Opioid use disorder (OUD) and treatment for opioid problems among OUD symptom subtypes in individuals misusing opioids.

Background: In 2021, approximately 60 million individuals worldwide and 9 million individuals in the United States (US) reported opioid misuse. In the US, 2.5 million have OUD, of which only about a third receive any substance abuse treatment. OUD is often regarded as a monolithic disorder but different opioid problem subtypes may exist beyond DSM-IV/5 criteria. Understanding the characteristics of these subtypes could be useful for informing treatment and intervention strategies. Methods: Latent class analysis was used to identify OUD symptom subtypes among persons in the US who reported misusing prescription opioids or heroin in the 2015-2018 National Survey on Drug Use and Health (n=10,928). Regression analyses were utilized to determine associations between class membership and treatment receipt, as well as demographic characteristics and other comorbid conditions. Results: Five classes were identified with unique OUD symptom patterns: Class 1: Asymptomatic (71.6%), Class 2: Tolerance/Time (14.5%), Class 3: Loss of Control/Pharmacological (LOC/Pharmacol) (5.7%), Class 4: Social Impairment (2.6%), and Class 5: Pervasive (5.6%). Nearly all persons in the LOC/Pharmacol, Social Impairment, and Pervasive classes met criteria for OUD (98-100%); however, they differed in receipt of past-year treatment for substance use (28%, 28%, 49%, respectively). Age, race, education, insurance status, and criminal activity were also associated with treatment receipt. Conclusions: There were considerable differences in OUD symptom patterns and substance use treatment among individuals who misused opioids. The findings indicate a substantial unmet need for OUD treatment and point to patterns of heterogeneity within OUD that can inform development of treatment programs.

Patterns of atypical antipsychotic therapy use in adults with bipolar I disorder in the USA.

OBJECTIVES: This study aims to describe the utilization patterns of atypical antipsychotics (AA) among insured patients with bipolar I disorder in the USA. METHODS: We studied patients with bipolar I disorder who newly initiated an oral AA between 2002 and 2008. Utilization measures included adherence [medication possession ratio (MPR) ≥80%], persistence (gaps ≤15 days between refills and an absence of ≥30 days of continuous concomitant non-index AA use), non-compliance (16-29 day gaps with no evidence of switch/augmentation), and discontinuation of the index AA (≥30 days without index AA, no evidence of switch/augmentation). RESULTS: The study included 16 807 patients: mean age 43.3 years, 67.7% female. Overall, adherence to the index AA was low (8.3%; mean MPR = 0.2). Only 10.5% of the patients were persistent to index AA, another 13.6% were non-compliant, and 63.4% discontinued index AA with an average time to discontinuation of 66 days. A majority (69.5%) of the discontinued patients did not resume any antipsychotic therapy. Results were similar across insurance types and index AA. CONCLUSION: Adherence to and persistence with AA treatment were low in new users with bipolar I disorder. Most patients discontinued the index AA and did not restart any antipsychotic treatment. Future study should distinguish physician-directed discontinuation versus patient non-adherence.

Oral buprenorphine utilization, concomitant benzodiazepines and opioid analgesics, and payment source: Trends from 2015 to 2019.

