Physiatry in Motion: Looking Ahead

By James E. Eubanks, MD, MS

As Technology Representative for the AAP RFC this year, one of my responsibilities is to serve as Editor of our quarterly newsletter, Physiatry in Motion (PiM). As awareness of and interest in physiatry continues to grow, it is important that we highlight the many exciting changes taking place in the profession, and empower each other to share the ways in which physiatrists are meeting the needs of our dynamic healthcare system.

There are a number of avenues through which we are now having important discussions about physiatry. Whether it is a Twitter chat about people with disabilities, a conference session about the growth of adaptive sports, sharing an article about the new ways we might think about tendinopathy treatment, or a publication about the progress of women in medicine, there is much to talk about and share. Something that makes our profession great is its genuine commitment to diverse healthcare needs, and to talk about them in diverse ways.

It is my hope as Editor of PiM this year that you will reach out and contribute to our growing publication. We are interested in hearing and sharing your personal stories as physiatrists and physiatrists-in-training, the challenges you see that are in need of solutions, and the many ways in which our clinical and research efforts are leading to meaningful successes. For the residents and fellows out there: this is an open invitation to become part of the discussion. The AAP RFC looks forward to the year ahead and expanding the work we do for you, with you.

Jim Eubanks is the 2019–2020 Technology Representative for the AAP RFC and Editor of Physiatry in Motion. He is a rising PGY-2 in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh Medical Center (UPMC). Follow him on Twitter @jeubanksMD

More than medicine: What I learned about my patients from an adaptive yoga training

by Sarah M. Smith, MD

“One of the big healing things for me was to recognize that my paralyzed body didn’t stop talking to my mind. It changed its voice.” These were the words of adaptive yoga instructor Matthew Sanford to our group of eager trainees — yoga instructors from all over the country and the world, who had come to learn how to teach adaptive students.

Matthew has a spinal cord injury himself. He sustained his injury when he was a child in a car accident that killed his father and his sister. He has been using yoga as a means to teach people how to reconnect with their bodies for many years now. I was a fourth year medical student at the time, and as a soon to be PGY-2 PM&R resident now, the benefits of my training continue to reveal themselves. I had already been teaching yoga for 6 years at that point, but most of my experience had been with students with little to no functional limitations. During my intensive training, I was able to learn from students with cerebral palsy, spinal cord injuries, brain injuries, prior CVAs, and multiple sclerosis. Adaptive yoga is quite different in practice than the average mainstream class that comes to mind when we usually think of yoga. In an adaptive class, an instructor leads a group of students, who may each have up to four volunteers working with them to assist them into postures. I was surprised to learn how sometimes it was the simplest of movements that had the greatest impact on my students. I will never forget the look on a student’s face when I spent a few moments stretching out and opening her spastic hand.

I enrolled in the training in order to learn how adaptive yoga could benefit my patients, but I did not anticipate how much it would help expand my own toolkit as a future physiatrist. Instead of focusing on what I knew about my students’ medical conditions, I sat back and let the students teach me about their bodies. “This probably won’t make sense to you,” one student started, “but since I’ve been doing yoga, I can feel my feet. I can’t feel them like you can feel them, but there is something there now that wasn’t there for the first few years after the accident.” This student had a complete thoracic spinal cord injury. It’s probably impossible to know exactly what this student was experiencing, but the point is that she was reconnecting to her body in a way that was changing her everyday experience. And as I’ve learned from my students and patients, feeling disconnected from your body can be one of the greatest challenges to overcome as an individual with adaptive needs.

I have to admit that I struggled with some of the concepts Matthew was trying to teach us that week. We weren’t focusing on the anatomy or the movement science. We were learning how to teach an experience to someone. I realized I was having a hard time asking students to be in touch with their bodies when I had spent that last four years being conditioned to suppress all of my own bodily needs. As a medical student, I had learned how to operate on little sleep, hold it when I needed to go to the bathroom, and skip meals to get work done. I actually fractured my wrist at the beginning of interview season and didn’t seek medical attention for several weeks, because I was worried about missing flights for interviews and potentially not matching.

