ok I'm starting

[MyNameIsTerry]

This is a very interesting situation.

Although the half-life of diazepam is quite long, the half-life of pregabalin is quite short.

Nevertheless, people often take diazepam for short-term problems, and pregabalin for long-term ones.

The only rationale that I can think of is that benzodiazepines are both fast-acting and intense, whereas pregabalin is neither.

The answer is that there is more than one half life. Because Benzo's are fast acting, you look at the Distribution half life. That's around a few hours max for Diazepam, it's typically one hour though. It also has an Absorption half life which differs slightly.

The half life you have been thinking of is the Elimination half life which is just a measure of your body getting rid of half the dose.

Meds like antidepressants are slow acting meds and so other than their absorption rate and peak time, we only think of how long they are in our bodies doing their work. fast acting meds can be largely doing nothing for the majority of their Elimination half life.

Pharmacokinetics
Absorption
After oral administration >90% of Diazepam is absorbed and the average time to achieve peak plasma concentrations is 1 – 1.5 hours with a range of 0.25 to 2.5 hours. Absorption is delayed and decreased when administered with a moderate fat meal. In the presence of food mean lag times are approximately 45 minutes as compared with 15 minutes when fasting. There is also an increase in the average time to achieve peak concentrations to about 2.5 hours in the presence of food as compared with 1.25 hours when fasting. This results in an average decrease in Cmax of 20% in addition to a 27% decrease in AUC (range 15% to 50%) when administered with food.

Distribution
Diazepam and its metabolites are highly bound to plasma proteins (Diazepam 98%). Diazepam and its metabolites cross the blood-brain and placental barriers and are also found in breast milk in concentrations approximately one tenth of those in maternal plasma (days 3 to 9 post-partum). In young healthy males, the volume of distribution at steady-state is 0.8 to 1.0 L/kg. The decline in the plasma concentration-time profile after oral administration is biphasic. The initial distribution phase has a half-life of approximately 1 hour, although it may range up to >3 hours.

Metabolism
Diazepam is N-demethylated by CYP3A4 and 2C19 to the active metabolite N-desmethylDiazepam, and is hydroxylated by CYP3A4 to the active metabolite temazepam. N-desmethylDiazepam and temazepam are both further metabolized to oxazepam. Temazepam and oxazepam are largely eliminated by glucuronidation.

Elimination
The initial distribution phase is followed by a prolonged terminal elimination phase (half-life up to 48 hours). The terminal elimination half-life of the active metabolite N-desmethylDiazepam is up to 100 hours. Diazepam and its metabolites are excreted mainly in the urine, predominantly as their glucuronide conjugates. The clearance of Diazepam is 20 to 30 mL/min in young adults. Diazepam accumulates upon multiple dosing and there is some evidence that the terminal elimination half-life is slightly prolonged

[hanshan]

Thanks so much for this, Terry. It explains a lot that wasn't aware of.

[skymaid]

ok the gp said to stay at 300mg for 4 weeks since she said the dose can take a month or so to kick in.

the shrink said I CAN go up to 600mg but not that I should or when

i'll see how it goes.

after a week or so on 300mg I dont feel mega calm or anything. going out is a bit easier but I still got pretty panicky going to the doctor. and I still feel weird/shakey in the mornings.

we shall see.

[skymaid]

Going up to 450mg now for a bit of extra umpf(?).

Ive gone up 50mg everyday 2 days but stopped at 400mg because i was getting a bit too wobbly and sleep. I'll probably go up to 450 in the next day or two.

Feeling noticeably calmer on 450mg vs 300mg

[aprilmoon]

That's good to hear,sky.
Good luck with the next increase

[djkhaled]

This is kind of crazy, I have emetophobia and have had Lyrica sitting at my house for about a year terrified to even try it because I'm scared it will make me sick even though I've never read about it making anyone sick and I've read so much stuff about it. SSRI's are a no go for me and if my anxiety/emetophobia doesn't improve soon I'm probably going to die.

[hanshan]

Hi Djkhaled,

Welcome to NMP. As you say, pregabalin is not usually linked to symptoms related to emetophobia, and if reduces your anxiety it may be helpful. It may be worth a try if you are getting to your wits' end.

[SmilingAlbert]

hi djkhaled,

The NHS here specifically says this:

"Pregabalin is less likely to cause nausea or a low sex drive than SSRIs or SNRIs."

http://www.nhs.uk/Conditions/Anxiety...Treatment.aspx

I never have felt sick as a result of taking it. Indeed, nausea as a result of anxiety was a major problem for me - Preg cured that.

Good luck,

Albert

[hanshan]

Hi Skymaid,

I hope you are going okay on the increased dose. You said it made you feel sleepy and wobbly as well as calmer. Hopefully, the sleepiness and wobbliness will wear off but the calmness remain. I did feel less coordinated for some time at first, but not now.

[skymaid]

Hi hansan. Yes its wearing off already. The dry mouth in the mornings is back though.

djkhaled: I have emetophobia too so i couldnt take ssri's either. My psychiatrist said he's never heard of anyone having any emetophobia related symptoms in 10 years or fo of prescribing it. The reason he suggested it was because of the mild side effects. My gp backed that up too. I was still really scared do they gave me a few 5mg diazepams to take when i started so i didnt care do much. That worked really well. I still got nervous but the diazepam stopped it turning into a panic. After taking a couple of doses i stopped worrying.

Although i got a bit nervous going up to the red capsules because i stupidly read on the internet the different colour pill capsules can effect the stomach differently. Which is probably rubbish - i hate the internet sometimes.

I did get some side effects but thetly were very mild: slighty clumsy, little bit of blurry vision but those went in a day or too (very mild). The ones that persisted a bit were a dry mouth in the morning (bottle of water by the bed) and constipation (bit more fibre fixed that and i got that anyway since i get ibs)

I went up another 50 to 450mg yesterday. No noticeable side effects. Slept like a log.