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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 26. This is the beginning of the thread.
Posted by alesta on August 20, 2004, at 14:59:27
well, i thought i'd keep y'all up-to-date concerning my research on benzos. i found an anecdote where someone states that klonopin is the only benzo that hasn't affected her memory or cognition. any thoughts? why do people prefer other benzos to this one?
from what i gather, klonopin does not cause euphoria and is a wonderful drug.
i've also found info stating that very small doses of benzos may actually increase cognition and alertness during the day, and that low-dose klonopin is most often used. comments?
i would really appreciate your input. :)
amy:)
Posted by chemist on August 20, 2004, at 15:17:41
In reply to kp.-benzo least likely to cause cogn. impair.?, posted by alesta on August 20, 2004, at 14:59:27
hello amy, chemist here...your post should generate quite a number of responses...as a fan of benzos and derivatives of the class, i can relate my experiences and thoughts....there is a finite bit of anterograde amnesia associated with benzos/xanax/hypnotics/``z-drugs.'' klonopin would, in my estimation, be on the lighter side of the memory/cognition impairment, as you note, although as with most substances, as one increases the dose, one can expect certain side-effects to rear their heads. i think the information you have presented is in the right ballpark, although i am not aware of small doses of benzodiazepines being touted for enhancing cognition: i am interested in your source of this info. as far as personal preference, you will likely receive a wide range of answers. i like alprazolam the best, although past experiences with valium, ativan, klonopin, and the sleep-oriented restoril, halcion, and dalmane were all positive (there were others, but these are the ones that i used extensively at one time or another). klonopin is probably the best bang for the buck, in terms of low abuse potential and efficacy for general anxiety...do keep us informed of your progress, i am certain it will be a successful trial! all the best, chemist
> well, i thought i'd keep y'all up-to-date concerning my research on benzos. i found an anecdote where someone states that klonopin is the only benzo that hasn't affected her memory or cognition. any thoughts? why do people prefer other benzos to this one?
>
> from what i gather, klonopin does not cause euphoria and is a wonderful drug.
>
> i've also found info stating that very small doses of benzos may actually increase cognition and alertness during the day, and that low-dose klonopin is most often used. comments?
>
> i would really appreciate your input. :)
>
> amy:)
>
Posted by alesta on August 20, 2004, at 15:38:20
In reply to Re: kp.-benzo least likely to cause cogn. impair.? » alesta, posted by chemist on August 20, 2004, at 15:17:41
hi, chemist :),
so they all will affect cognition to some degree. i don't like that.:( i guess i want the perfect drug!:) i don't know why i'm so terrified i'm going to lose my intelligence/personality (what there is of it, anyway:)) or who i am.
if i may ask, why do you prefer alprazolam?
i'm still looking for the source you requested...i'll get back to you on that one....
:) amy
Posted by alesta on August 20, 2004, at 15:49:52
In reply to kp.-benzo least likely to cause cogn. impair.?, posted by alesta on August 20, 2004, at 14:59:27
here's the source. not a great one (i never said it was, just that i'd read the info):), which is why i'm asking these questions.
http://www.immunesupport.com/library/showarticle.cfm/ID/5750/T/CFIDS_FM/cat/sleep/
(read the note at the end in small print)
Posted by chemist on August 20, 2004, at 15:52:40
In reply to Re: kp.-benzo least likely to cause cogn. impair.?, posted by alesta on August 20, 2004, at 15:38:20
hello there amy, again....i do hope damage-control can be achieved here....these drugs do not affect cognition (this i will expand upon more below, it is not an absolute) but memory. you can rest assured that using these meds will not shave points of your I.Q. the usual feeling is a bit of sedation, which goes away in time, and klonopin is not very ``heavy'' in this regard with respect to other choices. in a short time, you will notice that things that previously made you anxious do not push your buttons so much. that is the desired effect of the anxiolytics. i would warn against mixing alcohol, as the effects are additive, and the memory loss can be quite severe. your personality will not be changed (except you will be calmer, more of a behavioural trait, in my estimation). you inquire as to my preference for xanax: it has a very fast onset of action, and i have been prone to panic attacks over the years, and i have never been disappointed by the drug. there are memory problems, but i have either adjusted to them, or forgotten what they were to begin with, and i am far from the point of remembering where i live, who i am talking to, and so on - just a bit absentminded. start out slow with your klonopin, if it is not to your liking, you can taper with relative ease in the early stages.....all the best, chemist
> hi, chemist :),
>
> so they all will affect cognition to some degree. i don't like that.:( i guess i want the perfect drug!:) i don't know why i'm so terrified i'm going to lose my intelligence/personality (what there is of it, anyway:)) or who i am.
