Gabapentinoids, yet another dirty secret
Some people with MS are on ten or more concomitant medications including gabapentin or pregabalin. Are you?
It is pretty remarkable how many people with multiple sclerosis (pwMS) are unaware of why they are taking certain medications and the side effects and interactions of these medications. Are you one of them?
Many pwMS are prescribed concomitant medications (con-meds) to manage their many symptoms associated with a damaged or failing nervous system. There is a pharmacological treatment for virtually every MS-related symptom, whether a licensed or unlicensed medication. As a result of this, some pwMS are on ten or more con-meds. Are you?
Your con-meds must be reviewed when you have your six-monthly or annual review. What many pwMS don’t realise is that many medications interact with each other, and often, side effects are not merely additive but synergistic. This is particularly common for medications that are sedating. One that I commonly encounter is the use of a sedating tricyclic antidepressant, such as amitriptyline, in combination with a gabapentinoid (gabapentin or pregabalin), and this is often given on top of an antispastic agent such as baclofen or an opioid for pain.
The following screenshots are from a commonly used online drug interaction checker. This hints at the hidden problems associated with polypharmacy.
I have already written MS-Selfie newsletters on amitryptiline and baclofen, but not on their interactions.
Please see:
A big problem in MS practice is the so-called gabapentinoids (gabapentin and pregabalin). These are used for pain management, spasticity, restless leg syndrome, nocturnal spasms, partial seizures, hiccoughs, chronic cough, pruritus & itch, paraesthesia, the MS hug, Lhermitte’s phenomenon, oscilopsia, nystagmus, sedation, anxiety, etc...
Please be aware that gabapentinoids are only licensed for seizures and pain, so most of this use is off-label. Neurologists love this drug class because the liver does not metabolise them; they are excreted unchanged in the urine and have very few adverse events that need monitoring, such as abnormal liver function tests. In reality, these drugs are another ‘dirty little secret’ of the neurologist.
I became acutely aware of how potent these medications are when I was prescribed a combination of gabapentin with morphine for my acute radicular pain when I sustained my cervical fracture in late 2020. I could not think straight or stay awake for any significant period. I also developed hallucinations on the combination, which resolved when I stopped the gabapentin. My concentration and attention were very poor whilst taking gabapentin. I remember trying to read journals during my recovery and not remembering anything I had read an hour later. My attention and recall only returned to normal when I stopped the gabapentin.
The other downside of gabapentinoids is that you develop tachyphylaxis (needing higher doses to have a treatment effect), and you usually need to increase the dose. They have a short half-life, so you must take them several times daily. For gabapentin (Neurontin), you need 3 to 4 doses per day, and for pregabalin (Lyrica), 2 to 3 doses per day.
Most pwMS on gabapentinoids are unaware that they can become dependent on them, and as a result, they have a well-defined withdrawal reaction. Overall, the clinical presentation of gabapentin and pregabalin withdrawal appears to be similar to that of benzodiazepines: agitation and anxiety, diaphoresis, bodily pain, confusion, tremulousness, gastrointestinal distress, and tachycardia or palpitations. This is why you can’t stop them suddenly; they must be weaned slowly. Have any of you experienced a gabapentinoid withdrawal syndrome?
As a result of increasing abuse of gabapentin and pregabalin, they are now classed as schedule 3 controlled drugs (please see NHS letter, 2019). This means you can only be given and dispensed once, i.e., there are no repeat prescriptions, and the prescription must be dispensed within 28 days of the prescription date. These requirements mean that your GP or neurologist needs to provide you with a new prescription every month.
Despite these negatives, low-dose gabapentinoids, when used appropriately, can make a big difference to the quality of life of pwMS patients. They are excellent as an add-on for spasticity and to help with neuropathic or myelopathic pain. They are my new go-to for MS-related restless leg syndrome. I prefer to recommend them at night as the effect of daytime use on cognition and alertness is a big negative. You should always start these medications at a low dose and gradually increase the dose over weeks to months. Similarly, it would be best if you weaned them slowly.
If you need more information on gabapentin or pregabalin, I recommend reading their product description summaries.
As both of these agents are off-patent, numerous generic versions of these medications exist, so you may have to check the generic name of your medication to determine whether or not you are on them.
The gabapentinoids work via the alpha 2-delta subunits of presynaptic voltage-gated calcium channels and decreased excitatory neurotransmitter release. This mode of action explains why they are so sedating.
There are no specific contraindications to taking these medications, but care should be taken when using them in depressed patients because of suicide risk and in combination with opioids. They can cause rare hypersensitivity reactions and have been associated with rare cases of Stevens-Johnson syndrome. These medications are generally not recommended during pregnancy, and they cross into breast milk.
I would be interested to hear if any of you are taking one of the gabapentinoids and whether or not any of this information is new to you.
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General Disclaimer
Please note that the opinions expressed here are those of Professor Giovannoni and do not necessarily reflect the positions of Queen Mary University of London or Barts Health NHS Trust. The advice is intended as general and should not be interpreted as personal clinical advice. If you have problems, please tell your healthcare professional, who will be able to help you.
I am literally currently reducing my pregab/bac/Amitryptaline due to the terrible brain fog, I am completely outside of my life and have only recently realised that I could be living if I could be more present. Plus the pharmacist says drugs don’t generally work for nerve pain! This is a national scandal, why are we being prescribed meds that won’t work and will only cause adverse effects!
when i was bad i saw a pain med doctor, he said to me, I am not prescribing you anything, as to be honest the only things i can prescribe for you are designed to wipe you out and keep you quiet and your more likely to have an accident. oh i was kind of shocked to be honest. BUT i did try a couple baclofen made me dizzy and horrible 2nd night i fell getting to the commode as i felt so dizzy, gabapentin i felt horrible didn't like it at all and amitriptyline no thanks, so well after years 2000 i take 4mg of diazepam at night, and that's it. i can get up safely, I can think straight in fact my MS nurse is amazed for my age how screwed on i am at 73.
Yes i am in pain all the time, spasticity first thing is so bad i can barely stand up, the burning in legs etc sometimes makes me want to scream, but what i do is go online occupy my brain, take my mind off things, i try and walk a little each day in my bungalow i wont use my wheelchair in the house only outside as i cant walk but a few steps, I have PPMS. OH I EVEN tried SATIVEX definite no no lol. my neurologist understands and said some people are just sensitive to these drugs, so he respects my choices.
i have friends with MS who take all kinds of drugs and some have no idea what day it is, and are constantly falling. NO THANKS.