Disconnection with our bodies is not uncommon in the medical profession, and I do wonder how it impacts our ability to understand our patients’ experiences. A physiatrist’s job is to reconnect our patients with the world, but in order to do that effectively, we must reconnect our patients with themselves first. I realize this concept is abstract. It is not something we can quantify, like the number of feet a patient can ambulate. But despite being scientists, I think we can all recognize that the quantifiable aspects of rehabilitation are only one piece of the puzzle. I have not yet figured out how I will integrate all of this into my practice, but physicians can do more than order medications and perform procedures. The goal is not to leave any of the science behind; it is simply about using a different lens to see the patient. The data and diagnostics remain sturdily in the background, but the patient comes back into focus.

Sarah Smith is a rising PGY-2 in the Department of Physical Medicine and Rehabilitation at the University of Washington (UW). Follow her on Twitter: @DrSarahMSmith

The Secret’s Out: Skill-based fairs, social media, and remote mentorship as solutions to improve early PM&R exposure

by Emily Kivlehan, MD

“PM&R is the best kept secret in medicine.” As the only student in my class with early interest in physiatry, I heard this many times during my preclinical years. Now, as a member of one of the nation’s larger PM&R residency programs, I have newfound respect for the power in numbers. Some of my resident colleagues are brilliant physician-scientists seeking to make the world easier for those with disabilities, some have a passion for teaching and strive to continuously improve medical education, some have found ways to advocate nationally for disability, and others have the bedside manner I can only hope to emulate. And yes, some have it all. But for the most part, trainees have certain niches that ignite their passion. When we increase our numbers and diversity, we gain powerful physicians that can push the boundaries of our field. Ultimately, our experiences and expertise combine to help each of us provide the best rehabilitation care possible for our patients.

Unfortunately, physiatry still remains a secret for many preclinical medical students. A recent study reported that at one allopathic medical school, only about half of preclinical students were aware of PM&R. More concerning, the majority of respondents would not know who to contact to learn more about PM&R. Traditionally, student interest groups (SIGs) provide assistance with early specialty exposure. But with only 92 PM&R residencies and around 200 U.S medical schools, many students are left without a strong PM&R presence at their institution and may in turn lack the guidance and mentorship necessary to explore the field.

Regional medical student fairs, which survey data has shown increases interest and understanding of physiatry, have emerged as a possible solution. Importantly, baseline interest scores before one fair were noted to be high in attendees. This raises concern that while effective for those who attend, fairs may not be reaching students who are unsure of their interest or who have not heard of PM&R. In other words, these fairs are great for consolidating existing interest but may fail at generating new interest. As many of us remember, the free time of preclinical medical students is limited and valuable. However, students often plan their elective time while still in the preclinical stage. Most medical schools do not have a requirement for PM&R rotation, and those that do may not require it until the fourth year. It is important to increase exposure and promote interest during preclinical years so students can plan their schedules accordingly. One way to create broader appeal of fairs could be by framing fairs with skill training that is applicable across specialties. PM&R physicians are experts in anatomy, musculoskeletal and neurologic physical exam, and ultrasound skills. Regardless of future plans, preclinical medical students may be interested in improving these skill sets. Utilizing physiatrists as hosts can increase exposure and understanding of what we do. Last year, the AAP supported regional medical student fairs by providing grants to help fund 8 fairs which reached 400 students. You can apply for the grant here: https://www.physiatry.org/page/PMRFairs 

An additional modern avenue for medical students to obtain information is through social media. Even with fairs, access to physiatry mentorship may be difficult without residents. Multiple regional and national student led groups exist on social media to disseminate advice and information, such as PhysiatryNow and PMRScholars. Just this spring, the AAP Medical Student Council started an e-newsletter for SIGs around the country to help advertise opportunities and news for future physiatrists. The MSC and RFC have also created a resident-student mentorship program, providing students remote access to residents around the country.

