Complications from sickle cell disease (SCD) can affect education and life opportunities, and these complications have been associated with social determinants of health such as socioeconomic status, depression, health literacy, and level of education, according to Kelly M. Harris, PhD, of Washington University in St. Louis, and colleagues.
Pain is a hallmark of SCD, and “the current climate around pain management and opioid use has specific implications for individuals with [SCD], especially youth,” Dr. Harris said in an interview.
In a study published in JAMA Network Open, the researchers analyzed 2,264 participants (average age, 27.9 years; 56.2% were female) in the Sickle Cell Disease Implementation Consortium a study that includes patient assessment, treatment, and creation of a longitudinal registry.
The participants completed the Adult Sickle Cell Quality of Life Measurement Information System to provide data on the frequency and severity of pain episodes related to SCD over the past 12 months. Multivariable regression analysis was used to examine the associations of education, employment, and mental health with pain frequency and severity.
Overall, 79.8% of participants reported severe pain, and 47.8% reported more than four episodes of pain in the past year.
Notably, 20% of the participants were diagnosed with depression, and increased pain frequency was significantly associated with depression, although no significant association appeared between pain severity and depression, the researchers said.
A total of 47% of the participants reported using pain medication and 49% reported using hydroxyurea. In addition, 628 participants (28.0%) underwent regular blood transfusions.
Neither education level nor income was associated with increased pain frequency or severity. Age younger than 18 years was significantly associated with both pain frequency and severity, as was daily used of pain medication. Unemployment and female sex also were associated with increased pain frequency.
The findings were limited by several factors including the cross-sectional design that prevents conclusions of causality, and by the reliance on patient reports of depression, which likely led to underreporting, the researchers noted.
However, the results are consistent with previous studies suggesting that pain and negative feelings were associated with reduced quality of life in SCD patients, especially younger patients, and support the need to screen SCD patients for depression, especially those who report more severe and/or more frequent pain, they said.
Take a comprehensive approach to a complex condition
“When treating pain, we cannot just rely on medication,” Dr. Harris said. “It is important that providers consider the full experiences of patients and pursue holistic and comprehensive treatment approaches to reducing pain. Screening for depression should be a regular practice, particularly for patients experiencing frequent and/or severe pain.
“Racial discrimination, stigma, and bias impact pain diagnosis and treatment for individuals with SCD,” said Dr. Harris. “Increasing awareness of the associations between depression and pain frequency and severity ... may help address these barriers.”
Data highlight treatment gaps
Alexander A. Boucher, MD, a member of the division of pediatric hematology and oncology at the University of Minnesota, Minneapolis, noted the researchers included patients as young as midadolescence, with a majority being under 35 years old. “The 18- to 30-year-old range is an especially high-risk age window for increased acute health care utilization, even compared with other chronic adolescent/young adult conditions. “The demographics in the study group also reasonably approximate those for young adults with SCD in urban centers. By taking a multicenter approach across a several-state region, I believe the findings offer better generalizability, since health care access and mental health access can vary state-by-state,” and the current results show a more standard experience.
“It was a bit surprising that female [sex] maintained such an association with pain across the different components of the study,” and that the pain peak was in the 25- to 34-year-old age range, said Dr. Boucher. However, anecdotally, the late teens and early 20s “can be laden with mental health concerns due to the life transitions that accompany most people at that time. The note that hydroxyurea use was associated with more pain and depression symptoms was interesting, and serves as a reminder that what is happening to the red blood cells and in the blood vessels, such as red blood cell breakdown, sickling, and vaso-occlusion are only a part of what causes pain, and hydroxyurea is not likely to play a role in mitigating mental health aspects of pain.”
The findings that overall pain frequency and related pain medication use were associated with higher depression rates “may in part reflect a blind spot for physicians and medical teams, who often resort back to physical pain-based heuristics.” Physicians may misunderstand chronic pain and its management and look for quick fixes for pain out of uncertainty or urgency, said Dr. Boucher. “This serves to diminish the perspectives of patients as people first (not embodiments of a disease) and can lead to missed opportunities to tackle mental health challenges.”
Barriers and limitations
There are barriers to mental health screening in hematology care,” Dr. Boucher said. First, most hematologists are not experts in mental health and while they may have some from their medical training in these disorders, it can be difficult to maintain the level of health literacy needed to stay up to date on treatments. Second, depression screening may not be part of regular patient intake and the Patient Health Questionnaire–2 or PHQ-9 offer only short-term (2-week) snapshots of depression.
“Perhaps most critically, even if we do successfully screen, the access to mental health specialists is severely limited, just as it is across the medical landscape, so intervention opportunities may be suboptimal,” said Dr. Boucher. The problem is magnified if, as the current study suggests, the rates of depression in SCD are approximately three times greater than the population overall.
In the current study, “the fact that only half of those who self-reported depression symptoms actually had depression documented as a diagnosis in their medical records suggests that we are missing a lot of patients affected by mental health disturbances.”
This study is limited in measurement of the contribution of social determinants of health, he said, as they were primarily focused on employment status and income. The study does not describe other factors like support systems, housing, and transportation.
“I would like to see studies that not only identify associated drivers of pain, but also offer evidence for successful interventions,” Dr. Boucher said, and these studies should include patient-centered interventions versus disease-centered interventions.
Undertreatment persists
Other concerns with sickle cell anemia include the underuse of hydroxyurea to reduce complications associated with the disease such as pain, stroke, and even early death. Another recent study in JAMA Network Open suggested that use of hydroxyurea remained low in children and youth despite the issuing of guidelines, and that underserved populations were especially affected. In that study, the researchers found that the patients’ annual days’ supply of hydroxyurea in New York state did not change significantly after the guideline update.
SCD also has been associated with increased risk of other poor outcomes, such as stillbirth and increased risk of poor COVID-19–related outcomes and COVID-19–related deaths.
The study by Dr. Harris and colleagues was supported by the National Institutes of Health through the National Heart, Lung, and Blood Institute and the National Institute on Minority Health and Health Disparities. Dr. Harris had no financial conflicts to disclose. The hydroxyurea study was supported by the Agency for Healthcare Research and Quality and the NHLBI. The researchers had no financial conflicts to disclose. Dr. Boucher disclosed conducting research with SCL Behring, but had no relevant financial conflicts.
