Table 1: Overview of Studies

Authors; Year of Publication

& Level of Evidence (LOE)

Study Design





Levenson et al., [9]





Prospective cohort of PiSCES Project; Longitudinal study. Data collected from daily diary entries up to 6 months regarding sickle cell pain intensity, distress, interference, whether in SCD crisis or not, healthcare and opioid utilization. Variables include demographics, sickle cell genotype, lab data, HR-QOL, depression and anxiety

n = 232 SCD, aged 18 years or older. Enrolled in community settings and medical centers in Virginia.

To examine prevalence of depression & anxiety, determine relationship with pain (crisis and non-crisis), distress from pain, life interference, QOL, opioid usage and healthcare utilization.

Health Related QOL assessed via Medical Outcome Study 36 items short form (MOS SF-36) survey. Use of PHQ (Patient Health Questionnaire) for measurement of depression and anxiety. Combined major depressive syndrome and other depressive syndrome into one category of depression.

n = 64 (27.6%) were depressed. Significant association between depression and more days of pain (p < 0.001). Depression associated with higher mean pain, distress from pain and interfered with life on days when no crisis present. 

Hasan, S.P., Hashmi, S., Alahassen, M., Lawson, W. and Castro, O. 


LOE 4 [5]

Quantitative study using questionnaires.Collected data including demographics (age, gender, marital status, education level, employment and income), type of SCD, type of SCD, disease severity, pain and health car usage.



Convenience Sample of N = 50; 27 females, 23 males; Age range 21 years to 64 years; mean age 36. Outpatient SC clinic at Howard University Hospital. In stable health for at least a month prior.

Assess prevalence of depressive symptoms; determine if any contribution of demographics, severity of SCD, health care use to depressive symptoms

Beck Depression Inventory (BDI); using a cut-off score of 14-17 as mild and > 20 severe.

It is a 21 item self-report scale to measure presence and degree of depression and associated depressive symptoms. Commonly used in primary care for variety of chronic illnesses.


High prevalence (> 44%) of depression in the mild to severe range. Severe depression in n = 13. Depression caused more frequent ED visits and hospitalizations due to crisis.  

Low-income (< $10,000/yr) p = 0.001; educational attainment (less than high school) p = 0.04; female, p = 0.03; multiple blood transfusions (> 20 units) p = 0.03; uncontrolled pain (> 5 crisis in 12 months) p = 0.001; poor social support, p = 0.02; Hydroxurea prescribed, p = 0.03; history of frequent hospitalizations (> 5 in 12 months) p=0.0003 and ED visits (> 5 in 12 months, p =0.03 was statistically significant in predicting depressive symptoms.

Asnai, M., Fraser, R., Lewis, N. and Reid, M.

LOE 4 [11]

Cohort Study; The Jamaica Sickle Cell Cohort Study. Administered questionnaires on socio-demographics (age, sex, marital status, genotype, employment status, and educational attainment), disease severity, depression and loneliness.

N = 277 SCD, mean age 31 years and N = 65 AA without SCD mean age 33.6 years; equal males & females in each subgroup. Participants had SC-SS, SC disease, beta thalassemia

To determine prevalence of depression and factors associated with depression and loneliness in SCD compared to matched AA controls.

SCD group: Demographic questionnaire including questions regarding utilization the SC clinic, frequency of pain crisis, presence of leg ulcers or not.  Depression measured using BDI-II using a cut-off score of 17.  Loneliness measured using UCLA-8 scale. Abbreviated version of UCLA-20; UCLA 8 highly correlated (r=0.91) with original. BDI reported:α=0.95; UCLA reported :α=0.82

AA group: only socio-demographic questions.  BDI-II for depression, and UCLA-8 for loneliness.

Two fold increase in depression in SCD group compared to AA group; 21.6% vs. 9.4%. SCD group increased mean loneliness scores compared to AA group (16.9 ± 5.1vs. 14.95 ± 4.69).  SCD group: depression significantly correlated with unemployment (p = 0.01); complication of leg ulcer (p = 0.001), frequent healthcare visits (p = 0.019); uncontrolled pain/multiple crisis (p = 0.035).  Loneliness in SCD correlated with unemployment (p = 0.004) and higher educational attainment (p < 0.001) with adjustment of SCD genotype. Whether SCD was present or not, depression was associated with unemployment (p < 0.001) and loneliness was associated with unemployment and lower educational attainment (p = 0.002)

Sogutlu, A., Levenson, J., McClish, D., Rosef, S. and Smith, W.

