Carmen Scheibenbogen: Off-label drugs and B-cell depletion trials for ME/CFS and Long COVID
Why five existing drugs may help some patients now, while real disease-modifying trials take shape
Prof. Dr. Carmen Scheibenbogen
Episode aired Sep 22, 2025·Page synthesised Jun 8, 2026·Last reviewed Jun 8, 2026
What this episode covers
- A German medical commission has proposed five existing drugs for off-label use in ME/CFS and Long COVID, including Low-Dose Naltrexone and Metformin.
- If German health insurance approves, doctors could prescribe these drugs without the legal and financial risk that current off-label use carries.
- Research at the Charité is also testing whether removing autoantibody-producing immune cells could lead to lasting recovery for a subset of patients.
Why it matters
If autoantibodies drive a meaningful subset of ME/CFS and Long COVID cases, then treatments may emerge that act on the underlying immune disturbance, not just on fatigue, pain, sleep, autonomic problems, and brain fog one symptom at a time. The current trial roadmap may shape what real disease-modifying care for these illnesses looks like over the next 5 years.
What stands out
- Metformin started within 3 days of a COVID infection may cut Long COVID risk by about two-thirds, far more than any post-onset treatment has shown (Bramante 2023 controlled trial + 2024 follow-up)
- Naltrexone at 1.5 to 4.5 mg works through different mechanisms than at the standard 50 mg dose, with the low dose reducing inflammation rather than blocking opioids (multiple small trials + mechanistic studies)
- For a subset of ME/CFS patients, the disease appears immune-driven and may respond to treatments developed for autoantibody-mediated conditions (Charité immunoadsorption study)
Best-supported action
The single highest-leverage move from this episode, anchored in the strongest evidence the speaker presents.
Consider asking a physician familiar with ME/CFS or Long COVID whether a Low-Dose Naltrexone trial at 1.5 to 4.5 mg for 8 to 12 weeks may apply to your case.
Other supported actions
Further actions discussed in this episode, ordered from strongest to weakest evidence. This is one expert's view, the full topic compares and ranks across experts.
- Consider asking a specialist familiar with ME/CFS or Long COVID about a Low-Dose Naltrexone trial, especially if pain, fatigue, or inflammatory symptoms dominate.Moderate evidence
- If a household member has just been diagnosed with COVID, consider discussing early metformin (started within 3 to 7 days) with a physician, particularly for people with risk factors for Long COVID.Strong evidence
- For severe persistent ME/CFS with elevated autoantibody markers, consider seeking evaluation at a specialist center that can assess eligibility for trial-based B-cell or plasma-cell depletion therapy.Limited evidence
Full context, impact ratings, and timing — available in related topics
Questions to take to your doctor
- Given my Long COVID symptoms, is a Low-Dose Naltrexone trial appropriate for my case, and how would we measure whether it is working?
- Given my recent COVID exposure and my history of inflammatory conditions, is early metformin a reasonable option for me?
- Given my severe ME/CFS and limited response to standard care, would referral to a specialist center for autoantibody evaluation change my treatment options?
Full doctor prep with ranked questions available in the full topic page
Context
Academic clinician-researcher focused on ME/CFS, Long COVID, and the immune mechanisms behind both. Tends to view a meaningful subset of these illnesses as autoantibody-driven, while acknowledging clinical heterogeneity means no single mechanism explains all patients.
This does not prove that any of the five off-label drugs will cure ME/CFS or Long COVID; they aim at symptom relief while research advances.
This does not prove that all patients should try the same treatments; the field increasingly recognizes distinct subtypes.
This does not prove that B-cell depletion will succeed in trials; results are still pending for most arms.
This does not mean you should change or stop any current medical treatment on your own.
Where people go wrong
- Self-discontinuing approved medications in favor of unproven off-label experiments.May cause symptom rebound or worsening, and may forfeit the controlled, supervised setting in which dose adjustments and side-effect monitoring can happen safely.
- Assuming all ME/CFS or Long COVID patients have the same mechanism and will respond to the same treatment.May waste months on therapies unlikely to apply to your specific subtype. Clinical heterogeneity is now established; what works for autoantibody-driven cases may not help mitochondrial or microclot-driven cases, and vice versa.
What to expect over time
- Weeks 1 to 2Find a physician familiar with ME/CFS and Long COVID. Compile symptom history, prior trials, and any test results. Discuss whether any of the five off-label drugs (LDN, Metformin, Agomelatine, Vortioxetine, Ivabradine) may apply to your case.
- Months 1 to 3If LDN is appropriate, expect a gradual dose increase (typically starting at 0.5 to 1 mg and titrating up). Pacing remains essential during this period; new therapies may help but cannot replace careful activity management.
- Months 3 to 12Reassess response with the prescribing physician. Some patients see partial improvement; some do not. For severe cases with autoantibody markers, this may be the window to investigate trial-based therapies if available locally.