Prescription opioid dispensing patterns among patients with schizophrenia or bipolar disorder.

BACKGROUND: Patients with schizophrenia (SZ) or bipolar disorder (BD) may have increased risk of complications from prescribed opioids, including opioid-induced respiratory depression. We compared prescription opioid pain medication dispensing for patients with SZ or BD versus controls over 5 years to assess dispensing trends. METHODS: This retrospective, observational study analysed US claims data from the IBM® MarketScan® Commercial and Multi-State Medicaid databases for individuals aged 18-64 years with prevalent SZ or BD for years 2015-2019 compared with age- and sex-matched controls. Baseline characteristics, comorbidities, and medication use were assessed. Proportions of individuals dispensed prescription opioids chronically (ie, ≥70 days over a 90-day period or ≥ 6 prescriptions annually) or nonchronically (≥1 prescription, chronic definition not met) were assessed. RESULTS: In 2019, the Commercial and Medicaid databases contained records for 4773 and 30,179 patients with SZ and 52,780 and 63,455 patients with BD, respectively. Patients with SZ or BD had a higher prevalence of comorbidities, including pain, versus controls in each analysis year. From 2015 to 2019, among commercially insured patients with SZ, chronic opioid-dispensing proportions decreased from 6.1% (controls: 2.7%) to 2.3% (controls: 1.2%) and, for patients with BD, from 11.4% (controls: 2.7%) to 6.4% (controls: 1.6%). Chronic opioid dispensing declined in Medicaid-covered patients with SZ from 15.0% (controls: 14.7%) to 6.7% (controls: 6.0%) and, for patients with BD, from 27.4% (controls: 12.0%) to 12.4% (controls: 4.7%). Among commercially insured patients with SZ, nonchronic opioid dispensing decreased from 15.5% (controls: 16.4%) to 10.7% (controls: 11.0%) and, for patients with BD, from 26.1% (controls: 17.5%) to 20.0% (controls: 12.2%). In Medicaid-covered patients with SZ, nonchronic opioid dispensing declined from 22.5% (controls: 24.4%) to 15.1% (controls: 12.7%) and, for patients with BD, from 32.3% (controls: 25.9%) to 24.6% (controls: 13.6%). CONCLUSIONS: The proportions of individuals dispensed chronic or nonchronic opioid medications each year were similar between commercially and Medicaid-insured patients with SZ versus controls and were higher for patients with BD versus controls. From 2015 to 2019, the proportions of individuals who were dispensed prescription opioids chronically or nonchronically decreased for patients with SZ or BD and controls.

Characteristics and treatment preferences of individuals with opioid use disorder seeking to transition from buprenorphine to extended-release naltrexone in a residential setting.

BACKGROUND AND OBJECTIVES: Treatment for individuals receiving medication for opioid use disorder (MOUD) should follow an informed patient-centered approach. To better support patient autonomy in the decision-making process, clinicians should be aware of patient preferences and be prepared to educate and assist patients in transitioning from one MOUD to another, when clinically indicated. This posthoc analysis describes the characteristics of clinical trial participants (NCT02696434) with a history of opioid use disorder (OUD) seeking to transition from buprenorphine (BUP) to extended-release naltrexone (XR-NTX). METHODS: The posthoc analysis included adults with OUD currently receiving BUP (≤8 mg/day) and seeking transition to XR-NTX (N = 101) in a residential setting. Baseline participant characteristics and OUD treatment history were reviewed. All patients completed a screening questionnaire that asked about their reasons for seeking transition to XR-NTX and for choosing BUP. RESULTS: The most common reasons for initiating a transition to XR-NTX were "Seeking to be opioid-free" (63.4%) and "Tired of daily pill taking" (25.7%). Positive predictors of transition included a more extensive BUP treatment history and a history of prescription opioid abuse. Most participants stated they were not aware of XR-NTX as a treatment option when initiating BUP (78.2%). DISCUSSIONS AND CONCLUSIONS: Patients' reasons for seeking XR-NTX transition, more extensive BUP treatment history, and a history of prescription opioid abuse, may positively predict outcomes. SCIENTIFIC SIGNIFICANCE: These findings may assist clinicians in optimizing outcomes of the BUP to XR-NTX transition and supporting patients to make better informed MOUD decisions.

