Are Neuropathy Patients Likely To Be Heavy Smokers Or Vice Versa

Today's post from medscape.com (see link below) seems not to be sure on which side of the fence it sits. The statistics show that far more people with nerve pain smoke heavily than those with nociceptive pain (pain caused by injury and external factors). The article seems to suggest a link between the light analgesic qualities of tobacco/nicotine and that pattern - as if to say that nerve pain patients use cigarettes as a mild pain killer. Yet it is patently clear that the harmful effects of nicotine far outweigh the benefits so it is doubtful that patients consciously make the choice to smoke to chemically ease their pain. Is it not more likely that people with nerve pain are so stressed out by the nature of their symptoms that cigarettes perform their traditional role of 'comforter' in much the same way that over-eating and over-drinking do? The vast majority of neuropathy articles also point to smoking as a cause of neuropathy, so where does that leave us? Whatever the truth, the fact remains that there are more heavy smokers among neuropathy sufferers than those with other forms of pain - the question remains as to why!

People With Neuropathic Pain Twice as Likely to Smoke Cigarettes
Stephanie Doyle February 18, 2008

February 18, 2008 (Kissimmee, Florida) — Results of a new study suggest that people with chronic neuropathic pain are twice as likely to smoke cigarettes as those who have chronic nociceptive pain.

The study, led by Toby N. Weingarten, MD, from the Mayo Clinic College of Medicine in Rochester, Minnesota, showed that of the 205 smokers who participated in the study, 62% had been diagnosed with neuropathic pain, whereas only 33% had been diagnosed with nociceptive pain.

"To us that is surprising — we were surprised that smoking would influence what type of pain smokers had," Dr. Weingarten told Medscape Neurology and Neurosurgery.

The results were presented here at the American Academy of Pain Medicine 24th Annual Meeting.

Poor Response to Medications

Nociceptive pain is the common discomfort experienced as a result of injury, such as a broken bone or appendicitis. Neuropathic pain is associated with injury to a nerve or the central nervous system. Such injuries can give rise to paresthesias, such as numbness, tingling, or electrical sensations.

Nociceptive pain typically responds to anti-inflammatory agents and opiates, whereas neuropathic pain often responds poorly to such medications.

In the current study, the authors aimed to determine the percentage of community subjects with chronic neuropathic pain who smoke. Subjects were recruited from a large population-based study to assess the prevalence of chronic pain.

These adults had self-reported neuropathic pain, were identified from patient charts as having neuropathic pain, or had a positive score on the self-administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS), a tool designed to identify patients with neuropathic pain. They also self-reported current smoking status.

The percentage of participants confirmed as having neuropathic pain by clinical assessment who also smoked was 21%, compared with 13% in the overall sample (P = .009). Smoking was twice as common (62% vs 33%) in subjects who were diagnosed by clinical assessment as having neuropathic pain as nociceptive pain.

The percentages of those who smoked varied by positivity on screening tests for neuropathic pain: 18% for a positive S-LANSS score, 12% with self-reported neuropathic pain, and 8% of those with select ICD-9-CM codes from patient charts.

"The possible physiologic relation between smoking and development of chronic neuropathic pain deserves further evaluation," the authors conclude.

Not Advocating Smoking

"This study is intriguing," said Todd Sitzman, MD, MPH, president of the American Academy of Pain Medicine. "Clinical studies have shown a modest analgesic effect from nicotine. Although there is an association between nicotine and neuropathic pain, there is no direct causative effect."

However, Dr. Sitzman, who was not involved with the study, told Medscape Neurology and Neurosurgery: "I caution advocating smoking as a perceived treatment for neuropathic pain, since it is clear that the adverse risks of smoking outweigh any potential benefit."

Funding was provided by AstraZeneca and the National Institutes of Health. Dr. Weingarten has disclosed no relevant financial relationships.

American Academy of Pain Medicine (AAPM) 24th Annual Meeting: Abstract 100.

