New Guidance on the Use of Unproven Neurologic Therapeutics

Medscape

4 hours ago

A new position statement outlining guiding principles for navigating the use of unproven therapies for neurologic conditions that lack approval from the FDA or robust scientific evidence has been released by the American Academy of Neurology (AAN).
The statement is intended to support informed conversations between clinicians, patients, and policymakers about emerging or unproven treatments. While it includes examples of such therapies, the document stops short of offering clinical recommendations.
The use of emerging neurologic therapies not yet supported by science has been 'an ongoing concern,' with patients often asking providers about these therapies, the statement's lead author Larry B. Goldstein, MD, professor and chair of the Department of Neurology and associate dean for Clinical Research, University of Kentucky, Lexington, Kentucky, told Medscape Medical News.
Developed in response to requests from AAN members seeking guidance on emerging therapeutics, the statement outlines guiding principles to support clinical and policy discussions.
It was published online on June 25 in Neurology.
Lack of FDA-Approved Options
Many neurologic diseases have no available FDA-approved therapeutic options and no, or limited, evidence-based treatments. However, many potential treatments, both synthetic and naturally occurring, may be in varying stages of expert evaluation for neurologic conditions.
Psychedelics have emerged as potential therapies for pain disorders such as cluster headache, as well as psychiatric conditions including major depression, posttraumatic stress disorder (PTSD), generalized anxiety, and substance use disorders. However, data on psychedelics' risks and benefits for these indications are limited.
The AAN committee cites the example of midomafetamine combined with psychotherapy for the treatment of PTSD. Although this approach has generated interest, an FDA advisory committee recently recommended against its approval, citing significant methodological flaws in the supporting studies and advising the FDA to reject the Investigational New Drug Application.
'This illustrative example highlights the need for rigorous, placebo-controlled, double-blind trials to adequately test the effectiveness of these therapies while exhaustively documenting adverse events to characterize patient safety issues,' the statement's authors noted.
The AAN supports the FDA-accelerated review of novel therapeutics for neurologic conditions 'when this process is appropriate,' said Goldstein.
Off-Label Use
The statement also addresses the expanded use of therapies beyond their original FDA-approved indications — for example, the off-label use of alteplase for thrombolysis in ischemic stroke patients treated 3-4.5 hours after they were last known to be well, as well as the use of tenecteplase in select cases of acute ischemic stroke.
Goldstein noted that these examples reflect issues commonly encountered in hospitals nationwide.
'The AAN supports the off-label use of FDA-approved therapies in settings in which the high-quality evidence indicates that the benefit of the therapy outweighs the risks with shared decision-making between the patient and physician in the model of informed consent,' the statement authors noted.
Another example is natalizumab, a humanized IgG4κ monoclonal antibody approved for the treatment of relapsing-remitting multiple sclerosis (MS). The drug was initially withdrawn from the market following reports of progressive multifocal leukoencephalopathy. However, it was later reintroduced, as some patients with MS have no alternative therapies to effectively manage their disease.
Physician-patient discussions about unproven therapies might include situations where patients are considering their 'Right to Try.' Signed into law in 2018, the Right to Try Act allows individuals with a terminal illness who have tried all approved treatments and who are unable to participate in a clinical trial to receive an experimental treatment.
The statement also addresses the issue of adverse events reported after FDA approval. For example, the statin cerivastatin was approved for cholesterol reduction but was withdrawn from clinical use following reports of deaths and hospitalizations.
These cases, said Goldstein, illustrate the complexity of this issue.
'It's particularly challenging because healthcare providers must be constantly aware of new data that may become available as therapeutics enter general use after FDA approval,' said Goldstein.
In cases where a therapy is approved but carries significant risks or an incomplete adverse event profile, the statement advises that the AAN should generally refrain from taking a definitive position until further review by the FDA is completed.
Unproven 'Treatments'
The authors also address the use of therapeutics with limited or no supporting data, many of which have been popularized on social media, to treat or prevent conditions such as dementia.
Such use not only exposes patients to unknown risks but may also discourage them from pursuing evidence-based treatments or participating in clinical trials that could offer potential benefits, Goldstein noted.
When seeing patients, healthcare providers should discuss potential participation in a relevant trial and ask more detailed questions about the use of unproven therapies, he said.
'Physicians should routinely not only confirm their patient's prescribed medications but also ask about any other substances they may be using. Some, including certain supplements, may have potential toxicities or interactions with prescribed medications.'
Discussions between neurologists and patients about unproven therapies are becoming increasingly relevant.
'In the current climate of unfiltered, at times incorrect or misinterpreted information, having a trustworthy source of fact-based advice is critically important,' said Goldstein.
'The neurologist brings particular expertise and training related to neurological disorders and what is known about the risks and benefits of potential treatments to help inform patient decisions,' he added.
The AAN policy statement offers 'a framework' to guide neurologists in their role as patient advocates, Goldstein added. Although it does not address specific treatments, it does provide a structure for conversations with patients, said Goldstein.