Background/Purpose: Elevated levels of serum urate (sUA) are central to the pathogenesis of gout and have been associated with cardiovascular disease. Urate-lowering therapies are effective at treating gout and are being explored as novel approaches for cardiovascular disease.  However, less is known about factors that influence the effectiveness of urate-lowering therapies. Depression has shown strong relationships with treatment noncompliance, which may translate into reduced effectiveness of urate-lowering therapies. This study tested the role of depressive symptoms in the effectiveness of allopurinol for lowering sUA and treatment compliance in the context of a clinical trial.

Methods: Within a larger within-subject cross-over clinical trial of allopurinol vs. placebo, 67 patients had complete data for depressive symptoms at the beginning of each treatment period, as well as sUA before and after a 4-week treatment period with allopurinol and a 4-week placebo period (order of allocation was randomized). The 67 patients had average age 27.01 years (SD=6.5, range 18-40), 39% were African-Americans and 64% were males. Depressive symptoms were assessed with the Center for Epidemiologic Studies Depression Scale (CESD) 10 tool. Treatment compliance was assessed by oxypurinol levels being present at the end of the allopurinol allocation study period. Paired samples t-test evaluated change in sUA from pre- to post-treatment during active treatment and placebo. Then, linear regressions predicted change in sUA over each treatment period from pre-treatment depressive symptoms, adjusting for sex and race which were associated with baseline sUA levels. Logistic regression predicted treatment compliance during the medication period based on the same predictors.

Results: Over the 4-week active treatment period with allopurinol, sUA levels decreased from average 5.8 mg/dL (SD=1.2) to 4.4 mg/dL (SD=1.2), p< 0.001. However, sUA did not change during the 4-week placebo period (both 5.8 mg/dL, SD=1.1 and 1.3, p=0.707). Pre-treatment depressive symptoms ranged from “no symptoms” (0) to “severe symptoms” (16 or 20), with mean in the “no to mild” range (M=4.6, SD=4.1 before active treatment; M=6.1, SD=4.8 before placebo). After adjusting for pre-treatment sUA, sex and race, pre-treatment depressive scores predicted higher levels of sUA at the end of the active treatment period (b=.07, beta=.25, p=0.028) but not at the end of the placebo period (b=.03, beta=.11, p=0.102). After 4 weeks of allopurinol, the estimated difference in sUA between individuals with pre-treatment depressive scores of 0 vs. 16 was 1.12 mg/dL, which was similar to the average treatment effect of 1.4 mg/dL. Depressive symptoms did not predict treatment compliance (OR=0.93, p=0.39), perhaps because of reduced sample size (N=55).

Conclusion: Even in the absence of clinical diagnosis of depression, depressive symptoms are associated with reduced effectiveness of allopurinol treatment for hyperuricemia in the context of a clinical trial. We could not associate this with reduced compliance, assessed by presence of measurable oxypurinol. Our findings could have implications in gout and hyperuricemia research and clinical practice.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/depressive-symptoms-influence-success-of-allopurinol-in-reducing-serum-urate/