Medscape Medical News © 2008

http://www.medscape.com/viewarticle/570347

A Better Understanding Of Both Doctors And Patients Situations

Today's post from health.com (see link below) is pretty much a plea to give doctors a break. As neuropathic patients often in chronic pain and discomfort, we can get frustrated at our doctors' apparent lack of answers; especially if their bedside manner is also somewhat lacking. This article points out a few of the reasons why doctors need to be let off the hook now and then because of the stresses they're under from time management and a results culture. That's not to say that we shouldn't stand our ground now and then and refuse to accept shoddy medical attention but understanding a doctor's predicament will gain their appreciation and lead to better treatment anyway.

How to Get Your Doctor to Take Your Pain Seriously. How to get the treatment you need 

Last Updated: February 29, 2016

 

Good chronic pain treatment can be hard to find. A chronic pain patient has every right to believe that his or her doctor will listen sympathetically and prescribe the appropriate treatment, but that is not always the reality. Truth is, many doctors have not been trained to deal with the complex, changing area of chronic pain treatment. One 2001 survey of primary care physicians' attitudes toward prescribing certain medications found that only 15% said they enjoyed working with patients who have chronic pain.
This can lead to frustrating encounters at the primary-care level, especially if your doctor is rushed.

Pressures on doctors

"Doctors don't want patients to suffer, they want people to get better," says Bill McCarberg, MD, founder of the Chronic Pain Management Program at Kaiser Permanente in San Diego. "But they feel stress, they feel time constraints, they have to deal with pre-authorizations, it's not the kind of practice they wanted. They're stressed, and that leads to moving patients along."

"As a doctor in today's medical system, it's difficult to deal with chronic pain conditions," agrees S. Sam Lim, MD, a rheumatologist at Emory University School of Medicine in Atlanta. "Most practices are forced to see a certain number of patients in a limited amount of time. [With chronic pain] it's not so simple as five minutes, a few questions, and handing out a pill. It takes some time. And our system isn't set up for that."

"The patient needs to realize that the doctor may not be able to discern what's going on in the first visit. Often it takes a few visits," says Dr. Lim.

Doctors are frustrated by what they can't "fix"

In 25 years of caring for her chronically sick husband, who was injured in an industrial accident, Ann Jacobs, 62, of Laramie, Wyo., has watched physicians struggle with the trial-and-error progress of his treatment. "Doctors are programmed for success stories," she says.

Meanwhile, because of its complexity, pain treatment has emerged as a separate, multidisciplinary specialty. That's good, but pain patients often need to get to a pain specialist through their primary care physicians.

Emotions can cloud the diagnosis

The emotional effects of chronic pain may also make diagnosis more difficult. Maggie Buckley, 46, from Walnut Creek, Calif., learned this the hard way. She suffers from Ehlers-Danlos syndrome, a rare genetic tissue disorder that leaves her with chronically painful joints.

"If you say 'it's really depressing and upsetting me, I'm in so much pain,'" Buckley says, "doctors will see it in terms of emotion and treat it as an emotional problem, referring you to psychiatric care or antidepressants." That is sometimes the appropriate treatment route, because antidepressants can treat chronic pain and there is a link between pain and depression, but you need to stand your ground and make sure any treatment is addressing your specific problems.

Be gentle about your pain, but be firm

It's important to be clear about your pain and explain the way it impacts your life when you're talking to your doctor. Don't be intimidated. Stand your ground, calmly.

"Patients really need to be persistent about their complaints in a way that is constructive to get across to the physician that this is something real," says Dr. Lim. "There are some physicians who are more open to listening than others. It may take a few doctors to find a marriage."