Let’s start early aligning students with the AAP’s mission: discovery, leadership, mentorship. To promote the discovery of our diverse field, we must be creative and find ways to broadly appeal to medical students. Despite specialty plans, future physicians’ understanding of physiatry will expand our field and improve care of those with chronic illness and disability. Leadership, such as through the AAP’s Medical Student Council, which is now in its second year. The MSC provides a venue for medical students to engage in early national leadership opportunities. Lastly, the RFC Mentorship program circumvents the need for students to have direct, in-person access to a PM&R department in order to obtain a mentorship. What is clear is the enthusiasm and dedication of the upcoming physiatry generation in helping medical students discover our field. Publications such as Physiatry in Motion, and the volume of fairs and SIGs, embody the passion of the next generation of physiatrists. Help us grow the #RFCMentors program by signing up on the AAP website!

Emily Kivlehan is a rising PGY-4 at the Department of Physical Medicine and Rehabilitation at Shirley Ryan AbilityLab and the AAP RFC Medical Student Affairs Representative. Follow her on Twitter @EmilyKivlehanMD

References

Brane LB, Carson R, Susmarski AJ, Lewno AJ, Dicianno BE. Changing Perception Outcomes from a Physical Medicine and Rehabilitation Medical Student Interest Fair. Am J Phys Med Rehabil 2017;96:362–365

Le B, Parsiale J. Pre-clinical Medical Students’ Attitudes Toward Physical Medicine and Rehabilitation. Rhode Island Medical Journal 2019:26–28

Tips for Success in the Fellowship Match: An Interview with Stephanie Tow

by Allison Schroeder, MD

Stephanie Tow, MD, completed her residency in Physical Medicine and Rehabilitation at the University of Texas Southwestern in 2017 where she served as chief resident. She then completed a fellowship in Pediatric Rehabilitation at the University of Colorado in 2019. In July 2019, she will start a fellowship in Pediatric Sports Medicine at Children’s Mercy in Kansas City. She is one of only four people to pursue both a Pediatric Rehabilitation and Sports Medicine fellowship following residency in Physical Medicine and Rehabilitation. She has been successful in two fellowship matches and was willing to share some of the things she learned throughout the application and interview process.

Q: How did you choose a fellowship program that was the best fit for you?

A: I found that it was important to identify mentors that I could trust for advice. I could ask them what the good programs were. I would not just ask one person, but would ask as many people as possible. They gave me advice on which programs I should apply to and which programs would be the best fit for me. My mentors also knew my personality, and, for example, they were able to point me towards programs that had a lot of autonomy, good adaptive sports opportunities, and would allow me to continue my national work.

Applying broadly and interviewing at a good number of programs also allowed me to learn more about many programs, and helped me get a better sense of which ones were the best fit for what I was seeking. Depending on what your interests and needs are, you definitely want to know if the fellowship program will support you. For example, my Pediatric Rehabilitation Program supported my interest in Sports Medicine and allowed me to rotate with the Sports Medicine department. You will also want to look at how many faculty are doing what you want to be doing.

Q: Is there anything that you wish you had known prior to starting the fellowship application process?

A: I really wish that I had known when programs were going to interview. However, this changes every year and is outside the residents’ control. In terms of things that residents can control, if you are applying to pediatric sports medicine or another “niche” sub-specialty, include a description of how PM&R prepares you to be successful in that specialty. When filling in ERAS, also try to condense information and group information so that you do not look like you are trying to pad your CV, but also make sure to highlight and include everything that you have done. Also, if you do not hear back from a program (but are really interested), send them a specific email about why you are interested; this is especially important for competitive fellowships.

Q: Do you have any tips on how to balance travel for interviews with clinical and residency responsibilities?

A: I would advise residents to meet with your program director, coordinator, and chief resident who are in charge of the schedule and also set expectations with your program on the number of interviews you plan to attend and the number of days you will be away (consider getting this in writing). Look at the match statistics and come up with a plan for interview season and interview timing based on your individual competitiveness for a specialty. Consider saying something like: “I also want to prioritize my responsibilities in residency.” Be careful not to come off as entitled — take a humble approach. Also keep in mind that some programs will interview on Saturdays. For sports medicine, some programs also have you shadow sports coverage the night before or on weekends, so you will need to make travel plans accordingly.

