Pregabalin half life - 2/3 daily dose

I'm doing really well on this medication - currently on 150mg twice daily (300mg). I take my first dose at 5.30am (I go to work early so I am able to pick kids up from school) and it works a treat until around12-1pm when I feel I need my next dose (this has been consistent from 25mg twice daily right up to this dose). Trouble is I am waking up 2/3 am with anxiety/overthinking. The couple of occasions I've managed to take my last dose 7/8pm I've slept wonderfully.
I've asked my gp twice if I could take my dose 3 times daily and he has refused but has agreed to titeate me up over next 3 weeks to 225mg twice a day (450mg).
I'm concerned that I'll still have the problem of feeling anxiety from midday so taking my second dose and then missing out on the sleep benefits through the night (or am I actually going into withdrawals?) .
I'm pretty sure there is a cost issue that's stopping the 3 times dose so can anyone give me any advice if I need to ask again in 3 weeks for the 3 times per day? (Gp thinks the higher dose will take me through the day but I'm not convinced!)
Thank you any advice welcome,
Tal

I'm having the same issue with Gabapentin, which is a similar med. I had to restart it (long story). I found that it would wear off after 6 hours and then I would feel anxiety until I took the next pill. My doctor said to take it twice a day, although I think she said most people take it 3 times a day. If it's the same dosage spread out throughout the day, I don't see why it would be an issue. I would ask your doctor about taking three doses. That's what I plan on doing!
Keep us posted!

Unfortunately, a higher dose does not mean longer half life or it "lasting longer". I take 150mg thrice daily and found that the best regimen. Difference here though is, I take pregabalin for pain. GP tried switching me to higher dose twice daily but I felt it was wearing off after 4-5 hours.

A psych would have a better understanding of this and wouldn't be so constricted by cost issues like a GP is. You can only try asking again, explaining how you feel the effect is wearing off after several hours, leaving you prone to anxiety and disturbing your sleep patterns.

Yep, cost is a factor as it means prescribing more packs of a med and the more you redcue dosages, the less cost efficient they get too.

As far as the cost to the GP goes, all a psychiatrist can do is agree it. Unless that psychiatrist is doing the prescribing, it's your GP that will be doing it and they pay the cost. When you see psychiatrists in CMHT services once they hand you back, all cost is with your GP and even before then the psychiatrist can just be the approver & monitor with the cost remaining with the GP who referred you. It's just the same when see other specialists when it comes to long term meds.

When it comes to drugs you tend to hear about half lives. But which are they? Mostly it's the "elimination" half life. But there are ones for Distribution too to explain how the med is passed around and Absorption is another common one. These are atcually really important to understand with meds like Benzo's as the elimination half life is far longer than the effect of the drug because it's the distribution that matters and along with the absorption half life it explains how the drug kicks in & builds up it's effects. Just a point there in case it's ever any use.

With Pregabalin the elimination half life is 6.3 hours. At this point it has eliminated 50% of the dose. Each half life from there elimates a further 50% until it hits 0%. The standard pharmacokinetic calculation shows x5 half lives = <5% (clinical insufficient) and x7 half lives - 100% elimination. Some drugs match this calculation as shown in clinical studies although some don't, hence it's just a guide.

Pregabalin hits it's peak of absorption within 1.5 hours (studies also quite 0.7-1.3 hours). At this point you are getting the max it can provide of that dose (which is not the daily dose, it's the the max mg of the tablet taken at that point). If you overlap two doses then you still won't get full dose+full dose unless you also overlap the peak periods.

Going back to you question, it depends what they want to achieve if you purely look at the numbers in this.

By raising the dose it means that at 6.3 hours you are still at half but now at half of the max a 225mg dose can provide as opposed to a 150mg dose. That does then continues to be eliminated and at 12.6 hours you are at 25%. But that's now 25% of 225mg and not 150mg. Therefore your GP is raising the peak, the normal 100-50% treatment window plus the post 50% treatment window.

The other way is to spread the dose out. This won't mean the drug gets to 225mg as you are splitting a to 100mg X 3 per day so the max is 100mg. But what it will do is cause more overlap and reduce the length of the post 50% periods. You are also reducing the ability of the peak as it can no longer get to 150mg.

What this can depend on is whether you need to hit the peak. If a lower dose than the current one isn't enough, that might be an issue. However, consideration needed to how the 3 doses will overlap since that will mean you are getting more than you potentially are now at certain points of the day (which I believe is your thinking) because that current 50% may be elevated by the closer overlaps. Does that make sense?

You could try to calculate this but it won't be exact.

The standard pharmacokinetic calculation is also used in the oppsite direction to determine when a drug reaches "steady-state" in blood plasm when first starting a med or increasing a dose. Pregabalin reaches steady state in 24-48 hours. This is a large spread of hours when the elimination half life is only 6.3 hours since the standrad calc would give us 6.3X5 = 31.5 hours. This shows that Pregabalin doesn't quite conform to the standard calc, it varies below & above. The trouble with this spread is that it might take into account absorption issues in certain populations where it can take longer e.g. the elderly or renally impaired. So, from an elimination point of view, it might be 24-48 hours to reach complete elimination rather than going 5X6.3 = <5% & 7X6.3 = 0%. Incidentally, 7x would put it at 44.1 hours which is near the steady-state calculation when going the oppsosite way, which is interesting.

If accessing a psychiatrist is hard, how about asking a pharmacist? Pharmacokinetics is after all, their area rather than doctors.

I also seem to recall NHS Trust docs mentioning a lack of clinical evidence for 3X dosing and that might be a reason why your GP is taking this stance.

THanks for the replies - wow very interesting 👍🏼.

I am kind of resigned to taking the 2 doses as I do like my gp and don’t want to push too much. Plus sleeping better too anyway last couple of nights.

I can honestly say what a marvellous medication pregabalin is - has completely turned my life around!

It is possible to slice open capsules with sharp scissors or a blade, empty out the contents (powder) onto a sheet of paper, and carefully divide it up however you like. I've done this - the powder has a slightly bitter taste, but is easily swallowed with water or juice, etc. I scoop it up on the tip of a pocket-knife. The remainder can be carefully folded in the paper and set aside.