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For people on benzos
by s0up, Jul 25, 2007 07:41PM
I'm an organic chemist who in recent years, has been studying to become a developer for pharmaceuticals. After reading this forum for a while, i realized that there is quite a bit of misinformation on the topic of these drugs. Many people say it's mildly addicting, or that its a medication for treating withdrawals. Lots of you guys are prescribed it for years, including my brother.
Some basic facts:
These medications stop working completely after administration for a few months, if you think it's helping your anxiety go away.. check again, it's making your withdrawals go away.
Anything that inhibits the P450 enzyme(like grapefruit or MAOIs) will increase the effects of any benzodiazipine. As little as 250ml of grapefruit juice can make peak plasma levels of 10mg oral diazepam(valium) reach double the volume in the blood.(great for people who take it recreationally, horrible for people trying to quit)
This half life extension can be fatal for people with insufficient renal or liver function.
The addiction potential of the different medications is dictated almost soely on the medications half life. The faster it reaches peak plasma levels, the more "rush" and addiction potential there is.
Ativan = Higher addiction potential
Klonopin = Very high addiction potential
Valium = Lower addiction potential
Xanax = Mid-High
To stop taking these medications, it can be extremely hard to lower the dose on some of the more addictive ones. A great way to get off of the medication is to work out a switching schedule before a tapering one. Switching to a less addicting drug in the same family before lowering the dose works great.
Valium is probably the easiest drug to switch to by slowly lowering your dose of whatever you are taking, and substituting with an equal dose of valium(the mg is not the same so see a doctor.. 10mg of xanax is ALOT more than 10mg valium)
Once you are using a drug with a longer half life, you can start slowly lowering your dose accordingly.
Hope this clears up some misinformation.
Some basic facts:
These medications stop working completely after administration for a few months, if you think it's helping your anxiety go away.. check again, it's making your withdrawals go away.
Anything that inhibits the P450 enzyme(like grapefruit or MAOIs) will increase the effects of any benzodiazipine. As little as 250ml of grapefruit juice can make peak plasma levels of 10mg oral diazepam(valium) reach double the volume in the blood.(great for people who take it recreationally, horrible for people trying to quit)
This half life extension can be fatal for people with insufficient renal or liver function.
The addiction potential of the different medications is dictated almost soely on the medications half life. The faster it reaches peak plasma levels, the more "rush" and addiction potential there is.
Ativan = Higher addiction potential
Klonopin = Very high addiction potential
Valium = Lower addiction potential
Xanax = Mid-High
To stop taking these medications, it can be extremely hard to lower the dose on some of the more addictive ones. A great way to get off of the medication is to work out a switching schedule before a tapering one. Switching to a less addicting drug in the same family before lowering the dose works great.
Valium is probably the easiest drug to switch to by slowly lowering your dose of whatever you are taking, and substituting with an equal dose of valium(the mg is not the same so see a doctor.. 10mg of xanax is ALOT more than 10mg valium)
Once you are using a drug with a longer half life, you can start slowly lowering your dose accordingly.
Hope this clears up some misinformation.
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Thanks,
Chadry
First, let's take a look at your "basic facts":
--begin quote--
"These medications stop working completely after administration for a few months, if you think it's helping your anxiety go away.. check again, it's making your withdrawals go away."
--end quote--
This only applies to Benzodiazepines with a short half-life (Ativan, Serax, Xanax). This DOES NOT APPLY to the long acting Benzodiazepines (Klonopin, Librium, Valium). The Benzodiazepines with a short half-life do not accumulate or reach steady-state. Therefore, the peak and trough in the plasma levels of these drugs leads to rapid *tolerance* and loss of efficacy.
The long acting Benzodiazepines work on the principal's of steady-state and accumulation. After taking Klonopin/Valium/Librium for an "X" period of time, the drug reaches steady-state, and ultimately accumulates beyond steady-state. The maintanence of steady-state prevents tolerance from occurring. The maintanence of steady-state will prevent or minimize the symptoms of the disorder that it to treat. Accumulation for Klonopin ranges from 1.5 -3 times that of steady-state, and accumulation for Valium and Librium ranges from 5-10 times that of steady-state. Valium and Librium have more than one active metabolite, with the longest one, (Desmethyldiazepam) approaching a half-life of 200 hours.
Loss of efficacy is rare with the long acting Benzodiazepines, but is guaranteed with the shorter acting types if they are used inappropriately. Therefore, Ativan, Serax, and Xanax are for use only on an "as-needed" basis.
Klonopin, Librium, and Valium are for long term use. Two separate classes (short and long acting), with two separate indications (PRN use, and long term use respectively).
