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Friday, August 30, 2013

Cases: Anti-epileptic Medicines for Pain Management

Personal details in the case have been altered to protect patient privacy. These cases may reflect a composite image of many different cases to illustrate a teaching point.

Case:  Mr. LF is a 58 year-old gentleman with a history of metastatic lung cancer with metastases to the bone including the sacrum. He is seen in a palliative care clinic for severe right lower extremity burning pain lasting several months. Noting LF’s pain appeared to be neuropathic in nature, LF’s primary care physician prescribed, in succession, duloxetine and then amitriptyline. Unfortunately, neither of these interventions decreased his pain. His oncologist prescribed a fentanyl patch and oxycodone 5-10mg as needed. LF reports the opioid pain medications make him tired but do not relieve his pain. He wonders if there is anything else to try for his pain.

Discussion:  Tri-cyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs) and anti-epileptic drugs (AEDs) are the mainstays of adjuvant therapy for neuropathic pain.  This Case of the Month will focus on oral anti-epileptic neuropathic pain analgesics. Due to lack of head-to-head data, evidence is presented as numbers needed to treat (NNT) and numbers needed to harm (NNH). For instance, an NNT of 5 for 50% pain reduction means for every 5 patients treated with a drug, only 1 of them would achieve a 50% reduction in pain. Gabapentin (Neurontin) and pregabalin (Lyrica) are considered first-line anti-epileptics for the treatment of neuropathic pain.

Gabapentin is effective in treating central and peripheral neuropathic pain. According to a 2011 Cochrane review of the effect of gabapentin on chronic neuropathic conditions (including post-herpetic neuralgia, painful diabetic neuropathy, mixed neuropathic pain), the NNT is 5.8 (4.8-7.2) to achieve at least moderate benefit. This NNT is more conservative than those previously published due to better definitions of efficacy outcomes and an increased number of participants and studies evaluated.

Adverse effects are frequent and include drowsiness, dizziness and edema. Typically, if the dose is increased slowly these side effects are tolerable (1). Gabapentin should be dose adjusted for renal dysfunction. It should be withdrawn gradually to avoid precipitating seizures (2).

Pregabalin is effective in treating peripheral and central neuropathic pain. Since both gabapentin and pregabalin are chemical analogs of GABA, they are not used simultaneously in clinical practice. There are no comparison studies of gabapentin versus pregabalin. Pregabalin’s effectiveness increases as the dose approaches 600 mg/day. Based on a recent meta-analysis, at a dose of 600 mg/day the NNT to decrease pain by 50% for the following conditions is: 3.9 (range 3.1-5.1) for post-herpetic neuralgia; 5.0 (range 4.0-6.6) for diabetic neuropathy; and 5.6 (range 3.5-14) for central neuropathic pain. There was no difference in incidence of side effects among participants taking pregabalin vs. placebo and no indication of a dose response to side effects (3 - Open Access (OA)).

Carbamazepine is effective in treating neuropathic pain, specifically trigeminal neuralgia, but is not considered first-line therapy due to its adverse effects.  A 2011 meta-analysis focused on the use of carbamazepine for chronic neuropathic pain reported carbamazepine reduced pain compared to placebo (NNT of 1.7, range 1.5-2.0). However, adverse events occur frequently: NNH = 2.6, range 2.1-3.5 (4).  Common side effects include leukocytosis, thrombocytopenia, dizziness, drowsiness, ataxia, nausea/vomiting and blurred vision. Additionally, there is a risk of agranulocytosis, aplastic anemia, and Stevens Johnson syndrome. Laboratory tests (BUN, complete blood count, sodium, liver function tests, urinalysis) and serum drug levels should be checked at baseline and during treatment.  Oxcarbazepine is an analogue of carbemazepine which is equally effective at treating trigeminal neuralgia as carbemazepine (5) but with fewer side effects (6 - OA).

Valproic acid was evaluated in a 2011 meta-analysis for the treatment of neuropathic pain. There were insufficient data for reliable pooled analysis, and the authors recommend against its use as first-line therapy (7).

Several small studies (n less than 60) showed benefit of the use of valproic acid (maximum of 1200 mg/day in divided doses) over placebo in the treatment of diabetic neuropathy (8 - OA). However, this data is not convincing. Other studies of valproic acid have failed to find an effect (9). Adverse effects include liver function test abnormalities, dizziness, drowsiness and nausea (2).

