Thrombotic thrombocytopenic purpura patients' attitudes toward depression management: A qualitative study

Abstract Background and aims Thrombotic thrombocytopenic purpura (TTP) is a rare disorder characterized by acute episodes of systemic microvascular thrombosis; TTP is more common in adults, women, and African‐Americans (Blacks). Our Oklahoma TTP Registry documented that survivors have an increased prevalence of depression compared with the general population; however, many patients' depression remains untreated. Moreover, studies identifying attitudes toward depression management are lacking. The objective of this study was to identify TTP patients' attitudes towards pharmacotherapy. As a secondary question, we explored attitudes towards counseling. Methods We interviewed TTP patients with major depression who had experience with different management strategies (previous/current pharmacotherapy treatment versus no pharmacotherapy treatment). Eligibility criteria included (a) age > 18 years, (b) ADAMTS13‐deficient TTP, (c) enrolled in the Oklahoma Registry, and (d) moderate/major depression on either the Beck Depression Inventory II or Patient Health Questionnaire from 2004 to 2012. Qualitative purposive sampling was used to interview patients with a range of experiences with TTP and depression symptom management. Our study was based on the theoretical framework of the Theory of Reasoned Action. Patients were asked about their views on depression (attitudes), their family and friends' views (social norms), and ways they cope with depression. Results Semi‐structured interviews were conducted between June and October 2013. Data saturation was achieved after interviewing 16 patients (nine, pharmacotherapy and seven, no pharmacotherapy). The majority (88%) were women; 56% were Black, and the median age was 49 years. Patients in both groups believed TTP was life altering and traumatic and that counseling improved depressive symptoms. However, the pharmacologic group believed medication improved one's quality of life, whereas the no pharmacotherapy group was not sure pharmacotherapy was effective and expressed fears related to potential addiction and side effects. When asked about cultural views to depression management, many Black patients stated that in the Black community, a person is taught to deal with his/her emotional issues instead of asking strangers for help. Conclusion Ensuring effective depression management is a critical part of TTP care. Understanding attitudes toward management will assist in tailoring patient discussions.

tion of both, taking into account patient's preferences. 16 Although pharmacologic treatment and counseling can be effective in reducing depressive symptoms, the mental health needs of individuals within the United States are underserved. 17,18 Patients with depression sometimes struggle to identify with a medical depression diagnosis, and attitudes toward depression treatment often differ. 16 Studies evaluating attitudes to receiving management for major depression in TTP patients are lacking. Recognizing and understanding TTP patients' attitudes towards depression management may help a larger number of patients access proven therapies to relieve depression symptoms. 19 Therefore, our primary objective for this study was to identify TTP patients' attitudes regarding pharmacologic treatment for depression.
As a secondary question, we explored themes related to TTP patients' attitudes regarding counseling as a treatment for depression. To achieve the stated objective, we interviewed TTP patients with major depression who had experience with different depression management strategies. The theoretical framework of our study was guided by the Theory of Reasoned Action, which is a value expectancy model of decision making that states that a person's behavior is determined by intention and a person's intention is determined by (a) a person's attitude toward the behavior and (b) how others close to them view the behavior (subjective norms). 20 The Theory of Reasoned Action has been successfully used as a framework in studies of depression management to identify potentially modifiable factors such as patient attitudes (related to the effectiveness of depression treatment or attitude toward a type of depression treatment) and social norms (a loved one's views toward depression treatment impacted patient adherence to treatment) on depression management. This is important because these factors (attitude or social norms) have the potential to be modified by education or experience. [21][22][23] 2 | METHODS

| Study design
A qualitative descriptive study was conducted in order to understand TTP patients' attitudes toward depression management. The methodologic design of our study was guided by the Theory of Reasoned Action, 20 because it has been successfully used as a framework in studies of depression management. [21][22][23] Although sample size cannot be predetermined in a qualitative study, according to the theory, the goal is to conduct interviews with approximately 12 to 20 individuals, 24,25 about half of whom have performed the behavior under investigation (ie, use of pharmacologic treatment) and half of whom have not performed the behavior. 25 Interviews were conducted until no new comments were heard related to our key questions of interest, which is defined as data saturation. 24,26 The first author consulted with both a TTP expert and a qualitative expert to develop two similar interview guides (one for patients with current/previous use of pharmacologic treatment for depression and one for patients who had never used pharmacologic treatment). The interview guides were guided by the Theory of Reasoned Action. 20 The interview guides were then pilot-tested with three TTP patients and revised accordingly. The pilot test interviews were included in the analysis.
Patients were asked about their views on depression, their family and friends' views, and ways they cope with depression (Table 1). Specifically, patients were asked if there were any benefits or disadvantages associated with treating depression with medication or counseling (attitudes). Participants were also asked how family or friends feel about people taking medication or going to counseling for depression (subjective norms). Subjective norms were extended to include questions on cultural views of depression because previous studies have shown Blacks and Hispanics have more negative views regarding acceptance of pharmacologic treatment for depression management compared with Whites. 23  The Patient Health Questionnaire (PHQ)-9 was administered in 2012 and is a validated, self-administered depression screening instrument that has nine questions evaluating depressive symptoms over the previous 2 weeks. 31 Major depression is diagnosed when greater than or equal to 5 symptoms are present for at least "more than half the days" and one of those symptoms has to be either depressed T A B L E 1 Semi-structured interview guide

