Publications by authors named "Julie L Cunningham"

31 Publications

Pain catastrophizing as a treatment process variable in cognitive behavioural therapy for adults with chronic pain.

Eur J Pain 2021 Feb 27;25(2):339-347. Epub 2020 Nov 27.

School of Psychology, Queen's University Belfast, Belfast, UK.

Background: Interdisciplinary cognitive behavioural therapy (CBT) for chronic pain is effective at improving function, mood and pain interference among individuals with disabling chronic pain. Traditionally, CBT assumes that cognitive change is an active therapeutic ingredient in the determination of treatment outcome. Pain catastrophizing, a cognitive response style that views the experience of pain as uncontrollable, permanent and destructive, has been identified as an important maladaptive cognition which contributes to difficulties with the management of chronic pain. Consequently, pain catastrophizing is commonly targeted in CBT for chronic pain.

Objectives: To examine change trajectories in pain catastrophizing during treatment and assess the relevance of these trajectories to outcomes at posttreatment.

Methods: Participants included individuals with chronic pain (N = 463) who completed a 3-week program of interdisciplinary CBT. Pain catastrophizing was assessed weekly over the 3 weeks of treatment and latent growth curve modelling was used to identify trajectories of change.

Results: Findings indicated the presence of two classes of linear change, one with a significant negative slope in pain catastrophizing (i.e. improved class) and the other with a non-significant slope (i.e. unchanged class). Next, latent growth mixture modelling examined treatment outcome in relation to class membership. These results indicated that individuals in the 'improved' PCS class had significantly greater improvement in pain interference and mood, as well as physical and mental quality of life compared to the 'unchanged' class.

Conclusions: Implications for our findings, in relation to the CBT model, are discussed.
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http://dx.doi.org/10.1002/ejp.1671DOI Listing
February 2021

Prevalence of Opioid-Induced Adrenal Insufficiency in Patients Taking Chronic Opioids.

J Clin Endocrinol Metab 2020 10;105(10)

Division of Endocrinology, Diabetes and Nutrition, Department of Internal Medicine, Mayo Clinic, Rochester, Minnesota.

Context: Chronic opioid use may lead to adrenal insufficiency because of central suppression of the hypothalamic-pituitary-adrenal axis. However, the prevalence of opioid-induced adrenal insufficiency (OIAI) is unclear.

Objective: To determine the prevalence of OIAI and to identify predictors for the development of OIAI in patients taking opioids for chronic pain.

Design: Cross-sectional study, 2016-2018.

Setting: Referral center.

Patients: Adult patients taking chronic opioids admitted to the Pain Rehabilitation Center.

Main Outcome Measure: Diagnosis of OIAI was considered if positive case detection (cortisol < 10 mcg/dL, ACTH < 15 pg/mL, and dehydroepiandrosterone sulfate < 25 mcg/dL), and confirmed after endocrine evaluation. Daily morphine milligram equivalent (MME) was calculated.

Results: In 102 patients (median age, 53 years [range, 22-83], 67% women), median daily MME was 60 mg (3-840), and median opioid therapy duration was 60 months (3-360). Abnormal case detection testing was found in 11 (10.8%) patients, and diagnosis of OIAI was made in 9 (9%). Patients with OIAI were on a higher daily MME (median, 140 [20-392] mg vs 57 [3-840] mg, P = 0.1), and demonstrated a 4 times higher cumulative opioid exposure (median of 13,440 vs 3120 mg*months, P = 0.03). No patient taking  20 mg); however, specificity of MME cutoff >20 mg was only 19%. After opioid discontinuation, 6/7 patients recovered adrenal function.

Conclusion: The prevalence of OIAI was 9%, with MME cumulative exposure being the only predictor for OIAI development. Patients on MME of 20 mg/day and above should be monitored for OIAI.
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http://dx.doi.org/10.1210/clinem/dgaa499DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7470471PMC
October 2020

Provision of a Drug Deactivation System for Unused Opioid Disposal at Surgical Dismissal: Opportunity to Reduce Community Opioid Supply.

Mayo Clin Proc Innov Qual Outcomes 2020 Aug 5;4(4):357-361. Epub 2020 Aug 5.

Department of Pharmacy, Mayo Clinic, Rochester, MN.

Objective: To determine the impact of a drug deactivation system to post-surgical patients on the rate of opioid prescription disposal.

Patients And Methods: Two hundred post-operative patients discharged after inpatient surgery at a large academic medical center. This study was conducted August 20, 2018, through November 30, 2018. Patients were provided with a drug deactivation system (DDS) and instruction sheet along with their opioid prescription. Three to 4 weeks after dismissal, patients were surveyed about quantity of opioids remaining, use of DDS or other disposal methods, and satisfaction with DDS if used.

Results: One hundred forty-nine of 200 (74.5%) patients were surveyed. One hundred six reported leftover opioids and 29 (27.3%) had disposed of these medications. By the time of survey, 23 (21.2%) participants with leftover opioids had used the DDS to destroy their remaining supply and an additional 33 (31.1%) participants reported plans to use the disposal bag on a future date. Of the 23 participants who used the DDS, 22 (96.0%) reported that they were very satisfied with the disposal process.

Conclusion: Participants are willing to use a DDS and are satisfied with the process; however, additional education is needed to ensure timely disposal.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.04.007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7411158PMC
August 2020

The System Is Broken: A Qualitative Assessment of Opioid Prescribing Practices After Spine Surgery.

Mayo Clin Proc 2020 09 28;95(9):1906-1915. Epub 2020 Jul 28.

Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.

Objective: To elucidate factors that influence opioid prescribing behaviors of key stakeholders after major spine surgery, with a focus on barriers to optimized prescribing.