Patterns of withdrawal in patients with opioid use disorder (OUD) transitioning from untreated OUD or buprenorphine treatment to extended-release naltrexone.

BACKGROUND: Pharmacologic treatment is recommended for many individuals with opioid use disorder (OUD). For patients who select opioid antagonist treatment, effective management of opioid withdrawal symptoms during transition to antagonist treatment requires consideration of the patient experience. OBJECTIVES: To compare patterns of opioid withdrawal between those withdrawing from untreated opioid use and those withdrawing from buprenorphine. METHODS: We performed a post hoc, cross-study comparison of the temporal pattern of opioid withdrawal during 1-week induction onto extended-release naltrexone by similar protocols enrolling two participant populations: participants with OUD entering a study with untreated opioid use (N = 378, NCT02537574) or on stable buprenorphine (BUP) treatment (N = 101, NCT02696434). RESULTS: The temporal pattern of withdrawal from induction day 1 through day 7 differed between the two participant populations for Clinical Opiate Withdrawal Score (COWS) and Subjective Opiate Withdrawal Score (SOWS): participants with untreated OUD prior to study entry were more likely to experience an earlier relative peak in opioid withdrawal followed by a gradual decline, whereas participants on stable BUP treatment prior to study entry were more likely to experience a relatively later, though still mild, peak opioid withdrawal. The peak COWS was reached at a mean (standard deviation) of 1.9 (1.5) days for participants with untreated OUD and 5.0 (1.5) days for participants on stable BUP. Daily peak cravings were generally higher for participants with untreated OUD than participants on stable BUP. CONCLUSION: Awareness of population-specific variations in the patient experience of opioid withdrawal may help clinicians anticipate the expected course of withdrawal.

Transition of Patients with Opioid Use Disorder from Buprenorphine to Extended-Release Naltrexone: A Randomized Clinical Trial Assessing Two Transition Regimens.

BACKGROUND AND OBJECTIVE: When patients seek to discontinue buprenorphine (BUP) treatment, monthly injectable extended-release naltrexone (XR-NTX) may help them avoid relapse. The efficacy of low ascending doses of oral NTX vs placebo for patients transitioning from BUP to XR-NTX is evaluated in this study. METHODS: In a phase 3, hybrid residential/outpatient study, clinically stable participants with opioid use disorder (N = 101), receiving BUP for more than or equal to 3 months and seeking antagonist treatment, were randomized (1:1) to 7 residential days of descending doses of BUP and low ascending doses of oral NTX (NTX/BUP, n = 50) or placebo (PBO-N/BUP, n = 51). Both groups received standing ancillary medications and psychoeducational counseling. Following negative naloxone challenge, participants received XR-NTX (day 8). The primary endpoint was the proportion of participants who received and tolerated XR-NTX. RESULTS: There was no statistical difference between groups for participants receiving a first dose of XR-NTX: 68.6% (NTX/BUP) vs 76.0% (PBO-N/BUP; P = .407). The mean number of days with peak Clinical Opiate Withdrawal Scale (COWS) score less than or equal to 12 during the treatment period (days 1-7) was similar for NTX/BUP and PBO-N/BUP groups (5.8 vs 6.3; P = .511). Opioid withdrawal symptoms during XR-NTX induction and post-XR-NTX observation period (days 8-11) were mild and similar between groups (mean peak COWS score: NTX/BUP, 5.1 vs PBO-N/BUP, 5.4; P = .464). Adverse events were mostly mild/moderate. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Low ascending doses of oral NTX did not increase induction rates onto XR-NTX compared with placebo. The overall rate of successful induction across treatment groups supports a brief BUP taper with standing ancillary medications as a well-tolerated approach for patients seeking transition from BUP to XR-NTX. (Am J Addict 2020;00:00-00).

Psychoeducational Strategies During Outpatient Transition to Extended-Release Naltrexone for Patients With Opioid Use Disorder.

