Engaging Patients to Support Adherence

Transcription

1 Available at CurrentPsychiatry.com/BipolarDepression A SUPPLEMENT TO This promotional, non-cme program is intended only for health care professionals involved in the treatment of adult patients with bipolar disorder. FIRST IN A SERIES OF 3 NEWSLETTERS JANUARY 2017 Engaging Patients to Support Adherence This newsletter series was developed and brought to you by Sunovion Pharmaceuticals Inc. It did not undergo peer review by Current Psychiatry. Newsletter content was developed in collaboration with the faculty. Faculty Vivien K. Burt, MD, PhD Professor Emeritus of Psychiatry Department of Psychiatry and Biobehavioral Sciences David Geffen School of Medicine at University of California, Los Angeles Co-Director The Women s Life Center Department of Psychiatry and Biobehavioral Sciences Resnick Neuropsychiatric Hospital at UCLA Los Angeles, California Catherine R. Judd, MS, PA-C, CAQ-Psychiatry, DFAAPA Clinical Assistant Professor Department of Physician Assistant Studies University of Texas Southwestern Medical Center School of Health Professions Physician Assistant Mental Health and Behavioral Medicine Parkland Health and Hospital System Dallas, Texas Mauricio Tohen, MD, DrPH, MBA Professor and Chairman Department of Psychiatry The University of New Mexico Albuquerque, New Mexico DISCLOSURES Dr. Burt serves or has served as a consultant and speaker for various pharmaceutical companies, including Sunovion. Ms. Judd and Dr. Tohen serve or have served as consultants, speakers, and researchers for various pharmaceutical companies, including Sunovion. The clinical expert commentary reflects the view of an actual licensed clinician who has been engaged by Sunovion. The information contained herein is intended for general informational purposes only and is not a substitute for your professional medical advice and judgment. This supplement is sponsored by LATUDA, SUNOVION, and are registered trademarks of Sumitomo Dainippon Pharma Co., Ltd. Sunovion Pharmaceuticals Inc. is a U.S. subsidiary of Sumitomo Dainippon Pharma Co., Ltd Sunovion Pharmaceuticals Inc. All rights reserved. 11/16 LAT Please see Brief Summary of full Prescribing Information, including Boxed Warning, on page S5. LATUDA is indicated for treatment of major depressive episodes associated with bipolar I disorder (bipolar depression) as monotherapy and as adjunctive therapy with lithium or valproate. The efficacy of LATUDA was established in a 6-week monotherapy study and a 6-week adjunctive therapy study with lithium or valproate in adult patients with bipolar depression. The effectiveness of LATUDA for longer-term use, that is, for more than 6 weeks, has not been established in controlled studies. Therefore, the physician who elects to use LATUDA for extended periods should periodically re-evaluate the long-term usefulness of the drug for the individual patient. The efficacy of LATUDA in the treatment of mania associated with bipolar disorder has not been established. IMPORTANT SAFETY INFORMATION AND INDICATIONS FOR LATUDA Antidepressants increased the risk of suicidal thoughts and behavior in children, adolescents, and young adults in short-term studies. These studies did not show an increase in the risk of suicidal thoughts and behavior with antidepressant use in patients over age 24; there was a reduction in risk with antidepressant use in patients aged 65 and older. In patients of all ages who are started on antidepressant therapy, monitor closely for worsening, and for emergence of suicidal thoughts and behaviors. Advise families and caregivers of the need for close observation and communication with the prescriber. LATUDA is not approved for use in patients under the age of 18 years. A multidisciplinary panel of Clinical Experts contributed to the development of this 3-part newsletter series. Each issue explores strategies for the management of patients with bipolar disorder and features expert commentary from the psychiatry, primary care, or nurse-practitioner/ physician-assistant perspective. The Issue of Nonadherence in Bipolar Disorder Nonadherence to psychiatric medication is one of the main clinical challenges in the treatment of individuals with bipolar disorder. A recent cross-sectional study of 303 outpatients with the illness found that 69.3% had suboptimal adherence. 1 In multivariate analyses, depressive polarity of the last episode, current acute episode, presence of subsyndromal symptoms, and substance use or dependence emerged as predictors of poor treatment adherence. 1 Notably, patients with bipolar disorder spend the majority of their Watch a video about the impact of lifestyle factors on adherence and outcomes. Visit Supplement to Current Psychiatry Vol 16, No 1 January 2017 S1