Methods: In-person semi-structured interviews were performed with 20 surgical and medical professionals (January 23, 2019 to June 11, 2019) at a large academic medical center, including resident physicians, midlevel providers, attending physicians, and clinical pharmacists. Interviews centered on perceptions of postoperative prescribing practices were coded and analyzed using a qualitative inductive approach.

Results: Several unique themes emerged. First, wide interprovider variation exists in the perceived role of opioid prescribing guidelines. Second, there are important relationships between clinical experience, time constraints, and postoperative opioid prescribing. Third, opioid tapering is a major area of inconsistency. Fourth, there are serious challenges in managing analgesic expectations, particularly in those with chronic pain. Finally, there is currently no process to facilitate the hand-off or transition of opioid prescribing responsibility between surgical and primary care teams, which represents a major area for practice optimization efforts.

Conclusion: Despite increased focus on postoperative opioid prescribing, there remain numerous areas for improvement. The development of tools and processes to address critical gaps in postoperative prescribing will be essential for our efforts to reduce long-term opioid use after major spine surgery and improve patient care.
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http://dx.doi.org/10.1016/j.mayocp.2020.02.027DOI Listing
September 2020

Association Between Spine Surgery and Availability of Opioid Medication.

JAMA Netw Open 2020 06 1;3(6):e208974. Epub 2020 Jun 1.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, Minnesota.

Importance: Prolonged prescribing of opioids after spine surgery is often perceived as a negative outcome, but successful opioid reduction may occur despite continued prescribing. Improved characterization of opioid availability before and after surgery is necessary to identify these successes.

Objective: To evaluate the association between spine surgery and modification of opioid availability postoperatively by using consistent definitions to classify opioid availability before and after surgery.

Design, Setting, And Participants: This population-based cohort study included 2223 adults (age ≥18 years) who underwent spine surgery in Olmsted County, Minnesota, from January 1, 2005, through December 31, 2016. Data were analyzed from April 1, 2019, to December 1, 2019.

Exposures: Preoperative opioid availability based on prescription data in the 180 days before surgery in accordance with Consortium to Study Opioid Risks and Trends (CONSORT) definitions.

Main Outcomes And Measures: Successful modification of opioid availability, defined as an improvement in CONSORT status postoperatively (assessed from 181 to 365 days after surgery) compared with preoperative status, or continued absence of opioid availability for patients with no preoperative availability. Multivariable logistic regression was used to assess the association between preoperative opioid availability and successful modification by 1 year after undergoing surgery.

Results: Of 2223 patients included in the study, 1214 were male (54.6%), with a median age of 55 years (interquartile range, 43-68) years. Patients were classified as having no (778 [35.0%]), short-term (1118 [50.3%]), episodic (227 [10.2%]), or long-term (100 [4.5%]) preoperative opioid availability. Of the 2148 patients (96.6%) who were alive at 1 year, postoperative opioid availability was classified as no (1583 [73.7%]), short-term (398 [18.5%]), episodic (104 [4.8%]), and long-term (63 [2.9%]). A total of 1672 patients (77.8%) had successful modification of opioid availability, with success of 83.0% for those with no preoperative availability, 74.9% for those with short-term preoperative availability, 79.8% for those with episodic preoperative availability, and 64.4% for those with long-term preoperative opioid availability. In multivariable analysis, success was significantly associated with preoperative opioid availability (odds ratio [OR] for short term, 0.61 [95% CI, 0.48-0.77]; OR for episodic, 0.95 [95% CI, 0.64-1.40]; OR long term, 0.49 [95% CI, 0.30-0.82]; P < .001 overall vs no availability).

Conclusions And Relevance: In this study, when following standardized CONSORT definitions, 4 of 5 adults undergoing spine surgery in a population-based cohort met the criteria for a successful pattern of postoperative opioid prescribing. Similar methods to objectively assess changes in opioid prescribing may be clinically useful in other perioperative settings.
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http://dx.doi.org/10.1001/jamanetworkopen.2020.8974DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7317600PMC
June 2020

Treatment Effectiveness and Medication Use Reduction for Older Adults in Interdisciplinary Pain Rehabilitation.

Mayo Clin Proc Innov Qual Outcomes 2020 Jun 8;4(3):276-286. Epub 2020 May 8.

Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, MN.

Objective: To examine the effectiveness of an interdisciplinary pain rehabilitation program (IPRP) that incorporates medication tapering on improving pain-related and performance-based outcomes for older adults with chronic noncancer pain and determine the proportion who demonstrated reliable improvement in outcome.

Patients And Methods: This 2-year retrospective clinical cohort study examined treatment outcomes of 134 older adult patients 65 years or older with chronic noncancer pain who completed a 3-week IPRP with physician-supervised medication tapering between January 1, 2015, and December 31, 2017. Pain, pain catastrophizing, depressive symptoms, and quality of life were assessed at pretreatment, posttreatment, and follow-up. Physical performance and medication use were assessed pre- and posttreatment. Outcomes were examined using a series of repeated-measures analyses of variance, examining effect size and reliable change.

Results: Significant treatment effects (<.001) with large effect sizes were observed for all self-report and physical performance outcome measures at posttreatment and 6-month follow-up (42.5% response rate). There were no significant differences in outcome based on opioid use status at admission. Reliable change analyses revealed that 76.9% (n=103 of 134) evidenced improvement in at least 1 pain-related outcome measure at posttreatment, and 87.7% (n=50 of 57), at follow-up. Patients also had significant reductions (<.01) in medications at posttreatment (opioids, benzodiazepines, sedative-hypnotics, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors, tricyclic antidepressants, and anticonvulsants).