--begin quote--
"Anything that inhibits the P450 enzyme(like grapefruit or MAOIs) will increase the effects of any benzodiazipine. As little as 250ml of grapefruit juice can make peak plasma levels of 10mg oral diazepam(valium) reach double the volume in the blood.(great for people who take it recreationally, horrible for people trying to quit)
This half life extension can be fatal for people with insufficient renal or liver function. "
--end quote--
The grapefruit juice is an urban legend, and is most commonly associated with Xanax. It is not true. MAOI's such as Parnate can increase the plasma levels of certain Benzodiazepines, but this effect can not be attributed to the P450 enzyme. H2 receptor blockers such as Tagamet increase plasma levels of Benzodiazepines by delaying hepatic metabolism of the drug, by inhibiting the enzyme P450. Lorazepam (Ativan), has no bearing on enzyme P450, and this was a major selling point in the early 80's for folks with concomitant GI disturbances aggrevated by anxiety.
As far as being "fatal", Benzodiazepines are contraindicated in persons with hepatic insufficiency to begin with. As far as being "fatal" when combined with grapefuit juice, NO. Show me your clinical trials to prove that grapefruit juice has a bearing on Benzodiazepine metabolism.
--begin quote--
"The addiction potential of the different medications is dictated almost soely on the medications half life. The faster it reaches peak plasma levels, the more "rush" and addiction potential there is.
Ativan = Higher addiction potential
Klonopin = Very high addiction potential
Valium = Lower addiction potential
Xanax = Mid-High "
--end quote--
First of all, Benzodiazepines are not addictive, unless they are being abused. All of them lead to *dependency* by altering GABA(a) receptor sites in the brain. Dependency and addiction are NOT the same. Any drug that alters brain chemistry will lead to dependency, including the Tricyclics, Tetracyclics, MAOI's, and SSRI/SNRI's.
Xanax is most prone to causing dependency and tolerance, followed by Ativan.
Klonopin, Librium, and Valium cause dependency with prolonged use, but rarely do they lead to *tolerance*. For the management of anxiety disorders, dependency is a non-issue. The only issue is tolerance, which is to be avoided. To assure that tolerance is avoided, only a long acting Benzodiazepine should be chosen for the management of anxiety disorders.
--begin quote--
"To stop taking these medications, it can be extremely hard to lower the dose on some of the more addictive ones. A great way to get off of the medication is to work out a switching schedule before a tapering one. Switching to a less addicting drug in the same family before lowering the dose works great. "
--end quote--
Correct to a certain degree. Tapering directly off of Ativan or Xanax is difficult, primarily due to their short half-lives and rapid rebound. None of these drugs are addictive (as pointed out above), but switching to a longer acting Benzodiazepine allows for the user to gradually withdrawal the drug with less severe withdrawal phenomena. Klonopin and Valium are ideal for this. However, switching from Xanax to Klonopin, for instance, is not as easy as it appears. Klonopin reaches steady-state in two weeks, which leaves a two-week window of vulnerability open for withdrawal phenomena. Have you actually taken a Benzodiazepine before?
--begin quote--
"Valium is probably the easiest drug to switch to by slowly lowering your dose of whatever you are taking, and substituting with an equal dose of valium(the mg is not the same so see a doctor.. 10mg of xanax is ALOT more than 10mg valium) "
--end quote--
Correct, but making the transition to Valium may take upwards of one month, and during that one month, the patient would be subjected to withdrawal phenomena if he were using a short-acting Benzodiazepine prior to making the transition. 0.5 mg of Xanax is equal to 10 mg of Valium.
--begin quote--
"Once you are using a drug with a longer half life, you can start slowly lowering your dose accordingly. "
--end quote--
Precisely. 0.125 mg every four weeks for Klonopin, 2 mg every two weeks for Valium, and 5 mg every two weeks for Librium until the drug is discontinued.
--begin quote--
"Hope this clears up some misinformation."
--end quote--
You've spread misinformation for the most part. Remind me not to purchase your pharmaceuticals if they become available.
-Ryan
I want to see how knowledgable you are:
Assume you have a 200 mg piece of pure Sodium metal, saturated in mineral oil. Next, you place this piece of Sodium into a beaker containing 500 mL of chemically pure (distilled) water. A violent reaction will take place. Once the reaction has nulled, what I want to know is:
(A) What substance have you just created?
(B) If you place one mL of Phenolphthalein into the resultant soultion, what color will it turn?
(C) What does the color of the solution signify?
(D) Using only the Phenolphthalein indicator, how can you make the solution you've just created safe to drink? What would you need to add to it? And how much?
