Stephen D. Silberstein, MD

There appears to be no slow start to the new year in neurology, as the FDA has already approved new treatments for neurologic disorders, including intranasal diazepam for seizure clusters and expanded indications for vigabatrin and suvorexant in epilepsy and insomnia, respectively. In fact, neurology ranks second only to oncology in this year’s prospective drug pipeline, with nearly 30 potential drug approvals slated for 2020.

Within the headache specialty, my colleagues and I are fortunate to be on the receiving end of a steady flow of new drug development for patients with migraine and other headache subtypes. We closed out 2019 with the FDA approval of ubrogepant, a first-in-class small molecule inhibitor of calcitonin gene-related peptide for the acute treatment of migraine. We also look forward to the FDA’s upcoming decisions on another small molecule gepant, rimegepant, as well as eptinezumab, which if approved, will be the first anti-calcitonin gene-related peptide drug delivered via infusion.

In the end, an expanded armamentarium of treatments means more personalized therapeutic strategies for patients. It is truly an exciting time to be a neurologist as our ability to safely and effectively treat both common and rare diseases comes into focus, allowing us to take a step back and observe all of the facets that translate into a therapy being clinically meaningful for our patients

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NeurologyLive's editor in chief Stephen D. Silberstein, MD, discussed the ways to optimizing patient care. 

Options Are Key to Optimizing Patient Care

As 2019 comes to a close, I feel it’s important to reflect on breakthroughs and advances as it can help invigorate us and our practice in the new year. The past year saw dozens of drug approvals for common, well-known neurological disorders, such as headache and multiple sclerosis (MS), as well as lesser-known but serious disorders, including spinal muscular atrophy. Indeed, the neurology pipeline has been especially fruitful this year, and we have much to look forward to in 2020.

As a headache specialist, 2019 proved especially exciting as several new treatments have become available, including traditional pharmaceuticals as well as noninvasive devices. Notably, the FDA approved galcanezumab as the first drug for the treatment of episodic cluster headache, an incredibly disabling headache disorder with an extremely high unmet treatment need. The agency also recently approved lasmiditan, the first drug in a new class of migraine therapies aimed at optimizing acute relief. The specialty has also seen a surge in new technologies for the treatment of migraine headache, including wearables such as Nerivio, a smartphone-controlled device worn on the arm that promotes migraine pain relief through a conditioned pain response.

However, many other groundbreaking drugs entered other therapeutic areas over the course of the year. In MS, for instance, the FDA approved 2 new drugs just days apart— siponimod, which was the first oral drug approved for the treatment of active secondary-progressive MS as well as relapsing forms of the disease, was quickly followed by the approval of oral cladribine, which is also indicated for the treatment of active secondary-progressive disease and well as relapsing MS. Ongoing pursuits in immunotherapy for MS have also made an impact in 2019, with very promising data emerging from recent clinical trials of ofatumumab, as well as other therapeutic targets, including the S1P receptor modulator ponesimod. I look forward to following the research into 2020 knowing that more treatment choices will benefit both the clinician and the patient.

Perhaps one of the most intriguing developments of the year arrived in October, when Biogen and Eisai announced that they would put their anti-amyloid drug aducanumab in front of the FDA despite shelving the investigational therapy earlier in the year after a disappointing futility analysis. The companies announced that additional analysis of an expanded dataset revealed that patients who received the higher-dose drug for longer showed statistically significant improvements on a clinical dementia rating scale. Although clinical skepticism is especially high when looking at treatments for Alzheimer disease and dementia, I know that I am one of many who hope that the data is strong enough to support regulatory review and approval.

So much awaits us in 2020. I hope that you will stay with 

® as your source for the latest updates in neurology, as well as key insights on topics that matter to you and your practice.

The director of the Jefferson Headache Center at Thomas Jefferson University detailed the most notable achievements from 2019, and what to expect in the coming year. 

A Neurology Pipeline for the Ages

The importance of prescribing not only effective, but safe treatments for patients with neurological disorders is paramount. I’m confident that my colleagues in neurology would agree that weighing the benefits and risks of a particular therapy is a major and central component of their everyday practice, and it’s often the topic of conversation with a patient when initiating treatment for a disorder or making adjustments to the treatment plan throughout the course of disease.

Certainly, contraindications exist for a reason: They help us avoid introducing unnecessary risk and adverse effects in a person whose health is already compromised. However, in some cases, stated contraindications, which are typically established because those patient populations were not studied in clinical trials or an issue came to light in trials, may overly limit the use of what is otherwise a very effective and generally safe medication.

In headache medicine, we see this trend with triptans, which are generally contraindicated in patients with cardio- or cerebrovascular disease.

 Although triptans, which are highly effective for the treatment of acute migraine, have been on the market for nearly 30 years, they are grossly underutilized due to a fear of exacerbating vascular events. This fear is not unfounded, as patients with headache and migraine are known to be at an increased risk for ischemic events,

 but what is perhaps more concerning is how this fear can paralyze our ability to take further action for our patients.

In my practice, if a patient with episodic migraine—who would likely benefit from treatment with triptans&mdash;comes to me with uncontrolled hypertension, I do not hesitate to refer that patient back to their internist or a cardiologist to get their hypertension under control, after which I would feel more comfortable prescribing them a triptan.