INTRODUCTION: This study describes utilization patterns of oral buprenorphine products indicated for the treatment of opioid use disorder with a focus on patterns consistent with prescribing guidelines and the safe use conditions during induction and maintenance treatment outlined by the Risk Evaluation and Mitigation Strategy (REMS) Program, including trends over time. METHODS: Using an anonymized longitudinal patient-level dataset that captures information on medical and pharmacy claims in the United States (October 1, 2014 through March 31, 2020), buprenorphine prescriptions, days' supply, and daily dose were described overall and stratified by induction (month 1) vs. maintenance (month 2-6) treatment, along with duration of concomitant benzodiazepines or opioid analgesics. RESULTS: Overall, there were 1.5 million buprenorphine treatment episodes initiated between January 1, 2015 to September 30, 2019 (2015: 258,899; 2019: 351,378). Treatment episodes included an average of 6.8 buprenorphine prescriptions (standard deviation [SD] = 6.7), 16.8 days' supply per prescription (SD = 10.5), 94.2 total days' supply per treatment episode (SD = 71.4), and a mean daily dose of 13.6 mg (SD = 6.3), with the number of prescriptions and total days' supply per treatment episode declining over the study period. There was a lower mean number of days' supply per prescription in the first month of treatment compared to months 2-6 (month 1: 15.8 [SD = 11.0]; month 2-6: 19.0 [SD = 10.1]) and daily dose per prescription (month 1: 13.3 mg [SD = 6.4]; months 2-6: 14.3 mg [SD = 6.2]), and a higher mean number of prescriptions per month (month 1: 2.5 per month [SD = 1.7]; months 2-6: 1.8 per month [SD = 1.2]). From 2015 to 2019, there appeared to be a shift in payer mix, with increases in Medicaid/Medicare and declines in cash and commercial insurance. Concomitant benzodiazepine and opioid analgesic use declined over time; in 2019, 16.6 % and 14.3 % of treatment episodes had any concomitant benzodiazepine or opioid analgesic, respectively, and <5 % had chronic (>90 overlapping days) concomitant use (3.0 % and 0.4 %, respectively). CONCLUSIONS: The number of oral buprenorphine treatment episodes increased over the study period, and prescribing was generally consistent with the REMS and other treatment guidelines. There was a decline in concomitant buprenorphine and benzodiazepine or opioid analgesics, and chronic concomitant use was rare.

Assessing Motivations for Nonprescribed Buprenorphine Use Among Rural Appalachian Substance Users.

OBJECTIVE: Buprenorphine (Suboxone) is an effective treatment for opioid use disorder (OUD). However, there have been widespread reports of diversion and misuse. This study examined motivations for nonprescribed buprenorphine use among rural residents. METHODS: Eligible participants (N = 200) were at least 18 years old, had used any illegal or prescription drugs to get high, and had ever used nonprescribed buprenorphine. A questionnaire administered by a trained interviewer assessed demographic characteristics, substance use, and motivations for use. RESULTS: Primary motivations for first nonprescribed buprenorphine use included avoiding withdrawal and getting high, while at most recent nonprescribed use, motivations shifted toward maintaining abstinence from other drugs. In adjusted logistic regression analyses, past month use of stimulants decreased odds of nonprescribed buprenorphine use for the purposes of self-treatment by 68% (adjusted odds ratio, 0.26; 95% confidence interval, 0.11-0.61), whereas history of treatment for OUD more than doubled odds of use for self-treatment (adjusted odds ratio, 2.71; 95% confidence interval, 1.11-6.63). CONCLUSIONS: Results indicate that many individuals used buprenorphine without a prescription, motivated largely by behaviors consistent with self-treatment, and diversion of buprenorphine may be driven by these motivations more than desire to get high. While many participants attempted to access treatment, many were still using nonprescribed buprenorphine for self-treatment, and many were dissatisfied with care they had received as part of a treatment program. Thus, increasing quantity of providers may not be adequate to address the opioid epidemic, but particular attention should be paid to providing care targeted to the needs of those with OUD in rural areas.

The adverse effects of comorbid pain on depression outcomes in primary care patients: results from the ARTIST trial.

OBJECTIVES: To explore the effect of pain symptoms and improvements in pain on depression outcomes. METHODS: We analyzed data from A Randomized Trial Investigating SSRI Treatment (ARTIST), a randomized longitudinal effectiveness study comparing selective serotonin reuptake inhibitors (SSRIs) for the treatment of depression in primary care (n = 573). Depression outcome at month 6, defined as remission, partial response, and nonresponse using the Symptom Checklist-20, was the primary outcome. RESULTS: Compared to patients with no pain at baseline, those with severe pain were less likely to achieve remission (OR = 0.11, 95% CI 0.05-0.25) and partial response (OR = 0.24, 95% CI 0.10-0.59) vs nonresponse. Patients with moderate pain were less likely to achieve remission vs nonresponse (OR = 0.25, 95% CI 0.13-0.48). Patients with early improvement in pain were more likely to achieve remission (OR = 1.90, 95% CI 1.03-3.49). Accounting for missing data with last observation carried forward or multiple imputation yielded similar results. CONCLUSION: Pain symptoms are present in the majority of depressed primary care patients beginning antidepressant therapy. Pain symptoms are associated with worse depression outcomes, while improvement in pain is associated with significantly better depression outcomes. Attention to comorbid pain may be important in enhancing depression care.