-Ryan
For whatever it is worth. For whatever it is worth, it is not worth freaking folks out that are being helped for once in there life if they take something to help.
Amen.
Using 1/2 mg of Klonopin as-needed on an infrequent basis, your risk of dependency is zero. If it works for you, that is great. Quality of life is more important than anything else. Listen to the Neurologist.
As far as "Chemist" is concerned, I suspect this is just another anti-benzo plug. There are too many fragments in his post. Plus, organic chemists don't develop pharmaceuticals.
Sure they do! Numerous pharmaceutical agents are not available in "nature" - they are synthetic in origin and are prepared in the laboratory. Moreover, synthetic organic chemists routinely work in the pharmaceuticals industry modifying structually (derivatizing) known pharmaceuticals (that may be natural), developing novel "potential" drug candidates, and devising synthetic strategies to prepare biologically active molecules that are only available in small quantities from natural sources.
Triazolam AUC was increased 48% and Cmax increased 30% in healthy volunteers given triazolam with grapefruit juice. Drowsiness was significantly increased when triazolam was given concurrently with grapefruit juice. (Source: Hukkinen SK, Varhe A, Olkkola KT et al., Clin Pharmacol Ther 1995; 58: 127-31).
^
Benzos will always create physical addiction given enough time if they are taken every day.
As for the individual chemicals actual half lives, that's off the top of my head. Xanax possibly is more addicting partially because of it's action in the 5-HT receptor sites in the brain(which is arguable)
Wow.. this is starting to feel like school.. i did this in basic nonorganic chem... i believe the starting liquid was green and turned a pinkish purple..
----
sodium metal is usually kept with mineral oil.. but anyways.. if you reacted sodium metal with water it'd react and release hydrogen gas[sodium hydroxide] as well as sodium ions... phenolphthalein(just say universal indicator or you will **** your chemistry colleagues off.. but you're probably just trying to be more confusing)... either way it wouldn't be safe to drink... sodium metal will destroy your digestive tract.. but assuming you removed it, you would need to react it it until it had a neutral PH balance.
This is more basic chem, pharma r&d is more geared towards isolation of active alkaloids, and studying the pharmacokinetics for medical benefit.(yes you were right spade22.. thanks)
Either way, try contributing rather than correcting. Most of the numbers you threw out there were accurate though.
All of these drugs lose efficiency after time, even the ones with long half lives. The reason some may appear to lose it quicker is because the ones with shorter half lives are more prone to dose escalation :).
As for the addiction comparison to SSRIs and MAOIs .. it's not the same. I'm guessing you don't have experience directly from this drugs based on that comparison in addiction potential. Inhibition of neurotransmitter breakdown is different than modulation of a brain receptor site like GABA.
This is a really simple question, which could have been phrased much better, but I appreciate the challenge, as most people who post on forums rebuttle with absolutely no sources.
i'm not trying to back with my knowledge of chem.. moreso because I dealt with this problem helping my brother to get off of them, using valium as a switch over medication. And yes, you are right.. valium does take a while to switch over to.. but these drugs are all cheap and most people are on them for years..
Posted it to help people, not to get a lesson in begginning chemistry.
Essentially, there are two classes of Benzodiazepines, those that are short acting (Ativan, Serax, Xanax), and those that are long acting (Klonopin, Librium, Valium). There is a world of difference between these two classes, and the two classes carry different clinical indications. Ativan, Serax, and Xanax are only indicated for the short term or intermittent use only. This is where the "stigma" surrounding Benzodiazepines comes into effect, as these drugs are often prescribed over the long term (despite the fact that they have no indications for long term use). There is little doubt that Ativan, Serax, and Xanax cause rapid dependency and *tolerance*. I suspect that your brother was prescribed on of these three agents. If my assumption is wrong, please correct me. Obviously, long term use of these three agents will lead to tolerance issues (the need to increase the dose to produce the same desired effect).
On the other hand, Klonopin, Librium, and Valium are clinically indicated for long term use. They are indicated for the management of long term anxiety disorders and other conditions. I will use Klonopin as an example, as it is the most frequently prescribed maintanence drug for anxiety states.