When confronted with these situations, we should take a step back to evaluate what the real-life implications are. Are the contraindications realistic? Are they predictive of increased risk, beyond the risk that you would expect anyway?

If the answers to those questions are concerning, then I encourage you to reach out and incorporate the opinions of another specialist who can perform a dedicated evaluation to address your concerns, and in turn help you make a more educated decision for your patient.

It’s important that we look at contraindications not as a hard stop, but as a reason to further explore a patient’s medical history and improve their overall health.

1. Loder E. Triptan therapy in migraine. 

 2010;363(1):63-70. doi: 10.1056/NEJMct0910887.

2. Scher AI, Terwindt GM, Picavet HS, Verschuren WM, Ferrari MD, Launer LJ. Cardiovascular risk factors and migraine: the GEM population-based study [comment in 

 2005;64(4):614-620. doi: 10.1212/01.WNL.0000151857.43225.49.

NeurologyLive's editor in chief Stephen D. Silberstein, MD, discusses the importance of considering treatment contraindications in the context of individual patients. 

Navigating Contraindications in Real Life

As scientists, we're natural skeptics. So it’s not surprising to see that the adoption of complementary or wellness-based approaches in migraine care has been slower than some might hope. 

Despite reservations, quality clinical evidence shows that these approaches, including exercise, cognitive behavioral therapy, and breathing/meditation, can all be effective in patients with migraine and help reduce not only migraine frequency and severity but also the overall burden that the condition places on patients.

As with any other disease, there are things said in the media and unfounded claims made about purported migraine treatments that aren’t evidence-based. It’s our job as clinicians to clearly inform our patients and help them make educated decisions about their care. 

With the newest class of migraine therapies, we are clearly witnessing an unprecedented time in treatment. We are able to reduce migraine frequency and severity in patients with both chronic and episodic disease and even in patients with debilitating disorders like cluster headache. But we have to look at the big picture: Reducing just the number of monthly migraine days doesn’t necessarily mean that our patients are suddenly well; producing clinically meaningful change is very important and encompasses not only the number of migraines that a person experiences but also symptom management and how the disease affects their day-to-day life. In the end, if patients’ quality of life is still significantly affected by their disorder, we haven’t completely done our job. And that’s where complementary medicine has a place in your practice. 

Complementary therapies are especially relevant for patients who experience adverse effects from pharmaceutical treatments, have contraindications to those treatments, or have an inadequate response, as well as for patients who are planning for pregnancy, are pregnant, or are breast-feeding. An emphasis on lifestyle and behavioral changes can also benefit patients with medication overuse and those with high levels of stress. In many cases, clinicians can use wellness-based approaches in conjunction with pharmaceutical therapies to improve overall treatment benefit.

Several complementary therapies, though not conclusively supported by clinical evidence, are widely used with a good degree of success. These include acupuncture, chiropractic care, hypnosis, and physical therapy. 

"IN MANY CASES, CLINICIANS CAN USE WELLNESS-BASED APPROACHES IN CONJUNCTION WITH PHARMACEUTICAL THERAPIES TO IMPROVE OVERALL TREATMENT BENEFIT." 

Significant evidence also supports the use of behavioral therapies for headache and migraine; these include relaxation training, biofeedback, and cognitive-behavioral therapy.

 These therapies help teach the patient how to modify physiological responses related to headache or migraine, including how to reduce muscle tension and nervous system arousal and stress related to triggers. 

Clinicians also cannot forget the impact of other good lifestyle habits, including exercise, good sleep hygiene, hydration, and vitamin support, notably with B2 and magnesium. Indeed, results of a 2011 study by Varkey et al

 showed that exercise 3 times per week, regular relaxation exercises, and topiramate use were all equally effective in reducing the frequency of migraines. Exercise can help reduce stress and improve sleep—2 central migraine triggers. 

Providing patients with support, resources, and access to wellness-based care can help them play a direct role in their disease management beyond taking their prescribed pharmaceutical therapy. In the end, taking better care of themselves both physically and mentally will help improve not only their migraine management but also their lives. 

Stephen D. Silberstein, MD, is a professor of neurology and the director of the Jefferson Headache Center at Thomas Jefferson University in Philadelphia, Pennsylvania. He is also Editor in Chief of NeurologyLive.

1. Puledda F, Shields K. Non-pharmacological approaches for migraine. Neurotherapeutics. 2018;15(2):336-345. doi: 10.1007/s13311-018-0623-6. 

2. Penzien DB, Taylor FR. Headache toolbox. Behavioral and other nonpharmacologic treatments for headache. Headache. 2014;54(5):955-956. doi: 10.1111/head.12369. 

3. Varkey E, Cider A, Carlsson J, Linde M. Exercise as migraine prophylaxis: a randomized study using relaxation and topiramate as controls. Cephalalgia. 2011;31(14):1428-1438. doi: 10.1177/0333102411419681. 

Despite early reservations, available literature suggests that it may be time to invest in the utilization of wellness-based methods in the treatment of migraine.

Author | Stephen D. Silberstein, MD

Articles

Options Are Key to Optimizing Patient Care

A Neurology Pipeline for the Ages

Navigating Contraindications in Real Life

Wellness for Migraine: Should You Buy In?