction failures. Among participants successfully inducted (per-protocol population, n=474), 24 week relapse events were similar across study groups (p=0·44). Opioid-negative urine samples (p<0·0001) and opioid-abstinent days (p<0·0001) favoured BUP-NX compared with XR-NTX among the intention-to-treat population, but were similar across study groups among the per-protocol population. Self-reported opioid craving was initially less with XR-NTX than with BUP-NX (p=0·0012), then converged by week 24 (p=0·20). With the exception of mild-to-moderate XR-NTX injection site reactions, treatment-emergent adverse events including overdose did not differ between treatment groups. Five fatal overdoses occurred (two in the XR-NTX group and three in the BUP-NX group). INTERPRETATION In this population it is more difficult to initiate patients to XR-NTX than BUP-NX, and this negatively affected overall relapse. However, once initiated, both medications were equally safe and effective. Future work should focus on facilitating induction to XR-NTX and on improving treatment retention for both medications. FUNDING NIDA Clinical Trials Network.

MOOD DISORDERS IN HIV INFECTION

Summary Major depression and mania have increased prevalence in HIV-infected patients, particularb in clinical settings and at later stages of disease. Varied rates of major depression have been reported but dzzerences in definition, methods of study, and population may partly explain these dafferences. We describe the clinical characteristics, assessment and treatment of mood disorders in HIV-infected patients, with emphasis on aspects specific to the setting of HIV infection. Diagnosis and treatment are complicated by medical complexity, stigma and psychosocial stress. Treatment is associated with clinical improvement. Mood disorders are associated with impulsivity, substance abuse, hopelessness, and demoralization, all of which may increase risk for HIV infection. Also, HIV-associated subcortical damage may be a risk factor for mood disorders, which are increased in late stage HIV infection. We discuss the data supporting the thesis that both of these factors may be at work in producing the high rates of mood disorders seen, and speculate that aggressive treatment of mood disorders may improve outcome and risk behaviors in HIV-infected patients.

Clinical characteristics of treatment-seeking adolescents with opioid versus cannabis/alcohol use disorders

OBJECTIVES To assess the clinical characteristics of adolescents with DSM-IV opioid use disorder (OUD) and compare them to adolescents with cannabis/alcohol use disorders. METHOD 94 adolescents (ages 14-18 years) with a current OUD and 74 adolescents with a current non-OUD cannabis/alcohol use disorders were recruited from admissions, predominantly residential, to a substance abuse treatment program in Baltimore, ML. Participants were assessed cross-sectionally using standardized interviews and self-reports. Chi-square, t-tests and ANCOVA (adjusting for age, gender and treatment setting, race and residence) were performed to determine group differences on demographic, substance use, psychiatric and HIV-risk behaviors; logistic regression analyses, both unadjusted and adjusted for the above five factors were conducted to assess the strength of associations. RESULTS The OUD group was more likely to be Caucasian, to have dropped out of school and to live in the suburbs (trend). They also had greater substance use severity with higher proportion of current sedative and multiple substance use disorders (SUD). There were generally no differences in rates of criminal behaviors. Both groups had high rates of current psychiatric disorders (83% vs. 78%, n.s.) but the OUD adolescents reported higher depressive symptoms, mostly in the moderate range. Injection drug use (IDU) and needle sharing was almost exclusive to the OUD group, while both groups reported similar high rates of risky sexual behaviors. CONCLUSIONS While there were similarities between the two groups, OUD adolescents evidenced greater impairment in academic, substance use, depressive symptom and IDU-related HIV-risk areas. Findings suggest poorer long-term prognosis and highlight the need for specialized interventions for treatment-seeking OUD adolescents.

Predictors of Abstinence: National Institute of Drug Abuse Multisite Buprenorphine/Naloxone Treatment Trial in Opioid-Dependent Youth.

OBJECTIVE To examine predictors of opioid abstinence in buprenorphine/naloxone (Bup/Nal)-assisted psychosocial treatment for opioid-dependent youth. METHOD Secondary analyses were performed of data from 152 youth (15-21 years old) randomly assigned to 12 weeks of extended Bup/Nal therapy or up to 2 weeks of Bup/Nal detoxification with weekly individual and group drug counseling. Logistic regression models were constructed to identify baseline and during-treatment predictors of opioid-positive urine (OPU) at week 12. Predictors were selected based on significance or trend toward significance (i.e., p < .1), and backward stepwise selection was used, controlling for treatment group, to produce final independent predictors at p ≤ .05. RESULTS Youth presenting to treatment with previous 30-day injection drug use and more active medical/psychiatric problems were less likely to have a week-12 OPU. Those with early treatment opioid abstinence (i.e., weeks 1 and 2) and those who received additional nonstudy treatments during the study were less likely to have a week-12 OPU and those not completing 12 weeks of treatment were more likely to have an OPU. CONCLUSIONS Youth with advanced illness (i.e., reporting injection drug use and additional health problems) and those receiving ancillary treatments to augment study treatment were more likely to have lower opioid use. Treatment success in the first 2 weeks and completion of 12 weeks of treatment were associated with lower rates of OPU. These findings suggest that youth with advanced illness respond well to Bup/Nal treatment and identify options for tailoring treatment for opioid-dependent youth presenting at community-based settings. CLINICAL TRIAL REGISTRATION INFORMATION Buprenorphine/Naloxone-Facilitated Rehabilitation for Opioid Dependent Adolescents; http://www.clinicaltrials.gov; NCT00078130.

Precipitated withdrawal during maintenance opioid blockade with extended release naltrexone

Background There has been increasing interest in the use of extended release injectable naltrexone for the treatment of opioid dependence. Case description We report a case of precipitated withdrawal in a 17-year-old adolescent female receiving extended release naltrexone (Vivitrol) for opioid dependence, following her third serial monthly dose of the medication, several days after using oxycodone with mild intoxication. Conclusions This case suggests that, in some circumstances, the opioid blockade may be overcome when naltrexone levels drop towards the end of the dosing interval, producing vulnerability to subsequent naltrexone-induced withdrawal. This may provide cautionary guidance for clinical management and dosing strategies.

Predictors of attrition with buprenorphine/naloxone treatment in opioid dependent youth

BACKGROUND In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment. METHODS Opioid dependent adolescents and young adults (n=152), aged 15-21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression. RESULTS In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition. CONCLUSIONS Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics.