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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 13 of 13. This is the beginning of the thread.
Posted by cache-monkey on January 16, 2006, at 20:22:47
I'm also having a tough time tapering off of Klonopin (stuck at 0.875 mg/day) and am wondering if anyone on the board has experience with Keppra in this regard.
I've read that in a mouse model, high-doses Keppra might reduce the severity of withdrawal symptoms:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11937098&query_hl=4&itool=pubmed_docsum
I've also heard anecdotal reports of people using it for this purpose.I also wondering if anyone has experience with Keppra as a mood stabilizer for BPII, with depression and anxiety prominent. For me Depakote and Trileptal made me super depressed, Lithium makes me anxious, and the atypical APs give me akathisia something aweful. Is Keppra often depressiogenic (as, e.g., Depakote is for many) or is it rather benign in that regard?
Thanks for any info.
Best,
cache-monkey
Posted by SLS on January 16, 2006, at 20:48:14
In reply to Keppra for benzo taper and/or mood stabilizer... ?, posted by cache-monkey on January 16, 2006, at 20:22:47
Hi CM.
I postulated quite some time ago that anticonvulsants might act to mitigate the withdrawal syndromes that accompany the reduction in dosage or discontinuation of SRI antidepressants and benzodiazepines. I posted my thoughts on the "Withdrawal" board quite awhile ago when I first offered a kindling model to explain the worsening course of withdrawal syndromes through time. No one was able to offer an anecdote to corroborate these ideas unequivocally, as they were being treated with other drugs simultaneously. However, there seemed to be a trend towards a less severe withdrawal syndrome for those people already taking anticonvulsants. I haven't yet formed an opinion as to whether or not pro-GABAergic properties are essential to this reduction effect. My initial impression is that it is not. Anti-kindling properties might be sufficient, regardless of mechanism.
Keppra (levetiracetam) is a prototypic drug. It is the only anticonvulsant that acts to modulate the funtion of presynaptic vesicles. The synaptic vesicle protein SVA2 was singled out as a candidate binding site, and acts to regulate the vesicle fusion process with the neuronal terminal membrane.
In my experience, Keppra can be both antidepressant and depressogenic, depending on the dosage used. It is likely that there is a window of efficacy (upside-down U-shaped dosage-effect curve) when treating mood disorders. I find that 750-1000mg is ideal for me. At 2000mg, I felt worse than I did before starting it. Kenneth Kaufman, MD, wrote up a paper on a treatment-resistant rapid-cycling female who was stabilized on Keppra monotherapy. You should be able to find the abstract on Medline.
If you decide to use an anticonvulsant to mitigate the benzodiazepine withdrawal syndrome, please post your results. Thanks.
- Scott
Posted by cache-monkey on January 16, 2006, at 21:23:08
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » cache-monkey, posted by SLS on January 16, 2006, at 20:48:14
Hey Scott,
Good to hear your input. I remember that you had tried Keppra for a while, but then it looked like it started being a bad experience. I didn't realize that you were still on it. So, I assume that you think it's helping to some degree after all. What sort of benefits are you getting from it?
Also, I haven't seen you posting that much on babble lately. How are things going for you in general? Have you had some reprieve from your depression?
I'm currently on:
* 2.5 mg selegiline -- positive effect on mood, but makes me sleepy so I'm moving the dose to the evening
* 112.5 mg Lithium; in the process of tapering because it made me more anxious; I seem to do alright a couple days after each dose reduction; in between I get really tired and depressed
* 0.75 Klonopin; in the process of a smalll dose reduction because it makes me slow and contributes to my depressionSo there's a lot going on right now, with the double taper. But for me this makes sense: based on independent variation of each, the Lithium and Klonopin seem to have been working at odds with eachother. I'm going to get off the Lithium and see whether I can reduce the Klonopin in the process.
When that settles down, my pdoc and I are talking about either Neurontin or Keppra for mood stabilization and to help with the rest of the benzo taper. I will definitely keep you and anyone else interested posted.
Best,
cache-monkey> Hi CM.
>
> I postulated quite some time ago that anticonvulsants might act to mitigate the withdrawal syndromes that accompany the reduction in dosage or discontinuation of SRI antidepressants and benzodiazepines. I posted my thoughts on the "Withdrawal" board quite awhile ago when I first offered a kindling model to explain the worsening course of withdrawal syndromes through time. No one was able to offer an anecdote to corroborate these ideas unequivocally, as they were being treated with other drugs simultaneously. However, there seemed to be a trend towards a less severe withdrawal syndrome for those people already taking anticonvulsants. I haven't yet formed an opinion as to whether or not pro-GABAergic properties are essential to this reduction effect. My initial impression is that it is not. Anti-kindling properties might be sufficient, regardless of mechanism.