Q: What did you learn from your Pediatric Rehabilitation fellowship application process and from your Pediatric Rehabilitation fellowship that helped you be successful in the Sports Medicine fellowship match?

A: The processes were actually very different. The pediatric rehabilitation process was “easier” because I heard back quickly and was told far in advance for interviews, which was not the case in the sports match (which has more programs involved but is also more competitive). I learned that it was very important to talk to mentors so I would know which programs I should be seriously considering given my specific goals. I also found it helpful to contact programs ahead of time to see which programs fit my needs. This allowed me to determine which programs were more or less responsive.

Q: What aspects of a fellowship should applicants carefully consider when making their rank order list?

A: It seems that the most common reasons that people choose a specific fellowship program are culture, well-roundedness, and good clinical and procedural experience. Diversity of attendings you work with is also important. It is nice to see faculty who are not all inbred from one program, because you know that you will get a diversity of perspectives and experiences. The number of faculty also was important to me. Additionally, I was looking for a program that had more trainees, because those are people who will be your colleagues and who you will work with for the rest of your life. Geography is important for some people but was less important for me. Having autonomy was really important for me, but may be less so for others. I also wanted to make sure I could do the things I cared about — for me that was adaptive sports and continuing my involvement in leadership on a national level. You will not know if a program is the right match until you actually go there and experience it via an interview or away rotation.

Q: Do you have any advice on if you should do an away rotation?

A: It is very program-dependent on whether a specific fellowship prefers residents who do away rotations. Basically, it can be helpful, but it is not completely necessary. Many residencies do not allow for away rotations. However, if you have a specific program that you are interested in and if your current residency program will support you, you should definitely do it — but make sure you “wow” them. Just because you do a rotation at another program does not mean you will be at the top of their rank list. Also, if you are an internal candidate at a program, do not assume that you have “dibs” on their spot.

Q: Do you have any additional advice for fellowship applicants or those early in residency who are planning to pursue a fellowship?

A: Get involved with any clinical experience that interests you!! Be proactive and show you have interest in a certain sub-specialty. Contact your chief residents and coordinator to see if you can have certain experiences earlier in your training. Going to conferences is also helpful to keep up-to-date on current national discussions and for networking. Be present and always be professional. Just show them that you have a good reason to want to stay in the sub-specialty and that you have plenty of experience to be able to apply it. Doing an early rotation is also helpful to get letters of recommendation. For example, for pediatrics, I got involved in camps, and for sports I sought out sports coverage opportunities and tried to volunteer in as many as I could. I think it would also be helpful to have a separate CV from the start of residency that includes descriptions of what you have done, as you will need this for the ERAS fellowship application. In terms of applying, make sure you submit your ERAS application by the time ERAS will start sending applications to programs.

Allison Schroeder is a rising PGY4 and current Administrative Chief Resident in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh Medical Center (UPMC). She is also the AAP RFC Education and Well-Being Representative. Follow her on Twitter @A_SchroederMD

The Steroid Fallout

by Michael E. Farrell, MD

Not long ago, intraarticular steroids were believed to be somewhat of a panacea by patients. They were viewed as a safe, easy, and effective option for joint related aches and pains. Perhaps the optimistic attitudes patients held about steroid joint injections were for good reason. Historically, intraarticular steroid injections have been touted by physicians to be a generally benign procedure with very little risk of systemic side effects. However, more recent literature suggests that systemic effects, such as hypothalamic-pituitary axis (HPA) suppression, may be underestimated.[1] When coupled with reported side effects of chondrotoxicity and subsequent cartilage volume loss, we can appreciate why the routine use of intraarticular steroids has come under recent scrutiny. Within our continuity clinic at MedStar National Rehabilitation Hospital, I’m beginning to notice a pattern of more patients asking questions regarding the safety of steroid injections. This forces us to ask: what are some key points from the literature that physiatrists and physiatrists-in-training should know when attempting to discuss the recent steroid fallout with patients?