>
> if i may ask, why do you prefer alprazolam?
>
> i'm still looking for the source you requested...i'll get back to you on that one....
>
> :) amy
Posted by chemist on August 20, 2004, at 15:55:12
In reply to Re: kp.-benzo least likely to cause cogn. impair.?, posted by alesta on August 20, 2004, at 15:49:52
thanks much, who am i to argue?.....all the more reason to take them, i suppose :) cheers, chemist
> here's the source. not a great one (i never said it was, just that i'd read the info):), which is why i'm asking these questions.
>
>
> http://www.immunesupport.com/library/showarticle.cfm/ID/5750/T/CFIDS_FM/cat/sleep/
> (read the note at the end in small print)
Posted by alesta on August 20, 2004, at 16:13:59
In reply to Re: kp.-benzo least likely to cause cogn. impair.? » alesta, posted by chemist on August 20, 2004, at 15:52:40
thank you, chemist. it is just kind of scary trying a benzo for the first time (for me). i guess a slight forgetfulness wouldn't be anything to worry about. i just don't know why i'm so hesitant...after taking it, i'll probably wish i had taken it sooner:)
thank you so much for your help.....
amy :)
> hello there amy, again....i do hope damage-control can be achieved here....these drugs do not affect cognition (this i will expand upon more below, it is not an absolute) but memory. you can rest assured that using these meds will not shave points of your I.Q. the usual feeling is a bit of sedation, which goes away in time, and klonopin is not very ``heavy'' in this regard with respect to other choices. in a short time, you will notice that things that previously made you anxious do not push your buttons so much. that is the desired effect of the anxiolytics. i would warn against mixing alcohol, as the effects are additive, and the memory loss can be quite severe. your personality will not be changed (except you will be calmer, more of a behavioural trait, in my estimation). you inquire as to my preference for xanax: it has a very fast onset of action, and i have been prone to panic attacks over the years, and i have never been disappointed by the drug. there are memory problems, but i have either adjusted to them, or forgotten what they were to begin with, and i am far from the point of remembering where i live, who i am talking to, and so on - just a bit absentminded. start out slow with your klonopin, if it is not to your liking, you can taper with relative ease in the early stages.....all the best, chemist
>
>
> > hi, chemist :),
> >
> > so they all will affect cognition to some degree. i don't like that.:( i guess i want the perfect drug!:) i don't know why i'm so terrified i'm going to lose my intelligence/personality (what there is of it, anyway:)) or who i am.
> >
> > if i may ask, why do you prefer alprazolam?
> >
> > i'm still looking for the source you requested...i'll get back to you on that one....
> >
> > :) amy
>
Posted by zeugma on August 20, 2004, at 18:23:56
In reply to Re: kp.-benzo least likely to cause cogn. impair.?, posted by alesta on August 20, 2004, at 16:13:59
hi amy (and you're welcome for the brief answer i provided above), my guess is that (as chemist probably said above, but i can't remember :))the memory problems are dose related, and minimal with klonopin anyway. I take 1 mg a day as a maintainance dose; if I ever go over that for something anxiety-provoking like a visit with the family, I get slightly groggy, but can still remember most of what transpired (for better or worse!). I would guess that on balance, the number of things I forgot due to anxiety far outweighs what I've forgotten due to klonopin-related effects,during a similar time-period. Anxiety can be a mind-killer too.
-z
Posted by alesta on August 20, 2004, at 18:39:31
In reply to Re: kp.-benzo least likely to cause cogn. impair.?, posted by zeugma on August 20, 2004, at 18:23:56
> Anxiety can be a mind-killer too.
