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Treatment Persistence: The Importance of Staying the Course Podcast


Andrew Cutler, MD, and Greg Mattingly, MD, highlight the importance of treatment persistence and its impact on patient outcomes, and strategies clinicians can implement to help support patients in staying committed to their mental health treatment plans.  

Transcript:

AC: Hello, and welcome to the Psych Navigator’s Peer Insights podcast, entitled “Treatment Persistence: The Importance of Staying the Course”! I am Dr Andrew Cutler, clinical professor of psychiatry at SUNY Upstate Medical University and Chief Medical Officer of the Neuroscience Education Institute. 

GM: And I am Dr Greg Mattingly, an associate clinical professor at Washington University School of Medicine and a physician and principal investigator in clinical trials for Midwest Research Group. Thank you for joining us as we discuss treatment persistence, a really crucial and yet often overlooked topic in mental health.  

AC: Well, that’s right, Greg. And you know, it’s really wonderful to be here with you today. Greg and I are old friends and colleagues who have been having these important discussions for a long time. So, today’s topic is really important for both clinicians and patients. As with all disease conditions, treatment persistence is a critical factor that can have a significant impact on patient outcomes. Alright, so, to begin, let’s define what we mean by persistence. Persistence refers to a patient taking a medication as prescribed throughout the intended course of treatment, and it’s a key component of adherence.1  

GM: That’s right, Andy. As you know, if a patient doesn’t take the medicine, it’s probably not gonna be very effective. Unfortunately, in psychiatry, mental disorders such as major depression and bipolar I disorder (BP-1) require long-term management, and treatment persistence can play an important role in patient outcomes. In moderate and severe major depression, as you know, the first-line pharmacologic treatment recommended by the American Psychiatric Association is antidepressant therapy.2 The antidepressant treatment of major depression occurs in three phases: number 1) an acute phase of 6 to 12 weeks intended to help induce remission of symptoms, number 2) a continuation phase of four to 9 months aimed at reducing relapse, and number 3) a maintenance phase intended to prevent recurrence.2,3 For patients with a higher risk of recurrence, maintenance therapy for up to two years or more is recommended for our patients.2,4,5 Unfortunately, research shows that up to 75% of patients discontinue their antidepressants within just 6 months of starting them, with more than 50% of patients who continue treatment for 6 months showing poor or inadequate adherence.1,3 Furthermore, about 25%, one out of four patients, discontinue their antidepressants within just one month, and 44% discontinue within three months.1 

AC: Wow, that’s really not encouraging. Well, for patients with bipolar disorder, the APA-recommended treatments include mood stabilizers and atypical antipsychotics, as either monotherapy or combination therapy, depending on the mood episode and severity of symptoms.6 Studies examining treatment persistence in patients with BP have shown that approximately 41% to 58% are adherent to their atypical antipsychotic treatments during a 12-month treatment period.7,8 In fact, one study found that only about 18% of patients taking atypical antipsychotics for BP remained persistent one year after starting treatment. So, Greg, these are not good numbers. On average, patients receiving atypical antipsychotics became non-persistent within approximately three months, with less than half of patients taking clinically recommended doses of atypical antipsychotics after two months of treatment.7 And Greg, we know that bipolar is a chronic illness and probably requires ongoing treatment. 

GM: Andy, those findings are important to emphasize because of the impact low treatment persistence and nonadherence can have on patient outcomes and real-world functional outcomes. You know, when antidepressants are discontinued, there is an increased risk of relapse or recurrence, and that risk is highest in the first 6 months.3 In a study involving more than 117,000 patients with depression, the rate of relapse or recurrence was 32.2% among patients who discontinued their antidepressant therapy early, compared to 12.1% among those who had continuous treatment.9 If we take a look at another study of 478 patients with major depression, that found that among those who had been taking antidepressants for more than 9 months and felt well enough to stop therapy, the risk of relapse by 52 weeks was greater in patients who had discontinued antidepressants than those who had maintained the antidepressant therapy. So, feeling well doesn’t always mean being well. So, the study also found that patients who discontinued their medications had more symptoms of depression, anxiety, and withdrawal than those who continued their medications in the maintenance phase.10  

AC: Well, Greg, I guess what we’re saying then like you said above is that medications don’t work so well if people don’t take them. You know, studies on bipolar disorder echo these findings. In a longitudinal study of 1,341 European patients receiving treatment for manic or mixed episodes of BP-1, nonadherence to treatment was significantly associated with a 35% decreased likelihood of recovery and a 70% increase in the likelihood of recurrence. Nonadherence was also associated with a 2.4-fold increase in relapse, a 2.9-fold increase in hospitalization, and Greg, a 2.8-fold increase in suicide attempts, which is really the worst outcome. These negative impacts on patient outcomes were reflected in healthcare costs as well. The total healthcare costs of nonadherent patients was approximately 39% higher, with the inpatient cost of nonadherent patients being more than double that of adherent patients. In another study based in the United States, the hospitalization costs of nonadherent patients with BP were found to be 6 times higher than those of adherent patients over a year, underscoring the negative economic impact of treatment nonadherence in BP-1 and MDD.11   