"You have to go very gently to start with," advises Ann Jacobs. "Listen to what the doctor has to say first." Then, if you're not satisfied, press harder. But remember that the most important thing is to create a relationship with your doctor in which you're a team, both looking for the best way to alleviate your pain. After he or she has assessed your needs, you can consider seeing a pain specialist.

http://www.health.com/health/condition-article/0,,20188093,00.html

How Keeping Axons Alive May Benefit Neuropathy Patients

Today's post from futurity.org (see link below) tries to explain the new findings regarding the death of nerve cells and nerve axons and how this may eventually lead to significantly better treatments for neuropathy patients. Another post here a few days ago (scroll down to May 3rd) announced the results of this research but as with many articles like this, many people might have found it difficult to follow. This article takes care to explain the science in words we can all understand and for that reason deserves a gold star from this blog. Worth a read - they may be onto something here.

Can saving axons keep nerves alive?
Washington University in St. Louis rightOriginal Study Posted by Caroline Arbanas-WUSTL on May 5, 2015

You are free to share this article under the Attribution 4.0 International license.

New research highlights how nerves—whether harmed by disease or traumatic injury—start to die.

The discovery unveils new targets for developing drugs to slow or halt peripheral neuropathies and devastating neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease, and amyotrophic lateral sclerosis (ALS).

Peripheral neuropathy damages nerves in the body’s extremities and can cause unrelenting pain, stinging, burning, itching, and sensitivity to touch. The condition is commonly associated with diabetes or develops as a side effect of chemotherapy.

Nerve cells talk to each other by transmitting signals along communication cables called axons. Such signals underlie vital activities, such as thinking and memory, movement, and language.

As part of a study published in Science, the researchers showed they could prevent axons from dying, a finding that suggests therapies could be developed to counteract the withering away of nerve axons.

“We have uncovered new details that let us piece together a major pathway involved in axon degeneration,” says senior author Jeffrey Milbrandt, professor in, and head of, the genetics department at Washington University School of Medicine in St. Louis.

“This is an important step forward and helps to identify new therapeutic targets. That we were able to block axon degeneration in the lab also gives us hope that drugs could be developed to treat patients suffering from a variety of neurological conditions.” 

Energy supply

A common thread among many neurological disorders and traumatic nerve injuries is the degeneration of axons, which interrupts nerve signaling and prevents nerves from communicating with one another. Axon degeneration is thought to be an initiating event in many of these disorders. In fact, an unhealthy axon is known to trigger its own death, and researchers are keenly interested in understanding how this happens.

Working in cell cultures, fruit flies, and mice, Milbrandt and coauthor Aaron DiAntonio, professor of developmental biology, and their colleagues showed that a protein already known to be involved in axon degeneration acts like a switch to trigger axon degeneration after an injury.

Moreover, they found that this protein, once unleashed, causes a rapid decline in the energy supply within axons. Within minutes after the protein—called SARM1—is activated in neurons, a massive loss of nicotinamide adenine dinucleotide (NAD), a chemical central to a cell’s energy production, occurs within the axon.

“When a nerve is diseased or injured, SARM1 becomes more active, initiating a series of events that quickly causes an energetic catastrophe within the axon, and the axon undergoes self-destruction,” says first author Josiah Gerdts, an MD/PhD student in Milbrandt’s laboratory.
Keeping axons alive

Working in neurons in which SARM1 was activated, the researchers showed they could completely block axon degeneration and neuron cell death by supplementing the cells with a precursor to NAD, a chemical called nicotinamide riboside. The neurons were able to use nicotinamide riboside to keep the axons energized and healthy.

Nicotinamide riboside has been linked in animal studies to good health and longevity, but its benefits have not been shown in people. The researchers say much more research is needed to know whether the chemical could slow or halt axon degeneration in the body.

“We are encouraged by the findings and think that identifying a class of drugs that block SARM1 activity has therapeutic potential in neurological disorders,” Milbrandt says. “The molecular details this pathway provides give us a number of therapeutic avenues to attack.”

The National Institutes of Health (NIH) and Vertex Pharmaceuticals supported the work.

