Depression in adult patients with primary immune thrombocytopenia
Authors: Deirdra R. Terrell, Jessica Reese, Danielle Branesky, Kaelyn Lu, Shirley I. Watson, Jecko Thachil, Sara K. Vesely, James N. George
Journal: American Journal of Hematology (2016)

To the Editor: A recent study of primary immune thrombocytopenia (ITP) patients revealed an unexpected increased frequency of symptoms of fatigue 1. We suspected that depression may be increased in patients with ITP because fatigue is a common symptom of depression. Our objectives were to systematically review published reports to identify articles describing depression in patients with ITP, to estimate the prevalence of depression in ITP patients and determine the characteristics of ITP that are associated with depression. We searched MEDLINE and EMBASE to identify articles (English language only) describing depression in patients with ITP. Articles were selected that contained both an ITP term and a depression term. We evaluated two cohorts of adult patients with ITP, one from the United Kingdom (UK) and one from the United States (US). Both cohorts included patients with active ITP, as well as patients with a history of ITP but no currently active disease. The UK patients were members of the ITP Support Association. The US patients were enrolled in the Oklahoma ITP Registry. The Oklahoma ITP Registry is approved by the Institutional Review Board of the University of Oklahoma Health Sciences Center for periodic surveys. Current depression was evaluated by the PHQ-8, a standard screening instrument which asks about depressive symptoms during the previous two weeks. Current depression was defined using the clinical scoring severity score ≥10, which represents moderate, moderately severe, or severe depressive symptoms. Surveys were sent out June, 2015 and no incentives were provided. For the UK Cohort, surveys were mailed by The ITP Support Association with the June issue of The Platelet. For the US Cohort, patients who had not returned their survey were reminded up to three times. For continuous variables, a Wilcoxon/Mann-Whitney test was used to determine whether the distribution of data was different between the two cohorts; and for categorical variables, a chi-square was used. Odds ratios and 95% confidence intervals were calculated to estimate the association between depression and each of the patient variables. For variables that had small sample sizes, a Fisher's exact test was used. Indirect standardization methods were used to determine the expected proportion of individuals with depression based on age and gender specific rates from the US National Health and Nutrition Examination Survey (NHANES), 2009–2012. All analyses were done using statistical software (SAS version 9.4) and an alpha of 0.05. One hundred-six articles were identified by our search; 98 were excluded by review of titles and abstracts. The full text of eight articles was reviewed; only one article reported relevant data 2. In this article, depression was documented in 7/36 patients with rare bleeding disorders. Although 15/36 patients had ITP, the bleeding disorders of the 7 patients with documented depression was not described. Therefore whether depression occurred in the patients with ITP is not known. For the UK cohort, 110 (11%) of the 1039 ITP Support Association members who were ≥18-years-old returned completed surveys. For the US cohort, 68 (66%) of the 103 surveys were returned. Patients in the US cohort were younger, the duration of their ITP had been longer, and they were more likely to have had a splenectomy than patients in the UK cohort (Supporting Information Table SI) Patients in the UK cohort had lower platelet counts, were more likely to be currently taking corticosteroids or other medications for their ITP, and had bruising symptoms more often than patients in the US cohort. Both cohorts had similar frequencies of other diagnosed medical conditions. The frequency of current depression was not different between the cohorts (Table 1). The prevalence of depression in the UK (25%) was significantly greater than expected (3%; P < 0.001). The prevalence of depression in the US (16%) was also significantly greater than expected (2%; P < 0.001). The odds of depression were not associated with the patients' age, gender, duration of ITP, history of splenectomy, platelet count, or medications for ITP (Supporting Information Table SII). The odds of depression were significantly higher among patients who reported "bruising: sometimes, often, always" more frequently in both cohorts. In the UK cohort, the odds of depression were significantly higher among patients who reported the occurrence of bleeding symptoms on the day the survey was completed. In the US cohort, the prevalence of depression was significantly higher in patients who reported that they had other diagnosed medical conditions. Depression is the leading cause of disability among adults in high-income countries and is associated with increased mortality 3. Our survey documented that 25% of the UK ITP patients and 16% of the US ITP patients had at least moderate depression. This is the first report describing the prevalence of depression in ITP patients. The high frequency of depression emphasizes the importance of screening for depression as part of routine follow-up of ITP patients. Additionally, our survey documented that the occurrence of depression is associated with the bleeding symptoms of ITP. Limitations of our study include that patients who join the UK ITP Support Association and who are identified for enrolment in the Oklahoma Registry may be more symptomatic than other ITP patients, and the low response rate among the UK patients, suggests the potential for volunteer bias. Patients who returned their survey may have been more symptomatic and therefore more motivated to return their surveys. A strength of this study was that we used the PHQ-8, an established screening measure for depressive symptoms that has been validated in large clinical studies 4. Another strength was the inclusion of patients from different countries who were identified by different methods, increasing the probability that these data are generalizable to other ITP patients. The increased prevalence of depression in ITP patients is comparable to the increased prevalence of depression in other autoimmune disorders 5, 6. Screening for depression as part of routine follow-up care for patients with ITP is appropriate. The PHQ-8 is a freely available, self-administered questionnaire that is completed in less than five minutes. With the PHQ-8, a score of ≥10, represents levels of depression which require medical attention. Effective treatment of depression can improve the lives of ITP patients. Deirdra R. Terrell,1* Jessica Reese,1 Danielle Branesky,1 Kaelyn Lu,1Shirley I. Watson,2 Jecko Thachil,3 Sara K.Vesely,1 James N. George1 1Department of Biostatistics and Epidemiology, College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma; 2ITP Support Association, Bolnhurst, United Kingdom; 3Department of Clinical Haematology, Manchester Royal Infirmary, Manchester Haemophilia Comprehensive Care Centre, Manchester, United Kingdom Additional Supporting Information may be found in the online version of this article. Supporting Information Table 1. Supporting Information Tables. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.