Topiramate was evaluated in a 2010 systematic review for the treatment of neuropathic pain. Of four randomized placebo-controlled trials, three were negative and one positive for the treatment of painful polyneuropathy. No studies were found to evaluate its efficacy in the treatment of post-herpetic neuralgia, peripheral nerve injury or central pain (9).  Serious adverse events thought to be related to topiramate included convulsion and bradycardia plus syncope. Additional adverse effects include sedation, nausea, diarrhea and metabolic acidosis (2).
Summary:  Neuropathic pain remains best treated with TCAs, SNRIs, and the AEDs gabapentin and pregabalin. For patients who are intolerant to or who experience pain unresponsive to those medications, one can consider therapy with other anti-epileptics. However, these agents are associated with more side effects and lower rates of efficacy.

Resolution of the case:  LF was started on gabapentin and titrated up to a dose of 900mg three times a day with moderate pain relief. His opioids were tapered and discontinued.

  1. Moore RA, Wiffen PJ, Derry S, McQuay HJ. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews. 2011, Issue3, Art No.: CD007938. DOI: 10.1002/14651858.CD007938.pub2
  2. Micromedex® Healthcare Series [Internet database]. Greenwood Village, Colo: Thomson Reuters (Healthcare) Inc. Updated periodically.
  3. Moore RA, Straube S, Wiffen PJ, Derry S, McQuay HJ. Pregabalin for acute and chronic pain in adults. Cochrane Database of Systematic Reviews. 2009, Issue 3. Art. No.: CD007076. DOI: 10.1002/14651858.CD007076.pub2. Open Access PDF
  4. Wiffen PJ, Derry S, Moore RA, McQuay HJ. Carbamazepine for acute and chronic pain in adults. Cochrane Database of Systematic Reviews.  2011, Issue 1. Art. No.: CD005451. DOI: 10.1002/14651858.CD005451.pub2.
  5. Zakrzewska J, Linskey M. Trigeminal Neuralgia. Clinical Evidence. 2009; 3(1207). Retrieved Nov 15, 2011 from
  6. Finnerup NB, et al. Algorithm for neuropathic pain treatment: An evidence based proposal. Pain. 12005; 18:289-305.PMID: 16213659. Open Access PDF
  7. Gill D, Derry S, Wiffen PJ, Moore RA. Valproic acid and sodium valproate for neuropathic pain and fibromyalgia in adults.Cochrane Database of Systematic Reviews. 2011, Issue 10. Art. No.: CD009183. DOI: 10.1002/14651858.CD009183.pub2.
  8. Kochar DK, et al. Sodium valproate for painful diabetic neuropathy:  A randomized double-blind placebo-controlled study. Quarterly J Med. 2004; 97:33-8. PMID: 14702509 Open Access PDF
  9. Finnerup NB, et al. The evidence for pharmacological treatment of neuropathic pain. Pain. 2010; 150: 573-581. PMID: 20705215

 Original Case by Rene Claxton, MD, Edited by Christian Sinclair, MD

Pallimed Case Conference Disclaimer: This post is not intended to substitute good individualized clinical judgement or replace a physician-patient relationship. It is published as a means to illustrate important teaching points in health care.

Friday, August 30, 2013 by Christian Sinclair ·

Friday, August 23, 2013

Hospice is Still Special

When socializing with fellow young physicians, most of whom are not in palliative medicine, I am reminded, in Hospice and Palliative Medicine, I have the unique opportunity to share time and attention with my patients. We reflect on “the old days” of medicine, where physicians had long standing relationships with their patients which allowed them to more easily direct medical decision-making which was appropriate for the individual patient. I often tell others I chose this field because it is the closest thing to that particular kind of medicine, where we can still do ‘the right thing’ for patients, most of the time. That although many parts of hospice are very rigid (eg. 6 month prognosis, palliative goals only) we still have significant freedom to adjust the plan of care to meet the needs of our individual patients.

My friends envy the extended visits I have with patients where I learn about their family and friends and, by doing so, also learn about their goals and fears. The time I am permitted to invest in my patients allows me to find out who the person is and then work to match the medicine to their needs. My colleagues often talk about the opposite - how their job is to make the people fit the medicine. We've marveled over this golden part of medicine where, at least as they die, hospice provides patients what they really need to live well.