Klonopin was designed in 1976 by Roche Pharmaceuticals for the treatment of certain forms of epilepsy. Epilepsy is more often than not, a chronic disorder. Benzodiazepines possess potent anticonvulsant and anxiolytic properties. Klonopin was designed solely as a long term viable option for the treatment of certain forms of epilepsy. Klonopin carries a 50-hour half-life, and works on the principal's of steady-state and accumulation. Since the half-life is prolonged, and the drug reaches steady-state in the plasma and ultimately accumulates between 1.5 - 3 times that of "steady-state", the risk of *tolerance* is very low, thus making Klonopin an attractive long term option for a chronic disorder. It was soon discovered that Klonopin also possessed powerful anxiolytic/anti-panic properties, and the drug was used off-label for many years in the treatment of panic disorder. In 1998, Klonopin was approved for both certain forms of epilepsy and panic disorder. The drug has proven efficacy over the long term, unlike Ativan, Serax, or Xanax. This efficacy can be attributed to Klonopin's long half-life, maintanence of steady-state plasma levels, and accumulation. Librium and Valium are similar, but have many active metabolites in addition to the parent compound. Of those metabolites, Desmethyldiazepam carries the longest half-life of 200 hours, however, Desmethyldiazepam itself has no beneficial actions.
ALL Benzodiazepines create psychological and physical *dependency*, but not addiction, unless they are being used recreationally or are being abused in combination with other drugs/alcohol. The very definition of addiction points towards abuse. Dependency is to be expected, as a certain aspect of brain chemistry is being altered (GABA). Therefore, the abrupt cessation of Benzodiazepines that were taken for prolonged periods of time will lead to withdrawal or rebound phenomena. The same argument could be raised for other drugs as well. Take beta-blockers for example: Abrupt cessation of a beta-blocker would lead to rebound hypertension and a hypersensitivity to the effects of Catecholamines on the myocardium. In that respect, beta-blockers cause dependency, as do other drugs that alter normal physiological chemistry.
Therefore, any drug that alters normal chemistry has the potential to cause dependency, which would manifest upon abrupt cessation of the particular drug involved. Benzodiazepines are often "singled out" as they are often improperly prescribed, or prescribed for the wrong indications. This is why there is such a strong "stigma" attached to them.
Properly prescribed, Benzodiazepines are perhaps, the most effect agents at targeting anxiety/panic directly. Proper use is key, and proper use will largely eliminate the risk of *tolerance*
Xanax has no bearing on 5-HT receptor sites. Xanax, a Benzodiazepine, only has a bearing on GABA(a) receptor sites in the brain. The SSRI class of drugs target 5-HT receptors, but do so in a non-selective manner. This explains why folks respond to these drugs on an individualized basis. For some, an increase in anxiety occurs, while for others, a reduction in anxiety or depression occurs. There are numerous 5-HT receptors, and SSRI's are largely non-selective in which specific HT receptor sites they target. In general, folks suffering from true anxiety states will not respond favorably to SSRI's.
I apologize if my little trivia question insulted your intelligence, I just threw it out there to confirm that you were indeed a chemist. Sodium combined with distilled water produces Sodium Hydroxide. Adding Phenolphthalein indicator to the solution would verify that it is an alkaline solution by turning a pinkish-purple color. To neutralize the OH- solution, an acid (6M HCl) could be used to titrate the pH to 7.0. However, it was a trick question, as Phenolphthalein is a laxative. Therefore, you could not make the solution safe to drink. This is where the basic and organic aspects collide, as the organic chemist would be very familiar with Phenolphthalein and it's pharmacological effects on the body. I did not mention "indicator", but mentioned Phenolphthalein specifically for this reason. I too, like a little challenge every once in a while. It keeps things interesting.
"Posted it to help people, not to get a lesson in begginning chemistry."
Understandable, considering what your brother experienced. However, I suspect that he was prescribed one of the short acting drugs (Ativan, Serax, Xanax) over the long term, which resulted in him having difficulties.
I think the best approach is to educate folks on the various indications of the Benzodiazepines, rather than trying to scare them out of what could potentially be a "life changing" (in a positive sense) pharmacological option. Used properly, and for the proper indication, Benzodiazepines are extremely effective agents at treating a host of disorders. Often times, they are the only agents that offer any significant benefit in true anxiety states.
From my own personal experience with Klonopin, I can attest to the fact that the drug has maintained its efficacy.
Since you are a researcher, you may want to look into Dopamine, Norepinephrine, GABA(a), and 5-HT, and their influence on behavior.
Best regards,
Ryan
Just kidding, you guys are very intelligent people. I have respect for all of you.
wmac
As far as Stevie is concerned, I'm sure the Klonopin was the least of her problems. It's easy to blame Klonopin when you're taking massive doses, and snorting crack at the same time. I'm not sure using Stevie is the best example.
Folks that have a "hard time" getting off of Xanax had no business taking it in the first place. You don't "get off" of Xanax, you take it as needed, infrequently. Otherwise, you ride the rollercoaster straight to hell.
