BACKGROUND
Psychological distress is common and consequential for patients undergoing hematopoietic stem cell transplantation (HSCT). Due to the negative impact of psychiatric disorders on overall survival,(1) psychiatric disturbance (depression or anxiety) are included in the Hematopoietic Cell Transplantation Comorbidity-Index scoring system.(2) However, routine HSCT care commonly lacks systems for adequate recognition and management of these disorders.(3) Many patients lack timely access to mental health treatment, much less a psychiatrist familiar with the complexity of HSCT. Access barriers, paired with under-recognition psychiatric disorders underscore the need for innovative models of care.
Developed by Katon, et al., collaborative care is a team-based approach to the treatment of mental illness in primary care or specialty medical settings. Compared to usual care, this model increases treatment adherence, reduces psychiatric symptom burden, and improves quality of life in patients with medical illness.(4, 5) Despite demonstrated benefits of this approach, collaborative care interventions have not been previously tested in HSCT. The purpose of this study was to evaluate the feasibility and acceptability of a collaborative care intervention for depression and anxiety in patients undergoing allogeneic bone marrow transplant (CC for BMT).
METHODS
This was a single arm, prospective study of 20 patients undergoing allogeneic HSCT (autologous HSCT patients were excluded for this pilot due to their shorter post-transplant follow-up in the BMT clinic). Eligible patients were English-speaking adults (age >18 years) with a scheduled pre-transplant clinic visit and without a history of bipolar or psychotic disorder. All participants provided written informed consent. The study was approved by the Institutional Review Board (16–3258) and registered with ClinicalTrials.gov (NCT04025190).
CC for BMT description:
HSCT clinicians (primarily Advanced Practice Providers) administered and scored the Hospital Anxiety and Depression Scale (HADS) pre-transplant and on transplant days 0, +14, +30 and +60. Participants with pre-transplant clinically significant anxiety or depression symptoms (≥8 on either subscale)(6) were offered care through CC for BMT. Patients with scores <8 were provided usual care and did not receive further symptom monitoring or intervention through the study.
Weekly CC for BMT meetings between HSCT clinicians and a psychiatrist to review participants’ clinical status and HADS scores. The psychiatrist provided pharmacologic recommendations to the clinicians but did not personally evaluate patients. The psychiatrist also provided recommendations for psychosocial counseling referrals.
Primary management of depression and anxiety by the HSCT clinicians through a HSCT-specific management (medication/counseling) algorithms (Supplemental Figure 1, Supplemental Figure 2) and CC for BMT meetings through transplant day +60.
A Supplemental Appendix provides additional information about the intervention.
Statistical Analysis
We used descriptive analyses to summarize feasibility, acceptability, and exploratory outcomes. We assessed feasibility by the proportion of approached patients who enrolled in the study (recruitment rate, rate of consent to treat) and proportion of recruited patients with HADS scores ≥8. We estimated it would take six months to enroll and screen patients at a rate of 2 patients/week. We hypothesized the following feasibility outcomes: 60% of approached patients would consent to the study; of these patients, 20% would report a HADS subscale score ≥8 (screening); and among these patients, 60% would consent to participation in the intervention.
We assessed acceptability by investigator-designed satisfaction surveys (patients, providers). Exploratory outcomes were the frequency of mental health interventions, participant transplant-related outcomes, and post-enrollment HADS scores. This study was not powered to evaluate changes in clinical or HADS outcomes.
RESULTS
Demographic data are presented in Table 1.
Table 1.
Participant Demographics for patients who did and did not receive the Collaborative Care for Bone Marrow Transplant (CC for BMT) intervention
| Characteristic | Did not receive intervention† | Received intervention‡ |
|---|---|---|
| 11 (%) | 9 (%) | |
| Age in years, median | 60 | 54 |
| Male | 8 (73) | 4 (44) |
| Caucasian | 8 (73) | 9 (100) |
| Diagnosis | ||
| Acute leukemia | 6 (55) | 5 (56) |
| Chronic leukemia | 2 (18) | 1 (11) |
| Other | 3 (33) | 3 (33) |
| Hematopoietic Cell Transplantation-Comorbidity Index | ||
| 1 | 2 (18) | 1 (11) |
| 2 | 7 (64) | 3 (33) |
| ≥3 | 2 (18) | 5 (56) |
| Pre-HSCT Psychiatric Diagnosis Count | ||
| Depressive Disorder | 3 | 4 |
| Anxiety Disorder | 1 | 4 |
| Other Psychiatric Diagnosis* | 0 | 2 |
| HADS Depression | Mean (SD) | Mean (SD) |
| Baseline | 2.6 (1.7) | 4.4 (2.4) |
| Day 0 | -- | 4.3 (2.4) |
| Day 14 | -- | 4.6 (2.5) |
| Day 30 | -- | 5.1 (3.7) |
| Day 60 | -- | 3.4 (1.9) |
| HADS Anxiety | Mean (SD) | Mean (SD) |
| Baseline | 3.3 (2.3) | 10.2 (1.4) |
| Day 0 | -- | 7.1 (2.0) |
| Day 14# | -- | 4.9 (2.2) |
| Day 30 | -- | 6.6 (4.3) |
| Day 60 | -- | 6.4 (4.4) |
Not treated patients had HADS <8
Treated patients had HADS >8
Attention Deficit Hyperactivity Disorder, Adjustment Disorder
Completed by 8 participants since 1 participant experienced temporary cognitive changes at the time of Day 14 assessment.
