Withdrawal during outpatient low dose buprenorphine initiation in people who use fentanyl: a retrospective cohort study.

BACKGROUND: Buprenorphine is an effective treatment for opioid use disorder (OUD); however, buprenorphine initiation can be complicated by withdrawal symptoms including precipitated withdrawal. There has been increasing interest in using low dose initiation (LDI) strategies to reduce this withdrawal risk. As there are limited data on withdrawal symptoms during LDI, we characterize withdrawal symptoms in people with daily fentanyl use who underwent initiation using these strategies as outpatients. METHODS: We conducted a retrospective chart review of patients with OUD using daily fentanyl who were prescribed 7-day or 4-day LDI at 2 substance use disorder treatment clinics in San Francisco. Two addiction medicine experts assessed extracted chart documentation for withdrawal severity and precipitated withdrawal, defined as acute worsening of withdrawal symptoms immediately after taking buprenorphine. A third expert adjudicated disagreements. Data were analyzed using descriptive statistics. RESULTS: There were 175 initiations in 126 patients. The mean age was 37 (SD 10 years). 71% were men, 26% women, and 2% non-binary. 21% identified as Black, 16% Latine, and 52% white. 60% were unstably housed and 75% had Medicaid insurance. Substance co-use included 74% who used amphetamines, 29% cocaine, 22% benzodiazepines, and 19% alcohol. Follow up was available for 118 (67%) initiations. There was deviation from protocol instructions in 22% of these initiations with follow up. 31% had any withdrawal, including 21% with mild symptoms, 8% moderate and 2% severe. Precipitated withdrawal occurred in 10 cases, or 8% of initiations with follow up. Of these, 7 had deviation from protocol instructions; thus, there were 3 cases with follow up (3%) in which precipitated withdrawal occurred without protocol deviation. CONCLUSIONS: Withdrawal was relatively common in our cohort but was mostly mild, and precipitated withdrawal was rare. Deviation from instructions, structural barriers, and varying fentanyl use characteristics may contribute to withdrawal. Clinicians should counsel patients who use fentanyl that mild withdrawal symptoms are likely during LDI, and there is still a low risk for precipitated withdrawal. Future studies should compare withdrawal across initiation types, seek ways to support patients in initiating buprenorphine, and qualitatively elicit patients' withdrawal experiences.

The Howard Street Method: A Community Pharmacy-led Low Dose Overlap Buprenorphine Initiation Protocol for Individuals Using Fentanyl.

OBJECTIVES: Buprenorphine treatment significantly reduces morbidity and mortality for people with opioid use disorder. Fear of precipitated withdrawal remains a barrier to starting buprenorphine for patients who use synthetic opioids, particularly fentanyl. We aim to evaluate the development and implementation of a buprenorphine low dose overlap initiation (LDOI) protocol in an urban public health community pharmacy. METHODS: We performed a retrospective chart review of patients with nonprescribed fentanyl use (N = 27) to examine clinical outcomes of a buprenorphine LDOI schedule, named the Howard Street Method, dispensed from a community pharmacy in San Francisco from January to December 2020. RESULTS: Twenty-seven patients were prescribed the Howard Street Method. Twenty-six patients picked up the prescription and 14 completed the protocol. Of those who completed the protocol, 11 (79%) reported no symptoms of withdrawal and 3 (21%) reported mild symptoms. Four patients (29%) reported cessation of full opioid agonist use and 10 (71%) reported reduction in their use by the end of the protocol. At 30 days, 12 patients (86%) were retained in care and 10 (71%) continued buprenorphine. At 180 days, 6 patients (43%) were retained in care and 2 (14%) were still receiving buprenorphine treatment. CONCLUSIONS: We found that a LDOI blister-pack protocol based at a community pharmacy was a viable intervention for starting buprenorphine treatment and a promising alternative method for buprenorphine initiation in an underresourced, safety-net population of people using fentanyl.

Triple Threat: Response to the Crises of COVID-19, Homelessness, and Opioid Use Disorder With a Novel Approach to Buprenorphine Delivery: A Case Series.

OBJECTIVES: In the setting of a 50% increase in opioid overdose deaths, the coronavirus disease 2019 crisis opened housing opportunities in the form of Shelter in Place (SIP) hotels to homeless San Francisco residents. Many who entered SIP hotels had opioid use disorder. In fall 2020, Community Behavioral Health Services Pharmacy partnered with SIP hotel medical staff to launch a pilot project, where on-site SIP medical providers prescribed buprenor-phine (BUP) and clinical pharmacists hand-delivered BUP to SIP residents to increase BUP initiation and engagement. METHODS: A retrospective chart review of 3 patients living in SIP hotels starting BUP to demonstrate the feasibility of a SIP hotel BUP delivery program. RESULTS: In all 3 cases, patients were able to start and continue BUP with on-site medical staff visits and delivery of medications by pharmacists. Each case highlights different barriers that were overcome by this system. CONCLUSIONS: Our findings suggest that this system of onsite medical care with pharmacist delivery is possible and has the potential to allow for greater outreach and increased ease of obtaining medications for patients.