2 ENGAGING PATIENTS TO SUPPORT ADHERENCE Skill Open-ended questions Affirmations Reflective listening Summaries TABLE 1. MOTIVATIONAL INTERVIEWING SKILLS AND EXAMPLES 4 Example Question(s) or Statement(s) Tell me about not taking your medication. What is good about it? And what is the other side? What worries you about not taking your medication? I understand that you didn t want to come back to the hospital, but you did anyway. I admire you for coming back to get help, knowing that it wasn t easy for you. You have recently lost a job, and that seems to be very hard for you. Let me stop us here and summarize some of the things that we ve just talked about. So you ve told me that you don t want to continue taking your medication because you have gained weight in the past. But at the same time, it sounds like you have had trouble managing your symptoms without your medication, which has impacted your marriage, your work, and your overall health. Did I miss anything? How do you feel about all these things? Laakso LJ. Motivational interviewing: addressing ambivalence to improve medication adherence in patients with bipolar disorder. Issues Ment Health Nurs. 2012;33(1):8-14. Reprinted by permission of Taylor & Francis Ltd. symptomatic time 68% in 1 study experiencing depressive symptoms, and the lifetime rate of comorbid substance use disorder in this population is 48%, suggesting that several of the factors that predict poor adherence predominate the bipolar disorder clinical picture. 2,3 The consequences of nonadherence in this patient population include increased total medical expenditures and outpatient mental health care costs due to greater risk for symptom exacerbation and recurrence, as well as lower treatment effectiveness and poorer treatment outcomes. 4 Several studies have found that patients with poor adherence also experience worse functional outcomes. 1 The effect of poor adherence to psychiatric medication may extend beyond a patient s mental health. In a recent study, Levin and colleagues found that greater depression severity particularly the presence of vegetative symptoms and retardation was significantly correlated with poor adherence to nonpsychiatric medication (P=.011 and P=.005, respectively), based on the Tablets Routine Questionnaire. 5 This finding is noteworthy because it demonstrates that nonadherence to psychiatric medication may cascade into nonadherence to medication for the treatment of medical comorbidities that are prevalent in patients with bipolar disorder. 6 Barriers to adherence in patients with bipolar disorder include both intentional factors (eg, anosognosia, or limited insight or lack of awareness about having a psychiatric disorder, and dislike of or concerns about side effects) and unintentional factors (eg, forgetting to take medication, possibly due to executive functioning deficits and lack of routines). External factors, such as financial problems, high cost of medication, lack of health insurance coverage, and poor relationships with health care professionals, may contribute to nonadherence. 4,8 Internal factors, such as lack of symptoms during euthymia and, in some cases, pleasure from the high energy and increased self-esteem experienced during mania, can make it difficult for patients with bipolar disorder to adhere to treatment regimens. 4 Furthermore, taking medication can reinforce for patients and family members the stigma frequently associated with mental illness. 4 The reasons for nonadherence are multifactorial and may transcend the individual patient. It is important for health care professionals to appreciate their role in treatment adherence, starting with a strong therapeutic alliance with their patients. 8 Strategies to Motivate Treatment Adherence Several strategies that can be employed by the multidisciplinary care team may improve adherence in patients with bipolar disorder. One strategy motivational interviewing involves a deeply humanistic approach to actively hearing patients own motivations for change and helping them to resolve the ambivalence with which they approach treatment. 4,9 The principles of motivational interviewing are: Expressing empathy so that patients feel understood and accepted 4 Encouraging patients to recognize a personally meaningful discrepancy between their goals and their current state to motivate change 4 Exploring patient resistance to better understand the individual s point of view, personal struggles, and obstacles to adherence, and then using these perspectives as a resource for finding answers and solutions 4 Supporting patients confidence in their ability to change (self-efficacy) 4 Four interaction techniques, known by the mnemonic OARS, form the foundation of this patient-centered approach (Table 1). 4 Psychoeducation is another strategy that specifically addresses misconceptions regarding bipolar disorder; it can be provided in a group setting or to patients and their partners or families. 10 Other efficacious approaches include cognitive-behavioral therapy, in which a patient s pattern of thoughts and feelings about medication and illness is systematically challenged to produce healthier behaviors and beliefs. 10 Regardless of the strategy used to explore and address a patient s motivation, knowledge gaps, or cognitive patterns, the plan should be individualized in terms of its accessibility, affordability, and practicality to optimize its implementation. 8 Effective interventions also encompass family members, whenever possible, and encourage continual interaction between patients and health care professionals, with the goal of fostering an understanding of bipolar disorder and its treatment options by all involved in the care of individuals with the illness. 10 Listen to a Clinical Expert talk about the use of motivational interviewing in clinical practice. Visit S2 Please see Brief Summary of full Prescribing Information, including Boxed Warning, on page S5. January 2017 Vol 16, No 1 Supplement to Current Psychiatry

