Adults living with sickle cell disease (SCD) contend with frequent, painful, vasoocclusive episodes, often leading to hospitalizations and other acute and chronic complications over the lifespan. Such complications negatively impact the quality of life and — when combined with other psychosocial factors such as loss of income — contribute to the mental health burden in the SCD population.1 Mood disorders such as depression have long been recognized as a potential contributor to morbidity in SCD, given their close association with emergency room visits and hospitalizations.2 Furthermore, depression and anxiety are better predictors of pain-related outcomes than biological factors such as hemoglobin and genotype,3,4 underscoring the need to better understand, screen, diagnose, and manage the burden of psychiatric disorders in adults living with SCD.
In this comprehensive narrative review, Adrienne Mishkin, MD, MPH, and colleagues carefully summarize the body of evidence related to psychiatric disorders in SCD, including their impact on SCD outcomes. Several studies have reported a high prevalence of depression in patients with SCD (~24-30%), which is much higher than that in the general and Black populations. Precise estimates of prevalence remain unknown given differences in methodology among studies, the inherent overlap between symptoms of depression and SCD, and the frequent use of screening instruments without diagnostic confirmation via a structured clinical interview by a mental health professional. Despite the limitations of previous research, it is apparent that depression is associated with greater healthcare utilization, more pain, older age, and distress/interference from pain. However, there are no convincing data yet to suggest that targeted psychosocial interventions for depression will improve these outcomes.5,6
As there was insufficient evidence to draw any meaningful conclusions on the relationships between SCD and posttraumatic stress disorder, psychotic disorders, and bipolar and personality disorders, the authors reviewed the literature for studies focused on anxiety and neurocognitive impairment. Evidence concerning the prevalence of anxiety was similarly limited by a lack of validated screening tools for SCD, comorbidity with depression, and confounding distress related to SCD. Reported prevalence estimates for clinically significant anxiety ranged from 6.5-29%. Strokes, silent cerebral infarction, and aging were identified as the predominant contributors to the burden and prevalence of neurocognitive impairments in adults living with SCD. The authors advocate for improvements in neuropsychological screening, diagnosis, and treatments, surmising that such efforts may improve behavioral outcomes, reduce healthcare utilization, and prevent further neurological damage.
The most salient aspect of this review is the comprehensive examination of the literature on the interactions between psychiatric disorders, pain, and opioid use in SCD. Most adults living with SCD experience chronic pain,4,7 which does not consistently respond to opioid therapy, disease-modifying therapies such as hydroxyurea, chronic transfusions, or even curative therapies such as hematopoietic stem cell transplant (HCT). Different strategies for coping with pain (e.g., catastrophizing and negative thoughts), along with depression, likely worsen the pain burden and are associated with greater opioid use. The available literature is not robust enough to ascertain how various factors (chronic opioid use, pain burden, and mood disorders) impact one another. More likely, these factors all influence each other to some degree, requiring a flexible, multi-pronged approach to reducing the pain burden in SCD.
The authors also reviewed other factors that impact psychiatric outcomes in SCD, including substance use, sleep, fatigue, adherence to therapy, and the medical comorbidities of SCD. The available evidence suggests that these factors all impact psychiatric outcomes. Even treatments with curative intent such as allogeneic HCT may lead to depression, fatigue, pain, and anxiety after transplant, though this phenomenon has been insufficiently studied.
In Brief
Psychiatric disorders, especially depression and anxiety, are common in adults living with SCD. Chronic pain and high levels of opioid use likely contribute to and/or are impacted by comorbid psychiatric disorders. Despite the prevalence of depression, anxiety, and chronic pain, there is insufficient research to inform providers on the optimal strategies for screening, diagnosing, and managing psychiatric disorders in the context of SCD. These disorders do not reliably improve with disease-modifying therapy and HCT, strongly suggesting that concurrent interventions focused on mental health should be pursued. At minimum, mental health providers including psychiatrists and psychologists must be readily accessible to any patient with SCD and, ideally, embedded within any comprehensive SCD center. Further, more interventional studies are needed to inform providers on the optimal management of psychiatric disorders in this vulnerable population. This, in turn, will reduce morbidity and improve the quality of life for adults living with SCD.
Competing Interests
Dr. Wilson indicated no relevant conflicts of interest.