BACKGROUND: The United States is experiencing an opioid epidemic. Better approaches to encourage outpatient utilization of Food and Drug Administration-approved medications for the treatment of opioid use disorder, including extended-release naltrexone (XR-NTX), are needed. Withdrawal management before initiation of XR-NTX is challenging for clinicians and patients and represents a major barrier to treatment. AIMS: To review psychoeducational strategies that support patients during outpatient withdrawal management and transition to XR-NTX. METHOD: We reviewed the literature on psychoeducational strategies used during opioid withdrawal management and described the role that nurses can play in facilitating transition to XR-NTX in a Phase 3, placebo-controlled, outpatient trial comparing induction regimens. RESULTS: Supportive interventions include general psychoeducation on addiction, overcoming ambivalence, treatment adherence, anticipating XR-NTX induction, managing psychological and physiological aspects of opioid withdrawal, risks of opioid use, and sources of support during recovery. CONCLUSIONS: Psychoeducational strategies led by nurses can promote treatment adherence during withdrawal management and induction onto XR-NTX.

Antagonists in the medical management of opioid use disorders: Historical and existing treatment strategies.

BACKGROUND AND OBJECTIVES: Opioid use disorder (OUD) is a chronic condition with potentially severe health and social consequences. Many who develop moderate to severe OUD will repeatedly seek treatment or interact with medical care via emergency department visits or hospitalizations. Thus, there is an urgent need to develop feasible and effective approaches to help persons with OUD achieve and maintain abstinence from opioids. Treatment that includes one of the three FDA-approved medications is an evidence-based strategy to manage OUD. The purpose of this review is to address practices for managing persons with moderate to severe OUD with a focus on opioid withdrawal and naltrexone-based relapse-prevention treatment. METHODS: Literature available on PubMed was used to review the evolution of treatment strategies from the 1960s onward to manage opioid withdrawal and initiate treatment with naltrexone. RESULTS: Emerging practices for extended-release naltrexone induction include the use of agonist tapers and adjuvant medications. Clinical challenges frequently encountered when initiating this therapy include managing withdrawal and ongoing opioid use during treatment. Clinical factors may inform decisions regarding patient selection and length of naltrexone treatment, such as recent opioid use and patient preferences. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Treatment strategies to manage opioid withdrawal have evolved, but many patients with OUD do not receive medication for the prevention of relapse. Clinical strategies for induction onto extended-release naltrexone are now available and can be safely and effectively implemented in specialty and select primary care settings. (© 2018 The Authors. The American Journal on Addictions Published by Wiley Periodicals, Inc. on behalf of The American Academy of Addiction Psychiatry (AAAP);27:177-187).

The effects of ibudilast, a glial activation inhibitor, on opioid withdrawal symptoms in opioid-dependent volunteers.

Glial activation is hypothesized to contribute directly to opioid withdrawal. This study investigated the dose-dependent effects of a glial cell modulator, ibudilast, on withdrawal symptoms in opioid-dependent volunteers after abrupt discontinuation of morphine administration. Non-treatment-seeking heroin-dependent volunteers (n = 31) completed the in-patient, double-blind, placebo-controlled, within-subject and between-group study. Volunteers were maintained on morphine (30 mg, QID) for 14 days and placebo (0 mg, QID) for the last 7 days of the 3-week study. Volunteers also received placebo (0 mg, PO, BID) capsules on days 1-7. On days 8-21, volunteers were randomized to receive ibudilast (20 or 40 mg, PO, BID) or placebo capsules. Subjective and clinical ratings of withdrawal symptoms were completed daily using daily using the Subjective Opioid Withdrawal Scale (SOWS) and Clinical Opioid Withdrawal Scale (COWS). Medication side effects were also monitored. Relative to the first 2 weeks, all groups exhibited withdrawal during the third week as assessed by the SOWS and COWS (P ≤ 0.0001). Although overall SOWS scores did not differ between groups, exploratory analyses pooling the two ibudilast groups demonstrated that they had lower ratings of withdrawal symptoms on SOWS items ('anxious,' 'perspiring,' 'restless,' 'stomach cramps') during detoxification relative to the placebo group. Ibudilast was well tolerated; no serious adverse events occurred during the study. Pharmacological modulation of glial activity with ibudilast decreased some subjective ratings of opioid withdrawal symptoms. These exploratory findings are the first to demonstrate the potential clinical utility of glial modulators for treating opioid withdrawal in humans.

A review of a national training initiative to increase provider use of MAT to address the opioid epidemic.

