JOURNAL CLUB CONSULTATION-LIAISON TEAM Dr.AL-SABHAN TEAM PREPEARED BY Dr.AL-ENEZI

Depression and Anxiety in Adults With Sickle Cell Disease Psychosomatic Medicine 70:192–196 (2008)

Objective This study measured prevalence of depression and anxiety in SCD adults and their effects on: i.Crisis and non crisis pain. ii.Quality-of-life. iii. Opioid usage. iv.Healthcare utilization.

Methods The Study is a prospective cohort study in 308 SCD adults. Baseline Data included demographics, genotype, laboratory data, and daily pain diary data for up to 6 months were collected between July 2002 and August Two hundred thirty-two subjects met the inclusion criteria of filling at out at least 1 month of diaries.

Subjects aged 16 years and older were eligible. After informed consent was obtained, subjects were screened with the mini mental status examination to assure capacity to provide reliable data (none were excluded on this basis).

Diary Data Filled out daily for up to 6 months, the diary asked subjects to report about the previous 24 hours: 1.the worst sickle cell pain intensity (“how badly I hurt”) 2. the worst distress (“how upset I felt because of pain”) 3. the worst interference (“How much the pain kept me from work, school, housework, family/friends”)

A pain day was defined as a day with pain greater than zero. On a scale from 0 (none) to 9 (worst); whether or not they were in a sickle cell crisis, and whether they had gone for a scheduled or unscheduled physician visit, Emergency Department visit or were hospitalized.

Mean daily pain was calculated as: the sum of the pain intensity for all diary days, divided by the total number of diary days. The mean was separately calculated on days the subject reported being in a crisis, and on days when a crisis was not reported. Similar measures were calculated for distress and interference.

The percent of days with utilization was calculated, with utilization defined as: unscheduled clinic visits, ED visits or hospitalizations for SCD. This was also calculated separately for days with unscheduled clinic visits, ED visits, and days with hospitalizations. A sickle cell crisis episode was defined as consecutive days in which the patient marked “crisis” on the diary. Missing diary days immediately preceded and followed by a crisis were considered part of the same crisis. Pain episodes and utilization episodes were constructed similarly.

Baseline Data Health related quality of life was assessed at baseline using the Medical Outcome Study 36 item a well-known and accepted generic measure of health related to functional status and well being. For this study, genotype was obtained either from blood specimen at enrollment or from the patient’s medical record.

Depression and anxiety were measured using the Patient Health Questionnaire PHQ. For the purposes of this study, they combined the two depression diagnoses generated by the PHQ (major depressive syndrome, other depressive syndrome) into a single category of depression. We similarly combined the two anxiety diagnoses (panic syndrome, other anxiety syndrome) into a single category of anxiety.

Statistical Methods Chi-squared tests were used to compare categorical variables. t-tests were used for continuous variables. Wilcoxon rank sum test was used with ordinal variables to compare subjects included and excluded for analysis, and those with and without depression at baseline. Analysis of covariance was used to compare quality of life variables between depressed and non depressed subjects when controlling for covariates such as genotype, pain, and variables that differed between groups at baseline.

Mixed models were used to compare daily pain, distress, interference, and relief between depressed and non depressed subjects. For binary variables representing pain days, crisis days, opiate use and health care utilization, generalized estimating equations (GEE) methods were used. Analyses were repeated to compare subjects with and without anxiety. All analyses were performed using SAS Version 9.1 statistical software.

Results The mean age was 34 (16–64), 61.6% were women, and subjects were predominantly with low-income; 62% earn $20,000 annual income. We found that 27.6% of subjects were designated as depressed on the PHQ. Depressed subjects were a little older, to be poor than those without depression.

But did not differ on marital status, education, length of study participation, or hematologic measures. The percentage of depressed women was higher than the percentage of depressed men (31.5% versus 21.3%) but this fell short of significance (p.09).