| Oklahoma TTP-HUS Registry
• What are the first 5 to 10 things that immediately come to your mind when I say the word "depression"?
• Can you describe to me a time in your life when you felt depressed?
• Who are some of the people that you trust that you talk to about your depression?
• How do you think your depression is viewed by your family?
• How do you think your depression is viewed by your friends?
• There are a lot of ways to deal or cope with depression. What are some of the ways you personally deal or cope with your depression?
• One of the ways people treat depression is by talking with a professional. What do you think about treating depression with counseling?
• (Attitude toward counseling) What, if any, are the some of the benefits of talking with a counselor for depression?
• (Attitude toward counseling) For you, what, if any, are the negatives of talking with a counselor for depression?
• (Subjective norms toward counseling) How do your family/friends feel about people going to a professional counselor for depression?
• We have in our records that you have/have never taken medicine for depression. Is that true? Can you tell me some reasons? Have you ever started and stopped? Tell me more about that.
• (Attitude toward pharmacologic treatment) What, if any, are the benefits of treating depression with medicine?
• (Attitude toward pharmacologic treatment) Now, what, if any, are the negatives of treating depression with medicine?
• (Subjective norms toward pharmacologic treatment) How do your family/friends feel about people taking medication for depression?
• Can you describe for me certain things or circumstances where you would get some treatment for your depression?
• (Subjective norms toward depression) Can you tell me how you think people who are around the same age as you or who grew up around the same time as you think about a person who has depression?
• (Subjective norms toward depression) How do you think people who are the same race or culture as you think about a person with depression?
• (Subjective norms toward depression) In what ways do you think thoughts or opinions about mental health or depression as you were growing up influences the way you think about it?
• How do you think those views impact or affect someone with depression trying to get help?
• Is there anything else you would like to tell me about depression or treating depression?
Note. Attitude is defined as the positive or negative evaluation of performing a behavior. Subjective norms are defined as the social influences and normative pressures an individual may perceive. mood ("feeling down, depressed, or hopeless") or anhedonia ("little interest or pleasure in doing things"). Other depression is diagnosed if 2 to 4 depressive symptoms are present for at least "more than half the days" and one of those symptoms has to be either depressed mood or anhedonia. If the final question, "thoughts that you would be better off dead or of hurting yourself in some way," is present during the previous 2 weeks, then it is also counted as one of the symptoms. 31 A study coordinator scored the depression instruments immediately during the patient's annual evaluation, and results were given to the patient. All patients with moderate or major depression were given depression referral information. Additionally, we notified their hematologist and/or primary care physician with their depression results.
For this study, patients with severe depression with the BDI-II screening test are described as having major depression, to maintain consistent terminology between the BDI-II and the PHQ-9. A nonprobabilistic purposive sampling approach was utilized to select individuals from whom the most could be learned. 32 To ensure diversity and a range of experiences with TTP and depression symptom management, the goal was to include at least one male and one Black participant within both groups. A study using data from the United States National Ambulatory Medical Care Survey showed that racial disparities (Blacks and Hispanics compared with Whites) exist in both the diagnosis of depression and the utilization of pharmacologic treatment. 33 In addition, a study reported that Blacks and Hispanics are less likely to perceive a need for mental health treatment as compared with Whites even after adjusting for severity of mental illness. 34 Fifty-six patients in clinical remission from acquired TTP had been screened for depression between 2004 and 2012; 50 patients were alive in 2013 when this study was performed; 24 of these patients had a score of moderate or major depression on at least one assessment. Our goal was to interview patients until we reached data saturation, defined as redundancy in the comments. 24,26 Given that the principal investigator knew the majority of these patients from previous Registry studies, we used a simple random sample program (SAS version 9.3, SAS Institute, Cary, NC)

| Participants
to determine the order in which the eligible patients should be approached and asked about their willingness to participate in the approximately 60-to 90-minute interview. Of the patients who were randomly selected to be approached, none of them refused our invitation for an interview. However, two patients (one male in the no pharmacologic treatment group; one female in pharmacologic treatment group) originally selected by the random number program were unable to be contacted due to inaccurate contact information and were thus replaced with other patients selected by the random number program.