The first is that it appears as though systemic absorption, and subsequent HPA suppression, is dependent on the total number of joints injected rather than the total dose of glucocorticoid.[2] Just as orally administered systemic glucocorticoids can impact the HPA, at doses as low as 2.5mg to 7.5mg daily, so can small doses of intraarticular steroid injections. In one study by Armstrong et al., doses of 40mg or greater of methylprednisolone caused near complete cortisol suppression for several days. For patients with pre-existing endocrine disorders, or those concerned about systemic effects, we should be prepared to discuss options for mitigating these risks. This may mean advising against multiple, or bilateral, joint injections at a single office visit and will require a more thoughtful approach to their treatment plan.

Besides systemic effects, another common question is whether or not steroid injections are bad for joints locally through direct harm to cartilage? As physiatrists, we know that functional goals are of the utmost importance when discussing treatment options. In a 2017 JAMA study, receiving as little as four steroid joint injections per year resulted in cartilage volume loss as documented by MRI.[3] Additionally, in a recent systematic review in PM&R Journal by Jayaram et al., the chrondrotoxic effects of commonly used anesthetics were found to be dose-dependent, duration-dependent, and exacerbated with concurrent use of steroids.[4] Concerns raised by these findings have shifted our conversations towards discussing expectations and functional goals. For older patients with severe osteoarthritis whose function is severely limited, the benefits after steroid injections may outweigh the perceived risk of worsening cartilage damage. This is especially the case when total knee replacement is planned as part of the long-term treatment strategy. Still, it seems that more elderly patients have become computer savvy and are using the internet more frequently to obtain their healthcare information. This will ultimately result in voiced concerns about the impact of steroids on joint health. Their questions will provide an excellent opportunity to review clinical anatomy, go over any diagnostic imaging, and revisit their beliefs regarding their long-term treatment plans and goals.

Lastly, an increasing number of patients have become concerned about the total dose of steroid injections they receive over a given period of time. Previous literature has recommended that the maximum doses for epidural injections but never reached consensus on the total dose recommendations for intraarticular injections. In the last month’s issue of PM&R Journal, there was a very helpful article that discussed this very topic. In that article, the recommendations from Stout et al. were as follows: For postmenopausal women and potentially for men over age 50, a maximum cumulative whole body triamcinolone/methylprednisolone dose of 200mg per year and 400mg per 3 years should be considered. In addition, those with osteoporosis and, especially anyone with a fragility fracture, treatment with bisphosphonates could be considered.[1] Considering my own patient population, strict adherence to this recommendation would prove difficult as many have multiple pain-producing joints that impact their function throughout the year. Armed with this info, there has been a surge in patient interest regarding alternative treatment options.

Two potential options with interest from patients are PRP and stem cell injections. PRP, or Platelet Rich Plasma, works on the premise of fractioning out a portion of the blood containing growth and healing factors for injection back into a joint. The other option is the use of stem cell therapy which uses mesenchymal stem cells are harvested from adipose or bone marrow to be injected into the desired area. The largest advantage of either of these procedures is their reported safety within the literature.[5] Many patients seem to be keen on moving away from a pharmacologic approach and like the idea of using their bodies own self-healing mechanisms. In addition, the low side effect profile is highly desirable. The disadvantages are the premium cost incurred by the patient, and the fact that patient selection is key for the procedure to produce results. Either way, it is reasonable to suspect that as more patients begin to question the safety of steroid injections, physiatrists will see a rise in interest in regenerative medicine procedures in outpatient clinics.

Ultimately, as the literature evolves, we must be prepared to provide education to our patients. As physiatrists, our patient’s functional goals and prior response to treatment will most definitely drive these conversations. It is inspiring to see the number of quality research papers being produced by physiatrists within this space. As we get closer to finding more definitive answers on the safety of intraarticular steroid injections, I believe it will be physiatrists who continue to lead the way.

