Antihistamines and Colchicine Show Modest, Short-Term Benefit for Long Covid Fatigue in Landmark UK Trial
Key Insights
A large UK trial found antihistamines and colchicine provided a small additional reduction in long Covid (search) fatigue at 12 weeks (1.5 points on a 40-point scale), but the benefit was not sustained at 24 weeks after stopping treatment.
The blood thinner rivaroxaban showed no benefit for long Covid (search) fatigue, and the researchers concluded results do not support anticoagulation for this condition.
All trial groups, including those receiving only specialist long Covid (search) care, experienced meaningful fatigue improvement (4.3 points), underscoring the value of integrated multidisciplinary clinic care.
Nearly 800 adults with long Covid (search) across England and Scotland participated in one of the largest randomized controlled trials to date testing repurposed medications for post-COVID-19 condition fatigue. The STIMULATE-ICP trial, published in The Lancet Infectious Diseases, found that over-the-counter antihistamines and the prescription anti-inflammatory colchicine offered a small but statistically significant reduction in fatigue at 12 weeks—though the benefit disappeared 12 weeks after participants stopped taking the drugs.
The open-label trial, funded by the National Institute for Health and Care Research (NIHR (search)) and led by UCL and University College London Hospitals (UCLH (search)), randomly assigned participants to usual specialist care or one of three drug regimens: a combination of antihistamines (famotidine–loratadine), colchicine (used to treat gout), or the blood thinner rivaroxaban.
Modest gains that fade after treatment cessation
All groups experienced a meaningful reduction in self-reported fatigue over 12 weeks, improving an average of 4.3 points on a 40-point fatigue scale. Those receiving antihistamines and colchicine saw an additional 1.5-point improvement at the 12-week mark. However, at 24 weeks—12 weeks after treatment discontinuation—this additional benefit was no longer detectable.
Rivaroxaban showed no benefit at any time point. "The blood thinner, rivaroxaban, had no benefit and so our results do not support the use of anti-coagulation medicine for long Covid (search)," said Professor Amitava Banerjee of the UCL Institute of Health Informatics, corresponding author of the study.
The value of specialist long Covid (search) care
A striking finding was the consistent improvement across all trial arms, including those receiving only usual care through specialist long Covid (search) clinics. "It is heartening that people had a significant reduction in fatigue across all arms of the trial. This is more than you would expect based on time alone, given that participants had severe fatigue at recruitment and been ill for more than a year on average," said Dr. Melissa Heightman, clinical lead for the post-Covid service at UCLH (search) and co-chief investigator.
Professor Banerjee added: "This level of improvement shows the importance of specialist long Covid (search) care. These services in England offer integrated care from a range of specialties with community-based rehabilitation to develop a plan for a person based on their symptoms and all of the ways the condition affects them."
Biological insights and future directions
The trial's design was informed by patient experiences and emerging biological hypotheses about long Covid (search). "Because long Covid is such a new and complex condition, when it came to designing the trial, we started by listening to what patients were telling us about their symptoms and experiences, then looking for biological signals that might explain them and treatments that might help," said Professor Emma Wall, Clinical Research Group Leader at the Crick and Professor of Infectious Diseases at Queen Mary University of London.
Professor Banerjee noted that both antihistamines and colchicine affect the immune system: "It may be that they address the immune dysregulation that long Covid (search) has been linked to, but further research is needed to understand the possible mechanism."
Professor Wall emphasized the broader significance: "The value of these results is not only that they suggest a potential treatment approach, but that they help us understand the biology of long Covid (search) itself. Every signal we see in the trial helps us refine our understanding of the immune and inflammatory mechanisms that may be driving the disease, to develop new, better targeted treatments for future trials."
A benchmark for the field
Professor Daniel Altmann, Professor of Immunology at Imperial College London, who was not involved in the study, described STIMULATE-ICP as "a landmark study" and "a gold standard, benchmark study within the international Long Covid (search) field." He noted that long Covid is estimated to affect some 400 million people globally, with massive impact on patients' lives and economies.
"The current treatment landscape, for those few able to access care, is a rather patchy one of symptom-based approaches. The field has been rather dogged by under-powered and poorly evidenced approaches," Altmann said. He acknowledged the modest findings reflect "what an exceptionally challenging condition this is," adding that disease-mechanism studies remain a work in progress.
Professor Danny McAuley, Scientific Director for NIHR (search) Programmes, underscored the practical implications: "Finding even modest benefits for these inexpensive drugs, which are safe and commonly used for other conditions, is incredibly important to improve the evidence-based treatment of this complex condition."
The trial was conducted across 12 long Covid (search) clinics ranging from Hull and the Highlands to Leicester and London, with UCLH (search) recruiting approximately half of all patients. The University of Lancashire Clinical Trials Unit coordinated all recruiting sites. Participants were adults with long Covid who had not been hospitalized, and fatigue was assessed using a validated questionnaire at baseline, 12 weeks, and 24 weeks.
Professor Banerjee concluded: "We have shown it is possible to conduct a large clinical trial for long Covid (search) and to test treatments as we would for any other condition."