Excellent point! you got that right. not to mention sleep loss due to anxiety contributing to memory/concentration problems! man, i am sold!
just ooone question....please...do the memory problems go away when you go off the klonopin? i'm sure the answer is yes, but i feel compelled to ask anyway....thanks for your patience, zeugma!
amy :)
Posted by chemist on August 20, 2004, at 18:53:56
In reply to Re: kp.-benzo least likely to cause cogn.--zeugma, posted by alesta on August 20, 2004, at 18:39:31
amy (zeugma, excuse the jumping in, if you would be so kind....): i swear on my every neuron - and they work pretty well, still - that you will be tip-top on klonopin and should you stop, all of life's pleasures, memories, pains, anxiety, and so forth will return in their previous form, with no deletions/insertions. or your money back! honest. i swear. no joke. i'll even give you my private email and home address should you wish to flog me upon the highly unlikely event that klonopin will make your situation worse: just use the handy babblemail feature, or sift through the archives......Dr. Chemist, B.A, M.A., Ph.D. and devout klonopin endorser!!!!
> > Anxiety can be a mind-killer too.
>
> Excellent point! you got that right. not to mention sleep loss due to anxiety contributing to memory/concentration problems! man, i am sold!
>
> just ooone question....please...do the memory problems go away when you go off the klonopin? i'm sure the answer is yes, but i feel compelled to ask anyway....thanks for your patience, zeugma!
>
> amy :)
Posted by zeugma on August 20, 2004, at 18:58:04
In reply to Re: kp.-benzo least likely to cause cogn.--zeugma, posted by alesta on August 20, 2004, at 18:39:31
sorry amy, i don't know the answer to that question, as i myself have not gone off it (been on about eight mos.) but I really think that benzo-related impairments have been overblown. What I have read about are stories of people who take one, relatively high dose, and then have some amnesia... the classic story i've read about is of businessmen taking a benzo to fall asleep on a business trip then waking up and forgetting why they crossed the Atlantic. This could well go in that 'folk mythology' category though, as my sister takes lorazepam for business flights, and has never told me she messed up her project due to forgetting what she came for... i should add that she takes it only for this purpose (ie PRN).
I suspect that a lot of the stories, if not folk mythology, are results of the kind of demonizations of the kinds common to any kind of psychotropic medication. Consult the collected works of Peter Breggin if you want claims that TCA's are 'neuroleptics in disguise,' that Prozac is as neurotoxic as methamphetamine, and other colorful but absurd claims, all made by someone who puts 'M.D.' after his name.-z
Posted by zeugma on August 20, 2004, at 19:02:41
In reply to pardon the hijacking, please.... » alesta, posted by chemist on August 20, 2004, at 18:53:56
amy, please believe chemist, as he has even more academic credentials than Peter Breggin, and is a most amiable hijacker of threads :)
-z
Posted by chemist on August 20, 2004, at 19:12:54
In reply to Re: pardon the hijacking, please.... » chemist, posted by zeugma on August 20, 2004, at 19:02:41
> amy, please believe chemist, as he has even more academic credentials than Peter Breggin, and is a most amiable hijacker of threads :)
>
> -zwell, all in good company, zeugma! if i could remember what all this is about.....now, where is that bottle of xanax.......i'll, um, reply about the thing y'all were talking about....right.....okay, i've misplaced my shoes again.......more later, i promise. Andy and Zebra, be well, i will remember you always :)
best, tjm
Posted by alesta on August 20, 2004, at 19:14:17
In reply to pardon the hijacking, please.... » alesta, posted by chemist on August 20, 2004, at 18:53:56
thank you, chem (lol)!
highjack away. :) got a good laugh out of that one:)...that *really* was the last question! for now.....:)
thanks!
amy :)
Posted by chemist on August 20, 2004, at 19:24:14
In reply to Re: pardon the hijacking, please...., posted by alesta on August 20, 2004, at 19:14:17
Hello my old friend there, Aztec. You and Zeus and all the other friends here at WaterWorld have been very supportive of my plans to infuse citrus produce with Vitamin C. Thank YOU!!!! now, if i could just find those shoes, i could go out and fire up my kite in time for the eclipse.......and, yes, i will help myself to another xanax, why not? Ahoy, Charlie. Over and Out.
> thank you, chem (lol)!
>
> highjack away. :) got a good laugh out of that one:)...that *really* was the last question! for now.....:)
>
> thanks!