Source: Washington University in St. Louis 

http://www.futurity.org/nerves-neuropathy-axons-914382/

A Doctors Letter To Chronic Neuropathy Patients Recommended

Today's post from more-distractible.org (see link below) should be required reading for every neuropathy patient and every neuropathy patient's doctor. It's an exercise in humility we could all learn from and will help everybody with chronic pain understand where their doctors are coming from. If you like it, pass on the link to your friends or other people you know with chronic pain. This doctor deserves all our thanks for being honest and giving a side of the discussion we rarely get to see. (See another post on the same subject tomorrow on the blog)

A Letter to Patients With Chronic Disease

by Dr. Rob Lamberts on July 14, 2010 in BEING A DOCTOR, BEST OF, JUST STUFF KIND OF THINGIES, PERSONAL MUSINGS

Dear Patients:

You have it very hard, much harder than most people understand. Having sat for 16 years listening to the stories, seeing the tiredness in your eyes, hearing you try to describe the indescribable, I have come to understand that I too can’t understand what your lives are like. How do you answer the question, “how do you feel?” when you’ve forgotten what “normal” feels like? How do you deal with all of the people who think you are exaggerating your pain, your emotions, your fatigue? How do you decide when to believe them or when to trust your own body? How do you cope with living a life that won’t let you forget about your frailty, your limits, your mortality?

I can’t imagine.

But I do bring something to the table that you may not know. I do have information that you can’t really understand because of your unique perspective, your battered world. There is something that you need to understand that, while it won’t undo your pain, make your fatigue go away, or lift your emotions, it will help you. It’s information without which you bring yourself more pain than you need suffer; it’s a truth that is a key to getting the help you need much easier than you have in the past. It may not seem important, but trust me, it is.

You scare doctors.

No, I am not talking about the fear of disease, pain, or death. I am not talking about doctors being afraid of the limits of their knowledge. I am talking about your understanding of a fact that everyone else seems to miss, a fact that many doctors hide from: we are normal, fallible people who happen to doctor for a job. We are not special. In fact, many of us are very insecure, wanting to feel the affirmation of people who get better, hearing the praise of those we help. We want to cure disease, to save lives, to be the helping hand, the right person in the right place at the right time.

But chronic unsolvable disease stands square in our way. You don’t get better, and it makes many of us frustrated, and it makes some of us mad at you. We don’t want to face things we can’t fix because it shows our limits. We want the miraculous, and you deny us that chance.

And since this is the perspective you have when you see doctors, your view of them is quite different. You see us getting frustrated. You see us when we feel like giving up. When we take care of you, we have to leave behind the illusion of control, of power over disease. We get angry, feel insecure, and want to move on to a patient who we can fix, save, or impress. You are the rock that proves how easily the ship can be sunk. So your view of doctors is quite different.

Then there is the fact that you also possess something that is usually our domain: knowledge. You know more about your disease than many of us do – most of us do. Your MS, rheumatoid arthritis, end-stage kidney disease, Cushing’s disease, bipolar disorder, chronic pain disorder, brittle diabetes, or disabling psychiatric disorder – your defining pain - is something most of us don’t regularly encounter. It’s something most of us try to avoid. So you possess deep understanding of something that many doctors don’t possess. Even doctors who specialize in your disorder don’t share the kind of knowledge you can only get through living with a disease. It’s like a parent’s knowledge of their child versus that of a pediatrician. They may have breadth of knowledge, but you have depth of knowledge that no doctor can possess.

So when you approach a doctor – especially one you’ve never met before – you come with a knowledge of your disease that they don’t have, and a knowledge of the doctor’s limitations that few other patients have. You see why you scare doctors? It’s not your fault that you do, but ignoring this fact will limit the help you can only get from them. I know this because, just like you know your disease better than any doctor, I know what being a doctor feels like more than any patient could ever understand. You encounter doctors intermittently (more than you wish, perhaps); I live as a doctor continuously.

