Double Dapsone Protocol for Lyme disease

Lyme disease, caused by the Borrelia burgdorferi bacterium, is often treated with a combination of antibiotics. However, a subset of patients develop Chronic Lyme Disease (CLD) or Post-Treatment Lyme Disease Syndrome (PTLDS), where symptoms persist despite standard treatment. The Double Dapsone Protocol, developed by Dr. Richard Horowitz, has gained attention for its effectiveness in treating these persistent cases, but it also comes with significant risks.

What is the Double Dapsone Protocol?

The Double Dapsone Protocol (DDD) is an advanced antibiotic regimen designed to target "persister" forms of Lyme bacteria that survive standard treatments. This protocol typically combines a double dosage of dapsone, originally approved as a drug to combat leprosy, with other antibiotics (such as doxycycline and rifampin) over a period of seven to eight weeks. The protocol has shown a significant improvement in symptoms for many patients, with a reported success rate of around 98% in some studies​. 

Dapsone works by inhibiting the synthesis of dihydrofolic acid, a form of folic acid, that bacteria require to multiply. By doubling the dosage, this protocol aims to target both the resistant biofilm and intracellular forms of Borrelia that evade standard antibiotic treatments. This protocol has been reported to induce long-term remission in about 58% of patients for a year or longer, which is a promising outcome compared to other treatments. 

Dr. Horowitz's Double Dapsone Protocol builds upon earlier treatments using dapsone. Initially, the protocol involved a single dose of dapsone combined with other antibiotics; however, an accidental doubling of the dose in one patient led to a significant reduction in Lyme symptoms, prompting further investigation into this approach. The double dapsone regimen typically involves a higher dosage of dapsone (up to 200 mg) combined with antibiotics like doxycycline and rifampin, aimed at breaking down the resilient bacterial biofilms and eliminating persister cells.

This treatment is administered in “pulses” (high doses over short periods) intended to maximize bacterial eradication, while minimizing the adverse effects typically associated with long-term antibiotic use.

Dr. Horowitz has conducted in vivo clinical research about adding low dose dapsone (50 mg) treatment to antibiotic therapy for those with PTLD as an alternative for those that are not able to tolerate the double dapsone protocol for 8 weeks. Low dose dapsone is typically added to doxycycline and rifampin to target the persistent form of the lyme bacteria. This has allowed patients that are not able to complete the double dapsone treatment protocol the opportunity to benefit from the use of dapsone.   

Additional clinical research is being conducted by Dr. Horowitz to determine if a Quad Dapsone treatment is as effective or more effective than the original double dapsone treatment protocol. Currently limited information is available on this newest protocol, as the clinical research has yet to be published.

Efficacy and Research Findings

Clinical observations and early studies suggest that the Double Dapsone Protocol can lead to sustained symptom remission in a significant percentage of patients with chronic Lyme disease. One study reported that approximately 50% of patients experienced a year or longer of symptom remission after undergoing this treatment. Another study highlighted the protocol's efficacy in reducing eight major Lyme symptoms, including fatigue, pain, and cognitive issues, by utilizing the drug's ability to penetrate the central nervous system and target persistent forms of the disease.

Research indicates that dapsone works by blocking folate metabolism in bacteria, which helps eliminate the persister cells. However, this same mechanism also affects the patient’s red blood cells, potentially leading to side effects like severe anemia, which must be carefully managed during treatment.

Side Effects and Considerations

  • The Double Dapsone Protocol is not without risks. Dapsone can cause several side effects, including severe Herxheimer reactions, anemia, allergic reactions, and a condition called methemoglobinemia, where the blood's ability to release oxygen to tissues is impaired. Patients undergoing this treatment typically need to take supplements, such as folate, to counteract some of these side effects.

  • Due to the intensity and potential risks of this treatment, this protocol is generally recommended only for patients who have not responded to other treatment regimens, including both oral and intravenous antibiotics. Patients must be carefully selected, including a blood test of G6PD to ensure that the patient can properly break down Dapsone. Ongoing monitoring throughout the treatment process is recommended to ensure that the patient does not develop methemoglobinemia or anemia.

Pros of the Double Dapsone Protocol

  • The protocol has been particularly effective in patients with PTLDS, where conventional treatments have failed. The combination of dapsone with other antibiotics has been shown to improve symptoms in 98% of patients, with a substantial percentage achieving remission for an extended period​. 

  • Dapsone is effective against persister forms of Lyme bacteria, which are typically resistant to other antibiotics. This makes it a viable option for chronic cases where the bacteria have formed protective biofilms or have gone intracellular. The protocol not only addresses Lyme disease, but is also effective against co-infections like Babesia and Bartonella, which often accompany Lyme and complicate treatment. 

Cons of the Double Dapsone Protocol

  • The use of high-dose dapsone can lead to severe side effects, including hemolytic anemia, methemoglobinemia and significant gastrointestinal issues. These side effects are severe enough to require close monitoring and, in some cases​, can be life-threatening. 

  • The protocol can cause severe Herxheimer reactions, where the rapid die-off of bacteria leads to a worsening of symptoms like fever, muscle pain, and fatigue. These reactions can be debilitating and may require adjustments in dosage or supportive treatments. 

  • Due to its mechanism of action, dapsone depletes folate levels in the body, necessitating high doses of folate supplements to prevent anemia and other complications. Managing these supplements effectively is critical for patient safety. The regimen requires a high level of medical oversight and weekly blood tests to monitor for complications, making it expensive and more difficult to access for some patients. Insurance companies often do not cover such treatments, adding to the financial burden.

Frequently Asked Questions About Double Dapsone Protocol

  • The Double Dapsone Protocol is a treatment regimen developed by Dr. Richard Horowitz to target persistent forms of Lyme disease. It involves using a combination of dapsone, an antibiotic traditionally used to treat leprosy, with other antibiotics such as doxycycline and rifampin. This protocol aims to eradicate the biofilm and intracellular forms of Borrelia burgdorferi, the bacteria responsible for Lyme disease, which can resist standard treatments. The regimen is typically administered over a period of seven to eight weeks.

  • The Double Dapsone Protocol has shown a high success rate in improving symptoms of chronic Lyme disease and PTLDS, with some studies reporting symptom improvement in up to 98% of patients. Approximately 58% of these patients remained in remission for at least one year. The protocol is particularly effective against the persistent forms of the bacteria and can also address common co-infections like Babesia and Bartonella.

  • While the protocol can be effective, it carries significant risks, including severe side effects like hemolytic anemia, methemoglobinemia, and gastrointestinal issues. Herxheimer reactions, which are a worsening of symptoms due to bacterial die-off, can also occur and may be severe. Patients are advised to take folate supplements during the treatment to mitigate some of these effects. Due to these risks, the protocol requires careful medical supervision. Methylene blue can also be prescribed to decrease the likelihood of developing methemoglobinemia during double dapsone treatment.

  • The Double Dapsone Protocol is generally recommended for patients with chronic Lyme disease who have not responded to other treatments, including long-term antibiotic therapy. It may also be considered for those who have tried IV antibiotics without significant improvement. However, the treatment is not suitable for everyone, particularly those with certain health conditions or those who cannot tolerate the side effects. Patients should undergo a thorough evaluation by a Lyme-literate physician to determine if this protocol is appropriate for their case. Patients who do not have adequate levels of the enzyme G6PD to break down dapsone are not recommended to use this form of treatment.