> amy :)
>
Posted by alesta on August 20, 2004, at 19:24:45
In reply to Re: pardon the hijacking, please.... » chemist, posted by zeugma on August 20, 2004, at 19:02:41
thank you, zeugma, for sharing your information with me. i most appreciate it! and i will trust chemist, as you so eloquently requested. wishing you a nice evening.
amy :)
Posted by Kon on August 20, 2004, at 22:37:26
In reply to kp.-benzo least likely to cause cogn. impair.?, posted by alesta on August 20, 2004, at 14:59:27
> i found an anecdote where someone states that klonopin is the only benzo that hasn't affected her memory or cognition. any thoughts?
This is somewhat consistent with what I've come across in the literature. Chouinard (2004)writes,"The relative solubility of benzodiazepines contributes to memory impairment. The greater the lipid solubility, the greater the likelihood of memory damage...clonazepam has low lipid solubility and is least likely to cause memory impairment."
The lipid solubility (i.e. HPLC retention index (relative to diazepam)given in that paper are:
Diazepam-1.0
Xanax-0.54
Lorazepam-0.48
Clonazepam 0.28If this is accurate and all other things being relatively equal (?), clonazepam would seem to be one of the better benzos wrt memory while diazepam one of the worse.
See: J Clin Psychiatry 2004;65 (Suppl 5):7-12.
Posted by chemist on August 21, 2004, at 0:15:53
In reply to Re: kp.-benzo least likely to cause cogn. impair.? » alesta, posted by Kon on August 20, 2004, at 22:37:26
> > i found an anecdote where someone states that klonopin is the only benzo that hasn't affected her memory or cognition. any thoughts?
>
>
> This is somewhat consistent with what I've come across in the literature. Chouinard (2004)writes,
>
> "The relative solubility of benzodiazepines contributes to memory impairment. The greater the lipid solubility, the greater the likelihood of memory damage...clonazepam has low lipid solubility and is least likely to cause memory impairment."
>
> The lipid solubility (i.e. HPLC retention index (relative to diazepam)given in that paper are:
>
> Diazepam-1.0
> Xanax-0.54
> Lorazepam-0.48
> Clonazepam 0.28
>
> If this is accurate and all other things being relatively equal (?), clonazepam would seem to be one of the better benzos wrt memory while diazepam one of the worse.
>
> See: J Clin Psychiatry 2004;65 (Suppl 5):7-12.
>
>
>
hello there, chemist here...i admit to reading the abstract of the paper you cite above, as i do not have it on hand. before morphing into a theoretical chemical physicist, i was a chromatographer, using a Waters system with UV-Vis and conductance to determine - usually - high explosive concentrations in soils. run-of-the-mill HPLC determination of cations/anions present in groundwater was another facet, yet reverse-phase (C-18 column) was the method of choice (EPA 8330). given the aromatic or semi-aromatic character of the 1,4-benzodiazepines, and examining their structures, i am assuming that the author you cite used reveresed-phase HPLC with either uv-vis in the 310 or so nm range detection and/or fluoresence or, finally a PDA (photodiode array). relative retention times - assuming the mobile phase was lipophobic or, at the least, a 1:1 (v/v) eluent of methanol/water (18 Ohm) - are direct measurement the partitioning of the solute between the mobile phase and the stationary phase, usually silica beads (the immobile phase substrate) onto which a long chain (18-mer) aliphatic is chemisorbed. aside from functional groups and molecules of differing molecular weights affecting retention times, sometimes there is a bona-fide reaction that enhances or diminishes the mobility of the analyte. let's have a look at diazepam (DZ) and clonazepam (K). the phenyl moiety in K is substituted in the 1 position; in DZ, the phenyl group is not substituted at all. the chloro group is a weak ortho/para director for electrophilic attack (K). however, no resonance from the Cl group with the phenyl group, and thus we settle with all those electron pairs that afford hydrogen-bonding opportunities with water, to name one solvent. moving on to DZ: the six-membered ring is substituted with a chloro moiety, yet given the same opportunity to form hydrogen bonds with water, i would expect the para activation and partial conjugation at the para site to offset to a small degree the nucleophilic strength of this group: in K, the same position is occupied by a meta-director (nitro group) which deactivates the ring, thus slowing electrophilic reactions but more importantly, providing numerous electon pairs and resonance from the nitrogen and the aromatic ring. so far, the stats are somewhat comparable. the seven-membered ring is where the action is: a keto group is present in both K and DZ, and in the same position. hiwever, the neighboring nitrogen in K is a secondary amine, while the analogous