Mike Farrell is a rising PGY-3 in the Department of Physical Medicine and Rehabilitation at MedStar National Rehabilitation. Follow him on Twitter: @mefarrellii

References

1. Stout, A. , Friedly, J. and Standaert, C. J. (2019), Systemic Absorption and Side Effects of Locally Injected Glucocorticoids. PM&R: The Journal of Injury, Function and Rehabilitation, 11: 409–419. doi:10.1002/pmrj.12042

2. Armstrong RD, English J, Gibson T, Chakraborty J, Marks V. Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate. Ann Rheum Dis. 1981;40:571–574.

3. McAlindon TE, LaValley MP, Harvey WF, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA.2017;317(19):1967–1975. doi:10.1001/jama.2017.5283

4. Jayaram, P. , Kennedy, D. J., Yeh, P. and Dragoo, J. (2019), Chondrotoxic Effects of Local Anesthetics on Human Knee Articular Cartilage: A Systematic Review. PM&R: The Journal of Injury, Function and Rehabilitation, 11: 379–400. doi:10.1002/pmrj.12007

5. Jayaram, P. , Ikpeama, U. , Rothenberg, J. B. and Malanga, G. A. (2019), Bone Marrow–Derived and Adipose‐Derived Mesenchymal Stem Cell Therapy in Primary Knee Osteoarthritis: A Narrative Review. Journal of Injury, Function and Rehabilitation, 11: 177–191. doi:10.1016/j.pmrj.2018.06.019

Time for FOCUS: Does fluoxetine really help with functional recovery after acute stroke? A new RCT puts the heat on the 2011 FLAME trial

by James E. Eubanks, MD, MS, Patrick J. Polsunas, MD and William H. Jarrard, MD

The Background

In 2011, Chollet et al. published, “Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): A randomised placebo-controlled trial” in The Lancet Neurology that changed the way we think about motor recovery in ischemic stroke.[1] Prior to this, several small clinical trials showed encouraging results on the use of selective serotonin reuptake inhibitors (SSRIs) after ischemic stroke using motor recovery as the primary outcome. The FLAME trial sought to address the following question: Does early administration of fluoxetine, in addition to conventional physical therapy, improve motor recovery following ischemic strokes?

A 2014 systematic review and meta-analysis by McCann et al. proposed that the mechanism for improvement in motor recovery following the use of SSRIs pertains to a serotonin-mediated suppression of post-stroke hyperexcitability, with concomitant improvement in neuroplasticity.[2] While SSRIs did not affect infarct volume, and existing trials suffered from potential publication bias when reporting on neurobehavioral outcomes, SSRIs nonetheless appeared to improve neurobehavioral outcomes by an average of 51.8% and increased neurogenesis by 2.2 SD. Accordingly, we have taken the potential use of SSRIs in motor recovery following ischemic stroke very seriously.

The FLAME Trial

The 2011 FLAME trial followed 113 patients recruited from nine stroke centers in France 5–10 days after acute ischemic stroke with hemiplegia/paresis, and randomized them to either 20mg of daily fluoxetine, or placebo. Patients, caregivers and physicians were blinded. The fluoxetine group was found to have higher Fugl-Meyer Motor Scale (FMMS) scores compared to their placebo counterparts at 90 days (34.0 vs. 24.3; P=0.003). The FMMS, the primary outcome measure in FLAME, benefits from excellent intra-rater and inter-rater reliability and validity. Given that fluoxetine was well tolerated, this was an impressive change when combined with usual physical therapy. Despite sufficient power and good design, the generalizability to clinical practice may be limited by a narrow inclusion criteria and the relatively short-term follow-up period of three months.

