Is there evidence to support the use of antimalarials (e.g. hydroxychloroquine, mefloquine) for treating chronic Lyme disease?

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No Evidence Supporting Antimalarials for Chronic Lyme Disease

There is no evidence to support the use of antimalarials such as hydroxychloroquine or mefloquine for treating chronic Lyme disease, and additional antibiotic therapy is not recommended for patients with persistent symptoms following standard treatment for Lyme disease. 1

Understanding Chronic Lyme Disease and Post-Treatment Symptoms

  • The term "chronic Lyme disease" is used inconsistently and may refer to different patient groups, including those with untreated late-stage infection, those with persistent symptoms after treatment (post-treatment Lyme disease syndrome), or those with unexplained symptoms that may or may not have positive Lyme disease serology 2

  • The 2020 guidelines from the Infectious Diseases Society of America (IDSA), American Academy of Neurology (AAN), and American College of Rheumatology (ACR) strongly recommend against additional antibiotic therapy for patients with persistent or recurring nonspecific symptoms following recommended treatment for Lyme disease 1

  • Studies have shown that most patients diagnosed with "chronic Lyme disease" either have no objective evidence of previous or current infection with Borrelia burgdorferi or have what should be classified as post-Lyme disease syndrome 3

Evidence Against Extended Antibiotic Treatment

  • Four randomized placebo-controlled studies have shown that extended antibiotic therapy offers no sustained benefit to patients with post-Lyme disease syndrome 3

  • A 2016 randomized, double-blind, placebo-controlled trial found that longer-term antibiotic treatment (including clarithromycin plus hydroxychloroquine) did not provide additional beneficial effects on health-related quality of life compared to shorter-term treatment 4

  • Extended antibiotic therapy (≥6 months) can cause significant harm and has resulted in at least one death 5

Recommended Treatment Approaches for Lyme Disease

  • For early Lyme disease, the recommended treatment is 3-4 weeks of oral antibiotics such as doxycycline, amoxicillin, or cefuroxime axetil 6

  • For Lyme arthritis, oral antibiotic therapy for 28 days is recommended 1

  • For Lyme carditis, 14-21 days of total antibiotic therapy is suggested, with oral options including doxycycline, amoxicillin, cefuroxime axetil, and azithromycin 1

  • For neurological manifestations of Lyme disease, IV ceftriaxone, cefotaxime, penicillin G, or oral doxycycline is recommended for 14-21 days 1

Important Clinical Considerations

  • Evidence of persistent infection or treatment failure would include objective signs of disease activity, such as arthritis, meningitis, or neuropathy, not just subjective symptoms 1

  • There is no clear evidence that post-Lyme disease syndrome is caused by persistent infection with Borrelia burgdorferi 3

  • For borrelial lymphocytoma (a manifestation of Lyme disease), oral antibiotic therapy for 14 days with doxycycline, amoxicillin, or cefuroxime axetil is recommended, but this does not include antimalarials 7

  • The pathogenesis of persistent symptoms after Lyme disease treatment is unclear, but evidence suggests these patients do not have ongoing Borrelia burgdorferi infection and thus do not benefit from additional antibiotic therapy 2

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Chronic Lyme disease: a review.

Infectious disease clinics of North America, 2008

Research

Perspectives on "chronic Lyme disease".

The American journal of medicine, 2008

Guideline

Treatment of Lymphadenitis

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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