nitrogen in DZ is a tertiary amine, to which a highly hydrophobic methyl group is tethered. in that nordiazepam is the active and long-lasting metabolite of DZ (K does not have a significant active metabolite) upon demethylation, it becomes more lipophilic than K, because the nitro group persists. what does all this have to do with memory and/or cognition? residence time, allosteric binding, and selectivity for certain sites within the GABA_{A} (primarily) receptor sub-type. nordiazepam has a half-life of 50-100 hours: K is 18-50 hours. in prn dosing, DZ has a quicker onset than ativan (lorazepam) because even unmetabolized parent DZ can cross the BBB faster than can lorazepam, which is more soluble due to the presence of 2 chloro groups and, more importantly, a hydroxyl moiety adjacent to a keto group in the 7-membered ring. interestingly, the action of ativan once across the BBB is sustained longer than that of DZ/NDZ, and is a bit stronger in anxiolytic action. back to memory: given that these drugs affect neurotransmitters from aspartate to GABA to glutamate to glycine and so on, it is prudent to examine not only laboratory results for solubility measures (which are typically performed in K_{ow} experiments, and are not indicative of a physiological environment that includes metabolic transformation) and retention times in a model system (isocratic flow, pure eluent, etc.) such as an HPLC or LC-MS, but the binding affinity to the receptor as well as variations on a theme that run contradictory to all the above. why is flunitrazepam (rohypnol) such a bane to society? take K, and in the phenyl group, replace Cl with F. replace the hydrogen in the secondary amine in the 7-membered ring with a methyl group (a la DZ), and now you have a date-rape drug. the active metabolite is identical to K with the only difference being the fluoro group in desmethylflunitrazepam vs. the chloro group in parent K. eventually, the 7-position nitro group (in DMFZ) is reduced to an amino group, lowering the solubility and changing the nature of the substituent from meta-directing to ortho/para directing. this last bit is not of great import, but affects binding affinity to certain sites (type I, in the case of FZ). just a late-night meandering......all the best, chemist
Posted by chemist on August 21, 2004, at 0:53:37
In reply to Re: kp.-benzo least likely to cause cogn. impair.? » alesta, posted by Kon on August 20, 2004, at 22:37:26
hello there, chemist again: i actually do have the paper you referenced. do have a look at the last coloumn in table 1, page 8 in the article you reference. note that, while lipid solubility of diazepam is judged to be greater than that of oxazepam by a factor of two (and yes, i am aware that this compound in particular is the end-game for most 1,4-benzos, but not all) but the binding affinity of the active metabolite - desmethyldiazepam or nordiazepam, your choice - is half that of oxazepam. the alprazolam conundrum - aside from targeting (at least) the omega site in GABA_{A} - is flawed, according to these data: it is indicated to be only slightly more lipophilic than lorazepam - unlikely given the triazolo group present in alprazolam, increasing aromaticity and decreasing solubility in polar solvents - yet binds in the uM range only by a factor of 2.5 times greater than lorazepam. of course, the HPLC data are now 18 years old, as are the numbers for binding affinities: that is a problem with these review articles, especially when every single article in the series (i do have them all) was ``supported by an unrestricted educational grant from Solvay Pharmaceuticals,'' and wouldn't you know that the orally-disintegrating Klonopin wafers marketed by - surprise - Solvay - are mentioned in every article in a positive light. aside from this obvious self-promotion, lorazepam and alprazolam are different chemical entities, yet the data presented herein do not support observed findings in re: memory and cognition, at least from a chemical standpoint. the half-lives of both drugs are quite similar (12-15 hr for A, 10-20 for L, neither with an active metabolite). all the best, chemist
Posted by jlbl2l on August 21, 2004, at 2:55:22
In reply to kp.-benzo least likely to cause cogn. impair.?, posted by alesta on August 20, 2004, at 14:59:27
alesta -
I basically agree with everything you said in your post. I would go with the Klonopins, lower dose to start out with, like .5, if that doesnt work move up. It doesn't cause euphoria like Xanax is more likely too, but it is still of course abuseable which im sure i dont have to say!
jlbl2l
Posted by jlbl2l on August 21, 2004, at 3:08:45
In reply to Re: kp.-benzo least likely to cause cogn. impair.?, posted by jlbl2l on August 21, 2004, at 2:55:22
amy,
addendem :
i like the post from immunesupport.com about kpins enhancing some peoples cognition etc..
