Benefits and harms of drugs for “neuropathic” pain

Benefits and harms of drugs for “neuropathic” pain | Therapeutics Initiative – January 19, 2016

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 no

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.

In 2009 Therapeutics Letter 75 on gabapentin 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.

Benefits

Although all pain metrics have limitations 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.

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.

The greatest potential bias comes from the likelihood that patients and investigators were unblinded by observing drug adverse effects

almost all RCTs included in the Cochrane reviews were funded by drug manufacturers.

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

Harms

Withdrawals due to adverse effects compared with placebo were higher with gabapentin, pregabalin, duloxetine and venlafaxine

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.

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

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.

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. (See Why Most Published Research Findings Are False)
  • 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.

Despite so few positive and so many negatives, the CDC insists such non-opioid medications are “better” than opioids for pain.

In light of research results, this is just ridiculous.

Advertisements

20 thoughts on “Benefits and harms of drugs for “neuropathic” pain

  1. leejcaroll

    am one who benefits from Gabapentin. I have changed the way I take it, my docs always tell me, do what you think best – since been with this so long. I bow take it only when I get pain “tics” from my phantonm pain as opposed to having taken it daily at decent dose. I did find after some time I had trouble finding my words. When I changed to just prophylactically I no longer had the problem. The trade off is now getting these “tics” which the gabapentin had stopped.
    Trump taking away research dollars from the NIH which may well mean even less drugs out there/research to help us deal with the neuropathic pain

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      That’s interesting – I’ve never read anything even suggesting gabapentin can be taken on an as-needed basis. There is so much to be learned from individuals’ experience that will never be studied.

      This could be very helpful for folks like me that cannot tolerate taking it consistently. I wouldn’t mind the horrible dizziness if it was only for a limited time, like a day or less when Im having a pain flare.

      How long after you take it before it has an effect? And how long before it wears off? What dose do you take?

      You’ve given me new hope for using this non-opioid medication.

      Like

      Reply
      1. leejcaroll

        well first as I said I changed it on my own so I ma not givving advice just my experience. After I get a bad tic I will take one or even half a one not sure dose and I tend not to get “tics for at least a few days. (most of the time very rarely I will continue to get them the next day and will take another and that is sufficient for me. Unfortunately because the ‘tics’ are sporadic I cant give you an answer as to how long it lasts. I do know I tend not to get any more tics within maybe half hour or hour and then it will usually be days, that being said I often go for long time without any so I am afraid my answer isnt of much help. I just know it does stop them for an unknow period of time. (I may be unusual though when I took my first gabapentin many many years ago I had the orrendous depression with it. Doc gave me paxil. I took one pill and it runed it around and never had the depression with it again so it just may be my personal body chemistry. sry I cant be of more help

        Liked by 1 person

        Reply
        1. Zyp Czyk Post author

          Thanks for telling your experience. It’s always true that what works for us and how it works for anyone else can be different, but I always want to know anyway because it gives me ideas to try.

          For instance, it would never have occurred to me to try taking gabapentin “as needed”, but now the idea is in my head and the next time my opioids are insufficient, I’ll definitely try that.

          Maybe it’ll work for me too, maybe not, but it gives me another alternative in these times of opioid restrictions and for that, I’m very grateful.

          Like

          Reply
      2. JENNIFER R

        HI, MY NAME IS JENNIFER. I HAVE BEEN ON AND OFF GABAPENTIN FOR 17 YEARS (AS OF MARCH OF THIS YEAR). I HAVE HAD NOTHING BUT AWFUL SIDE EFFECTS WITH IT. SUCH AS; EXTREME FATIGUE, SWELLING, SICKNESS (NAUSEA), HEADACHES, EXTREME WEIGHT GAIN, ANTI SOCIAL BEHAVIOR, SEXUAL INTERRUPTION (NO SEX DRIVE) AND WITHDRAW FROM ANY OUTSIDE ACTIVITIES.
        THERE ARE SO MANY REASONS THAT I AM COMPLETELY AGAINST THIS MEDICATION. DOES ANYONE ELSE OUT THERE SEEM TO SUFFER FROM IT AS I HAVE? I AM CURRENTLY ON ANTI DEPRESSANTS TO HELP OFFSET THE WHIRLWIND OF NASTY SIDE EFFECTS FROM THIS CRAP!

        Liked by 1 person

        Reply
        1. Zyp Czyk Post author

          It sure seems like you should stop taking gabapentin. If it has such terrible side effects, why do you have to take it? Does it help with pain at all?

          Like

          Reply
          1. JENNIFER R

            I REALLY DO NOT FEEL AS THOUGH IT’S HELPED ME WHATSOEVER! I HAVE ALSO REDUCED MY RECOMMENDED DOSES BECAUSE I WAS JUST FEELING LIKE CRAP. IT DOES NOTHING FOR MY NERVE PAIN ASSOCIATED WITH RSD/CRPS. IT DOES NOTHING WITH MY PAIN ASSOCIATED WITH DERCUM’S DISEASE. BUT IT DOES MAKE ME SICK TO MY STOMACH, DIZZY, SWOLLEN, TIRED , INCREASES MY MIGRAINES AND ON TOP OF IT ALL….I GAIN MORE WEIGHT!

            Like

            Reply
  2. Emily Raven

    “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.”