So let me be so bold as to give you advice on dealing with doctors. There are some things you can do to make things easier, and others that can sabotage any hope of a good relationship:

Don’t come on too strong – yes, you have to advocate for yourself, but remember that doctors are used to being in control. All of the other patients come into the room with immediate respect, but your understanding has torn down the doctor-god illusion. That’s a good thing in the long-run, but few doctors want to be greeted with that reality from the start. Your goal with any doctor is to build a partnership of trust that goes both ways, and coming on too strong at the start can hurt your chances of ever having that.

Show respect – I say this one carefully, because there are certainly some doctors who don’t treat patients with respect – especially ones like you with chronic disease. These doctors should be avoided. But most of us are not like that; we really want to help people and try to treat them well. But we have worked very hard to earn our position; it was not bestowed by fiat or family tree. Just as you want to be listened to, so do we.

Keep your eggs in only a few baskets – find a good primary care doctor and a couple of specialists you trust. Don’t expect a new doctor to figure things out quickly. It takes me years of repeated visits to really understand many of my chronic disease patients. The best care happens when a doctor understands the patient and the patient understands the doctor. This can only happen over time. Heck, I struggle even seeing the chronically sick patients for other doctors in my practice. There is something very powerful in having understanding built over time.

Use the ER only when absolutely needed – Emergency room physicians will always struggle with you. Just expect that. Their job is to decide if you need to be hospitalized, if you need emergency treatment, or if you can go home. They might not fix your pain, and certainly won’t try to fully understand you. That’s not their job. They went into their specialty to fix problems quickly and move on, not manage chronic disease. The same goes for any doctor you see for a short time: they will try to get done with you as quickly as possible.

Don’t avoid doctors – one of the most frustrating things for me is when a complicated patient comes in after a long absence with a huge list of problems they want me to address. I can’t work that way, and I don’t think many doctors can. Each visit should address only a few problems at a time, otherwise things get confused and more mistakes are made. It’s OK to keep a list of your own problems so things don’t get left out – I actually like getting those lists, as long as people don’t expect me to handle all of the problems. It helps me to prioritize with them.

Don’t put up with the jerks – unless you have no choice (in the ER, for example), you should keep looking until you find the right doctor(s) for you. Some docs are not cut out for chronic disease, while some of us like the long-term relationship. Don’t feel you have to put up with docs who don’t listen or minimize your problems. At the minimum, you should be able to find a doctor who doesn’t totally suck.

Forgive us – Sometimes I forget about important things in my patients’ lives. Sometimes I don’t know you’ve had surgery or that your sister comes to see me as well. Sometimes I avoid people because I don’t want to admit my limitations. Be patient with me – I usually know when I’ve messed up, and if you know me well I don’t mind being reminded. Well, maybe I mind it a little.

You know better than anyone that we docs are just people – with all the stupidity, inconsistency, and fallibility that goes with that – who happen to doctor for a living. I hope this helps, and I really hope you get the help you need. It does suck that you have your problem; I just hope this perhaps decreases that suckishness a little bit.

Sincerely,

Dr. Rob

http://more-distractible.org/2010/07/14/a-letter-to-patients-with-chronic-disease

Is Amitriptyline Of Benefit To Neuropathy Patients

Today's post from nzdoctor.co.nz (see link below) talks about the effectiveness of Amitriptyline for the relief of neuropathic symptoms. Amitriptyline is one of the first line of drugs generally prescribed for neuropathy problems, after the over the counter analgesics. It's an anti-depressant and seems to work for some patients and not others. The article here suggests that it is probably ineffective for chemotherapy or HIV-related forms of neuropathy but possibly works for diabetes-related nerve problems and neuropathy stemming from other conditions. Unfortunately, it doesn't explain why or how these conclusions have been reached and that is what we really need to know. Doing further research on the internet yourself will undoubtedly give you more information, or failing that, doing a search here on this blog (on the right of the page) for amitriptyline will bring up more articles about its use in treating neuropathy. You could also ask your doctor, or specialist to explain the differences in effectiveness. Many patients will be confused that a medication is thought to work for neuropathy caused by one disease but not another, especially when the symptoms are very much the same, irrespective of the cause - further information is therefore necessary. The article also fails to mention the possible side effects of taking amitriptyline, which once again, can be a problem for some but not for others.

