Long-term effect of cognitive behavioural therapy and doxycycline treatment for patients with Q fever fatigue syndrome: One-year follow-up of the Qure study

Background: Previously, we reported a randomized placebo-controlled trial, the Qure study, showing that cognitive behavioural therapy (CBT), and not doxycycline, was significantly more effective than placebo in reducing fatigue severity in Q fever fatigue syndrome (QFS) patients. This follow-up study evaluates the long-term effect of these treatment regimens, 1 year after completion of the original trial. Methods: All patients who completed the Qure study, CBT (n = 50), doxycycline (n = 52), and placebo (n = 52), were included in this follow-up study. Between twelve and fifteen months after end of treatment (EOT), patients filled out web-based questionnaires including the main outcome measure fatigue severity, assessed with the Checklist Individual Strength (CIS), subscale fatigue severity. Results: Fatigue severity in the CBT, but not doxycycline or placebo, group was significantly increased at follow-up compared to EOT (respective means 39.5 [95% CI, 36.2–42.9] and 31.3 [95% CI, 27.5–35.1], mean difference 8.2 [95% CI, 4.9–11.6]; P <.001). Fatigue severity scores of CBT (adjusted mean 39.8 [95% CI, 36.1–43.4]) and doxycycline (adjusted mean 41.0 [95% CI, 37.5–44.6]) groups did not significantly differ from the placebo group (adjusted mean 37.1 [95% CI, 33.6–40.7]; P =.92 and P =.38, respectively). Conclusion: The beneficial effect of CBT on fatigue severity at EOT was not maintained 1 year thereafter. Due to its initial beneficial effect and side effects of long-term doxycycline use, we still recommend CBT as treatment for QFS. We suggest further investigation on tailoring CBT more to QFS, possibly followed by booster sessions.