ABBREVIATIONS: HSCT = Hematopoietic Stem Cell Transplant; HADS = Hospital Anxiety and Depression Scale
Feasibility and Acceptability
We approached 22 individuals, stopping recruitment when the primary enrollment endpoint was met (5 months). Twenty individuals consented to HADS screening; two declined participation due to lack of interest. The estimated consent rate was 91%.
Pre-transplant, nine participants reported HADS Anxiety or Depression scores ≥8 (N=9 for anxiety, N=1 for depression; 1 met criteria for both). Among these nine participants, all (100%) received CC for BMT and completed the intervention; they completed a total of 44/45 HADS surveys.
CC for BMT was highly acceptable for enrolled patients. All reported the HADS was “easy to fill out,” facilitated communication with their HSCT team, and that the intervention helped them cope with their hospitalization (Table 2). Provider satisfaction was similarly high. All identified screening and weekly meetings as helpful and compatible with standard workflow (Table 2). Written comments revealed that providers experienced increased confidence and knowledge about mental health treatment.
Table 2:
Patient and Health Care Provider Satisfaction Survey Scores
| Strongly agree | Agree | Disagree | Strongly disagree | N/A | |
|---|---|---|---|---|---|
| Patient satisfaction (N = 9) | |||||
| It was easy to fill out the study survey | 4 | 5 | 0 | 0 | |
| The survey helped me tell my provider how I was feeling throughout transplant | 2 | 7 | 0 | 0 | 0 |
| The Comprehensive Cancer Support Program counselors helped me cope with my hospitalization | 2 | 4 | 1 | 0 | 2 |
| The antidepressant and/or anti-anxiety medications helped me cope with my hospitalization | 2 | 7 | 0 | 0 | 0 |
| I recommend that other patients receive counseling or antidepressant medications during their transplant† | 3 | 5 | 0 | 1 | 0 |
| Provider Satisfaction (N = 8) | |||||
| The survey was easy to score. | 3 | 4 | 0 | 0 | 1 |
| The survey interrupted the workflow of the Pre-Admission Visit appointments. | 0 | 0 | 6 | 2 | 0 |
| I felt comfortable speaking to patients about the psychotropic medication interventions. | 4 | 2 | 0 | 0 | 2 |
| I felt comfortable speaking to patients about the intervention. | 5 | 2 | 0 | 0 | 1 |
| I felt supported by our Psychiatry colleagues when questions or concerns arose about patients. | 5 | 2 | 0 | 0 | 1 |
| The Depression treatment algorithm was helpful. | 5 | 2 | 0 | 0 | 1 |
| The Anxiety algorithm was helpful. | 4 | 3 | 0 | 0 | 1 |
| The weekly meetings with Psychiatry were helpful. | 5 | 2 | 0 | 0 | 1 |
| I feel that screening patients for anxiety or depressive symptoms prior to transplant hospitalization was helpful. | 5 | 3 | 0 | 0 | 0 |
| This study helped my patients cope better with their transplant hospitalization. | 3 | 4 | 0 | 0 | 1 |
One participant reported he would not recommend other patients to pursue psychosocial counseling or psychiatric medications during their transplant but did report that the medications helped him cope through transplant and the surveys helped him communicate with his providers about how he felt.
Exploratory outcomes
All participants in CC for BMT were prescribed at least one psychoactive medication during the study period and received a mean of 4 (Standard Deviation, 1) agents; these were used for physical and/or psychiatric symptoms and were prescribed on a scheduled, as needed, or one-time basis (Supplemental Table 1). Six participants (66%) had at least one psychiatric diagnosis listed in the electronic medical record (EMR).
The CC for BMT team held 31 weekly meetings, resulting in 32 recommendations (20 psychiatrist-initiated changes, 11 initiated by HSCT clinicians using a pre-specified algorithm). HSCT clinicians followed the intervention algorithm with high fidelity: HSCT clinicians attended all meetings, all psychiatrist-initiated changes were implemented, and there were no deviations with the intervention algorithms. Three participants were referred for psychosocial counseling and one participant to the psychiatry consult team for treatment of anxiety.