Most of us practicing in this field recognize this could not continue indefinitely. With increasing complexity of hospice patients, an aging population and less options for debilitated patients with poor social supports, it was inevitable that the growing cost of hospice would catch someone’s eye and become a target for cutbacks. We've seen necessary layoffs and closings of hospices across the country. Last month this became a personal reality when the hospice I work for was shaken by a downsizing where we lost 19 valued colleagues. We consolidated our two hospice units into one with a loss of four beds. This was made necessary by the increased scrutiny and decreased payments we have received for the care we provide. We now pick apart each component of the GIP stay to be sure patients meet criteria. We second-guess enrollment of patients whose prognoses are in question even when their symptom burden clearly demands hospice support. Our ability to ‘do the right thing, because it is the right thing to do’ has gotten more limited as we rely more heavily on benevolence funds to provide care for patients for whom insurance does not cover the bill. Increasingly, the feeling that I, too, force my patients to fit into the mold of medicine is creeping up on me.

On the day our agency announced the consolidation, I was caring for a young woman in our inpatient center. During her stay she had been very verbal about her appreciation for the way the hospice team cared for her and worked together to provide comprehensive care. She felt a level of respect and humanity she had not felt anywhere else in her long experience with medicine both personally and professionally. When she read about the changes in the news paper the next day and sensed the grief we were all feeling she was appalled  hospice would cut back like other areas of medicine. She made it a point to tell us,
“No matter whether you get lumped in with the rest of medicine, you are still special. What you do here is still special. That needs to be recognized.”
I’ve chosen to believe her. Because if I didn’t, it would be hard to continue to do what we do, knowing we now have one hand tied behind our backs. What we do is special. The people in this field are special. As financial resources continue to change, the field will be forced to change as well. What will not change is that there will always be caring nurses, physicians, counselors, and friends who recognize the value of meeting patients where they are and maximizing their lives as they live with serious illness. Seemingly, hospice and palliative medicine is unique in the way we still place value on time and attention to the person. We cannot lose this focus. The way we deliver the care may change. The setting in which we deliver the care may change. I am hopeful the commitment to care will not.

So where do we go with all of our compassion and commitment? I’m grateful to inspired leaders who lead us in the right direction where we can apply these skills. Grateful for the thoughts of leaders in the field like David Casarett, MD, MA who proposes an alternate method of delivering palliative care at home which does not force patients to give up curative treatments or have a prognosis of 6 months in order to get the care they need. And the work of CAPC and Diane Meier MD FACP who argue for expansion of palliative medicine instead of the limitation of it. And organizations like NHPCO’s Hospice Action Network who advocate for policies to ensure the best care for patients and families facing the end of life. Their recent activity at Capitol Hill aims to help maintain the quality care we deliver.

Because the care we deliver is still special. And the needs of our patients don’t always fit into a mold. Let’s not forget that.

Photo Credit: Heart Shaped Hands by nippe011

Friday, August 23, 2013 by K Newport ·

Thursday, August 22, 2013

How Wellness Programs Support Palliative Care in Cancer Related Fatigue

"I know it when I see it."

Famously attributed to Justice Potter Stewart, this phrase suggests that it’s not what you call it but how you perceive it that matters. (Actually, we prefer Sean Connery's use of the phrase in Goldfinger. You can probably check it out on cable tonight, or tomorrow, or this weekend, or...).

One of the risks of starting or growing a palliative care programs is that your constituents, both practitioners and patients, will interpret what that means in the context of their own biases. Too often, the first interpretation is that palliative care means hospice. It's something we all fight. And even if we can get practitioners to get past this hurdle, they can get pretty protective about how their patients are approached. Even if the practitioner knows better, it doesn't mean that the patients will understand. In both cases, I don't think you get the opportunity to have people get a chance to "...see it..."

In our practice, we had more than one failed attempt to integrate palliative care. But we didn't quit; and we didn't lament our failures. We learned from them. We learned that we needed to focus less on what we call it, and on finding ways to make it happen.

Hiring a certified cancer exercise specialist doesn't sound like starting a fledgling palliative care program...but it turns out it is. Focusing on quality of life and helping folks become more able to do what they used to do are central components of a solid palliative care program.

All too often fatigue is simply the way it is for patients with metastatic disease. After multiple treatments, numerous medical appointments and simply feeling terrible, patients spend a significant amount of time in bed dealing with or adding medications to deal with side effects. And that's simply the way it is. Is it really? Hardly.

Over 90% of patients with cancer report fatigue and there are very few solutions offered by traditional medical providers. We can focus on an education and solutions based approach that empowers patients and supporters under our three pillars of wellness; exercise, nutrition and mind/body activities. Why wellness? Wellness is defined as a healthy and proactive approach to living well and being healthy? In patients with metastatic disease? Absolutely!