I thought you were taking Ativan?
Ryan
Ativan 1/2 mg, twice daily, initially, may produce some small benefit. But much like Xanax, it really wasn't designed for prolonged use. Therefore, tolerance to the effects develops rapidly, rendering the drug ineffective or less effective than it was when you initially started taking it.
1/2 mg of Ativan is comparable to 1/4 mg of Klonopin. If you switched to 1/2 mg of Klonopin twice daily, the efficacy (usefulness) would be re-established, and you would likely notice a reduction in your symptoms.
I think you mentioned that you tried Klonopin, but with bad results. In that case, you could start out with a dose comparable to your dose of Ativan (0.25 mg of Klonopin twice daily). This would prevent any excessive sedation. Once you are stabilized on Klonopin, the dosage could then be increased to 1/2 mg, twice daily. The transition period from Ativan to Klonopin is variable - between 3 days to 2 weeks. After two weeks, Klonopin reaches steady-state and the transition is complete. It is easier to switch from Ativan to Klonopin, than from Xanax to Klonopin, so you do have an advantage here.
If you can tolerate Klonopin (I'd give it a one month evaluation), you are likely to see a large improvement. The effects of Klonopin would be maintained (unlike Ativan).
In short, I would not increase the Ativan dosage. I'd speak with the doctor about switching from Ativan to Klonopin.
Folks with "addictive personalities" usually take it upon themselves to increase the dosage of a given drug. The fact that you have not would lead me to believe that you don't have an addictive personality. On the contrary, most folks with anxiety disorders have a "drug phobia", and almost never take it upon themselves to increase the dose. If anything, they take less than the recommended or prescribed dose.
Ryan
Thanks
Donnie
Your risk of dependency is slim to none. However, if one were taking the drug on a daily basis, twice daily, one would only know if they were "dependent" if they stopped using the Klonopin abruptly. The result would be a severely heightened sense of anxiety.
If your symptoms recur on a daily basis, talk to the doctor about prescribing a dose of 0.5 mg, twice daily. Taken everyday, twice a day, it will minimize or prevent anxiety from recurring. The full effect will be noticable in two weeks.
Dependency, by the way, is of no significance in treating long term anxiety disorders. The benefits outweigh the risks, and your quality of life would be much improved. If you need to come off of it in the future, it can be done easily, but slowly.
Ryan
Ativan has a half-life that is variable from between 8-12 hours, and generally, it is indeed 8 hours. Twice a day dosing at 1 mg may leave you vulnerable for 8 hours. The short half-life would lead to rapid tolerance, rendering the drug less effective or ineffective. At some point, you would be taking Ativan for the sole purpose of preventing withdrawal phenomenon. In short, it's not a long term viable option, because the effects wear off over an "X" amount of time (typically four months). Taken three times daily would further increase the risk of tolerance.
It isn't clear why Klonopin made you sick, but it may have been a withdrawal type reaction from the Ativan, or perhaps, one of the inactive ingredients in the Klonopin didn't agree with you. All generics are not created equal. TEVA and Caraco appear to be the best two manufacturers of Clonazepam, while Watson, Mylan, and Purepac are the worst three. Clonazepam itself would not make you sick.
As far as the drug phobia, try not to read the prescribing information! Keep in mind that roughly 1/2 of the reported "adverse effects" are somatic in origin (imaginary). Often times, a Placebo induces the exact same effects, even though no active component is present. That is why the active drug is always compared with a Placebo. Folks with a "suggestible" personality anticipate the worst, and are on the look out for side effects. They anticipate that something bad will occur, and then it does.
Ryan
Quote^
That's all of the things that involve behavior and emotion.. all of the neurotransmitters involved in psychiatric disorders. Ive been actually looking into the actual legal technicalities of alexander shulgins clever idea of adding a N-hydroxyl to any active amine.. allowing u to get past patent protection.. basically if you make a n-hydroxyl analog of any active amine chemical.. it will pretty much always have the same pharmacological effect.. so you could create variations of just about any medication out there that contains this type of structure and it's technically unique :P
Did klonopin actually keep helping? I would like a daily solution but instead i just take valium or xanax as needed.. once or twice a week ..physical dependence is scary
anna
Vistaril is an old-school antihistimine similar to Benadryl, but it is more sedating. In the late 50's/early 60's, it was widely used to treat anxiety states, but it doesn't actually work. It is sedating, but it's not a true anxiolytic. Today, it is used to treat allergic reactions, such as hives. It is also used to treat nausea and motion sickness.
I can give you some recommendations once you post your symptoms.
Ryan