Post DAWS: Pregabalin Augmentation

Hi, All. I found a couple of older threads started by Joolsg inviting comments on some studies that suggested that the risk of augmentation was lower for pregabalin than it was for the dopamine agonists. Given their age--and since there is a slight twist to my story--I've enlarged the Subject to include the impact of last year's DAWS experience.

Following last year's experience with DAWS Hell, I noted a positive side-effect: absent medication, my RLS had diminished during the late morning, afternoon, and early evening hours. Pregagalin was re-prescribed for me about a month ago to handle my late evening and early morning RLS. But things didn't go quite as anticipated.

If I took 1 x 75 mg pregabalin @ Midnight, I would be awakened two hours later with horrific RLS discomfort; if I took a second 1 x 75 mg pregabalin @ 2:00 AM, I again would be awakened two hours later with horrific RLS discomfort; if I took the third 1 x 75 mg pregabalin @ 4:00 AM, I would sleep for about five hours, but would be awakened with horrific RLS. Perhaps the reason that I slept for about five hours following the dose taken @ 4:00 AM might be because, even without pregabalin, my RLS might have abated anyway after about two hours? And perhaps pregabalin was not augmenting my RLS but instead was causing my RLS?

Taking the initial dose two hours earlier neither increased the duration of relief following the Midnight dosing, nor eliminated my 2:00 AM awakening. And, if I "doubled-up" on the dosage (i.e, took 2 x 75 mg pregabalin in a single late evening or early morning dose), I not only experienced insomnia, but the RLS discomfort at awakening was unbearable. I did not look forward to being awakened in pain @ 2:00 AM and @ 4:00 AM each morning. Time for a change.

Yesterday, I ceased pregabalin. I now am celebrating the longest period--at any time within more than the past 25 years years--during which I have not taken--nor felt the need to take-- any RLS medication. The result: I slept soundly this past evening, without interruption. Minor discomfort aside, my late morning and afternoon discomfort today has been much less than it had been in more than 25 years. Did I have RLS? Yes. Was it bad? Very much so. Was it primary? Absolutely! My father before me had suffered nightly with this horrific malady. What changed?

Though it may be too early to draw fixed conclusions, for now, my working hypothesis is that the "shock" of last year's DAWS Hell caused my brain to compensate by increasing the amount of dopamine otherwise produced. With the passage of time since then, the amount of dopamine being produced appears still to be on an upward trajectory. Whether and when it may reach a plateau (or reverse its ascent) is to be determined.

In hindsight--even with the knowledge that my RLS discomfort would be substantially diminished once I had emerged from DAWS Hell--I am not sure that I would have chosen to endure that horror. Still, for those at the brink of RLS despair, it may be worth discussing with a qualified health care provider whether or not there may be an eventual positive outcome for those who experience DAWS and, if so, whether or not they may be an appropriate candidate.

Be well.

[SueJohnson]

I know you no longer believe it was augmentation but to set the record straight the study said the rate of augmentation on 182 people taking 300 mg of pregabalin was only 1.7% to 2.1%.

[Hidden in reply to SueJohnson]

Good evening, SueJohnson, and thanks for reply. Yes, I realize that the study said that the rate of augmentation was relatively low (~2%). But if memory serves, it also said that the rate of augmentation from dopamine agonists--though somewhat higher--was also relatively low (~6%). Apologies if my memory is faulty on this score, but if my memory of the relative percentages of augmentation is even close to accurate, they strike me as absurdly low. In fact, in my opinion anyway, so low as to render the current argument against the use of dopamine agonists as a "first line" treatment for RLS to be without significant basis.

Be well.

[SueJohnson in reply to Hidden]

Up to 70%. of people on DAs will suffer from augmentation.

[Hidden in reply to SueJohnson]

Good morning, SueJohnson. Sorry for brief delay in reply: not content to leave well enough alone, I "experimented" early this morning (~1:45 AM local time) and took a single capsule of 1 x 75 mg pregabalin to see its effect on relatively minor RLS. As expected, no perceptible relief; insomnia.

As to the comparison of percentages of persons experiencing augmentation while using pregabalin v. dopamine agonists: I haven't yet re-found the original thread started by Joolsg in which the older stud(ies) to which I referred were cited. However, a quick search just now found a 2014 study initially published in the New England Journal of Medicine. In pertinent part:

"The rate of augmentation over a period of 40 or 52 weeks was significantly lower with pregabalin than with pramipexole at a dose of 0.5 mg (2.1% vs. 7.7%, P=0.001) but not at a dose of 0.25 mg (2.1% vs. 5.3% ..." My emphasis. P=0.08).pubmed.ncbi.nlm.nih.gov/245...

Again, it is my contention that, even if the augmentation rate were 2.1% for pregabalin v. 7.7% for everyone who used a dopamine agonist regardless of the dose or length of usage, that statistic would not justify the abandonment of pramipexole as a first line RLS treatment in favor of pregabalin.

Clearly 70% augmentation would. However, to the best of my memory, the findings based on the data cited in the older stud(ies) to which my initial post referred were nowhere near 70% augmentation.

Be well.

[SueJohnson in reply to Hidden]

It is not surprising that 75 mg of pregabalin provided no relief. I would have been surprised if it did. That's just a starting dose. There are several sources for the UP TO 70%. One is the Mayo Clinic Updated Algorithm for RLS. "this occurs in about 40% to 70% of patients during a 10-year period or at an annual rate of 8% per year for at least the first 8 years of use. Another one is the Spring Night Walkers 2022 which says "7-8% develop augmentation each year. By 10 years almost 80% will have augmented." The problem is the article you cited was only for 1 year and it is pretty close to what is stated in the above.

[Hidden in reply to SueJohnson]

Good afternoon, SueJohnson, and thanks for your further reply.

Yes, I am aware that 1 x 75 mg is regarded as only a starter dose. However, I re-started pregabalin on December 6, 2022, and titrated to daily Not-to-Exceed of 3 x 75 mg pregabalin. I omitted from original post the substance of my discussions with my neurologist just a few days ago. I informed her of my atypical experience following individual doses of 1 x 75 mg each, and that I did not favor awakening in pain every two hours just to take another 1 x 75 mg capsule. She suggested that I continue as I had been. I opted to cease altogether later that day.

There have been other studies in the years since those to which I initially referred. The earlier studies were no less authoritative, and were subscribed to by some world-renowned sleep experts, including the late Dr. Richard Allen. These early studies--not the later studies--began the trend away from dopamine agonists in favor of pregabalin.

Though the "algorithm de jure" now endorses pregabalin rather than dopamine agonists as a first-line treatment for RLS due to the "70%" rate of augmentation, I venture than some of us yet may live to see pregabalin's fall from grace in favor of a renewed interest in dopamine agonists.

I earlier posted elsewhere a link to a different website that includes ratings and user reviews for various of the more popular RLS medicines. For convenience, I'm doing so again. drugs.com/condition/restles... A quick look-see shows that some of the more popular dopamine agonists were rated with equal or greater favor as pregabalin.

Be well.

[SueJohnson in reply to Hidden]

Of course they were. They work great until augmentation occurs which is far removed from when they rated the drug. And initially there are few if any side effects for DAs which bring down the rating for pregabalin which only had 13 reviews. And more people on pregabalin probably can't live with the side effects and so also don't give it as good a review. And look at the 121 ratings for gabapentin for gabapentin which is basically the same thing as pregabalin.