The impact of a reformulation of extended-release oxycodone designed to deter abuse in a sample of prescription opioid abusers.

BACKGROUND: Prescription opioid abuse is a significant public health concern that requires strategies to reduce its impact, including development of abuse deterrent formulations. OxyContin, an extended-release oxycodone (ERO) formulation, has been widely abused. This study assessed the effects of reformulated ERO, designed to be more difficult to manipulate for purposes of intranasal and intravenous abuse, on patterns of opioid abuse among a sample of individuals from rural Appalachia with a history of ERO abuse. METHODS: Structured interviews assessing opioid abuse (past 30-day abuse and retrospectively reported abuse prior to the reformulation in August 2010) were completed by 189 individuals between December 2010 and September 2011. RESULTS: The past 30-day prevalence and frequency of reformulated ERO abuse through any route (33%, 1.9 days/month), snorting (5%, 0.2 days/month), and injecting (0.5%, <0.1 days/month) were low and infrequent compared to that of IR oxycodone (any route: 96%, 19.5 days/month; snorting: 70%, 10.3 days/month; injecting: 51%, 10.5 days/month) and retrospectively reported abuse of original ERO in August 2010 (any route: 74%, 13.4 days/month; snorting: 39%, 6.0 days/month; injecting: 41%, 8.6 days/month). After the reformulation, the prevalence of original ERO abuse significantly declined while abuse of reformulated ERO remained steadily low. Heroin abuse was rare in this sample. CONCLUSIONS: In this sample, abuse of reformulated ERO was low, and lower than abuse of original ERO retrospectively and IR oxycodone concurrently, particularly through injecting and snorting routes of administration. There was no evidence to suggest that reformulated ERO became a substitute for original ERO.

Depression and comorbid panic in primary care patients.

BACKGROUND: Comorbid panic symptoms may complicate depression treatment. However, most research focuses on specialty care, and the evidence in primary care is mixed. METHODS: We analyzed data from a randomized trial investigating Selective Serotonin Reuptake Inhibitor (SSRI) Treatment, a longitudinal effectiveness study comparing 3 SSRIs for the treatment of depression in primary care (n = 573). Depression at month 6 was measured using the Symptom Checklist-20; remission was defined as a score < or = 0.5; partial response was defined as > or = 50% improvement but not to a level of < or = 0.5. Nonresponse, the referent level for all analyses, was defined as patients who do not meet either of these criteria. Panic symptoms (yes/no) were measured using a screening question. RESULTS: Rates of remission vs. nonresponse [OR=1.06 (95% confidence interval 0.67, 1.67)] or partial response vs. nonresponse [OR=0.92 (95% CI 0.54, 1.57)] were similar among patients with baseline panic symptoms, adjusting for baseline depression severity. However, patients with persistent panic symptoms were less likely to experience remission (OR=0.38, 95% CI 0.18, 0.81), while the lower likelihood of partial response did not achieve statistical significance (0.66, 95% CI 0.33, 1.33). Results were similar using complete case, last observation carried forward, and multiple imputation methods, and were robust to varying the sensitivity and specificity of the panic screening question. CONCLUSION: Panic symptoms that persist are associated with worse depression outcomes in the maintenance phase. Consequently, improvement in panic symptoms may be important for improved depression outcomes and primary care physicians should be attuned to the presence of panic symptoms when making treatment decisions.