GM: Treatment persistence is a critical factor that significantly impacts the long-term patient outcomes. However, barriers to treatment persistence can be multifactorial. They can involve patient-related, provider-related, and systemic factors. Andy, what are some of the patient factors that might contribute to low persistence among patients receiving treatment for bipolar I and major depressive disorder?  

AC: Well, Greg, there are many factors that may influence treatment persistence in patients. So, when we discuss treatment persistence, we also need to address that some patients may experience residual symptoms despite their treatments. According to the Sequenced Treatment Alternatives to Relieve Depression (or STAR*D) study, a very large naturalistic study sponsored by the National Institute of Mental Health, about half of patients with MDD respond to their first antidepressant therapy12—Greg, I really should say only about half respond—and patients with partial or no response had residual symptoms of depression after their initial treatment.13-15 In fact, in the STAR*D study, more than 90% of the remitted patients reported at least one residual symptom.16 When patients experience residual symptoms of depression, they may perceive the treatment as not working and lose confidence in its effectiveness, and they are at increased risk of relapse. And you know, Greg, some symptoms are probably more important than others and may be even more important factors driving adherence.17,18

GM: So, symptom persistence, or residual symptoms, tend to contribute to poor adherence and poor patient outcomes. You know, one of the things I see, Andy, is that many patients may have multiple antidepressant trials before finding the one that’s effective. That can leave them disappointed, frustrated, angry, you know, feeling kind of hopeless and apathetic that they are gonna find something that’s gonna work, and that can really complicate issues around low persistence.2,17  

AC: Yeah, Greg, I’m glad you emphasized that concept of hopelessness. I think that’s an important thing for us to consider and address, and part of our goal, I guess, is to inspire hope, instill hope in our patients. I think we can do this by really paying attention to the selection of our medications to match up the patient symptom complex. Another common reason for low persistence is medication side effects. So, for patients with MDD, antidepressants can lead to weight gain, sexual dysfunction, insomnia, but also somnolence, and emotional flattening.17,19 For patients with BP taking atypical antipsychotics, as we all know, there’s potential adverse effects as well, and those can include weight gain, metabolic problems like glucose and lipid dysregulation, and drug-induced movement disorders, such as extrapyramidal symptoms, or EPS, and tardive dyskinesia, or TD.20-22 Now, these side effects can negatively affect a patient’s quality of life and increase the likelihood of patients being less adherent to their medication. So, in a survey of 200 patients with BP-1 taking oral antipsychotics, 48% of the patients reported discontinuing treatment due to side effects.23 In one study with MDD patients, somnolence increased the odds of treatment discontinuation 8.42 times.19,24  

GM: You know, some patients may have uncertainties about the long-term risks of the medications, and some may even be in denial or have misconceptions about their diagnosis. Then, there are also factors related to the perceived stigma associated with depression, or mental illness in general.17 There may be a fear of drug dependence, and some of the patients may have comorbidities, such as alcohol dependence and cardiovascular disease, and metabolic conditions, that can influence their treatment persistence.25,26  

AC: Yeah, these are all good points, Greg, but you know, something else we might not often consider is that there might be barriers to accessing medications, and the cost may be prohibitive for some patients in the long term.25  

GM: That’s an important consideration. Well, we’ve discussed the patient and systemic factors that may act as barriers to treatment persistence. What about us as providers? What are some of the ways that providers may be contributing to reduced persistence in patients with MDD who are undergoing treatment? 

AC: Yeah, there are several factors from the provider’s side that may lead to low persistence. First, not engaging in shared decision-making during treatment selection can hinder adherence. It’s crucial to discuss and consider the patient’s specific needs, their specific symptom complex and presentation, their circumstances, and their goals when creating a treatment plan that they can follow, and it’s really important, Greg, to align our goals with our patients’ because they may have slightly different goals than ours, and we just want to make sure we’re on the same page. Second, failing to provide sufficient education about the diagnosis and treatment can leave patients unaware of their prognosis and the need to continue their medication. Failing to prescribe US Food and Drug Administration (or FDA)-approved or evidence-based medicines and to follow treatment guidelines can result in ineffective or unnecessary treatments.27 Complicated dosing regimens and multiple medications can be confusing or make adherence difficult.28 Finally, inadequate or infrequent follow-up with patients can also contribute to low persistence.1 Issues, including long clinic wait times and frequent medication refills, can also negatively affect persistence.25  

