High use of pain, depression, and anxiety drugs in hemophilia: more than 3000 people with hemophilia in an 11-year Nordic registry study

Abstract

Background: Pain is a common feature of hemophilia, but prevalence of depression and anxiety is less studied. Registry data on prescription drugs can provide an objective measure of the magnitude of these complications.

Objectives: To identify treatment patterns of prescribed pain, antidepressant, and antianxiety medications compared with those of matched controls in 4 Nordic countries.

Methods: The MIND study (NCT03276130) analyzed longitudinal individual-level national data during 2007-2017. People with hemophilia (PwH) were identified from National Health Data Registers by diagnosis or factor replacement treatment and compared with population controls. Three subgroups were defined by the use of factor concentrates and sex (moderate-to-high factor consumption (factor VIII [FVIII] use of ≥40 IU/kg/week or FIX use of ≥10 IU/kg/week), low factor consumption, and women including carriers).

Results: Data of 3246 PwH, representing 30,184 person-years, were analyzed. PwH (including children and adults) used more pain, depression, and anxiety medications compared with controls. This was most accentuated in the moderate-to-high factor consumption group and notably also observed in men with low factor consumption and women including carriers, usually representing a milder phenotype. A higher opioid use was observed across all age groups: 4- to 6-fold higher in the moderate-to-high factor consumption group and 2- to 4-fold higher in the low factor consumption group.

Conclusion: The consistent higher use of pain, depression, and anxiety medications among PwH compared with population controls, regardless of age, sex, or factor consumption, in broad national data suggests a need for improved bleed protection and hemophilia care for all severities including mild hemophilia.

Keywords: analgesics, opioid; anxiety; case-control studies; depression; drug utilization; female; hemophilia A; hemophilia B; pain; prescription drugs.

Figure 1

Outline of study design by description of the data collection process, including identification of study population and key variables in the analysis. FIX, factor IX; FVIII, factor VIII; PwH, people with hemophilia.

Figure 2

Percentage distribution of the duration of opioids for individuals with ≥1 filled prescription of opioids during 2007-2017 in (A) Finland, (B) Norway, and (C) Sweden. Figure shows PwH vs. control for moderate-to-high factor consumption, low factor consumption, and women including carriers depending on the data availability. Brackets denote the number of person-years. P values indicate the Kruskal-Wallis difference in distribution between PwH and control groups. Percentages may not sum to 100 due to rounding. The number of women in Finland was low and thereby did not permit subgrouping. Matched controls from population registries could not be obtained in Norway due to national regulations. DDD, defined daily dose; PwH, people with hemophilia; PY, person-years.

Figure 3

Proportion of individuals with ≥1 filled prescription of opioids during 2007-2017 by age category for PwH and controls in Sweden: (A) moderate-to-high factor consumption, (B) low factor consumption, and (C) women including carriers. Age category measured as first observed age in years during study period. Five-year age categories are shown unless pooled; categories were pooled for (A) 0-10 years and 70+ years, (B) 85+ years, and (C) 85+ years. P values indicate Pearson’s chi-square difference between PwH and control for each age group. ∗P = .003. No data were available from Denmark for post-hoc analysis across age groups. PwH, people with hemophilia.