3 LATUDA: A Treatment Option for Bipolar Depression The efficacy of LATUDA was established in a 6-week monotherapy study and a 6-week adjunctive therapy study with lithium or valproate in adult patients with bipolar depression. The effectiveness of LATUDA has not been established for longer-term use (more than 6 weeks) or for the treatment of mania associated with bipolar disorder. 11 The results of a phase 3, randomized, multicenter, double-blind, placebo-controlled clinical trial that examined the efficacy and safety of LATUDA monotherapy for patients with bipolar I depression were published in the February 2014 issue of The American Journal of Psychiatry. 12 Adult patients (N=505) with major depressive episodes associated with bipolar I disorder, with or without rapid cycling and without psychotic features, were evaluated for eligibility. 12 All psychotropic medications were tapered off, and patients were randomly assigned to 1 of 3 treatment groups: flexibly dosed LATUDA mg/day (N=166), flexibly dosed LATUDA mg/day (N=169), or placebo (N=170). 12 LATUDA dosing adjustments were permitted for patients in both LATUDA groups to optimize efficacy and tolerability. 12 Study medication was taken once daily in the evening by mouth with a meal (eg, dinner) or within 30 minutes after eating. 12 Short-term Efficacy Figure 1 shows the improvement in depressive symptoms for the LATUDA and placebo groups from baseline to Week 6 as measured using the Montgomery-Åsberg Depression Rating Scale (MADRS) score, which was the study s primary efficacy endpoint. 12 The MADRS is a 10-item, clinician-rated scale with scores ranging from 0 to 60. At Week 6, LATUDA mg/day and mg/day were associated with significantly greater improvement in MADRS score from baseline to the 6-week endpoint than placebo (-15.4 for both LATUDA treatment groups vs for the placebo group; P<.001 for each LATUDA group vs placebo). 12 The higher dosage range ( mg/day) did not provide additional efficacy, on average, compared with the lower dosage range (20-60 mg/day). 12 Short-term Safety Figure 2 shows the incidence of adverse reactions occurring in 2% of patients in either LATUDA group and at greater incidence than placebo during acute therapy (up to 6 weeks in patients with bipolar depression). 11 Treatment was discontinued prematurely due to adverse events by 20 of 331 patients (6.0%) who received LATUDA mg/day, and by 9 of 168 patients (5.4%) who received placebo. 11 In the short-term study of LATUDA as monotherapy, the mean change in body weight from baseline to Week 6 was +1.2 pounds for patients who received LATUDA mg/day, 0.0 pounds LS Mean Change From Baseline Baseline Baseline mean = for patients who received LATUDA mg/day, and -0.1 pound for patients who received placebo. 11 Increase of body weight of at least 7.0% was noted for 2.4% of patients who received LATUDA versus 0.7% of patients who received placebo. 11 Changes in fasting glucose and lipids for the LATUDA and placebo groups are shown in Table The median prolactin concentration increased by 1.7 ng/ml for the LATUDA mg group, 3.5 ng/ml for the LATUDA mg Patients (%) FIGURE 1. PRIMARY EFFICACY ENDPOINT: MADRS SCORE 12 Time (Weeks) LATUDA mg (n=161) * ** Effect size: LATUDA mg: 0.51 LATUDA mg: 0.51 * ** LATUDA mg (n=162) Placebo (n=162) group, and 0.3 ng/ml for the placebo group. For male patients, the median change from baseline to Week 6 was +1.2 ng/ml, +1.9 ng/ml, and +0.4 ng/ml for the low-dose LATUDA, high-dose LATUDA, and placebo groups, respectively; for female patients, the corresponding median changes from baseline were +1.8 ng/ml, +5.3 ng/ml, and 0.0 ng/ml, respectively. 11 Extrapyramidal symptoms (EPS) observed during the 6-week LATUDA monotherapy study included ** *** ** *** *P<.05; **P<.01; ***P<.001. Abbreviations: LS, least squares; MADRS, Montgomery-Åsberg Depression Rating Scale. MADRS scale range, FIGURE 2. ADVERSE REACTIONS IN 2% OF LATUDA-TREATED PATIENTS AND AT GREATER INCIDENCE THAN PLABEBO LATUDA mg (N=164) Nausea Akathisia Somnolence* Dry Mouth LATUDA mg (N=167) EPS Diarrhea Anxiety Nasopharyngitis Back Pain Vomiting Placebo (N=168) UTI Influenza *** *** <1 <1 <1 <1 Abbreviations: EPS, extrapyramidal symptoms; UTI, urinary tract infection. *Somnolence includes adverse event terms: hypersomnia, hypersomnolence, sedation, and somnolence. EPS includes bradykinesia, cogwheel rigidity, drooling, dystonia, extrapyramidal disorder, glabellar reflex abnormal, hypokinesia, muscle rigidity, oculogyric crisis, oromandibular dystonia, parkinsonism, psychomotor retardation, tongue spasm, torticollis, tremor, and trismus. Please see Brief Summary of full Prescribing Information, including Boxed Warning, on page S5. Supplement to Current Psychiatry Vol 16, No 1 January 2017 S3

