Abstract
BACKGROUND: Patients' negative expectations about medication can exacerbate side effect burden leading to low adherence and persistence. A novel intervention involves targeting mindsets about non-severe symptoms; reframing them as encouraging signs of medication working. PURPOSE: This study aimed to assess whether a brief symptom-mindset intervention can improve symptom experience and adherence in patients starting methotrexate to treat an inflammatory rheumatic disease. METHODS: A randomized controlled trial was conducted with patients starting methotrexate. Participants were randomly assigned (1:1) to a mindset intervention or standard information control condition. Symptom mindset was assessed after 4 weeks to check intervention efficacy. The primary outcome was symptom experience after 4 weeks. Secondary outcomes were adherence and motivation to take methotrexate (4 weeks), as well as continuation and C-reactive protein (12 weeks). RESULTS: Forty-seven participants were randomly assigned to the intervention (n = 24) or control group (n = 23). All participants completed the study. After 4 weeks, compared to the control group, intervention participants endorsed more positive symptom mindsets, experienced less symptom burden (mean difference -2.70 [95% CI, -4.50, -0.90] P = .005), fewer general symptoms (3.53 [-6.99, .79] P = .045) and a similar number of methotrexate-specific symptoms (-0.79 [-2.29, 0.71] P = .295). The intervention group had better motivation and adherence to methotrexate at 4 weeks and better continuation, and C-reactive protein at 12 weeks than the control group. There was no difference in side effect attribution. CONCLUSIONS: In patients starting methotrexate, a mindset intervention reframing the role of non-severe side effects is a promising approach for improving symptom experience and early stage medication persistence.