Rapid Overlap Initiation Protocol Using Low Dose Buprenorphine for Opioid Use Disorder Treatment in an Outpatient Setting: A Case Series.

OBJECTIVES: Fear and risk of precipitated withdrawal are barriers for initiating buprenorphine in individuals with opioid use disorder, particularly among those using fentanyl. A buprenorphine rapid overlap initiation (ROI) protocol (also knownas "rapidmicro-dosing") utilizing small, escalating doses of buprenorphine can overcome this barrier, reaching therapeutic doses in 3 to 4 days. We sought to demonstrate the feasibility of implementing a buprenorphine ROI protocol for buprenorphine initiation in the outpatient setting. METHODS: We conducted a retrospective chart review of patients prescribed an outpatient ROI protocol at the Office-based Buprenorphine Induction Clinic from October to December 2020. The ROI protocol utilizes divided doses of sublingual buprenorphine tablets and blister packaging for easier dosing. Patients were not required to stop other opioid use and were advised to follow up on day 4 of initiation. RESULTS: Twelve patients were included, of whom eleven (92%) were using fentanyl at intake. Eleven patients picked up their prescription. Seven patients returned for follow-up (58%), and all 7 completed the ROI protocol. One patient reported any withdrawal symptoms, which were mild. At 30 days, 7 patients (58%) were retained in care, and 5 (42%) were still receiving buprenorphine treatment, 4 (33%) of whom had been abstinent from nonprescribed opioid use for ≥2 weeks. CONCLUSIONS: The ROI protocol was successful in initiating buprenorphine treatment for patients in our outpatient clinic, many of whom were using fentanyl. The ROI protocol may offer a safe alternative to traditional buprenorphine initiation and warrants further study.

Acceptability of Naloxone Dispensing Among Pharmacists.

BACKGROUND: The San Francisco Department of Public Health initiated naloxone prescribing at 6 safety net clinics. We evaluated this intervention, demonstrating that naloxone prescribing from primary care clinics is feasible and acceptable. OBJECTIVE: To evaluate acceptability of naloxone dispensing to patients prescribed opioids among pharmacists serving clinics participating in a naloxone intervention. METHODS: We surveyed 58 pharmacists from November 2013 through January 2015 at pharmacies that serviced San Francisco safety net clinics. Surveys collected information on demographics, experiences in dispensing naloxone, and interest in prescriptive authority. We conducted descriptive analyses and assessed bivariate relationships. RESULTS: Most respondents were staff (56.9%) or supervising pharmacists (34.5%). Most (92.9%) were aware their pharmacy stocked naloxone and 86.8% felt it should be prescribed to some or all patients on long-term opioids. Most (82.1%) dispensed naloxone at least once in the past 12 months. More than half were comfortable providing naloxone education. Nearly half (43.4%) indicated they would want authority to furnish without a prescription. Over half (55.2%) reported no problems dispensing. The common problem was insufficient naloxone knowledge. Only 12% reported more than one problem in dispensing naloxone, which was associated with being uncomfortable with educating patients (P = .03). CONCLUSION: Naloxone dispensing was acceptable among pharmacists. Their most cited problem was insufficient naloxone education. This may be resolved with improved instructional materials, incentives for patient education, or mandatory training.

Evaluation of the Impact of a Multimodel Intervention on Prescribing Patterns of Sedative-Hypnotics in a Behavioral Health System.

OBJECTIVE: To describe the effect of a multimodal intervention targeting chronic benzodiazepine and sedative-hypnotic prescriptions in a large behavioral health system. METHODS: This retrospective study analyzed chronic sedative-hypnotic prescription rates in patients seeking mental health services in a large behavioral health system. The multimodal intervention consisted of provider education, coordination of care with all providers involved in patient care, and guideline development and implementation for safe prescribing of sedative-hypnotics. Three time periods were analyzed: preintervention (October 2013-December 2013), 12-month assessment (October 2014-December 2014), and 24-month assessment (October 2015-December 2015). The primary outcome of the study was the change in frequency of chronic (≥ 60 days) sedative-hypnotic prescriptions received before and after the multimodal intervention. The secondary outcome included the change in prescription rates in a priori-defined cohorts: patients on methadone maintenance therapy and patients ≥ 60 years of age. RESULTS: There were 32,944 prescriptions during the study period. The rate of chronic sedative-hypnotic prescriptions decreased from 1,764 (15.3%) to 1,634 (14.9%) to 1,018 (9.8%) between the 3 assessment periods, respectively. A significant decrease occurred between the preintervention period and 24-month assessment (5.5%, P < .0001) and between the 12-month assessment and the 24-month assessment (5.1%, P < .0001). In the elderly, prescription rates decreased significantly between the preintervention period and the 24-month assessment (3.6%, P < .0001) and the 12-month and 24-month assessments (3.2%, P = .0001). In patients in methadone maintenance programs, rates of concomitant chronic sedative-hypnotic prescriptions decreased significantly between all assessment periods: preintervention and 12-month assessment (8.2%, P = .001), 12-month and 24-month assessment (6.3%, P = .002), and preintervention and 24-month assessment (14.5%, P < .0001). Additionally, prescription rates increased significantly for antidepressants (4.1%, P < .05), hydroxyzine (1.1%, P = .01), buspirone (2.1%, P < .05), gabapentin (6.3%, P < .05), and melatonin agonists (0.3%, P < .05) between the preintervention and 24-month assessment periods. CONCLUSIONS: Implementation of a multimodal intervention led to a significant decrease in rates of chronic sedative-hypnotic prescriptions in a large behavioral health system.