Limited evidence for benefit of amitriptyline for neuropathic pain and fibromyalgia in adults

Wednesday 13 March 2013, 11:23AM

PEARLS 382, February 2013, written by Brian R McAvoy.

(DownloadsPEARLS 383 PDF)

Clinical question
How effective is amitriptyline for neuropathic pain and fibromyalgia in adults?

Bottom line
Amitriptyline probably does not work in neuropathic pain associated with HIV or treatments for cancer. Amitriptyline probably does work in other types of neuropathic pain (painful diabetic neuropathy, post-herpetic neuralgia, and post-stroke pain, and in fibromyalgia), though we cannot be certain of this. A best estimate is that amitriptyline provides pain relief in about 1 in 4 (25%) more people than does placebo (NNT* = 4.6 [95% confidence interval 3.6Ð6.6]), and about 1 in 4 (25%) more people than placebo report having at least 1 adverse event, probably not serious but disconcerting.*NNT = number needed to treat to benefit 1 individual.

Caveat
There were no studies that could provide an answer that was trustworthy or reliable because most studies were relatively old, and used methods or reported results that we now recognise can make benefits seem better than they are.

Context
Amitriptyline is a tricyclic antidepressant that is widely used to treat chronic neuropathic pain and fibromyalgia, and is recommended in many guidelines. These types of pain can be treated with antidepressant drugs in doses below those at which the drugs act as antidepressants.

Cochrane Systematic Review
Moore RA et al. Amitriptyline for neuropathic pain and fibromyalgia in adults. Cochrane Reviews, 2012, Issue 12. Art. No.: CD008242.DOI: 10.1002/14651858. CD008242.pub2.

This review contains 21 studies involving 1437 participants.

http://www.nzdoctor.co.nz/gp-resources/pearls/2013/march-2013/13/limited-evidence-for-benefit-of-amitriptyline-for-neuropathic-pain-and-fibromyalgia-in-adults.aspx

The Scandal Of Lyrica Gabapentin And Cymbalta For Neuropathy Patients

Today's post from ti.ubc.ca (see link below) reinforces the latest evidence that shows that Lyrica, gabapentin and Cymbalta (pregabalin, gabapentin and duloxetine) have very little effect on patients' nerve pain when compared to placebos. It's enough to make you hopping mad (if hopping weren't so painful!) when you realise that very successful pharmaceutical company advertising campaigns have promoted these drugs to the top of doctors' lists when treating neuropathic pain. The patient clearly comes last in the equation and for years now people have been exposed to these drugs and their side-effects without any proven benefits. Time to have a serious discussion with your doctor or specialist, wherein you can ask them how they can justify their prescriptions. The idea that doctors turned to these drugs to prevent a rapid progression towards opioids is just to weak for words.

Benefits and harms of drugs for “neuropathic” pain 
January 19, 2016 Therapeutics  Cochrane reviews

Chronic pain (at times presumed to be “neuropathic” in origin) is a common problem in clinical practice. It is now well recognized that the results of drug treatment are more often disappointing than not.1 Despite this, from 2005-2014 the number of British Columbians prescribed gabapentin increased 1.8 fold, pregabalin 17 fold, and duloxetine 3.6 fold (from 2008). Use of venlafaxine (mostly for depression/anxiety) has remained relatively stable.

Most gabapentin, pregabalin, and duloxetine use in B.C. is for chronic pain, driven partly by concern about problems with long-term opioid therapy. For the same reason, tricyclic antidepressants (amitriptyline, nortriptyline, imipramine, desipramine) are often prescribed for “neuropathic” pain.