LOE  4 [10]

Prospective cohort of PiSCES Project. Collected baseline demographic data, genotype. Participants used diaries to document daily entries on SCD pain, health care utilization secondary to SCD for up to a 6 months.  Used questionnaires to measure SSB and HR-QOL.

Enrolled 308 in PiSCES Project; N = 230 SCD, aged at least 18 years. Mean age 34.4 years. Answered SSB questionnaire. All were from Virginia.

To examine somatic symptom burden (SSB) in SCD and its impact on pain, depression, anxiety, healthcare utilization and QOL.

Baseline data collected: age, gender, income, education, marital status, genotype, if receiving care at SCD center.

SSB measured:PHQ-15 abridged to PHQscd (to exclude four common areas of pain in SCD: limb, back, stomach and chest; α = 0.75). Total scores on PHQ-15 range from 0-30; 15 cut-off of high SSB. Study cutoff is score of 11 excluding for 4 common areas of pain.

HRQOL measured by: MOS SF-36.

More women had high SSB then men (24.6% vs. 9.1%, p = 0.0033). High SSB noted in n = 42(18.3%) of participants. Prevalence of depression noted n = 64(27.8%); of those n = 24(37.5%) had high SSB. High SSB burden was associated with increased percentage of days with complaints of pain (chronic/non crisis pain). There is no difference between low SSB and high SSB group regarding crisis pain.  High SSB group had higher hospitalizations, healthcare utilization related to pain than low SSB (p < 0.05).

Jenerette, C., Funk, M., Murdaugh, C.

LOE 4 [12]

Part of a larger cross-sectional descriptive study.  Completed questionnaire packet including demographic data.  Provided a list of potential complications experience d/t SCD.

Convenience sample of N = 232 AA aged 18 years or older living with SCD. Avg. age 35 yrs. More female than males.


To evaluate depressive symptoms in SCD

Demographic/Vulnerability/Knowledge Instrument

Depression measured using Beck Depression Inventory Fast Screen (BDI-FS). 7 item self-report scale. Shorter version of BDI-II. Completed by n = 221 (95%) of the sample. α was 0.84

Most common symptom reported was lack of pleasure and enjoyment. Least common experienced was suicidal ideation. Reported depression was n = 61(26.3%) compared to n = 70 (32%) scored in depression range on BDI-FS. Found a higher rate of depression in SCD than general population; 9.5%. Significant correlation (p = 0.02) between depressive symptoms on BDI and frequency of pain crises.


 et al.


LOE 4 [17]

Cross-sectional survey part of a longitudinal evaluation.

N = 67 AA aged 18-70yrs with SCD. Mean age 36.82 ± 11.47.
Males = 30, Females = 37. Recruited from Duke Comprehensive SC Center

Exploration of self- reported depression, suicidal ideation and/or attempts.

Longitudinal Exploration of Medical and Psychosocial Factors in SCD (LEMPFSCD). 700 questions to measure pain, demographics, and 8 validated instruments measuring psychiatric, behavioral and social function.

Depression measured using BDI.

A significance (p < 0.0007) was noted for reporting suicidal ideation in n = 19 (29%) of participants.

n = 14 (22%) scored in mild or greater range on BDI (score > 14).

Self- reporting of depressive symptoms in past 30 days was n=24 (36%). n = 5 (8%) reported previous suicide attempt. Significant association found depression and suicidal ideation (p = 0.02) and previous suicide attempts (p = 0.001).

Smith et al.


LOE 4 [20]

Prospective cohort study; part of longitudinal study: PiSCES Project.

N = 232 AA living with SCD. Aged 18 years or older. More females than males.

Examine the prevalence and relationship among  self-reported pain in SCD

Daily pain diaries completed for up to 6 months; minimum of 30 days consisting of 31, 017 diary patient days.

n = 125 (54%) self-reported pain on more than half of the days.

Chronic pain/daily pain was reported in n = 67 (29%) of participants consisting of > 95% of diary days. In remaining 5% of diary days only n = 32 (14.2%) reported pain. Significance noted as percentage of days with pain increased so did mean pain intensity regardless if crisis, non-crisis or total pain (p<0.001). Substantially lower of days of healthcare utilization (3.5%) vs. 12.7% for crisis pain.

Wellington et al.

LOE 4 [21]

Cross-sectional survey of 1st of 5 years of data from a longitudinal study

N = 156 adults aged 18-75 years.