Conclusion: Older adults with chronic noncancer pain demonstrated improved pain-related outcomes, physical performance, and decreased medication use following IPRP treatment. Results support the effectiveness of IPRPs in enhancing the physical and emotional functioning of older adults with chronic pain while also facilitating the reduction of medications that place them at risk for adverse events.
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http://dx.doi.org/10.1016/j.mayocpiqo.2020.01.004DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283568PMC
June 2020

Examining the effectiveness of pain rehabilitation on chronic pain and post-traumatic symptoms.

J Behav Med 2020 12 25;43(6):956-967. Epub 2020 May 25.

Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, 200 First Street SW, Rochester, MN, 55905, USA.

Patients with co-morbid chronic pain and post-traumatic stress disorder (PTSD) pose significant treatment challenges. This study evaluated the effectiveness of an interdisciplinary pain rehabilitation program (IPRP) in improving pain and PTSD outcomes, as well as reducing medication use. In addition, the mediating effect of pain catastrophizing, which is theorized to underlie the pain and PTSD comorbidity, was examined. Participants included 83 completers of an IPRP with chronic pain and a provisional PTSD diagnosis. Significant improvements were found for pain outcomes, PTSD symptomatology, depressive symptoms, physical performance, and medication use (i.e., opioids and benzodiazepines). At discharge, 86.7% of participants reliably improved in at least one key measure of functioning and 50.6% demonstrated reliable improvement in PTSD symptomatology. Change in pain catastrophizing mediated improvements in pain interference and PTSD symptomatology. Results support the potential utility of an interdisciplinary pain treatment approach in the treatment of patients with comorbid pain and PTSD.
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http://dx.doi.org/10.1007/s10865-020-00160-3DOI Listing
December 2020

An Institutional Approach to Managing the Opioid Crisis.

Mayo Clin Proc 2020 05 11;95(5):968-981. Epub 2020 Mar 11.

The Robert D. and Patricia E. Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN.

The opioid crisis is a major concern of most health care institutions, including our large academic center. In this article, an organized approach to managing the epidemic institutionally is discussed. An Opioid Stewardship Program was instituted at our tertiary-care center with multiple sites and states of practice, which included diverse membership and expertise. Charges of the program included reviewing current practice, workflows, and external and internal guidelines and evaluating and standardizing prescribing practices. The development of an Opioid Stewardship Program resulted in: (1) an understanding of our diverse prescribing practices and the formation of patient- and procedure-specific guidelines to manage them, (2) education tools for our patients and providers, and (3) workflows and practice advisories within the electronic health record to support appropriate prescribing and monitoring of patients. This ongoing work continues to evolve in response to the needs of our patients, changing regulatory environments, and our improved understanding of our practices.
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http://dx.doi.org/10.1016/j.mayocp.2019.11.019DOI Listing
May 2020

The professional sabbatical: A systematic review and considerations for the health-system pharmacist.

Res Social Adm Pharm 2020 Dec 24;16(12):1632-1644. Epub 2020 Feb 24.

Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.

Background: Sabbaticals are considered a professional development experience meant to foster growth and revitalize careers. The personal accounts of sabbaticals among medical professionals indicate high value from this experience. Benefits seen at the institutional and individual level include, but are not limited to, reduced burnout and increased job retention. Staffing issues, determining eligibility, and justifying time utilized may be just some barriers to implementing a sabbatical program accessible to the health-system pharmacist. In the literature, there is a dearth of information related to sabbaticals granted to the health-system pharmacist. However, many published experiences of nurses and physicians exist.

Objectives: A systematic review was performed to synthesize a qualitative yet evidence-based summary of information regarding sabbaticals. The primary aim of this review was to assess the reported benefits and prohibitive factors of taking a sabbatical as it may apply to the health-system pharmacist.

Methods: Three hundred twenty-eight English-language articles were identified through searching Ovid Medline, PsycINFO, Embase, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, CINAHL and Scopus from database inception through December 6, 2019.

Results: A total of 172 articles consisting of studies, descriptions of institutional processes, individual accounts, editorials and letters to the editor, and review articles were included in this systematic review. Rejuvenation and new perspectives/skills to bring back to practice should be regarded as important benefits by institutional/departmental leadership as well as the benefits of reduced turnover and improved job satisfaction. Numerous barriers to completing a sabbatical can be overcome with proper planning.

Conclusion: This review provides limited insight into benefits and barriers to taking sabbaticals and serves as a basis for health-system pharmacy departments to consider initiating a program if one is not currently in place. Mini-sabbaticals may allow the health-system pharmacist to take a professional time away. Corollaries are drawn between a longitudinal pharmacy research award granted at Mayo Clinic - Rochester and ideas are provided for clinical or educational sabbaticals. It is clear that health-system pharmacy-specific information is lacking, and pharmacy department leadership should be encouraged to continue to share experiences of sabbaticals and outcomes.
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http://dx.doi.org/10.1016/j.sapharm.2020.02.011DOI Listing
December 2020

A Practical Approach for the Management of the Mixed Opioid Agonist-Antagonist Buprenorphine During Acute Pain and Surgery.

Mayo Clin Proc 2020 06 13;95(6):1253-1267. Epub 2020 Feb 13.

Department of Anesthesiology and Perioperative Medicine, Mayo Clinic, Rochester, MN; Division of Pediatric Anesthesiology, Mayo Clinic, Rochester, MN.