The FOCUS Trial

In 2018, the FOCUS Trial Collaboration published new data in Lancet. FOCUS, which stands for “Effects of fluoxetine on functional outcomes after acute stroke,” was a pragmatic, multicenter, double-blind, randomized controlled-trial.[3] The large socioeconomic burden of stroke-related disability, combined with the success of the smaller FLAME trial in 2011 meant that new efforts to study the full potential of fluoxetine in stroke management have been prioritized. In 2012, a Cochrane review found that SSRIs appeared to improve dependence, disability, neurological impairment, anxiety and depression after stroke.[4] The Cochrane review highlighted heterogeneity between trials and methodological limitations, calling for large, well-designed trials to determine whether SSRIs should be given routinely to patients with stroke.

Recruiting from 103 hospitals in the United Kingdom, 3,127 patients with a clinical diagnosis of stroke that included neurological deficit and confirmation of stroke via brain imaging (ischemic or hemorrhagic, but not subarachnoid) were randomly assigned between days 2–15. The two groups again consisted of 20mg of fluoxetine daily or placebo. The primary outcome in FOCUS was an ordinal analysis of the modified Rankin Scale (mRS), which measures degree of disability after a stroke.

FOCUS ultimately found that the use of 20mg of fluoxetine daily for six months after acute stroke did not improve patients’ functional outcomes as measured by the mRS, nor did it improve survival at 6 or 12 months. There was a benefit of decreased depression at six months, but an observation of increased bone fractures as well.

The Future of Fluoxetine in Stroke Rehabilitation

Importantly, the FLAME trial’s legacy continues to inspire important work. There are several ongoing trials building on the study of SSRIs in stroke recovery, such as the AFFINITY trial (which includes a more diverse patient population from Australia, New Zealand and Vietnam) that is looking at the potential value of fluoxetine in cognition, fatigue, mood and function. Additionally, the Swedish EFFECTS trial is underway. There is also a plan for a pooled analysis of FOCUS, AFFINITY and EFFECTS once results are in.

In an editorial in Lancet, Bart van der Worp outlines some of the essential considerations when we compare FLAME and FOCUS.[5] First, while FLAME only enrolled patients with ischemic stroke and FOCUS included hemorrhagic stroke, FOCUS employed predefined subgroup analyses to show that fluoxetine was not effective in ischemic stroke populations. There is also an issue of the timings of outcome assessments; FLAME evaluated patients only at three months whereas FOCUS went to six months. Another potentially important difference is the approach to stroke rehabilitation in the UK, which may not have been as intense based on the way rehabilitation protocols were organized. It is possible that the use of FMMS in FLAME may be better able to detect motor changes than the mRS that FOCUS utilized.

Emphasizing specific limitations in the kind of information gathered between FLAME and FOCUS, we are left at this moment with some uncertainty about the use of fluoxetine that must be considered in the interim while more data comes in. While clinical practice over the past several years has moved to employ fluoxetine specifically and SSRIs in general in ischemic stroke recovery because of the FLAME trial, FOCUS is a legitimate challenge to ongoing arguments that SSRIs should be the standard of care in ischemic stroke motor recovery.

Jim Eubanks is a rising PGY2 in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh.

Patrick Polsunas is a rising PGY3 in the Department of Physical Medicine and Rehabilitation at the University of Pittsburgh.

Howell Jarrard is a rising PGY3 in the Department of Neurology at the University of Pittsburgh.

References

1. Chollet F, et al. Fluoxetine for motor recovery after acute ischaemic stroke (FLAME): a randomised placebo-controlled trial. The Lancet Neurology. 2011. 10(2):123–130.

2. McCann SK et al. Efficacy of antidepressants in animal models of ischemic stroke: a systematic review and meta-analysis. Stroke. 2015 Oct;45(10):3055–63.

3. FOCUS Trial Collaboration. Effects of fluoxetine on functional outcomes after acute stroke (FOCUS): a pragmatic, multicenter, double-blind, randomized controlled trial. Lancet. 2018;393:265–74.

4. Mead GE et al. Selective serotonin reuptake inhibitors (SSRIs) for stroke recovery. Cochrane Database Syst Rev. 2012; 11.

5. van der Worp B. Fluoxetine and recovery after stroke. Lancet. 2019;393:206–07.