Low-threshold extended-release naltrexone for high utilizers of public services with severe alcohol use disorder: A pilot study.

Extended-release naltrexone (XRNTX) is an effective treatment for alcohol use disorder (AUD). We sought to evaluate the feasibility, acceptability, and preliminary effectiveness and cost-effectiveness of XRNTX delivered as a stand-alone service to persons with severe AUD who are high utilizers of multiple urgent and emergency medical services (HUMS). Of 15 HUMS persons with severe AUD selected based on chart review, 11 agreed to participate. Participants received a mean of 4.5 injections (range 2-7). Modest benefits from XRNTX were observed in terms of patients' Urge-to-Drink Score and the costs of emergency medical services utilized. Though limited by a small sample size, costs including client utilization and study related expenses during the post-enrollment period were less than client utilization costs in the pre-enrollment period. We also observed non-significant improvements in the number of drinking days, but no change in quality of life as measured by the EQ-5D. Eighty-eight percent of participants perceived XRNTX as helping with their drinking. Findings need to be replicated in a larger study, however if replicated, the cost savings could be substantial.

Intolerance of sublingual buprenorphine-naloxone during induction in a patient with end-stage liver disease: A case report.

INTRODUCTION: Sublingual buprenorphine is indicated for opioid dependence. It comes in 2 formulations: a mono buprenorphine product (BUP) and a combination product containing naloxone (BUP-NAL), which functions as an abuse deterrent. Sublingual naloxone does not reach clinically significant levels except in cases of hepatic impairment, where its metabolism can be impaired. Substantial naloxone accumulation could block the therapeutic effects of buprenorphine. The risk of hepatic impairment is elevated in the opioid dependence population, and our case highlights the need for careful evaluation of hepatic function and consideration of BUP. CASE/RESULTS: We report a patient with end-stage liver disease who began BUP-NAL induction with modest improvement on treatment day 1 followed by sustained withdrawal after receiving an observed dose on day 2. He returned to the clinic 2 days after his second successive day of BUP-NAL, vomiting and complaining of persistent withdrawal. To avoid potential accumulation of naloxone, the patient was eventually switched to and stabilized on BUP with good response. DISCUSSION/CONCLUSION: The clinical course this patient experienced during induction makes a case that naloxone can accumulate and interfere with the effectiveness of buprenorphine in the presence of liver dysfunction. Our case highlights the need for consideration of BUP in circumstances where patient safety and effective treatment outweigh the risks of prescribing a product with abuse deterrent properties.

Detection and treatment rates for perinatal depression in a state Medicaid population.

BACKGROUND: The purpose of this investigation was to assess detection and treatment rates for perinatal depression among women enrolled in the California State Medicaid (Medi-Cal) program in comparison to female beneficiaries of reproductive age who did not give birth during the same study period. METHODS: Investigators conducted a retrospective longitudinal cohort analysis of women between the ages of 18 and 39 years old who were continuously enrolled in the Medi-Cal fee-for-service program between January 2006 and December 2009. The perinatal cohort consisted of women with evidence of a live birth occurring between October 2007 and March 2009. The control cohort consisted of women in the same age group and health plan without evidence of pregnancy during this time frame. The primary outcome of this investigation was diagnosis of depression during 3 contiguous 9-month time frames: immediately prior to presumed conception, during pregnancy, and throughout the postpartum period. Secondary outcomes included within-group and cohort comparisons of treatment patterns (antidepressant or psychotherapy). A multivariable analysis of demographic factors predicting depression diagnosis or treatment was conducted as well. RESULTS: A total of 6030 women was identified in the perinatal cohort, and 56,709 women were included in the control group. The perinatal cohort was significantly less likely than nonpregnant controls to receive a diagnosis of depression both during pregnancy (prevalence=1.6% vs 3.5%; OR=0.45; 95% CI=0.35-0.55) and postpartum (2.2% vs 3.6%; OR=0.59; 95% CI=0.50-0.71). Similar differences were noted in antidepressant prescribing patterns apparent during these 2 time frames. A subgroup analysis of women who received a depression diagnosis revealed that only 48% of the perinatal cohort was provided any treatment during pregnancy (vs 72% of the control group; p<0.0001) or postpartum (57% vs 73%; p<0.0001). Specific demographic factors predicting a lower prevalence of depression detection or treatment included Hispanic descent, age <25 years, or primary residence in an rural setting. CONCLUSIONS: Depression was often overlooked and undertreated among women who are pregnant or postpartum in comparison to services delivered to similar nonpregnant controls. Significant disparities in the healthcare received by certain subpopulations of perinatal women suggest that research into barriers to care and subsequent interventions are warranted.