The use of buprenorphine, a mixed opioid agonist-antagonist, for the management of chronic pain and/or opioid use disorder is increasing. As such, medical providers will more frequently encounter patients on this therapy. In this paper, we synthesize existing knowledge (derived through keyword searches using MEDLINE databases) in a novel conceptual framework for patients on buprenorphine presenting with acute pain or for those requiring surgical or invasive procedures. This framework is based on three unique domains: the patient, the features of the acute pain insult, and the environment. We discuss important considerations regarding the unique aspects of buprenorphine formulations and dosing, and we describe the importance of multidisciplinary planning and multimodal analgesic strategies. We also highlight important differences in management strategies based upon the presence or absence of opioid use disorder. All medical providers must be prepared to guide the patient on buprenorphine safely through the acute care episode, which includes adequate treatment of acute pain and avoidance of iatrogenic harm, including both short-term complications (eg, respiratory depression) and long-term complications (eg, relapse to opioid use).
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http://dx.doi.org/10.1016/j.mayocp.2019.10.007DOI Listing
June 2020

Implementation of a pharmacogenomics education program for pharmacists.

Am J Health Syst Pharm 2018 Dec 9;75(23):1939-1946. Epub 2018 Oct 9.

Department of Pharmacy, Mayo Clinic, Rochester, MN.

Purpose: The development, implementation, and evaluation of a pharmacogenomics education program for pharmacists in a large, integrated multicampus health system are described.

Summary: Pharmacogenomics has been described as tailoring medications to each patient's unique genetic sequence with the goals of minimizing harmful effects and optimizing therapeutic effects. Pharmacists are uniquely trained to lead the implementation of pharmacogenomics in clinical care. After assessment of pharmacists' comfort with pharmacogenomics, different approaches were explored to develop, pilot test, and disseminate pharmacogenomics education across a multicampus academic medical center. Limited success with large-audience, single-lecture didactic education led to development and delivery of targeted, competency-based online modules using the institution's academic virtual learning environment and course management system. Implementation steps included (1) collaboration with the Mayo Clinic Center for Individualized Medicine to create an interprofessional development team and project charter, (2) galvanizing pharmacy leadership support across multiple campuses, (3) development of competency-based interactive modules, and (4) assessment of the quality of and learner satisfaction with the modules. Significant improvements in competency scores were observed with each module and across the multiple campuses. Satisfaction with the education program was assessed at the end of a 4-module series.

Conclusion: A pharmacogenomics educational program targeting pharmacists was developed through interprofessional collaboration and provided a novel opportunity to construct an educational infrastructure to support enterprise health-system campuses with limited educational resources.
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http://dx.doi.org/10.2146/ajhp170771DOI Listing
December 2018

Longitudinal Treatment Outcomes for an Interdisciplinary Pain Rehabilitation Program: Comparisons of Subjective and Objective Outcomes on the Basis of Opioid Use Status.

J Pain 2018 06 2;19(6):678-689. Epub 2018 Mar 2.

Department of Psychiatry and Psychology, Mayo Clinic College of Medicine, Rochester, Minnesota.

Chronic pain is a major public health concern, and widespread use of prescription opioids for chronic pain has contributed to the escalating problem of opioid use disorder. Interdisciplinary pain rehabilitation programs (IPRPs) can be highly effective in discontinuing opioids in patients with chronic pain while also improving functional status. This study sought to examine self-report and performance-based functional outcomes of 2 cohorts of patients enrolled in a 3-week IPRP: patients engaged in interdisciplinary pain treatment and physician-supervised opioid taper versus nonopioid users engaged in interdisciplinary treatment. Immediate and long-term treatment outcomes were assessed using a series of 2 (group: opioid use, no opioid use) × 2 (period: pretreatment, post-treatment) and 2 (group: opioid use, no opioid use) × 2 (period: pretreatment, 6 months post-treatment) mixed model analyses of variance. Group × Period interactions were nonsignificant whereas period effects were significant for all outcomes in directions indicating improvement (Ps < .001) at discharge from the program and at 6 months, irrespective of opioid use status. Results support the assertion that IPRPs lead to significant improvements in subjective as well as objective indices of function, irrespective of opioid use status. Implications for our findings are discussed.

Perspective: This article provides support for the effectiveness of interdisciplinary, rehabilitative models of care in improving physical and emotional functioning of patients with chronic pain while simultaneously discontinuing opioid use. The reach of this work is substantial, because opioid dependency and chronic pain are public health problems in the United States.
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http://dx.doi.org/10.1016/j.jpain.2018.02.010DOI Listing
June 2018

A Lack of Systemic Absorption Following the Repeated Application of Topical Quetiapine in Healthy Adults.

Am J Hosp Palliat Care 2018 Aug 17;35(8):1076-1080. Epub 2018 Jan 17.

1 Hospital Pharmacy Services, Mayo Clinic Hospital, Rochester, MN, USA.

In the absence of suitable oral or intravenous access for medication administration and when the intramuscular medications are undesirable, alternative routes for drug delivery may be considered. Antipsychotics administered via an inhaled, intranasal, rectal, or topical route have been described in the literature. Topically administered antipsychotics have been previously reported to produce negligible systemic absorption despite being used in clinical practice for nausea and behavioral symptoms associated with dementia. Additionally, the American Academy of Hospice and Palliative Medicine recommends against the use of topical medications that lack supporting literature. Three studies have assessed the systemic absorption of different antipsychotics after administration of only a single, topically applied dose. To evaluate whether the repeated administration of a topically applied antipsychotic may result in detectable serum levels in an accumulating fashion, a pharmacokinetic study was conducted. Five healthy, adult participants consented to receive extemporaneously prepared topical quetiapine in Lipoderm every 4 hours for a total of 5 doses. Blood samples were drawn at baseline and hours 2, 4, 8, 12, 16, and 24, and serum quetiapine concentrations were measured using high-performance liquid chromatography. Quetiapine was undetectable in every sample from 3 participants. Two participants had minimally detectable serum quetiapine levels no sooner than hour 12 of the study period. Extemporaneously prepared quetiapine in Lipoderm resulted in nonexistent or minimal serum level following repeated topical administration. The use of topically applied quetiapine should still be questioned.
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http://dx.doi.org/10.1177/1049909117753828DOI Listing
August 2018

Comparison of Bioavailability of Single-Dose Extended-Release Venlafaxine Capsules in Obese Patients Before and After Gastric Bypass Surgery.