    So much for this utter nonsense that “you have to give it time.” I always knew from listening to others and my own experiences it was a bunch of malarky, but this only confirms they just want to squeeze in those 4 or 5 extra months of Rx to make the drug companies and their employers happy all the while letting the patient suffer horrific side effects on top of untreated pain. (I know, it works for a few people. But treating it like it should work for everyone because of your cherry picked examples is just bad science on top of unethical. Id never say take the drugs off the market because of the few people they DO help so they should be available, but we need REAL talks about risk/harm meanwhile doctors try to tell you they’re as safe as a sugar pill.)

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      Re: treating it like it should work for everyone because of your cherry picked examples is just bad science on top of unethical

      It is truly absurd in this era of knowledge about the vast genetic differences between individuals they would still presume that what can be shown to work for a small subset of patients will work for everyone. These limited studies show barely significant results only by using questionable statistical methods and don’t come close to simulating real life situations.

      You’d think they were completely unaware of the many and significant genetic differences among individuals. Meanwhile, our government is (or was) spending billions of dollars on the recent “precision medicine initiative” intended to individualize treatments precisely because “standardized” treatments are so ineffective for so many people.

      It’s callous and cruel that when a drug doesn’t work and only leads to horrible side effects, they keep insisting you need to take it longer. And if you refuse, they call you noncompliant, a “problem” that needs to be shunted aside and ignored until it goes away (or dies).

      I believe it’s because business people have taken over medical care, with only profit as the guiding principle. You’d think that the agony of atients only exists to create profit for medical corporations. When everything is measured only in financial terms, our care is subjugated to the profits of the corporatation that owns our medical care.

      Liked by 1 person

      Reply
      1. leejcaroll

        I agree wiht you both to some degeree however many meds such as antidepressants can take time, even weeks, before they sow a result. altough it was an implant and not medication I will use myself as an example. I had dorsal column implant. didnt work. eurosurg and I agreed might as well remove it. I didnt want another surgery so didnt do anything. One night 3 months later, long after there was any hope there could be a benefit. the implant started working and 85% of my pain was gone. Had I given up when the doc and I both agreed I might as well i would not have had the benfit for the length o=f time I did.apples and oranges in terms of implant vs med but I think the point of the example holds.

        Liked by 1 person

        Reply
        1. Zyp Czyk Post author

          Your experience is a very strange one and defies explanation. But again, it’s an idea that will stick in my mind if I’m ever in that situation.

          The difference with my experience is the horrible side effects the medications cause. It sounds like the implant wasn’t giving you any trouble and that’s why there was no rush to remove it. If it had made you so dizzy you could barely walk, I think you would not have tolerated leaving it in so long.

          I wouldn’t mind taking a pill that was ineffective for a long time if only the side effects weren’t so awful.

          Like

          Reply
          1. leejcaroll

            (re the implant actually they found once they paid attention to it (!) it was quite common for it take weeks to a few months) I understand what youre saying lyrica and cymbalta for instance gave me such terrible side effects immediately that I refused to take a second one. The neurontin though I was willing to see if something would reduce/end the depression. I recall tegretol gave me terrible balance issues cloudiness speech problems and more but I stayed on it because it was specific for trigmeinal neuralgia. Fighting thru it it did work for me for many years.It always comes down to risk benefit and we each have to decide tat for ourselves.

            Liked by 1 person

            Reply
    2. JENNIFER R

      I HAVE BEEN GOING THROUGH MY ISSUES FOR OVER 17 YEARS NOW….AS FAR AS YOU HAVE TO GIVE IT SOME TIME GOES….HOW LONG WOULD THEY LIKE US TO GIVE IT A CHANCE?

      Like

      Reply
  3. Angela M. Oddone LCSW, Resiliency Strategies LLC

    I’ve also begun to use gabapentin as needed for what I assume is neuropathic pain in my stomach/gut — the enterric nervous system and, perhaps, the vagus nerve. I don’t like the side effects, which is why I take the least amount that’s helpful – 1 100 mg. capsule as needed, usually 0-3 capsules/day. That’s quite different from how it’s prescribed, gradually increasing the dose until it’s at the “therapeutic” dose of 900 mg./day. I’m taking none or between 1/9th & 1/3 of the “therapeutic” dose. Even then, I still experience some side effects, mostly some depression and slight brain fog. They’re much less than when taking it as prescribed which I found wasn’t worth it. I hope to replace it entirely with stress management, neurofeedback and acupuncture.

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      Who knew gabapentin could be used like this?!?

      We pain patients get pretty resourceful in our search for relief and thanks to you two, I now have another trick to try. Even though my response will undoubtedly be different, this gives me a whole new area of experimentation for my own pain.

      Doctors may know ALL about medicine, but no one knows our bodies better than we do. It takes working together, each with their own expertise, to wrestle with chronic pain – a partnership, not a dictatorship.

      Liked by 2 people

      Reply
  4. leejcaroll

    I saw a pain management specialist today. When I told him I changed my neurontn to prn he told me he has many patients who do it that way and he likes it being used as a prn. Just thght Id let you know maybe this practice is not that unknown

    Liked by 1 person

    Reply
    1. Zyp Czyk Post author

      This is terrific info – thanks so much!

      I still have some leftover Lyrica (pregabalin instead of gabapentin) and I’m going to try that next time I’m in a bad flare. My opioids work well most of the time, but when that ferocious pain grabs my viscera, they seem ineffective. Now I feel better-armed :-)

      Liked by 1 person

      Reply

Other thoughts?

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s