Pharmacokinetic comparison of two nicotine transdermal systems, a 21-mg/24-hour patch and a 25-mg/16-hour patch: a randomized, open-label, single-dose, two-way crossover study in adult smokers.

BACKGROUND: A comparison of the 21-mg NiQuitin patch with other marketed nicotine patches reported significant differences in pharmacokinetic profiles, even among patches of the identical labeled dose strength. The 25-mg Nicorette Invisi patch became available in the United Kingdom at the end of 2008. No published studies have directly compared the pharmacokinetic profile of this new patch with that of the 21-mg NiQuitin patch. OBJECTIVES: This study was conducted to compare the single-dose pharmacokinetics of the 21-mg/24-hour patch and the 25-mg/16-hour patch. To determine whether any pharmacokinetic differences might be related to differences in wear time, a post hoc exploratory analysis evaluated the nicotine delivery profiles of the patches under the assumption that the 21-mg patch was removed after 16 rather than 24 hours. METHODS: This was a single-center, randomized, open-label, single-dose, 2-way crossover study in healthy adults who smoked >10 cigarettes per day in the 6 months before the study. Eligible subjects were housed at the study center for 2 baseline and 2 treatment sessions; no smoking was permitted during the baseline or treatment sessions. Subjects were allocated to receive either the 21-mg patch (removed after 24 hours) or the 25-mg patch (removed after 16 hours) during the first treatment session, after which they crossed over to the alternative sequence in the second treatment session. Blood samples were obtained at predetermined time points before and after patch application. The primary pharmacokinetic parameter was the AUC(0-infinity), an indication of total nicotine exposure. Secondary pharmacokinetic parameters included AUC(0-t), C(max), and T(max). Post hoc exploratory parameters were the AUC(0-16) and the AUC(0-infinity) assuming a 16-hour application time for the 21-mg patch. The differences in AUC(0-infinity), AUC(0-t), Cmax, AUC(0-16), and AUC(0-infinity) assuming a 16-hour application time for the 21-mg patch were considered significant if the lower limit of the 90% CI for the geometric mean ratio (21 mg:25 mg) was >100%. T(max) values were compared using a signed-rank test. Adverse events were elicited using a standard open-ended question on each day of confinement; spontaneously reported events were also captured. The topical effects of the patch (erythema; edema; extent of erythema/papules/pustules; self-reported pruritus) were assessed by study staff before patch application and 1 and 8 hours after patch application using a 4-point rating scale; any topical effects were recorded as adverse events. RESULTS: Fifty otherwise healthy smokers (29 men, 21 women) were enrolled; 47 (94%) were white. Their mean (SD) age was 31.5 (9.57) years (range, 20-53 years), mean weight was 70.24 (9.56) kg (range, 51.0-95.9 kg), and mean height was 173.0 (8.02) cm (range, 156-194 cm). Subjects reported smoking between 11 and 40 cigarettes per day before the study. The AUC(0-infinity) was significantly higher for the 21-mg patch worn for 24 hours than for the 25-mg patch worn for 16 hours (382.36 vs 243.69 ng/mL . h, respectively; geometric mean ratio: 156.90%; 90% CI, 148.10%-166.23%; P < 0.001). T(max) was reached significantly sooner with the 21-mg patch than with the 25-mg patch (6.0 vs 12.0 hours; P < 0.001). C(max) was significantly higher for the 21-mg patch compared with the 25-mg patch (18.34 vs 16.56 ng/mL; geometric mean ratio: 110.72%; 90% CI, 104.82%-116.94%; P < 0.01). The exploratory analyses suggested that the 21-mg patch applied for 16 hours may provide greater total nicotine exposure than the 25-mg patch applied for 16 hours. Although most subjects reported adverse events (75.0% with the 21-mg patch, 89.8% with the 25-mg patch), the majority of these events were mild. CONCLUSIONS: In this single-dose study in adult smokers, the 21-mg patch was associated with significantly greater nicotine exposure compared with the 25-mg patch. The 21-mg patch provided a maximal nicotine concentration faster than did the 25-mg patch.