Pharmacotherapy 2017 Nov 10;37(11):1374-1382. Epub 2017 Oct 10.

Division of Biomedical Statistics and Informatics, Mayo Clinic, Rochester, Minnesota.

Study Objective: The extended-release (ER) form of venlafaxine is preferred because of improved patient adherence, but the immediate-release (IR) form is frequently used after Roux-en-Y gastric bypass (RYGB) surgery because of concerns for malabsorption. The objective of this study was to determine whether a statistically significant and predictable change in the bioavailability of venlafaxine ER capsules occurs after RYGB.

Design: Prospective nonblinded single-dose pharmacokinetic study.

Setting: Clinical research unit at a large tertiary care medical practice.

Patients: Ten adult pre-bariatric surgery patients who met the criteria for noncomplicated RYGB were enrolled and served as their own controls.

Interventions: Patients were administered one venlafaxine ER 75-mg capsule at two visits-the first visit at least 1 week before undergoing RYGB and the second visit 3-4 months after RYGB. Blood samples were collected at predetermined intervals over 48 hours after each dose, and the pharmacokinetics of venlafaxine were measured.

Measurements And Main Results: Plasma levels of venlafaxine and its primary metabolite, O-desmethylvenlafaxine (ODV), were compared at baseline and 3-4 months after RYGB. The areas under the serum concentration-time curves from 0-24 hours (AUC ) for venlafaxine (mean ± SD 734 ± 602 vs 630 ± 553 ng·hr/ml, p=0.22) and ODV (mean ± SD 894 ± 899 vs 1083 ± 972 ng·hr/ml, p=0.07) were similar before and after RYGB. Using a bioequivalence approach, differences in pre-RYGB and post-RYGB values of AUC , peak serum concentration, and time to peak serum concentration were not statistically significant for either venlafaxine or ODV.

Conclusion: This study suggests that RYGB does not significantly alter the amount of venlafaxine or its active metabolite, ODV, absorbed from a venlafaxine ER capsule or the time over which it is absorbed.
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http://dx.doi.org/10.1002/phar.2022DOI Listing
November 2017

Medical cannabis use among patients with chronic pain in an interdisciplinary pain rehabilitation program: Characterization and treatment outcomes.

J Subst Abuse Treat 2017 06 6;77:95-100. Epub 2017 Apr 6.

Mayo Clinic Department of Pharmacy, 200 First St SW, Rochester, MN 55905, United States. Electronic address:

Introduction: Cannabis is increasingly being used in the treatment of chronic pain. However, there is a lack of available research in the population of patients with chronic pain who are using cannabis. The current study examines clinical and treatment characteristics for patients who are admitted to a 3-week outpatient interdisciplinary chronic pain rehabilitation program.

Method: Participants (N=48) included patients with a positive urine drug screen for 9-carboxy-tetrahydrocannabinol (THC(+); n=24) and a matched comparison sample of patients with a negative screen (THC(-); n=24). Participants were matched for age, gender, race, education, and current prescription opioid use. Measures of pain, functioning, and quality of life were completed at admission and discharge. Medical chart review was conducted to assess medication and substance use history.

Results: Participants with a positive screen for THC were more likely to report a past history of illicit substance use, alcohol abuse, and current tobacco use. Cannabis use was not associated with a significantly lower morphine equivalence level for participants using prescription opioids (n=14). Both groups of participants reported significant improvement in pain severity, pain interference, depressive symptoms, and pain catastrophizing. There were no group- or treatment-related differences in these outcome variables.

Discussion: Results provide preliminary evidence that patients with chronic pain using cannabis may benefit from an interdisciplinary chronic pain program. Patients with chronic pain using cannabis may be at higher risk for substance-related negative outcomes, although more research is needed to understand this relationship.
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http://dx.doi.org/10.1016/j.jsat.2017.03.012DOI Listing
June 2017

Benzodiazepine use in patients with chronic pain in an interdisciplinary pain rehabilitation program.

J Pain Res 2017 9;10:311-317. Epub 2017 Feb 9.

Department of Anesthesiology, Mayo Clinic, and Mayo Clinic College of Medicine, Rochester, MN, USA.

Objectives: In the context of widespread opioid use, increased emphasis has been placed on the potentially deleterious effects of concurrent benzodiazepine (BZD) and opioid use. Although use of opioids in chronic pain has been a major focus, BZD use is equally concerning. Thus, the primary aim of this study was to determine the associations between BZD and opioid use in adults with chronic pain upon admission to an outpatient interdisciplinary pain rehabilitation (IPR) program.

Methods: The study cohort involved 847 consecutive patients admitted to a 3-week outpatient IPR program from January 2013 through December 2014. Study variables included baseline demographic and clinical characteristics, Center for Epidemiologic Studies-Depression Scale, Pain Catastrophizing Scale, and the pain severity subscale of the Multidimensional Pain Inventory.

Results: Upon admission, 248 (29%) patients were taking BZDs. Patients using BZDs were significantly more likely to use opioids and to be female. Additionally, patients using BZDs had significantly greater depression, pain catastrophizing, and pain severity scores. In univariable logistic regression analysis, opioid use, female sex, and greater scores of depression, pain catastrophizing, and pain severity were significantly associated with BZD use. In multivariable logistic regression analysis adjusted for age, sex, pain duration, opioid use, depression, pain catastrophizing, and pain severity, only female sex and greater depression scores were significantly associated with BZD use.