Depressed SCD subjects did not differ on how often they were in crisis, but had pain on significantly more days than non depressed subjects. Depressed and non depressed subjects did not differ in their mean pain, their mean associated distress, or their mean life interference, considering only days when they were in an SCD crisi.

considering only non crisis days when they experienced pain depressed and non depressed subjects differed significantly. On these days, mean pain, mean distress from pain, and mean interference with their lives was higher. depressed subjects used opioids more often and received less pain relief from them, although these differences lost significance after controlling for age and income.

Depressed and non depressed subjects did not differ on measures of urgent health care utilization, i.e., unscheduled clinic visits, emergency room use, or hospitalization for SCD. The median of scheduled appointments for SCD for depressed subjects was about 50% greater than those not depressed, but this difference was no longer statistically significant after controlling for age and income (p.09).

Depressed subjects had significantly poorer functioning on all eight subscales of the SF-36 compared with non depressed subjects with mean scores 24% to 54% lower. In regression models predicting the quality of life subscales, depression accounted for more of the variance in SF-36 scores than did hemoglobin type. Further, depression remained a significant predictor in these regressions, even after controlling for demographics, hemoglobin type, and pain measures.

Results comparing subjects with anxiety disorder with those without generally followed the same pattern as depressed versus non depressed. Exceptions were that on crisis days subjects who were anxious reported more pain ( versus , p.004), more distress ( versus , p.002), and more interference, ( versus , p.05).

Anxious subjects used opioids more often at home (a significant difference with and without controlling for age and income). Anxious subjects also did not have significantly more scheduled doctor visits than subjects who were not anxious.

DISCUSSION They found a high (27.6%) prevalence of significant depression in adults with SCD. This rate is similar to that found in other chronic medical disorders like diabetes mellitus, coronary artery disease, or hepatitis C.

Depressed SCD subjects did not differ from non depressed subjects on how often they were in crisis or sought urgent medical care, but had pain on significantly more days. Further, on non crisis days when they still had pain, depressed subjects’ pain, distress, and interference from pain were more intense than that of non depressed subjects.

This is consistent with the findings in studies across a wide range of painful illnesses (e.g., rheumatoid and osteoarthritis, chronic back pain, headache, diabetic neuropathy, coronary artery disease) That depression is associated with more pain, more distress, and more impairment.

This study has identified associations between depression and pain variables in SCD, but it does not permit conclusions regarding to what extent depression in SCD causes more pain versus having more pain causes depression. Depression was a more potent predictor of physical and mental health-related quality of life than was genotype.

In this cohort study, patients with high anxiety mostly represented a subsample of anxious- depressed subjects. Therefore, not surprisingly, anxiety resulted in as much or greater an impact on pain and quality of life as did depression. Compared with those with lower anxiety, the high- anxiety subjects had more days in pain, more days in crisis, and higher pain, distress, and interference both on crisis and non crisis days.

As with depression, anxiety in our patients with SCD was associated with much poorer health-related quality of life, but no increase in urgent health care utilization.

They did not find any increase in unscheduled clinic visits, ED visits, or hospitalizations associated with baseline depression or anxiety. The one exception was that depressed subjects had 50% more scheduled outpatient visits than non depressed subjects, but this difference became non significant after controlling for age and income.

Because subjects in our sample with depression were poorer than were those without depression, we considered the potential influence of economic status on the study variables. Controlling for income reduced the significance of some of the differences in pain variables, but not in quality of life.

limitations Although the PHQ is considered reasonably valid as a diagnostic instrument in ambulatory medical subjects, it is based on self-report. Health care utilization and opioid use were also self-reported data. They considered the possibility of differential enrollment, diary completion, or dropout, but there was no evidence that those with more depression or anxiety were more likely to be excluded from the study, fail to fill out diaries, or drop out sooner.

Recommendations Recognition. Screening.

Conclusion Depression and anxiety predicted more daily pain and poorer physical and mental quality- of-life in adults with SCD, and accounted for more of the variance in all domains of quality- of-life than hemoglobin type.

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