BACKGROUND AND OBJECTIVES: The Providers' Clinical Support System for Medication Assisted Treatment (PCSS-MAT) initiative focuses on training and mentoring health professionals in the treatment of opioid use disorders (OUD) using pharmacological strategies. Led by the American Academy of Addiction Psychiatry (AAAP), PCSS-MAT is a consortium representing four of the five national professional organizations authorized by DATA 2,000-AAAP, American Osteopathic Academy of Addiction Medicine, American Psychiatric Association, and American Society of Addiction Medicine. DATA organizations are authorized to train physicians to prescribe buprenorphine for OUD treatment. The primary aim of PCSS-MAT is to substantially increase evidence-based practices with medications for OUD. METHODS: This review describes the development of PCSS-MAT, an ongoing national initiative funded by the Substance Abuse and Mental Health Services Administration (SAMHSA), to address the training needs posed by this critical public health problem. Core initiatives include: (1) Training and mentoring activities for primary care physicians; (2) Outreach to multidisciplinary professional organizations, (3) Creating a resource portal for families, patients, and communities for OUD treatment. RESULTS: Educational outreach to providers addresses the needs of patients with OUD and common co-occurring psychiatric and medical disorders. DISCUSSION AND CONCLUSIONS: The overall scope of PCSS-MAT is to increase access to evidence-based treatment of substance use disorders as a public health priority. Recently enacted legislation requires office-based opioid treatment programs to offer all Food and Drug Administration-approved (FDA) forms of MAT. SCIENTIFIC SIGNIFICANCE: Working with health care providers to effectively deliver MAT is key to integrating behavioral and physical medicine. (Am J Addict 2016;25:603-609).

Abuse potential of intranasal buprenorphine versus buprenorphine/naloxone in buprenorphine-maintained heroin users.

In spite of the clinical utility of buprenorphine, parenteral abuse of this medication has been reported in several laboratory investigations and in the real world. Studies have demonstrated lower abuse liability of the buprenorphine/naloxone combination relative to buprenorphine alone. However, clinical research has not yet examined the utility of the combined formulation to deter intranasal use in a buprenorphine-maintained population. Heroin-using volunteers (n = 12) lived in the hospital for 8-9 weeks and were maintained on each of three sublingual buprenorphine doses (2, 8, 24 mg). Under each maintenance dose, participants completed laboratory sessions during which the reinforcing and subjective effects of intranasal doses of buprenorphine (8, 16 mg), buprenorphine/naloxone (8/2, 8/8, 8/16, 16/4 mg) and controls (placebo, heroin 100 mg, naloxone 4 mg) were assessed. Intranasal buprenorphine alone typically produced increases in positive subjective effects and the 8 mg dose was self-administered above the level of placebo. The addition of naloxone dose dependently reduced positive subjective effects and increased aversive effects. No buprenorphine/naloxone combination dose was self-administered significantly more than placebo. These data suggest that within a buprenorphine-dependent population, intranasal buprenorphine/naloxone has reduced abuse potential in comparison to buprenorphine alone. These data strongly argue in favor of buprenorphine/naloxone rather than buprenorphine alone as the more reasonable option for managing the risk of buprenorphine misuse.

Baseline characteristics of patients predicting suitability for rapid naltrexone induction.

BACKGROUND AND OBJECTIVES: Extended-release (XR) injection naltrexone has proved promising in the treatment of opioid dependence. Induction onto naltrexone is often accomplished with a procedure known as rapid naltrexone induction. The purpose of this study was to evaluate pre-treatment patient characteristics as predictors of successful completion of a rapid naltrexone induction procedure prior to XR naltrexone treatment. METHODS: A chart review of 150 consecutive research participants (N = 84 completers and N = 66 non-completers) undergoing a rapid naltrexone induction with the buprenorphone-clonidine procedure were compared on a number of baseline demographic, clinical and psychosocial factors. Logistic regression was used to identify client characteristics that may predict successful initiation of naltrexone after a rapid induction-detoxification. RESULTS: Patients who failed to successfully initiate naltrexone were younger (AOR: 1.040, CI: 1.006, 1.075), and using 10 or more bags of heroin (or equivalent) per day (AOR: 0.881, CI: 0.820, 0.946). Drug use other than opioids was also predictive of failure to initiate naltrexone in simple bivariate analyses, but was no longer significant when controlling for age and opioid use level. CONCLUSIONS: Younger age, and indicators of greater substance dependence severity (more current opioid use, other substance use) predict difficulty completing a rapid naltrexone induction procedure. Such patients might require a longer period of stabilization and/or more gradual detoxification prior to initiating naltrexone. SCIENTIFIC SIGNIFICANCE: Our study findings identify specific characteristics of patients who responded positively to rapid naltrexone induction.