| Data collection
The history of TTP was obtained from medical chart review, patient demographics were obtained from self-reported data collected on the day of the interview, and self-reported information on mental health disorders was obtained from previous annual evaluations where the information was systematically collected.
Semi-structured interviews were used because they allow for flexibility in exploring participant experiences and attitudes related to depression management. 32 Interviews were conducted from June to October 2013, were 60 to 90 minutes in duration, and were digitally recorded. Rigor was enhanced by having DRT conduct all the interviews, and the majority of the patients knew her from their participation in previous Registry research studies; DRT is a doctoral level epidemiologist who has been a member of the TTP Registry research team since 2001. She has been trained in qualitative methods and has experienced conducting qualitative interviews.
The interviews were conducted in a private office at the University of Oklahoma Health Sciences Center in Oklahoma City, Oklahoma, on the same day as the patient's annual, in-person evaluation.
To enhance accuracy of the transcripts, a notetaker was present in the room for all interviews to record key responses and body language. Family members and friends, if present, were asked to leave the room prior to the start of the interview. In addition, participants were informed of the goal of the study in detail prior to the start of the interview. Interviews were conducted until we began to hear redundancy in the comments related to our key questions of interest, which is defined as data saturation. 24,26 Repeat interviews were not conducted. Transcripts were not returned to the participants for comment/correction and participants were not asked to provide feedback on the results.

| Analysis
Data were analyzed according to the framework of the Theory of Reasoned Action. We also looked at themes and key ideas outside of the framework of the Theory of Reasoned Action. Each interview was comments that were directly related to purpose of the study and the Theory of Reasoned Action. During the analysis, we identified similar patterns of beliefs across all interviews, unique insights, and the underlying meaning of the participants' comments. Once the analysis was completed individually by each of the four researchers, we met and discussed the findings. By discussing the results as a group, we attempted to remove personal bias that might influence the interpretation of the results. Discrepancies were discussed and resolved as a team, and after complete consensus, we identified broad themes and key ideas.
Themes were defined as clusters of codes representing an idea mentioned by at least half of the participants within each group (pharmacologic treatment vs no pharmacologic treatment). Key ideas were novel insights that were deemed important findings to include by the research team even though they were not mentioned by at least half of the participants. 35 We used the Consolidated Criteria for Reporting Qualitative Research (COREQ) checklist to promote a comprehensive report of the methods and findings. 36

| Compensation
All participants were compensated $40.00 for participation.

| Attitudes: Pharmacologic treatment
The majority of patients who had never tried pharmacologic treatment were unsure if a medication for depression could actually work to relieve their depressive symptoms. One patient also expressed concern about what would happen when the medication "wore off," won- Widowed (n, %) 2 (12)

Mental health (N = 16)
Self-reported history of mental health diagnosis prior to TTP (n, % yes) fears of potential side effects that would alter how they relate to their world and their families. A few patients described how they have seen family members or friends who were on antidepressants no longer act like themselves. These fears were enough to keep them from trying a medication for depression. An illustrative quote is as follows: A key idea in both groups was that a history of a negative experience with counseling made it more difficult for a person to want to try it again. These patients described personal experiences and stated sometimes they felt like they just could not connect with the counselor on a personal level and that a personal connection was essential for counseling to be effective.

| Subjective norms (family/friends' views): Pharmacologic treatment
We wanted to understand the social influences and normative pres-

| Subjective norms (family/friends' views): Counseling
A key idea in the no pharmacotherapy group was that their family or friends would support them going to counseling for depression. They stated they believed those close to them would be happy that they are getting help and getting better. However, in the pharmacotherapy group, half the patients believed their friends or family would support them going to counseling, but half of the patients kept it from their friends or family or thought they would be against the idea. The patients who did not tell their family or friends were afraid their loved ones would view them as "crazy" or view getting help as a sign of weakness.
We also extended social norms to include cultural views of depression. A theme identified in Blacks and Whites was the belief that there was a stigma associated with having a diagnosis of a mental health disorder. Some patients did not tell others they felt depressed because they were worried that people would think they were weak or treat them differently. Furthermore, some patients who had shared with others they suffered from depression said they felt like people thought they were crazy.