Discussion: Among patients participating in an outpatient IPR program, female sex and greater depression scores were associated with BZD use. Results identify a high prevalence of BZD use in patients with chronic pain and reinforce the need to weigh the risks versus benefits when prescribing in this patient population.
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http://dx.doi.org/10.2147/JPR.S123487DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5310637PMC
February 2017

Management of Psychotropic Drug-Induced DRESS Syndrome: A Systematic Review.

Mayo Clin Proc 2016 06 25;91(6):787-801. Epub 2016 Apr 25.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN.

Drug rash with eosinophilia and systemic symptoms (DRESS) is a severe cutaneous eruption that has been linked to several common drugs and drug categories, including antiepileptics, allopurinol, sulfonamides, and various antibiotics; however, because of a number of recent case reports linking psychotropic medications to this condition, DRESS is increasingly recognized among psychiatrists. We systematically reviewed all psychotropic drugs linked to DRESS syndrome, and this article summarizes the clinical management relevant to psychiatric professionals. A comprehensive search was performed using Ovid MEDLINE, Ovid EMBASE, Ovid Cochrane Database of Systematic Reviews, Web of Science, Scopus, and Litt's Drug Eruption and Reaction Database for articles published in English during the past 20 years (1996-2015) using the search terms (1) psychotropic drugs OR serotonin uptake inhibitors AND DRESS or (2) psychotropic drugs AND drug reaction (or rash) eosinophilia systemic syndrome, and all article abstracts were screened for inclusion and exclusion criteria by 3 reviewers. Two independent reviewers examined the full text of 163 articles, of which 96 (25 original articles, 12 review articles, 55 case reports, and 4 letters to the editor) were included in the systematic review. We identified 1072 cases of psychotropic drug-induced DRESS, with carbamazepine, lamotrigine, phenytoin, valproate, and phenobarbital being the most implicated drugs. Based on our review of the literature, we outline management principles that include prompt withdrawal of the causative drug, hospitalization, corticosteroid therapy, and novel treatments, including intravenous immunoglobulin, cyclophosphamide, and cyclosporine, for corticosteroid-resistant DRESS. Finally, we outline strategies for treating comorbid psychiatric illness after a DRESS reaction to the psychotropic medication.
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http://dx.doi.org/10.1016/j.mayocp.2016.03.006DOI Listing
June 2016

A Single-Dose Crossover Pharmacokinetic Comparison Study of Oral, Rectal and Topical Quetiapine in Healthy Adults.

Clin Pharmacokinet 2016 08;55(8):971-6

Department of Psychiatry and Psychology, Mayo Clinic Hospital-Rochester, 1216 2nd Street SW, Rochester, MN, 55902, USA.

Introduction: Quetiapine is an oral atypical antipsychotic drug commonly used to treat a large number of neuropsychiatric disorders and conditions. However, a substantial number of patients who may benefit from treatment with quetiapine are unable to ingest quetiapine or other medications by mouth and thus require alternative routes of administration. There are currently no studies evaluating non-oral compounded dosage forms of quetiapine.

Methods: We conducted a single-dose open-label crossover pharmacokinetic study in 10 healthy adults to determine whether quetiapine compounded as a rectal suppository or a topical cream achieved absorption similar to that achieved by a commercially available oral formulation.

Results: Rectal quetiapine produced an area under the plasma concentration-time curve from time zero to infinity (AUC∞) approximately 90 % greater than that produced by an equal (milligram per milligram) dose of oral quetiapine (15,333 ng/mL versus 8118.8 ng/mL, p = 0.005). However, only two of ten subjects who received topical quetiapine had detectable serum levels. When detected, serum levels achieved with topical quetiapine were delayed and low in comparison with those produced by the oral and rectal dosage forms.

Conclusion: Our results suggest that rectal, but not topical, quetiapine may be useful in clinical settings. Clinical outcome studies of rectal quetiapine are needed.
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http://dx.doi.org/10.1007/s40262-016-0368-5DOI Listing
August 2016

Opioid Tapering in Fibromyalgia Patients: Experience from an Interdisciplinary Pain Rehabilitation Program.

Pain Med 2016 09 11;17(9):1676-85. Epub 2016 Jan 11.

Psychiatry and Psychology, Mayo Clinic College of Medicine, Mayo Clinic, Rochester, Minnesota, USA.

Objective: Despite current guideline recommendations against the use of opioids for the treatment of fibromyalgia pain, opioid use is reported in approximately 30% of the patient population. There is a lack of information describing the process and results of tapering of chronic opioids. The purpose of this study is to describe opioid tapering and withdrawal symptoms in fibromyalgia patients on opioids.

Design, Setting, And Subjects: This retrospective research study included a baseline analysis of 159 patients consecutively admitted to the Mayo Clinic Pain Rehabilitation Center from 2006 through 2012 with a pain diagnosis of fibromyalgia completing a 3-week outpatient interdisciplinary pain rehabilitation program. Opioid tapering analysis included 55 (35%) patients using daily opioids.

Methods: Opioid tapering was individualized to each patient based on interdisciplinary pain rehabilitation team determination. Opioid withdrawal symptoms were assessed daily, utilizing the Clinical Opioid Withdrawal Scale.

Results: Patients taking daily opioids had a morphine equivalent mean dose of 99 mg/day. Patients on < 100 mg/day were tapered off over a mean of 10 days compared with patients on > 200 mg/day over a mean of 28 days (P < 0.001). Differences in peak withdrawal symptoms were not statistically significant based on the mean equivalent dose (P = 22). Patients taking opioids for <2 years did not differ in length of tapering (P =0.63) or peak COWS score (P =0.80) compared with >2 years duration. Patients had significant improvements in pain-related measures including numeric pain scores, depression catastrophizing, health perception, interference with life, and perceived life control at program completion.

