Treatment of chronic, neurological lyme can vary. In my clinical experience, often combination treatment with either oral cefixime, intravenous ceftriaxone, and ozone therapy is most useful.

Neurological lyme can be notoriously difficult to treat. The main symptoms can include pain, brain fog, fatigue, and other overtly neurological signs such as muscle weakness or paralysis. Assuming the diagnosis is not in question, the main treatment often offered is ceftriaxone intravenously.


In my experience, ceftriaxone intravenously can be an excellent treatment for neurological lyme when used as part of a comprehensive program, but it is difficult for patients to get, and has increased risk compared to oral antibiotic treatment for neurological lyme. Furthermore, when the diagnosis of chronic lyme does not fit the conventional, more rigid and restrictive guidelines of the Infectious Disease Society of America, it can be even more difficult for patients to get adequate treatment. There is published data going both ways in which ceftriaxone may be helpful, but also data as below showing that as a single treatment modality, it is not enough. It has significant risk.


One interesting study by Fallon et al in Neurology 2008 volume 70 compared 10 weeks of intravenous ceftriaxone to 10 weeks of placebo. At 12 weeks there was improvement in symptoms, with good effect size. This was significantly different from placebo.


At 24 weeks the placebo group ended up improving as well, so by week 24 there was no difference. However, improvements in pain and fatigue at week 12 did persist to week 24, was statistically different from placebo, and had a medium effect size.


This study showed that the better effects from treatment were shown for those who were more ill with neurological lyme to start with.


Of note: treatment was only given for 10 weeks. Thus, by 24 weeks with the neurological symptoms (aside from pain) being no different from no treatment, most doctors who treat by less restrictive guidelines feel that 10 weeks was too short a treatment, especially given that there was significant improvement just after the 10 week course.


The improvement at week 12 was significant, and was a large effect, but wore off when treatment was stopped after a further 3 months. Simply put, there was not enough treatment for these neurological lyme patients. Some interpret this to be not enough duration of antibiotic, others interpret that the antibiotics had no effect, while others (including myself) think that it may work for some patients but in general a more comprehensive program is needed. As is always the case, a patient-centered approach would be discussing risk and possible benefit. Patients take on the risk on starting the medications always, but only sometimes does the benefit come.


A study in Eur J Clin Microbiol Infect Dis (1998) 17 :715–719 showed that oral cefixime with probenecid (to increase blood levels) was as effective as intravenous ceftriaxone. One group of 30 patients took the oral medicines, the other group of 30 took intravenous ceftriaxone, and were followed up for one year.


12 out of 30, in each group, were totally symptom-free at 1 year. 14 in the oral group, and 16 in the IV ceftriaxone group, had barely noticeable symptoms at the end of follow up. 3 in the oral group, and 1 in the ceftriaxone group, had no response. No differences between the groups were found to be statistically significant. They had the same outcome.


Adverse effects were similar in both groups, with none requiring stopping of treatment. There were Herxheimer or die-off reactions in both groups. 2 out of 30 patients in each group had C difficile diarrhea from the antibiotics.


While the standard first treatment is typically doxycycline, this study is very promising for my neurological lyme patients. There have been studies that have looked at doxycycline being equivalent to intravenous ceftriaxone, but these have all been in newly diagnosed patients. This particular study that looked at oral cefixime vs IV ceftriaxone was in chronic patients. I am not aware of any head to head studies of cefixime vs doxycycline in any neurological lyme patient group, recently diagnosed or acute.