>
> Keppra (levetiracetam) is a prototypic drug. It is the only anticonvulsant that acts to modulate the funtion of presynaptic vesicles. The synaptic vesicle protein SVA2 was singled out as a candidate binding site, and acts to regulate the vesicle fusion process with the neuronal terminal membrane.
>
> In my experience, Keppra can be both antidepressant and depressogenic, depending on the dosage used. It is likely that there is a window of efficacy (upside-down U-shaped dosage-effect curve) when treating mood disorders. I find that 750-1000mg is ideal for me. At 2000mg, I felt worse than I did before starting it. Kenneth Kaufman, MD, wrote up a paper on a treatment-resistant rapid-cycling female who was stabilized on Keppra monotherapy. You should be able to find the abstract on Medline.
>
> If you decide to use an anticonvulsant to mitigate the benzodiazepine withdrawal syndrome, please post your results. Thanks.
>
>
> - Scott
>
>
Posted by 4WD on January 16, 2006, at 22:03:42
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » cache-monkey, posted by SLS on January 16, 2006, at 20:48:14
Hi Scott,
I'm glad to see you back. I hope you've been gone because you've been feeling great and been out there having a good time.
My pdoc now thinks I have med-induced bipolar (just like you, because of a one time hypomanic dysphoric episode due to an increase in Celexa). (Although I've been having mixed states and some rapid cycling for a while now).
I've just started Depakote. I'm wondering whether Keppra might have been a better choice? At far as I know, though, the Depakote should work more quickly. If Depakote doesn't work for mood stabilization, does that mean Keppra likely wouldn't either? And is Keppra useful as an anxiolytic, as Depakote supposedly is?
Sorry to inundate you when you've just stuck your toe back in the water.
Marsha
> Hi CM.
>
> I postulated quite some time ago that anticonvulsants might act to mitigate the withdrawal syndromes that accompany the reduction in dosage or discontinuation of SRI antidepressants and benzodiazepines. I posted my thoughts on the "Withdrawal" board quite awhile ago when I first offered a kindling model to explain the worsening course of withdrawal syndromes through time. No one was able to offer an anecdote to corroborate these ideas unequivocally, as they were being treated with other drugs simultaneously. However, there seemed to be a trend towards a less severe withdrawal syndrome for those people already taking anticonvulsants. I haven't yet formed an opinion as to whether or not pro-GABAergic properties are essential to this reduction effect. My initial impression is that it is not. Anti-kindling properties might be sufficient, regardless of mechanism.
>
> Keppra (levetiracetam) is a prototypic drug. It is the only anticonvulsant that acts to modulate the funtion of presynaptic vesicles. The synaptic vesicle protein SVA2 was singled out as a candidate binding site, and acts to regulate the vesicle fusion process with the neuronal terminal membrane.
>
> In my experience, Keppra can be both antidepressant and depressogenic, depending on the dosage used. It is likely that there is a window of efficacy (upside-down U-shaped dosage-effect curve) when treating mood disorders. I find that 750-1000mg is ideal for me. At 2000mg, I felt worse than I did before starting it. Kenneth Kaufman, MD, wrote up a paper on a treatment-resistant rapid-cycling female who was stabilized on Keppra monotherapy. You should be able to find the abstract on Medline.
>
> If you decide to use an anticonvulsant to mitigate the benzodiazepine withdrawal syndrome, please post your results. Thanks.
>
>
> - Scott
>
>
Posted by SLS on January 17, 2006, at 8:41:41
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » SLS, posted by cache-monkey on January 16, 2006, at 21:23:08
> Hey Scott,
Hey.
:-)
> Good to hear your input. I remember that you had tried Keppra for a while, but then it looked like it started being a bad experience. I didn't realize that you were still on it. So, I assume that you think it's helping to some degree after all. What sort of benefits are you getting from it?
I find that it helps with mental energy and motivation. However, as I mentioned in my previous post, there seems to be a window of efficacy. I became more depressed at 2000mg. I rechallenged myself with this higher dosage several times to confirm the cause-and-effect relationship.
> Also, I haven't seen you posting that much on babble lately. How are things going for you in general?
Not so well, but not horrendous.
My lack of posting recently is probably due mostly to PB burnout. However, some is due also to a preoccupation with the holidays and a new digital camera I've been playing with. We are fortunate that so many people offer aid to others in this community. Despite an observable rate of attrition, there are always people who are motivated and in a position to help others.
> Have you had some reprieve from your depression?