Participants reported more anxiety than depression symptoms. Median HADS-Depression score at baseline was 4 (range 1–8) and 3 (range 1–6) at post-transplant day +60. Median HADS-Anxiety scores decreased from 10 (range 8–13) pre-transplant to 6 (range 0–14) on post-transplant day +60. Mean (SD) scores are presented in Table 1.
Transplant-related outcomes were abstracted from the EMR and were similar for the 9 participants who received management via the intervention and the 11 participants who were not enrolled in the intervention (Supplemental Table 2).
DISCUSSION
This study suggests a HSCT-specific collaborative care intervention during the peri-transplant period can be feasible and acceptable. To our knowledge, this is the first study of a mental health collaborative care intervention in HSCT patients. Satisfaction with all aspects of the intervention were high among both clinicians and patients. Patients reported that routine screening facilitated communication with their clinicians, and clinicians reported increased awareness of and comfort with management of depression and anxiety disorders.
Results from this study add to the growing body of literature demonstrating the benefits of integrated care interventions in oncology. Two large collaborative care trials in the United Kingdom (SMaRT Oncology-2 and −3) demonstrated efficacy of this model for treatment of major depressive disorders among patients with cancer in the ambulatory setting.(7, 8) A recent trial for co-management of patients with cancer and co-occurring severe mental illness also shows promise.(9) The evidence base in HSCT remains nascent. Integrated care models demonstrating benefit only exist for inpatient palliative care (10), reflecting the need for care models that address the multi-phased nature of HSCT.
Clinical implications
This study underscores the feasibility of innovative approaches to provide depression and anxiety management for HSCT patients. The high satisfaction scores among HSCT clinicians underscores their interest and acceptance of this approach. Pre-transplant anxiety symptoms in our cohort was high with nearly half of participants exceeding the screening threshold at study enrollment. This high rate likely reflects the timing of survey administration, but also highlights the need to further explore how to efficiently and accurately identify HSCT patients at risk for psychiatric disorders.
Limitations and future directions
Study findings must be contextualized by its limitations. As a pilot feasibility study, it was not powered nor designed to assess changes in transplant or mental health outcomes. In addition, we defined feasibility outcomes a priori, but did not define similar cut-offs for acceptability outcomes. Given the early stage of intervention development, we did not use a control group comparator arm or care manager. By using a single assessment measure and enrollment time point, we likely did not capture the full range of psychiatric symptoms in our enrolled sample which was limited in scope and size.
Given the high acceptability of CC for BMT, future collaborative care interventions could address study limitations. Specifically, allowing for participant enrollment after the baseline assessment, additional symptom monitoring (for example, for post-traumatic stress disorder) and incorporating this study within the institutional BMT patient registry could enhance and extend the impact of this intervention. In addition, rigorous testing through randomized controlled trials are needed. Given the limited number of transplants conducted within institutions, larger trials will likely require multi-center studies. Capitalizing on existing partnerships among psycho-oncology programs or the Bone Marrow Transplant Clinical Trials Network could potentially support collaborations.
Conclusions
This study demonstrated that collaborative care for depression and anxiety can be successfully tested in an intensive peri-transplant period for HSCT patients. Given the intricacies of peri-transplant care and the multiple medications patients receive post-transplant, collaborative care interventions could be a powerful model to improve their mental health outcomes. Future studies are needed to further test this model of care in HSCT.
Supplementary Material
Key Points.
Psychiatric collaborative care interventions in patients undergoing Hematopoietic Stem Cell Transplant (HSCT) have not been previously tested.
Results of this study suggest that both patients and HSCT clinicians found the Collaborative Care for Bone Marrow Transplant (CC for BMT) intervention highly acceptable.
This study supports the feasibility of conducting a collaborative care intervention (CC for BMT) for identification and treatment of clinically significant depression and anxiety symptoms in HSCT.
We observed clinically significant pre-transplant anxiety symptoms in nearly half the sample; severe depression symptoms were uncommon.
Future randomized controlled trials can use the feasibility experiences of this pilot trial to study the efficacy of this approach.
Acknowledgments
The project was supported by the National Institutes of Health (Park, 5K07CA218167-03) and the Doris Duke Charitable Foundation (Park, 2015213).
Footnotes
Conflict of Interest
The authors have no conflict of interest to declare.
Data Availability Statement
The data that support the findings of this study are available from the corresponding author upon reasonable request.
Clinical Trials Registration: ClinicalTrials.gov NCT04025190
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