Ryan7591 : Clonazepam plasma levels

[Southie]

Ive been taking .25 mg qid of clonazepam for 9 months.  i still feel anxiety and panic feelings.  would taking .5 mg tid increase the levels in my plasma?  i realize that 1.5 mg a day is more than 1 mg, but have heard ryan say that the more times a day you take it the more it increases in your plasma.  so .25 mg a day will result in higher concentrations than 1 mg once a day.  so what would have higher concentration of plasma levels, .25 qid or .5 tid?

[RCA759I]

Klonopin works on the principals of steady-state and accumulation. When taken two-to-three times daily, Klonopin accumulates to steady-state within two weeks, and accumulates to 1.5 times that of the steady-state plasma level within an additional two weeks. Hence, for those taking 1/2 mg, b.i.d., the plasma equivalent is roughly 1.5 milligrams. Or, for those taking 1/2 mg, t.i.d., the plasma equivalent of roughly 2.25 milligrams.

Taken four times daily, the accumulation figure doubles, hence taking 1/4 mg, q.i.d. results in the plasma equivalent of roughly 2 milligrams.

The answer to your question is...You would have a higher plasma level taking 1/2 mg, t.i.d. in comparison to 1/4 mg, q.i.d. The plasma equivalent of an additional 1/4 mg.

-Ryan

[Southie]

thanks for that info.  on a side note, if i wanted to stay on a total of 1mg a day, if i stopped taking .25 qid and instead took .5 bid, would this change in plasma levels increase the risk of tolerance developing.  i know you say tolerance isnt an issue bc constatn plasma levels are maintained.  so i dont want my plasma levels to flucuate if this is a problem.  if it isnt a problem, how often can i make a change?  or do i need to stay the same for a long time.  i DONT want to do anything that will cause tolerance.  i think im going to take .5 bid because i have a hard time taking a pill qid.  also i am now taking brand name klonopin instead of teva and can tell its more powerful.  .5 mg of klonopin is noticeably stronger than .5 of teva clonazapam.  so i am hoping that the .5 bid is just as good or better than the weaker teva at .25 qid.  i greatly appreciate your knowledge and willingness to help others.

[Sue357]

Hi Ryan.  I have read many of your posts on here and am so grateful how you are so helpful.  I have a question about this post:  I take Klonopin .5 3 times a day.  I also take 60 mg. of Celexa.  I have been experiencing severe anxiety so my doc added 100 mg of Wellbutrin.  It has been a week since the Wellbutrin and I seem to be seeing a small positive change.  However, my question is about the Klonopin.  It has always worked well for me.  I have been on it for a few years.  I am wondering what is meant by the plasma levels, but most importantly, about the tolerance.  I am diagnosed clinical depressive ( since age 9) and about a year and a half ago, diagnosed GAD, after major surgery.  I am so afraid of developing a tolerance to the Klonopin,i.e. it not working any more.  Feedback?  Thanks so much.  Sue

[abby10]

You can reach tolerance with klonopin--it happens to a lot of people. To say you cannot reach tolerance with klonopin is untrue. Eventually, you will. The withdrawals can be horrible. Everyone's body is different. You are on low doses--stay there! Look up the word benzodiazepine and research it. Find out what's involved with tapering off when need be. It takes a while even on low dose klonopin to withdrawal but if done properly you will be fine. Don't updose! Wikipedia is very informative about benzodiazepine drugs.

Advise from a neurologist at John Hopkins Hospital for anxiety is CBT.


Best to you,

abby

[RCA759I]

"on a side note, if i wanted to stay on a total of 1mg a day, if i stopped taking .25 qid and instead took .5 bid, would this change in plasma levels increase the risk of tolerance developing."

^^^quote^^^

If you elect to dose the Klonopin b.i.d. rather than q.i.d., the plasma level will decrease slightly. This is of no significance, provided b.i.d. dosing is effective for you.

Do not decrease the dosage to 0.5 mg, b.i.d. immediately, but rather gradually make the transition to this level.

Example:

Days 1-7: Take 0.25 mg in the morning, 0.25 mg in the afternoon and 0.5 mg at night.

Day 7: Take 0.5 mg, b.i.d.

This will prevent any possible interdose symptoms from occurring while the plasma level is readjusted.

Tolerance is of no significant concern at either dosing interval. So long as Klonopin is dosed twice daily, it will accumulate adequately. What you have to look at is the duration of action....is 0.5 mg, b.i.d. holding you though the day, or is it wearing off after eight hours? If you find that you're experiencing interdose, take it three times daily (0.25, 0.25 and 0.5 mg - or any combination thereof). Tailor it to your needs, and as indicated by your physician.

But the answer you're looking for is...no. There is no increased or decreased risk of tolerance by dosing the drug b.i.d, t.i.d. or q.i.d. Efficacy is typically greater when dosed t.i.d. or q.i.d., as the plasma level is higher due to the overlap (accumulation).

I might also point out to the Registered Nurse above that the terminal half-life elimination of a Benzodiazepinew has no bearing on the clinical effect/ duration of action over a 24-hr span. To assess duration of action, one must look at protein binding, in addition to accumulation. The lower the protein binding of a Benzodiazepine, the greater its duration of action. The half-life of Klonopin (mean 36 hours) is prolonged, however, the clinical effect ranges from 8-12 hours. Administered once daily, the drug would not accumulate adequately in a maintenance regimen for anxiety/panic disorder. 67% of the drug would be excreted in the first 24-hrs. Hence, it is dosed multiple times daily to prevent its excretion, as to allow for an overlap (accumulation). The more frequent the dosing, the greater the accumulation and the greater the plasma level. A single daily dose of 1 mg would reach a sub-therapeutic steady-state level. Optimal efficacy is appreciated within the range of 15-60 ng/mL of plasma. Such a range will never be obtained with qd dosing, and hence the drug would be ineffective at maintaining recurring panic. It would wear off after 8-12 hours, leaving the patient riddled with rebound panic.

-Ryan

[abby10]

I know many people that report great complications with Klonopin after withdrawaling-- yourself included. Unless there are two Ryans on this site, (If so I truly apolozize). The binding capacity of Klonopin is believed to be the very reason for this problem. This has not been proven in a lab, but sometimes experience is the best teacher, as it has been proven that the pharmas fudge their stats--and the FDA knows it.

I truly believe in the benefits of Klonopin. I do know anxiety. But benzos are very powerful drugs. As I have stated before, Klonopin should be used for short term use only with a taper plan. What a drag when a doctor just yanks someone off their medication.

BTW your post on pharmacies was really very impressive. I have yet to have a pharmacist admitt that there is any difference between generic and brand. But when I look at their face... I'm not so sure. Doesn't the pharmacy owe their fuduciary responsibility to the customer.

abby

[Sue357]

Hi.  I had added a post to this one but fear it may have been overlooked.  You seem very knowledgable about benzos.  Can you develop a tolerance to Klonopin in that .5 mg 3 times a day would stop working?  It is a drug I have been on for a few years now and works well.  That is one of my fears: that it will stop working.  Thanks so much
Sue