4 ENGAGING PATIENTS TO SUPPORT ADHERENCE akathisia (noted for 8%, 11%, and 2% of patients in the LATUDA mg, LATUDA mg, and placebo groups, respectively), dystonia (0%, 2%, and 0%), parkinsonism (5%, 8%, and 2%), and restlessness (0%, 3%, and <1%). 11 EPS, akathisia, and dyskinesia were also examined using the Simpson-Angus Scale (SAS), the Barnes Akathisia Scale (BAS), and the Abnormal Involuntary Movement Scale (AIMS), respectively. 11 On the SAS, a shift from normal at baseline to an abnormal score at Week 6 (or at last observation carried forward for patients who discontinued prematurely) was noted for 3.7% of patients who received LATUDA mg/day versus 1.9% of patients receiving placebo. On the BAS, worsening from baseline to endpoint was noted for 8.4% versus 5.6% of patients who received LATUDA or placebo, respectively, whereas on the AIMS, worsening from baseline was noted for 3.4% of patients who received LATUDA versus 1.2% of those receiving placebo. 11 TABLE 2. CHANGE IN LABORATORY PARAMETERS FROM BASELINE TO WEEK 6 IN PATIENTS RANDOMIZED TO TREATMENT WITH LATUDA MONOTHERAPY OR PLACEBO 11 Parameter LATUDA mg LATUDA mg Placebo Glucose (mean) 0.8 mg/dl (n=140) +1.8 mg/dl (n=143) +1.8 mg/dl (n=148) Total cholesterol (mean) +1.2 mg/dl (n=140) 4.6 mg/dl (n=144) 3.2 mg/dl (n=147) Triglycerides (mean) +5.6 mg/dl (n=140) +0.4 mg/dl (n=144) +6.0 mg/dl (n=147) References 1. Montes JM, Maurino J, de Dios C, Medina E. Suboptimal treatment adherence in bipolar disorder: impact on clinical outcomes and functioning. Patient Prefer Adherence. 2013;7: Judd LL, Akiskal HS, Schettler PJ, et al. The longterm natural history of the weekly symptomatic status of bipolar I disorder. Arch Gen Psychiatry. 2002;59(6): Simon NM, Otto MW, Weiss RD, et al. Pharmacotherapy for bipolar disorder and comorbid conditions: baseline data from STEP-BD. J Clin Psychopharmacol. 2004;24(5): Laakso LJ. Motivational interviewing: addressing ambivalence to improve medication adherence in patients with bipolar disorder. Issues Ment Health Nurs. 2012;33(1): Levin JB, Krivenko A, Bukach A, Tatsuoka C, Cassidy KA, Sajatovic M. A reexamination of nonpsychiatric medication adherence in individuals with bipolar disorder and medical comorbidities [published online June 10, 2016]. J Nerv Ment Dis doi: /NMD Maina G, Bechon E, Rigardetto S, Salvi V. General medical conditions are associated with delay to treatment in patients with bipolar disorder. Psychosomatics. 2013;54(5): Weiner M, Warren L, Fiedorowicz JG. Cardiovascular morbidity and mortality in bipolar disorder. Ann Clin Psychiatry. 2011;23(1): Levin JB, Krivenko A, Howland M, Schlachet R, Sajatovic M. Medication adherence in patients with bipolar disorder: a comprehensive review. CNS Drugs. 