Conclusion: Fibromyalgia patients on higher doses of opioids were tapered off over a longer period of time but no differences in withdrawal symptoms were seen based on opioid dose. Duration of opioid use did not affect the time to complete opioid taper or withdrawal symptoms. Despite opioid tapering, pain-related measures improved at the completion of the rehabilitation program.
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http://dx.doi.org/10.1093/pm/pnv079DOI Listing
September 2016

Safety of electroconvulsive therapy in patients receiving dabigatran therapy.

Psychosomatics 2014 Jul-Aug;55(4):400-403. Epub 2013 Aug 9.

Department of Medicine, Mayo Clinic, Jacksonville, FL.

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http://dx.doi.org/10.1016/j.psym.2013.06.010DOI Listing
August 2016

Development and evaluation of a pharmacogenomics educational program for pharmacists.

Am J Pharm Educ 2013 Feb;77(1):10

Department of Pharmacy Services, Mayo Clinic, Rochester, MN 55905, USA.

Objectives. To evaluate hospital and outpatient pharmacists' pharmacogenomics knowledge before and 2 months after participating in a targeted, case-based pharmacogenomics continuing education program.Design. As part of a continuing education program accredited by the Accreditation Council for Pharmacy Education (ACPE), pharmacists were provided with a fundamental pharmacogenomics education program.Evaluation. An 11-question, multiple-choice, electronic survey instrument was distributed to 272 eligible pharmacists at a single campus of a large, academic healthcare system. Pharmacists improved their pharmacogenomics test scores by 0.7 questions (pretest average 46%; posttest average 53%, p=0.0003).Conclusions. Although pharmacists demonstrated improvement, overall retention of educational goals and objectives was marginal. These results suggest that the complex topic of pharmacogenomics requires a large educational effort in order to increase pharmacists' knowledge and comfort level with this emerging therapeutic opportunity.
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http://dx.doi.org/10.5688/ajpe77110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3578323PMC
February 2013

Hypovitaminosis D in psychiatric inpatients: clinical correlation with depressive symptoms, cognitive impairment, and prescribing practices.

Psychosomatics 2013 May-Jun;54(3):257-62. Epub 2012 Dec 1.

Department of Pharmacy, Mayo Clinic, 200 First Street SW, Rochester, MN 55902, USA.

Objective: The association of hypovitaminosis D with measures of depressive symptoms and cognitive impairment remains unclear. This correlation and subsequent prescribing practices of vitamin D supplementation were evaluated in a population of psychiatric inpatients.

Methods: A retrospective study was conducted of 548 patients with a serum 25-hydroxyvitamin D [25(OH)D] level measured during hospitalization. Outcomes included the association of hypovitaminosis D with Patient Health Questionnaire (PHQ-9) and Folstein Mini-Mental State Exam (MMSE) scores, including an evaluation of vitamin D dosing upon hospital discharge.

Results: Two hundred three patients (37%) had hypovitaminosis D. The majority [183 (90%)] had moderate (10-24 ng/mL), while 20 (10%) had severe hypovitaminosis D (<10 ng/mL). There was no significant association between hypovitaminosis D and PHQ-9 or MMSE scores (p = 0.107 and p = 0.271, respectively). Overall, 33% of patients with moderate hypovitaminosis D and 45% of patients with severe hypovitaminosis D were newly prescribed vitamin D or received a dose increase. Initiation of vitamin D or increased vitamin D dose was significantly higher in patients with hypovitaminosis D (p < 0.001).

Conclusions: No association was found between hypovitaminosis D and depressive symptoms or cognitive function. However, patients with hypovitaminosis D were more likely to be prescribed additional vitamin D at hospital discharge.
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http://dx.doi.org/10.1016/j.psym.2012.07.005DOI Listing
February 2014

Associations between spousal or significant other solicitous responses and opioid dose in patients with chronic pain.

Pain Med 2012 Aug 9;13(8):1034-9. Epub 2012 Jul 9.

Department of Pharmacy, Mayo Clinic College of Medicine, Rochester, MN 55905, USA.

Objective: The primary aim of this study was to determine the effects of spouse or significant other solicitous responses on morphine equivalent dose among adults with chronic pain.

Design: Retrospective design.

Setting: Multidisciplinary pain rehabilitation center.

Patients: The cohort included 466 consecutively admitted patients who had a spouse or significant other and were using daily opioids. Intervention. Three-week outpatient pain rehabilitation program.

Outcome Measures: Solicitous subscale of the Multidimensional Pain Inventory and morphine equivalent dose upon admission.

Results: The mean solicitous subscale score and morphine equivalent dose were 49.8 (standard deviation [SD] = 8.7) and 118mg/day (SD =149), respectively. Univariate linear regression analysis showed that greater subscale scores were associated with greater doses of opioids (P = 0.007). In a multivariate model adjusted for age, sex, ethnicity, years of education, employment status, pain duration, depression, and pain severity, the association retained significance (P = 0.007).

Conclusions: These findings suggest solicitous responses from a spouse or significant other may have an important influence on opioid dose among adults with chronic pain.
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http://dx.doi.org/10.1111/j.1526-4637.2012.01434.xDOI Listing
August 2012

Investigation of antidepressant medication usage after bariatric surgery.

Obes Surg 2012 Apr;22(4):530-5

Department of Pharmacy, Mayo Clinic, Rochester, MN, USA.

Background: Many patients seeking bariatric surgery have a history of mood disorders and are actively prescribed antidepressants. While extensive documentation exists on the impact of weight loss surgery on reductions in cardiac, diabetic, and hypertensive medications, little is known about the impact of bariatric surgery on the use of antidepressant medications.