Mast cell tryptase reduces junctional adhesion molecule-A (JAM-A) expression in intestinal epithelial cells: implications for the mechanisms of barrier dysfunction in irritable bowel syndrome.

OBJECTIVES: The objective of this study was to investigate how mast cell tryptase may influence intestinal permeability and tight junction (TJ) proteins in vitro and explore translation to irritable bowel syndrome (IBS). METHODS: We investigated the effect of: (1) tryptase on Caco-2 monolayers, (2) mast cell degranulation in a Caco-2/human mast cell-1 (HMC-1) co-culture model, (3) mast cell degranulation±tryptase inhibition with nafamostat mesilate (NM). Epithelial integrity was assessed by transepithelial resistance (TER), permeability to fluorescein isothiocyanate (FITC)-dextran and transmission electron microscopy (TEM). The expression of junctional proteins zonula occludens-1 (ZO-1), junctional adhesion molecule-A (JAM-A), claudin-1 (CLD-1), CLD-2, CLD-3, occludin and E-cadherin was determined by western blot analysis and immunofluorescence confocal microscopy. Based on the in vitro results, we further assessed JAM-A expression in biopsy tissue (cecum) from 34 IBS patients, 12 controls, and 8 inflammatory controls using immunofluorescence confocal microscopy and explored associations between JAM-A and IBS symptoms. RESULTS: ptase disrupted epithelial integrity in Caco-2 monolayers as shown by a significant decrease in TER, an increase in permeability to FITC-dextran, and a decrease in the expression of junctional proteins JAM-A, CLD-1, and ZO-1 within 24 h. Correspondingly, in the Caco-2/HMC-1 co-culture model we showed a significant decrease in TER, an increase in permeability to FITC-dextran, and the presence of open TJs (TEM) in response to mast cell degranulation within 24 h. In this co-culture model, mast cell degranulation significantly decreased JAM-A and CLD-1 protein expression at 24 h. Tryptase inhibition (NM) significantly reduced the effect of mast cell degranulation on the junctional protein JAM-A, TER, and FITC-dextran flux. In IBS, epithelial JAM-A protein expression was significantly reduced in IBS tissue compared with controls. Lower JAM-A expression was associated with more severe abdominal pain (rs=-0.69, P=0.018) and longer duration of symptoms (rs=-0.7, P=0.012) in IBS-alternating subtype. CONCLUSIONS: uced JAM-A expression in vitro appears to contribute to the underlying mechanisms of altered epithelial integrity in response to tryptase released from degranulating mast cells. In IBS, JAM-A expression was significantly reduced in the cecal epithelium and associated with abdominal pain severity. JAM-A may provide new insights into the underlying mechanisms in IBS.

Comparison of a drug versus money and drug versus drug self-administration choice procedure with oxycodone and morphine in opioid addicts.

This double-blind, placebo-controlled study investigated the effects of oral morphine (0, 45, 135 mg/70 kg) and oral oxycodone (0, 15, 45 mg/70 kg) on buprenorphine-maintained opioid addicts. As a 3: 1 morphine : oxycodone oral dose ratio yielded equivalent subjective and physiological effects in nondependent individuals, this ratio was used in the present study. Two self-administration laboratory procedures - that is, a drug versus money and a drug versus drug procedure - were assessed. Study participants (N=12) lived in the hospital and were maintained on 4 mg/day sublingual buprenorphine. When participants chose between drug and money, money was preferred over all drug doses; only high-dose oxycodone was self-administered more than placebo. When participants chose between drug and drug, both drugs were chosen more than placebo, high doses of each drug were chosen over low doses, and high-dose oxycodone was preferred over high-dose morphine. The subjective, performance-impairing, and miotic effects of high-dose oxycodone were generally greater than those of high-dose morphine. The study demonstrated that a 3: 1 oral dose ratio of morphine : oxycodone was not equipotent in buprenorphine-dependent individuals. Both self-administration procedures were effective for assessing the relative reinforcing effects of drugs; preference for one procedure should be driven by the specific research question of interest.