Examine the relationship among somatization, psychopathology and pain in SCD

Longitudinal Exploration of Medical and Psychosocial Factors in SCD (LEMPFSCD). 700 questions to measure pain, demographics, and 8 validated instruments measuring psychiatric, behavioral and social function.

Somatization significantly predicted pain intensity, severity and range of average of pain over time (p < 0.0001)

Somatization significant predictor of pain (p < 0.001)

Imhode, H., Ndom, R. and Ehon, A.


LOE 4 [22]

Descriptive study using questionnaires covering 5 sections: QOL, Depression, Social support, Demographics, Self Esteem

N = 52 participants from SC center in Benin City. More male than female (29 vs 23);

Examine how social support, self-esteem, gender and depression would impact QOL among SCD.


Demographics: age, level of education, gender and religious affiliation

QOL: adapted from FACT-G scale; higher scores = better QOL. SCD population reported cronbach’s α = 0.73

Depression: BDI- cut off score of 19 indicates moderate depression. Reported coefficient α = 0.68

Social Support: Social Support Scale- coefficient α reported for study = 0.87

Self-Esteem: Self Esteem scale; higher scores above mean = higher self-esteem. Reported coefficient α = 0.66

QOL significantly (p < 0.001) mutually impacted by self-esteem, depression and social support. Independently, social support significantly (p < 0.05) impact QOL. Depression significantly (p < 0.05) inversely impacted QOL

Dampier et al.


LOE 3 [23]

Clinical Trial: C-Data Project- a clinical database to record 62 SCD related complications.

19 were used in the study.

Non random sample of N = 1046 aged 18-72 years; average age 31.4 years. 545 women, 501 men. 90% Black, non-Hispanic ethnicity. Any genotype of SCD included. Enrolled from nine (9) Comprehensive Sickle Cell Centers

Examine relationship between multiple disease related complications of SCD and reported health related QOL (HR-QOL)

collected health history (Med History I), administered interviews assessing psychosocial and health behavior (Medical History II)

HR-QOL: measured by SF-36 version 2 questionnaire. Assess 8 aspects of health: physical functioning, physical role functioning, emotional role functioning, social functioning, pain, mental health, general health and vitality.

Median 4 SCD related complications experienced by participants.

As age increased; number of complications markedly increased (p < 0.001).

Self rating of health status as poor in n = 224 (22%) participants. Increasing age (p < 0.01), opioid usage (p < 0.01), history of crisis/vaso-occlusive pain (p < 0.01) and asthma (p < 0.05) associated with reports of poor health status.

All scores on SF-36 lower than mean (50) of general population: general health most decreased.

Chronic antidepressant usage: significantly (p < 0.05) scores on bodily pain, vitality, social functioning, emotional role, and mental health. Chronic opioid usage decreased all scale scores (p < 0.01). Mental health scores only decreased by antidepressant or opioid usage (p < 0.01)

Mann-Jiles, V. and Morris, D.

LOE 4 [24]

Descriptive study; cross-sectional survey

Convenience sample of N = 62 age 18 years or older. Outpatient hematologic and oncology clinic in urban Midwestern university medical center.

To examine QOL in SCD patients.

Demographic questionnaire

QOL scale (QOLS): used 7 point Likert-type scale. Higher scores equate to higher QOL; scores can range from 62-112.


Score ranged from 52-112; Mean QOL scores lower (83.6) compared to general population (90). 

Spirituality only significant (p <0.05) variable, all others non-significant.


No demographic variables, SCD type or personal characteristics had impact on QOL.

Gibson et al.

LOE 4 [25]

Descriptive study; cross-sectional survey

N = 143 Jamaican adults age 18 or older diagnosed w/SCD. Mean age: 36.4 ± 12.2 years; 48% male. Outpatient SC Unit at University of West Indies.

Explored relationship of locus of control (LOC), depression and QOL in SCD.

LOC: measured using Multidimensional Health Locus of Control (MHLC). External and Internal LOC.  Using Likert-type scale.

-external: “doctors”, “other people” and “chance”

- internal: “internal”

Depression: BDI-II

QOL: SF-36

No significant association between external LOC and QOL. Internal LOC significantly associated (p < 0.05) with higher QOL and decrease depressive symptoms.

Depression present in n = 18(13%) of participants External LOC “chance” significant (p < 0.01) higher scores compared to RA, chronic pain and DM


Levels of Evidence based upon Melnyk Pyramid