We know that exercise is one of the most powerful tools to fight cancer related fatigue, but understandably, it’s a very daunting task for most patients. Much of the fatigue that patients experience is loss of lean muscle tissue which is required to complete every single body action from getting out of bed, making meals, working at a job, playing with kids you name it. These muscles are the rocket boosters of moving the body. We all know the use it or lose it saying, this is exactly what happens for our patients. In those with advanced disease, the fatigue is typically greater from the cumulative treatments where patients frequently have a lot of side effects, rest more and are active less. They lose muscle at an even greater rate. This loss often won't show up on the scale as frequently muscle is replaced with body fat.

A cancer specific wellness program shares not only the importance of exercise but how to do it. Education might include tips on chair based strength training the best starting point for deconditioned patient instead of walking, improving core and posture for patients with lung disease.  Energy conservation and input from a dietitian are integral parts of cancer specific wellness programs.  Whenever possible it is best to individualize support even exploring mind body activities, such as meditation, guided imagery and yoga. An introductory class can give patients a taste of all of these so they can have the tools to use what they feel is the most impact for them.

We didn't call what we did palliative care, and we certainly didn't tie any of these services to end of life care. But we certainly gave patients with metastatic disease part of their lives back and there is little doubt it was appreciated.

At the end of the day, that's palliative care...I know it when I see it.

John Hennessy is Vice President, Operations for Sarah Cannon, the global cancer enterprise of Hospital Corporation of America (HCA). His focus areas at Sarah Cannon are medical oncology, survivorship, and palliative care.  He serves on the Board of Trustees of the Association of Community Cancer Centers (ACCC), and on several committees for the American Society for Clinical Oncology (ASCO), including the Clinical Practice Committee. This article was co-written with Sami Papacek a Certified Cancer Exercise Specialist at the University of Kansas Cancer Center.

Thursday, August 22, 2013 by John Hennessy ·

Wednesday, August 21, 2013

Hospice and Palliative Online Efforts Featured in The Atlantic

As longtime readers will know, we here at Pallimed have advocated for social media being an effective change agent for issues relevant to hospice and palliative care for many years. With a thriving blog community (43! But we could always use more blogs!*), a strong Twitter presence of senior leaders and new leaders, a weekly Tweetchat since 2010 and several quality Facebook pages, the specialty which emphasizes communication skills at the bedside has done a good job communicating to the world as well.

Paul Bisceglio (@PaulBisceglio) from The Atlantic featured some of these efforts and the newer trend of being very open about end-of-life issues online and in the public view in his article, "How Social Media is Changing the Way We Approach Death."  The article is nearing over 1000 likes on Facebook in just over 24 hours, which is really impressive for what some might consider taboo.  But what the article and the social media stats on this article tells us, as a field, is that people want to engage on this topic. What a call to us to make sure we are available not only online, but to our communities offline as well.  We as professionals and advocates for quality care for those facing serious illness need to realize the power in sharing the stories and research that we find online.

Sharing is the first and easiest step.  The next is commenting and adding to a fruitful discussion, whether on a blog, Facebook, or every Wednesday night (9p ET) at the #hpm tweetchat.  Even though there are some uncivil places in the comment sections of some sites (not ours!) a smart and genuine comment can really add a lot to an article, so please ignore the loud barks from those impolite faux-raconteurs. And lastly you can contribute by adding original thought and content.  I know there are some brilliant minds out there with great ideas to share.  There are platforms to deliver your message, you just have to try.

* If you know any blogs not on the list, please share.
Photo Credit: Unknown

Wednesday, August 21, 2013 by Christian Sinclair ·

Subscribers Moving to A New Email Delivery Platform

We are moving to a new email delivery system called MailChimp from the old delivery system Feedblitz.  (Yeah, all new companies seem to have silly names. I can't stop them.).  What does this mean for you?

1) No more random ads on the emails
2) Ability to choose your subscription frequency:

  • Daily (Full Post)
  • MWF (Full Post)
  • Weekly (Digest Version - short snippet of each post in the past week)
3) Ability for us to better understand the reasons why emails don't get delivered
4) Prettier looking emails that make you want to read and click
5) Clearer credits for the authors contributing to Pallimed

If you were a subscriber of the Pallimed: Arts and Humanities or Pallimed: Case Conferences blogs, you have been subscribed to the main blog, since that is where those posts will now show up.  Make sure to allow emails from on your email safe list.

I will be working with the look of the emails, so please be patient, let me know if your delivery gets interrupted and send feedback to 

And if you want to be giving, you could always forward this on to your colleagues and ask them to subscribe!

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by Christian Sinclair ·

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