This is actually TRUE. I have seen it with my own eyes. Sometimes people really become "stablized" and become more clear-headed. This is true in my case with benzos, mostly klonopin only i guess.
I also suffer from CFS and FMS, so i knew of Cheney et all and immunesupport.com and that study already...
For people with CFS and FMS, it seems especially true for some reason, I see it time and time again. I don't claim to know why though, but i would imagine it has something to do with the gaba/nmda receptor ratio or glutamate binding to nmda. perhaps chemist has some insight, but i would hardly worry about memory problems on klonopin. if it happens, it goes away after a week or so, same with sedation, which you will notice if you have never taken it before. The first time i took klonopin .5, i felt drunk! i was so sedated. The second, and third times, i started to just feel tired, and finally, i was just anxiety free by the 4th time or so and i loved it and i just lived much better and happier and was more clear headed. Just don't taper up to quickly or taper off to quickly and you will be fine.
Jlbl2l
(NCF Volunteer)
(Cfs Researcher)
Posted by Donia on August 21, 2004, at 6:23:29
In reply to Re: kp.-benzo least likely to cause cogn.--zeugma, posted by alesta on August 20, 2004, at 18:39:31
While I was on xanax, I felt I was able to concentrate more without the anxiety jumping in and confusing me. As long as I took as directed I just felt good and more functional.
Donia
Posted by alesta on August 21, 2004, at 16:13:24
In reply to Re: kp.-benzo least likely to cause cogn. impair.? » alesta, posted by Kon on August 20, 2004, at 22:37:26
hello, ken :),how ya doin'? thank you for contributing that! while i have no idea as to whether the info is valid or not, it certainly is interesting, and would confirm what she was saying. i appreciate your posting that! my instincts are telling me to go with K. please let me know if you find any more info. on this topic....
thank you!
amy :)
Posted by alesta on August 21, 2004, at 16:24:44
In reply to jlbl2l addendem post!, posted by jlbl2l on August 21, 2004, at 3:08:45
hi Jlbl21,
that is really fantastic that you have actually seen cognitive improvement on klonopin firsthand! thank you for writing in! and i am really going to have to take a look at that web site. appreciate that very much. :) also, thank you (i'm starting to sound like i'm receiving an award or something) for your support and reasurance. and your dosing instructions will save me a lot of research time. thanks!!!take care,
amy :)
> amy,
>
> addendem :
>
> i like the post from immunesupport.com about kpins enhancing some peoples cognition etc..
>
> This is actually TRUE. I have seen it with my own eyes. Sometimes people really become "stablized" and become more clear-headed. This is true in my case with benzos, mostly klonopin only i guess.
>
> I also suffer from CFS and FMS, so i knew of Cheney et all and immunesupport.com and that study already...
>
> For people with CFS and FMS, it seems especially true for some reason, I see it time and time again. I don't claim to know why though, but i would imagine it has something to do with the gaba/nmda receptor ratio or glutamate binding to nmda. perhaps chemist has some insight, but i would hardly worry about memory problems on klonopin. if it happens, it goes away after a week or so, same with sedation, which you will notice if you have never taken it before. The first time i took klonopin .5, i felt drunk! i was so sedated. The second, and third times, i started to just feel tired, and finally, i was just anxiety free by the 4th time or so and i loved it and i just lived much better and happier and was more clear headed. Just don't taper up to quickly or taper off to quickly and you will be fine.
>
> Jlbl2l
> (NCF Volunteer)
> (Cfs Researcher)
Posted by alesta on August 21, 2004, at 16:30:32
In reply to Re: kp.-benzo least likely to cause cogn.--zeugma, posted by Donia on August 21, 2004, at 6:23:29
hello, donia!
thanks, donia, for sharing your firsthand positive experience with xanax. it seems benzos really are a lifesaver for so many people....i'm glad it's working well for you. thanks again. :)
amy :)
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