2016;30(9): McKenzie K, Chang YP. The effect of nurse-led motivational interviewing on medication adherence in patients with bipolar disorder. Perspect Psychiatr Care. 2015;51(1): Sajatovic M, Davies M, Hrouda DR. Enhancement of treatment adherence among patients with bipolar disorder. Psychiatr Serv. 2004;55(3): LATUDA [prescribing information]. Marlborough, MA: Sunovion Pharmaceuticals Inc.; Loebel A, Cucchiaro J, Silva R, et al. Lurasidone monotherapy in the treatment of bipolar I depression: a randomized, double-blind, placebocontrolled study. Am J Psychiatry. 2014;171(2): AN EXPERT S PERSPECTIVE Commentary by Vivien K. Burt, MD, PhD Among the challenges frequently faced by patients with bipolar disorder is adherence to treatment plans. As noted in this newsletter, a number of factors predict poor adherence, including a recent history of depression, current depressive symptoms (both severe and subsyndromal), and illicit substance use. In particular, I have found that bipolar depression, which is often so pervasive that it is difficult for patients to get out of bed, to leave home, or to see any hope for emerging from its debilitating effects, makes adherence more difficult. My clinical experience underscores the effectiveness of emotionally connecting with patients and encouraging them to express their concerns about prescribed medications and other aspects of their treatment regimen. By resonating with patients concerns and expressing a sincere appreciation for their real-life stresses, a continuum of trust is established that fosters adherence to treatment plans made in a multidisciplinary team setting. Empathizing with patients who struggle with bipolar disorder opens up avenues to explore the thoughts that have triggered those feelings. Once these thoughts have been expressed and shared with a caring and involved team of health care professionals, substantive discussions can be held to address and effectively treat symptoms, side effects, and other issues that hinder treatment adherence. Involving significant others and encouraging patient feedback can also support these efforts. Ultimately, I have found that an ongoing patient-provider dialogue helps improve psychiatric and medical outcomes in patients with bipolar disorder. Vivien K. Burt, MD, PhD S4 Please see Brief Summary of full Prescribing Information, including Boxed Warning, on page S5. January 2017 Vol 16, No 1 Supplement to Current Psychiatry

5 Supplement to Current Psychiatry Vol 16, No 1 January 2017 S5

6 S6 January 2017 Vol 16, No 1 Supplement to Current Psychiatry

7 Supplement to Current Psychiatry Vol 16, No 1 January 2017 S7

8 S8 January 2017 Vol 16, No 1 Supplement to Current Psychiatry

9 Supplement to Current Psychiatry Vol 16, No 1 January 2017 S9

10 S10 January 2017 Vol 16, No 1 Supplement to Current Psychiatry

11 Supplement to Current Psychiatry Vol 16, No 1 January 2017 S11

12 S12 January 2017 Vol 16, No 1 Supplement to Current Psychiatry