Effects of repeated oxycodone administration on its analgesic and subjective effects in normal, healthy volunteers.

Tolerance to the analgesic effects of opioids has been demonstrated in laboratory animals after repeated drug administration; yet, this effect has been studied less frequently under controlled laboratory conditions in humans. This within-subject, double-blind, placebo-controlled study was designed to determine whether tolerance developed to the analgesic, subjective, and physiological effects of the commonly prescribed opioid oxycodone when it was administered daily for 5 days. The effects of oxycodone (0, 5, and 20 mg/70 kg, orally) were compared, using a within-session cumulative dosing procedure, on the first and fifth days of the 'daily' dosing phase to assess for tolerance; active oxycodone was administered on the second and fourth days of the daily dosing phase. Changes in the effects of oxycodone were also compared when the medication was only administered on the first and the fifth day of a 5-day 'intermittent' dosing phase; placebo medication was administered on the second and fourth days of the intermittent dosing phase. A 9-day 'washout' period occurred between phases during which no medication was administered. Healthy volunteers (N=10) with no history of drug dependence or current drug use participated in this outpatient study. Analgesia was assessed using the cold pressor test, pain and drug effects were measured using a variety of questionnaires, and pupil diameter was monitored as an index of physiological effects. When administered daily, no differences were observed in oxycodone-induced analgesia between the first and the fifth days, but tolerance did develop to some of the positive subjective effects of oxycodone. In contrast, oxycodone-induced analgesia and participant ratings of some positive subjective drug effects were greater on the fifth compared with the first day of the intermittent dosing phase. No differences in the miotic effects of oxycodone between the first and the fifth days of either dosing phase were detected. Although obtained under limited experimental conditions, these findings suggest that tolerance may not develop to the analgesic effects of therapeutic doses of oxycodone under short-term daily dosing conditions, even though some of its subjective effects may decrease. These data also suggest that intermittent administration may enhance the analgesic effects of oxycodone, while also increasing some of the drug's positive subjective effects related to abuse liability.

Patient characteristics associated with initiation of XR-naltrexone for opioid use disorder in clinical trials.

BACKGROUND: Extended-release injectable naltrexone (XR-naltrexone) is effective for treatment of patients with opioid use disorder (OUD), but initiation remains a barrier due to the challenge of tolerating opioid withdrawal prior to administration. Understanding factors associated with successful initiation of XR-naltrexone could facilitate its implementation through patient-treatment matching. METHODS: We combined data from five consecutive studies that sought to initiate patients with active opioid use onto XR-naltrexone using a rapid procedure consisting of minimal buprenorphine, non-opioid medications for treating opioid withdrawal, and ascending low doses of oral naltrexone. Associations between patient characteristics and initiating naltrexone were estimated with logistic regression models. To evaluate whether associations differed between inpatient and outpatient settings, patient characteristic-by-setting interactions were also estimated. RESULTS: 409 patients were included in the analyses and 228 (56%) received the first injection. A significantly greater percent of inpatients (62%) vs outpatients (48%) initiated XR-naltrexone. Initiation success was significantly more likely on an inpatient basis for heroin (60.9% inpatient vs 36.2% outpatient), intravenous (56.3% inpatient vs 22.5% outpatient), and speedball users (68.1% inpatient vs 32.3% outpatient). Prescription opioid users showed similar, higher initiation rates across settings (68.9% inpatient; 73.7% outpatient). CONCLUSIONS: An inpatient setting may be the preferred strategy for rapid initiation of XR-naltrexone for opioid users with greater severity, including heroin or speedball injection users or those who use opioids intravenously. Initiation on an outpatient basis may be more likely to succeed for prescription opioid users.

A pilot study of neurocognitive function in older and younger cocaine abusers and controls.