| Additional barriers to depression management
When asked what circumstances would need to change in order for the patient to get treatment for their depression, a key idea was the belief that their depression was not severe enough to get help.
Patients stated their depression was not "that bad yet." When asked to describe how severe their depression would need to be before they would consider counseling or pharmacotherapy, patients stated they would have to "wake up depressed" or it would have to be a daily occurrence. Patients also stated another measure of severity was if the depression felt like they could no longer handle it themselves (utilizing their own coping mechanisms such as talking with family or friends). An additional barrier expressed by a few patients was that counseling and/or pharmacotherapy was expensive regardless of insurance status.

| Impact of TTP on the patients' lives and the role of the hematologist
Important insights about surviving TTP were also identified. Specifically, a theme that arose was that surviving TTP was life altering and traumatic. Although some patients expressed that during their acute episode they feared they would die, it was actually the residual symptoms after their TTP was in remission (such as fatigue and mild cognitive impairment) that changed their lives. Many patients expressed the belief that surviving TTP had changed them both mentally and physically. Furthermore, patients described that fatigue made it difficult for them to do activities with their loved ones or hobbies they used to enjoy and, consequently, resulted in social isolation. Limitations of our study include that qualitative studies are not designed to be generalizable to the larger population. Also, the majority of the TTP patients who were not interviewed were White, and if they had been included, the themes are key ideas could have changed.
However, the qualitative nature of the study allowed us to gain an indepth understanding of patient perceptions of not only depression management but also the impact of TTP on their lives. Moreover, the intent of our study was to present the views of the TTP patients on depression management and not to validate the accuracy of the patients' beliefs and attitudes. We did not collect information on how long patients who were on pharmacotherapy had been taking the medication; therefore, patients were heterogeneous in their experiences. Our secondary research question on attitudes toward counseling was limited in that we did not systematically assess the history of counseling in our patients. As a result, some patients were likely reporting attitudes to counseling from personal experience, and others were reporting attitudes to counseling from vicarous experience of their friends and family. Another limitation is that we asked patients if they had a previous mental health diagnosis and patients could have said "no" to that question because of a social desirability bias or fear of stigma. Additionally, we did not explicitly ask about access to healthcare barriers. However, a few patients did mention that the cost of counseling sessions and/or pharmacologic treatment for depression was a potential barrier. Finally, our study was conducted in 2013, and views could have changed in the last few years.
However, this study is currently the first study to look at attitudes to depression management among TTP patients.
The American College of Physicians recommends that clinicians manage major depressive disorder with either antidepressants or counseling after taking into account patient preferences. 42 It has been shown that depression treatment acceptability is associated with treatment preference. 43 Consequently, it is imperative that hematologists or primary care physicians begin to routinely screen for depression in these patients and make appropriate referrals when the patient suffers from moderate or major depression. 8 The primary hematologist has a critical role, as they often serve the role of both a specialist and a primary care physician for these patients. Understanding management preferences will assist in tailoring discussions with the patient, and our results show that the majority of the TTP patients' attitudes towards pharmacologic management are similar to what has been found for persons with depression that have not recovered from TTP.
In conclusion, this is the first study to examine beliefs related to depression management in survivors of TTP. Our patients expressed that TTP was life altering and traumatic and that their physician plays a vital role in determining their depression management. Recognizing and ensuring effective depression management is a critical part of TTP follow-up care. TTP care following recovery may need to follow a more integrated care approach to reach the needs of these patients.

ACKNOWLEDGMENTS
The authors would like to thank the men and women who shared their personal experiences in our interviews. We would also like to thank Drs James George and Sara Vesely for access to the Oklahoma TTP Registry patients, assistance in the study, and feedback on the manuscript.

CONFLICTS OF INTEREST
The authors have no conflicts with this topic or the content of this manuscript.

TRANSPARENCY STATEMENT
Deirdra R. Terrell affirms that this manuscript is an honest, accurate, and transparent account of the study being reported; that no important aspects of the study have been omitted; and that any discrepancies from the study as planned (and, if relevant, registered) have been explained.

FUNDING INFORMATION
This project was supported by the National Heart, Lung, and Blood Institute of the National Institutes of Health under award number 1K01HL135466. Dr Terrell is supported by a career development award from the National Heart, Lung, and Blood Institute (NHLBI).
The NHLBI did not have any involvement in the study design, data collection, analysis, interpretation of the data, writing of the report, or the decision to submit the report for publication.

DATA AVAILABILITY STATEMENT
The signed consent allows the use of interview transcripts for this study but not for further sharing. As such, transcripts are not currently available for secondary use.