Methods: A retrospective study of 439 patients who had undergone Roux-en-Y gastric bypass (RYGB) from January 2001 to November 2004 was examined for postoperative changes in the use of antidepressant medications.

Results: After RYGB, 23% of the patients had an increase in their antidepressant use, 40% continued to require the same antidepressant, 18% had a change in antidepressant medication, and only 16% had a decrease or discontinued their antidepressant.

Conclusion: Unlike most medications, antidepressant usage did not decrease in the majority of patients after RYGB. These results highlight the prevalence of antidepressant prescription use in patients before and after RYGB and support the need for the careful monitoring of depressive symptoms.
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http://dx.doi.org/10.1007/s11695-011-0517-8DOI Listing
April 2012

Assessment of the pharmacogenomics educational needs of pharmacists.

Am J Pharm Educ 2011 Apr;75(3):51

Department of Pharmacy Services, Mayo Clinic, Rochester, MN 55902, USA.

Objectives: To evaluate the self-perceived knowledge and confidence of inpatient and outpatient pharmacists in applying pharmacogenomics information to clinical practice.

Methods: A 19-question multiple-choice, electronic needs-assessment survey instrument was distributed to 480 inpatient and outpatient pharmacists in a large, academic, multi-campus healthcare system.

Results: The survey response rate was 64% (303). Most respondents (85%) agreed that pharmacists should be required to be knowledgeable about pharmacogenomics, and 65% agreed that pharmacists should be capable of providing information on the appropriate use of pharmacogenomics testing. Sixty-three percent felt they could not accurately apply the results of pharmacogenomics tests to drug-therapy selection, dosing, or monitoring.

Conclusion: Pharmacists believe pharmacogenomics knowledge is important to the profession, but they lack the knowledge and self-confidence to act on the results of pharmacogenomics testing and may benefit from pharmacogenomics education.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3109805PMC
http://dx.doi.org/10.5688/ajpe75351DOI Listing
April 2011

Acute dystonia associated with paliperidone overdose.

Psychosomatics 2011 May-Jun;52(3):291-4. Epub 2011 Mar 2.

Department of Psychiatry and Psychology, Mayo Clinic, Rochester, MN 55905, USA.

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http://dx.doi.org/10.1016/j.psym.2010.12.004DOI Listing
September 2011

Electrolyte orders in the neuroscience intensive care unit: worth the value or waste?

Neurocrit Care 2011 Apr;14(2):216-21

Department of Pharmacy, Mayo Clinic, Rochester, MN 55905, USA.

Background: To assess the value of the practice of obtaining frequent electrolyte measurements in patients with extended stay in a neuroscience intensive care unit (NICU).

Methods: We identified consecutive patients 18 years or older, admitted to the NICU between January 1 and July 31, 2009 with length of stay ≥ 5 days. We collected potassium, sodium, magnesium, ionized calcium, phosphorus laboratory measurements and hemoglobin levels, and recorded electrolyte replacement orders and red blood cell transfusions. Average laboratory costs were estimated.

Results: 93 patients were included in the study (54 men, mean age 54 years, range 18-85 years). Mean length of stay was 10.4 days (range 5-36 days). Sodium and potassium were the electrolytes most frequently measured (averages of 14.1 and 13.1 per patient, respectively). More than 75% of the results were within normal range for all electrolytes measured and critical values were extremely uncommon. The number of phlebotomies for electrolyte measurements was strongly associated with the degree of hemoglobin drop (P < 0.0001). Electrolyte panels were ordered much more often than individual electrolytes with average cost exceeding $2200 per patient. Replacing half of these electrolyte panels with single sodium or potassium orders would have resulted in savings greater than $100,000 in our population.

Conclusions: Electrolytes measurements are very frequent in the NICU, but results are most often normal and only exceptionally critical. The phlebotomies required for these tests significantly worsen hemoglobin levels. A more conservative use of electrolyte measurements can result in reduction of blood loss and substantial cost savings.
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http://dx.doi.org/10.1007/s12028-010-9416-4DOI Listing
April 2011

Reduction in medication costs for patients with chronic nonmalignant pain completing a pain rehabilitation program: a prospective analysis of admission, discharge, and 6-month follow-up medication costs.

Pain Med 2009 Jul-Aug;10(5):787-96. Epub 2009 Mar 19.

Department of Pharmacy, Mayo Clinic College of Medicine, Rochester, Minnesota 55902, USA.

Objective: Chronic nonmalignant pain (CNMP) is both a prevalent and a costly health problem in our society. Pain rehabilitation programs have been shown to provide cost-effective treatment. A treatment goal for some rehabilitation programs is reduction in the use of pain-related medication. Medication costs savings from pain rehabilitation programs have not been analyzed in previous studies.

Design: This prospective cohort study of 186 patients with CNMP addresses the costs of medications at admission to a 3-week outpatient pain rehabilitation program, at discharge, and at 6-month follow-up. Medication use was determined through a detailed pharmacist interview with patients at admission and discharge. Patients were sent questionnaires 6 months after program completion, which obtained current medication information.

Results: Statistically significant medication cost savings were seen for program completers at discharge and at 6-month follow-up (P < 0.05). The mean (standard deviation) daily prescription medication cost reduction from admission to discharge was $9.31 ($12.70) using the average wholesale price of medications. From the original study cohort, 121 patients completed the 6-month follow-up survey. The mean daily prescription medication cost savings from admission to 6-month follow-up was $6.68 ($14.40).

Conclusion: Patients benefited from significant medication cost savings at the completion of the 3-week outpatient pain rehabilitation program and maintained significant savings after 6 months. This study adds to the current literature on the economic value of comprehensive pain rehabilitation programs.
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http://dx.doi.org/10.1111/j.1526-4637.2009.00582.xDOI Listing
November 2009