This pilot study compared basic neurocognitive functioning among older and younger cocaine abusers and control participants, as a preliminary assessment of whether specific cognitive deficits exist in an aged cocaine-abusing population. We hypothesized an interaction between aging and cocaine abuse, such that older cocaine abusers would exhibit decreased neuropsychological test performance relative to both younger cocaine abusers and older control participants. Four groups (n = 20 each) were examined: older cocaine abusers (ages 51-70), younger cocaine abusers (ages 21-39), and two non-illicit substance-using control groups. Basic neuropsychological and psychiatric measures were administered to all participants. Older participants performed more poorly than younger participants on the Mini-Mental State Examination (MMSE, p < .01), Digit Span Backward (p < .01), and Trail Making Test (TMT) Parts A and B (p < .01). Cocaine abusers performed more poorly than controls on TMT A (p < .01). Older and younger cocaine abusers used similar amounts of cocaine (p > .05). Older cocaine abusers performed more poorly than older control participants and younger cocaine abusers on the Digit Span Forward (p < .0125). Older cocaine abusers also performed more poorly than younger cocaine abusers on TMT A (p < .0125). This study provides preliminary evidence that older cocaine abusers use a significant amount of cocaine and that there is an interaction between aging and cocaine abuse on psychomotor speed, attention, and short-term memory. Future examination of neurocognitive function in older cocaine abusers is clearly warranted.

A comparison of independent depression and substance-induced depression in cannabis-, cocaine-, and opioid-dependent treatment seekers.

Depressive symptoms often coexist with substance use disorders (SUDs). The DSM-IV has identified two distinct categories for depression coexisting with SUDs-independent depression and substance-induced depression. While this distinction has important therapeutic and prognostic implications, it remains difficult to make in clinical practice; the differentiation is often guided by chronological and symptom severity criteria that patients may be unable to precisely provide. Furthermore, it is unclear whether the various substances commonly abused-cannabis, cocaine, and opioids-are equally associated with the two types of depression. Predictors, associations, and other markers may be helpful in guiding the diagnostic process. We, therefore, examined the differences between cannabis-, cocaine-, and opioid-dependent individuals contending with independent depression and those contending with substance-induced depression in regard to several variables, hypothesizing that independent depression is more commonly found in females, and that it is associated with higher symptom severity and psychiatric comorbidity. Cocaine-, cannabis-, and/or opioid-dependent, treatment-seeking individuals underwent a structured clinical interview for DSM-IV-TR disorders after providing consent at our clinical research site; those with co-existing primary depression or substance-induced depression diagnoses were provided with further questionnaires and were entered into this analysis (n= 242). Pair-wise comparisons were conducted between the groups classified as independent versus substance-induced depression with 2-by-2 tables and chi-square tests for dichotomous independent variables, and t-tests for continuous variables. Binomial logistic regression was performed in order to ascertain which of the variables were significant predictors. Women were more likely than men to have independent depression (p< .005). Cannabis dependence was highly associated with independent depression (p< .001), while cocaine dependence was highly associated with substance-induced depression (p< .05). Independent depression was associated with higher Hamilton depression scale scores (16 vs. 10, p< .005), and was more highly associated with the comorbid diagnosis of posttraumatic stress disorder (p< .05). Cannabis dependence (p< .001) and female gender (p< .05) were highly significant predictors of major depression specifically. Gender, cannabis dependence, psychiatric severity, and psychiatric comorbidity have variable, statistically significant associations with independent and substance-induced depression, and may be helpful in guiding the diagnostic process.

The association between naltrexone treatment and symptoms of depression in opioid-dependent patients.

OBJECTIVE: To examine the change in total symptoms, and symptom clusters, of depression in newly abstinent opioid-dependent individuals being treated with depot naltrexone (Depotrex; Biotek, Inc., Wellesley, MA). METHOD: In a series of opioid-dependent patients (N = 34) treated with naltrexone maintenance and relapse prevention therapy, mood was assessed with a 17-item Hamilton Depression (HAM-D) Scale and subscale scores at baseline, and after naltrexone induction at 2- and 4-week post-baseline. Data were analyzed using generalized estimated equation (GEE) models. RESULTS: Patients demonstrated high baseline affective burden and significant improvement of depression scores over a 4-week period post-baseline (F(2.66) = 8.88; p = .0004). Somatic and cognitive-affective subscale scores significantly declined as well as the seven individual item scores. By contrast, the "late insomnia" item score significantly increased at 2 weeks post-baseline. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Naltrexone induction and maintenance in newly abstinent opioid-dependent individuals does not appear to be associated with worsening of depression; however, it may be associated with sleep impairment early in treatment.