In 2009 Therapeutics Letter 75 on gabapentin2 concluded:
Gabapentin reduces neuropathic pain by < 1 point on a 0-10 point scale and benefits about 15% of carefully selected patients (NNT=6-8).
A similar proportion of people suffer harm (NNH=8).
A test of benefit/harm can be made after 1-2 days at a low dose (100-900 mg/day).
Benefit is unlikely to increase with higher doses or longer treatment.

This Letter updates information on gabapentin and critically appraises randomized clinical trials (RCT) assessing the benefits and harms of three other drugs promoted for neuropathic pain: pregabalin, duloxetine, and venlafaxine. It is based primarily on 4 Cochrane reviews.3-6 Like many systematic reviews, these either did not assess risk of bias, or did not fully reflect the implications of the risk of bias in their conclusions. We attempt to demonstrate how appreciation of the biases in RCTs can be incorporated into the conclusions of systematic reviews.

Benefits

Although all pain metrics have limitations7 a 50% or greater reduction from a baseline pain score has been promoted as a more clinically relevant outcome for “neuropathic” pain because it correlates with improvements in comorbidity, function and quality of life.4 Using this outcome across all 4 Cochrane reviews, the mean number of people who must be treated for one to achieve a ≥ 50% reduction in pain (NNT) compared to placebo is about 6. This calculation is based on all doses that were statistically significantly superior to placebo. The evidence is weakest for venlafaxine, but even for gabapentin, pregabalin, and duloxetine, this NNT is likely very optimistic, as we judged the included RCTs to have a high risk of bias.

The greatest potential bias comes from the likelihood that patients and investigators were unblinded by observing drug adverse effects such as somnolence. Loss of blinding has been shown to be associated with a 68% exaggeration of relative benefits for subjective outcomes such as pain.8 In addition almost all RCTs included in the Cochrane reviews were funded by drug manufacturers. A separate Cochrane review demonstrated that industry funded studies lead to “more favourable results and conclusions” than non industry funded studies.9 Accounting for these biases, we suspect the real NNT for benefit from these drugs is at least 10.

An alternative measure of meaningful benefit is the patient’s reported global impression of change (PGIC). PGIC was not reported in any venlafaxine RCT3 and no meaningful difference was found for duloxetine.4 For gabapentin and pregabalin, the estimated NNT for “much or very much improved” PGIC ranges from 6-10.5,6 Like the ≥50% pain score reduction, this is probably overly optimistic.

The evidence of benefit for tricyclic antidepressants for neuropathic pain is weaker and it is not possible to estimate a meaningful NNT.10-13
 
Harms

Withdrawals due to adverse effects compared with placebo were higher with gabapentin, pregabalin, duloxetine and venlafaxine.3-6 Approximately 80% of people receiving these drugs experienced at least one adverse effect. The most common were somnolence, dizziness, and nausea. Anticholinergic effects, such as dry mouth and constipation, were common with duloxetine. The rate of adverse effects reported in Cochrane reviews almost certainly underestimate the real world rates because patients at higher risk (e.g. from impaired kidney function, alcohol use, or with other morbidities) are excluded from RCTs. Furthermore, official product monographs for these drugs report higher rates of adverse effects than do the Cochrane reviews.

The most common adverse effects reported for the tricyclic antidepressants were dry mouth, sedation and constipation.10-13 Likewise official monographs provide a better and higher estimate of the incidence of harms than the systematic reviews. 

To whom do the Cochrane reviews apply?

Patients averaged 50 years of age, had moderate levels of neuropathic pain, and were free of medical conditions other than those being studied (diabetes, fibromyalgia, or post-herpetic neuralgia). RCTs varied with respect to allowed use of other analgesics from acetaminophen only to the use of multiple analgesics including opioids. 

How soon is pain reduced?

In the majority of trials pain reduction compared with placebo was demonstrable within the first week. Very little additional pain reduction occurred after the second week.

Is there evidence that increasing dose improves response?