GM: Let’s discuss some strategies we can address to overcome some of those barriers and help improve persistence in our patients with depression. First of all, patients with a major depressive episode should all be screened for bipolar I disorder because management approaches for bipolar are obviously different than those for major depression.2,6 Two useful screening tools that we use in our practice—we actually call them vital statistics—are the Mood Disorder Questionnaire and the Rapid Mood Screener.29,30 It is also vital to collect a thorough clinical and family history, including a medication history of what’s been previously effective, what hasn’t been effective, what’s been poorly tolerated, so you can think about your selection for the next appropriate treatment. Next, as you mentioned, establishing an alliance with the patient by actively listening to them and understanding their goals and expectations has been shown to be key in developing a personalized treatment plan that the patient is more likely to adhere to.31  

AC: All great points, Greg, and another critical component that goes hand-in-hand with the therapeutic alliance is providing adequate patient education on the treatment, including the rationale for selecting one medication over others, providing informed consent regarding side effects and risks, explaining how the medication can affect comorbid conditions, and addressing any other questions the patient may have.17 In addition, discussing expectations regarding how long it may take the patient to experience an improvement in symptoms before initiating therapy may help encourage treatment persistence. Patients need to understand that it can take four to 8 weeks before they may notice an improvement in their depressive symptoms, and improvement can continue for up to 12 weeks.2  

GM: You know, Andy, it’s really important to set expectations. You know, another essential strategy we can use to improve persistence is scheduling regular and consistent follow-ups to engage and monitor improvements and assess medication side effects that may drive nonadherence. Healthcare providers are encouraged to use validated standardized tools and instruments, such as the Patient Health Questionnaire-9 for symptoms of depression, to track the patient’s treatment response at each follow-up.32,33 Regular monitoring can help providers evaluate whether the treatment is effective and potentially detect adherence issues.31 And, as you mentioned earlier, Andy, identifying and addressing issues with treatment side effects that may negatively affect the patient’s quality of life is a really important part of helping to improve persistence and adherence. How’s your medication working? Is there anything that’s driving you to not want to take that medication? Let’s explore that together. 

AC: Yeah, Greg, together, these strategies may help improve treatment adherence in patients receiving pharmacologic treatment for MDD and bipolar I disorder. In fact, in a community-based study of 231 patients who were prescribed pharmacotherapy for depression by their primary care physicians, implementing a program comprising many of the key strategies we discussed today was shown to help improve adherence rates in patients fivefold. Now, this program, called the Treatment Initiation and Participation Program, or TIP, involved three 30-minute meetings in the first 6 weeks of the treatment and included: 1) reviewing symptoms and treatment barriers; 2) setting a personal adherence goal; 3) educating about depression and antidepressants; 4) addressing treatment barriers; and 5) creating an adherence strategy to empower patients to engage with their primary care providers. In addition to the improvement in adherence, the TIP program was actually associated with a greater symptom improvement earlier in the treatment process.34  

GM: Andy, this study is a good example of how prescribing FDA-approved or evidence-based medications, overcoming negative perceptions, implementing shared decision-making, addressing side effect concerns, closing gaps in communication through education, and regular follow-up with patients can help enhance treatment persistence and potentially long-term outcomes in patients with major depression. 

AC: Once again, Greg, you’re absolutely right. Absolutely. Thank you for joining us today. We hope today’s discussion offered useful clinical insights that you can incorporate into the care of your patients! 

GM: As always, Andy, great to be with you here today, and great to be with our audience. Thank you for joining us on Psych Navigator!  

Andrew Cutler, MD 
Andrew Cutler, MD, has extensive experience in psychopharmacology clinical trials, having served as a principal investigator on nearly 500 trials since 1993. Dr Cutler’s primary research focus is on disorders related to dopamine dysregulation, including schizophrenia, bipolar disorder, depression, and attention-deficit/hyperactivity disorder, with significant publications in these areas as well as anxiety and tardive dyskinesia. Additionally, he is actively involved in professional societies, has received multiple awards, and has extensive consulting experience with pharmaceutical companies, biotech, and financial firms.  

Greg Mattingly, MD 
Gregory Mattingly, MD, is the chief executive officer of Midwest Research Group and an associate clinical professor at Washington University. He has been the principal investigator for over 450 clinical trials across various therapeutic areas within psychiatry. Dr Mattingly is also the president of the American Professional Society of ADHD and Related Disorders (APSARD) and is a scientific advisory board member for the World Federation of ADHD. Additionally, Dr Mattingly serves as a speaker for multiple organizations, contributing to disseminating knowledge and advancements in treatment options.  


References
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