Evaluation of Opioid Overdose Reports in Patients Treated with Extended-Release Naltrexone: Postmarketing Data from 2006 to 2018.

INTRODUCTION: After treatment with naltrexone extended-release injectable suspension (XR-NTX), a µ-opioid receptor antagonist, opioid tolerance is reduced from pretreatment baseline. Patients may be vulnerable to opioid overdose if they attempt to override the blockade during treatment, at the end of a dosing interval, after missing a dose, or after discontinuing treatment. OBJECTIVE: We analyzed postmarketing data to characterize reporting rates of opioid overdose during treatment with and after discontinuation of XR-NTX. METHODS: Postmarketing adverse event reports within the XR-NTX safety database, received 2006-2018, for patients treated with XR-NTX for any indication were reviewed for opioid overdose cases. Assessable cases were categorized by timing of the event from the last dose of XR-NTX (latency): ≤28 days (on treatment), 29-56 days, and >56 days from last dose of XR-NTX. Within each latency group, cases were further classified as serious and, of those, cases that had a fatal outcome. RESULTS: During the 12-year period, an estimated 495,602 patients received XR-NTX. Opioid overdose was reported in 161 cases; of these, 66 contained sufficient information to determine latency. Reporting rates of opioid overdose per 10,000 patients treated were similar among latency groups: 0.54 for ≤28 days (0.24 fatal), 0.34 for 29-56 days (0.16 fatal), and 0.44 for >56 days (0.40 fatal) from the last dose of XR-NTX. CONCLUSIONS: Over the 12-year period, the reporting rates of opioid overdose were similar during treatment with or after discontinuation of XR-NTX and <10/10,000 patients exposed. Our findings are limited by the nature of spontaneously reported safety data.

Prescription use disorders in older adults.

The number of older adults needing substance abuse treatment is projected to rise significantly in the next few decades. This paper will focus on the epidemic of prescription use disorders in older adults. Particular vulnerabilities of older adults to addiction will be considered. Specifically, the prevalence and patterns of use of opioids, stimulants, and benzodiazepines will be explored, including the effects of these substances on morbidity and mortality. Treatment intervention strategies will be briefly discussed, and areas for future research are suggested.

Cognitive performance of patients with opioid use disorder transitioned to extended-release injectable naltrexone from buprenorphine: Post hoc analysis of exploratory results of a phase 3 randomized controlled trial.

BACKGROUND: Opioid use disorder (OUD) is associated with cognitive dysfunction. Understanding how pharmacotherapy may affect cognition is an important treatment consideration. METHODS: This was a hybrid residential-outpatient, randomized trial assessing transition regimens (naltrexone/buprenorphine [NTX/BUP] vs placebo-NTX/buprenorphine [PBO-N]/BUP) to extended-release naltrexone (XR-NTX) in patients with OUD seeking BUP discontinuation. Cognition was assessed at baseline, Day 22 (XR-NTX Day 14), and Day 36 (XR-NTX Day 28) using a range of measures (Brief Assessment of Cognition Symbol Coding test, Controlled Oral Word Association Task, Wechsler Memory Scale-III Spatial Span test, Continuous Performance Test, and Test of Attentional Performance). Pre-specified exploratory analyses compared treatment groups. Post hoc analyses were treatment-arm-independent analyses overall and by baseline BUP dose (<8 mg/day [low-dose] or 8 mg/day [higher-dose]). RESULTS: Baseline cognitive measures were similar between NTX/BUP and PBO-N/BUP groups and between BUP low-dose and higher-dose groups. There were improvements in several cognitive outcomes at Day 22 and Day 36 relative to baseline for the overall population, but no differences between NTX/BUP and PBO-N/BUP treatment groups were observed. Participants entering the study on low-dose BUP showed improvements at Day 36 relative to baseline in 5 of 7 cognitive outcomes; participants entering the study on higher-dose BUP generally did not show improvements in cognitive outcomes. CONCLUSIONS: Improvements in most cognitive domains were associated with the transition from BUP to XR-NTX, particularly in participants entering the study on low-dose (<8 mg/day) BUP. These improvements may be due to the discontinuation of BUP, the treatment with XR-NTX, or both.