For gabapentin, pregabalin, duloxetine and venlafaxine, RCTs demonstrated little or no benefit from doses higher than the lowest dose that was superior to placebo.3-6
 
Clinical implications

Evidence from 8 Cochrane reviews should temper expectations regarding the likelihood and magnitude of pain relief from gabapentin, pregabalin, duloxetine, venlafaxine, amitriptyline, nortriptyline, imipramine or desipramine. When initiating a therapeutic trial with one of these drugs in a patient, it is reasonable to start at the lowest recommended dose and assess the patient for benefit and harm at 1 week. If benefit harm ratio is unacceptable, consider stopping the drug. If insufficient but partial pain relief is achieved, increase the dose and reassess within 1 week. If functionally meaningful benefit is still absent, stop the drug and try something else. For patients who achieve clinically meaningful analgesia, use the lowest individualized effective dose to minimize adverse effects. Reassess regularly (e.g. every 2 weeks), as most patients treated with placebo also improve over time.

Conclusions 
 
The evidence base for drug treatment of neuropathic pain is weak, due to the small magnitude of clinically meaningful effects and the high risk of bias in the RCTs.

Probably less than 1 in 10 patients achieve a meaningful reduction in pain.
Most patients experience some adverse side effects like somnolence, dizziness, nausea, dry mouth and constipation.
To identify patients who respond, a therapeutic trial with early assessment is essential. Reassessment of drug utility is needed to detect people with spontaneous remission or placebo response.
Higher doses are unlikely to achieve greater pain reduction, but are more likely to cause harm.

References 
 
Moore A, Derry S, Eccleston C, Kalso E. Expect analgesic failure; pursue analgesic success. BMJ. 346:f2690, 2013.
Therapeutics Initiative. Gabapentin for pain. New evidence from hidden data. Therapeutics Letter. 2009; 75:1-2.
Gallagher HC, Gallagher RM, Butler M, et al. Venlafaxine for neuropathic pain in adults. Cochrane Database of Systematic Reviews, 2015 Issue 8. Art. No.: CD011091. DOI: 10.1002/14651858. CD011091.pub2.
Lunn MPT, Hughes RAC, Wiffen PJ. Duloxetine for treating painful neuropathy, chronic pain or fibromyalgia. Cochrane Database of Systematic Reviews 2014, Issue 1. Art. No.: CD007115. DOI: 10.1002/14651858.CD007115.pub3.
Moore RA, Straube S, Wiffen PJ, et al. 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.
Moore RA, Wiffen PJ, Derry S, et al. Gabapentin for chronic neuropathic pain and fibromyalgia in adults. Cochrane Database of Systematic Reviews, 2014, Issue 4. Art. No.: CD007938. DOI: 10.1002/14651858.CD007938.pub3.
Ballantyne JC, Sullivan MD. Intensity of Chronic Pain – The Wrong Metric? N Engl J Med 2015;373(22): 2098-9.
Hrobjartsson A, Thomsen AS, Emanuelsson F, et al. Observer bias in randomized clinical trials with measurement scale outcomes: a systematic review of trials with both blinded and nonblinded assessors. CMAJ 2013 Mar 5;185(4):E201-11.
Lundh A, Sismondo S, Lexchin J, et al. Industry sponsorship and research outcome. Cochrane Database of Systematic Reviews 2012, Issue 12. Art. No.: MR000033. DOI:10.1002/14651858.MR000033.pub2.
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The draft of this Therapeutics Letter was submitted for review to 60 experts and primary care physicians in order to correct any inaccuracies and to ensure that the information is concise and relevant to clinicians.
The Therapeutics Initiative is funded by the BC Ministry of Health through a grant to the University of BC. The Therapeutics Initiative provides evidence-based advice about drug therapy, and is not responsible for formulating or adjudicating provincial drug policies .

http://www.ti.ubc.ca/2016/01/19/96-benefits-and-harms-of-drugs-for-neuropathic-pain/