I guess the Keppra has been of some help. However, I remain mostly vegetative. This becomes most evident when I try to read and concentrate or perform chores around the house.
> I'm currently on:
> * 2.5 mg selegiline -- positive effect on mood, but makes me sleepy so I'm moving the dose to the eveningInteresting that it should make you sleepy. Does it act to reduce the amount of dreaming you experience?
> * 112.5 mg Lithium; in the process of tapering because it made me more anxious;
I've heard of this. It might be an indication that you are adversely affected by serotonergic drugs. Did it cause you to clench your teeth?
> I seem to do alright a couple days after each dose reduction; in between I get really tired and depressed
Similarly, I experienced a rebound antidepressant effect the first time I discontinued lithium.
> * 0.75 Klonopin; in the process of a smalll dose reduction because it makes me slow and contributes to my depression
It occurs that some people experience a mild to moderate depressogenic reaction to Klonopin. Personally, I attribute this to its serotonergic effects, although they are not yet well defined. This phenomenon sometimes dissipates over time at a stable dosage and consistent dosing schedule. It might be that the pro-serotonergic effects of both lithium and Klonopin are acting together to create more depression, not less.
> So there's a lot going on right now, with the double taper. But for me this makes sense: based on independent variation of each, the Lithium and Klonopin seem to have been working at odds with eachother. I'm going to get off the Lithium and see whether I can reduce the Klonopin in the process.
> When that settles down, my pdoc and I are talking about either Neurontin or Keppra for mood stabilization and to help with the rest of the benzo taper. I will definitely keep you and anyone else interested posted.Generally speaking, Neurontin does not make for an effective mood stabilizer unless it is combined with another one like Lamictal. It is used more as an anxiolytic now. Keppra has yet to prove itself. Lamictal is reported to be particularly effective for rapid-cycling.
Did you find the Kaufman paper?
- Scott
Posted by SLS on January 17, 2006, at 9:09:57
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » SLS, posted by 4WD on January 16, 2006, at 22:03:42
Hi Marsha.
> Hi Scott,
>
> I'm glad to see you back.Thanks. I doubt I'll be posting that much, though. Burnout.
> I hope you've been gone because you've been feeling great and been out there having a good time.
That would be extraordinarily cool were that the case. I guess in some ways it is. I've been busy doing things like doing Christmas shopping with my girlfriend, breaking up with my girlfriend, and playing with a new digital camera. I think Keppra 1000mg has helped supply me with enough energy to go out and do a few things. The breakup has been a bit taxing, but, fortunately, it has not triggered a worsening of bipolar depression.
> My pdoc now thinks I have med-induced bipolar (just like you, because of a one time hypomanic dysphoric episode due to an increase in Celexa). (Although I've been having mixed states and some rapid cycling for a while now).
According to the literature, Lamictal is often mentioned as being a particularly good choice for rapid cyclers.
How severe was your mania? Was it more severe than hypomania? Did you become delusional or psychotic? Bipolar III (as your presentation might soon be designated) might be closer to bipolar I than bipolar II.
> I've just started Depakote.
I found Depakote to be extremely effective at treating the mania, but only intermittantly and mildly effective at treating the depression. Upon chronic administration, I found it to be somewhat depressogenic. Zyprexa might be a better choice if the Depakote does not exert enough of an antidepressant effect for you.
> I'm wondering whether Keppra might have been a better choice?
Me too.
> At far as I know, though, the Depakote should work more quickly.
I would agree with you at this point.
> If Depakote doesn't work for mood stabilization, does that mean Keppra likely wouldn't either?
The two drugs are extremely different. I don't think one can conclude what a person's reaction to one drug will be based upon their experience with the other.
> And is Keppra useful as an anxiolytic, as Depakote supposedly is?
I wish I could tell you for sure. At least I didn't find it to be anxiogenic. I don't suffer from a constant background anxiety, just some social anxiety. As such, I don't think I represent a good subject to represent Keppra's efficacy as an anxiolytic. I'll try to take note of my current level of social anxiety. Keppra does not affect directly GABA function as does Depakote. That does not, however, rule out the possibility that it does have a secondary effect as a pro- GABAergic. For all I know, it might work by limiting the amount of synaptic release of excitatory neurotransmitters rather than increasing the activity of inhibitory neurons.
> Sorry to inundate you when you've just stuck your toe back in the water.
No problem. :-)
Please don't take it personally if I make my way back to my beach chair now...
- Scott
Posted by cache-monkey on January 17, 2006, at 13:45:26
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » cache-monkey, posted by SLS on January 17, 2006, at 8:41:41
< I find that it [Keppra] helps with mental energy and motivation. >
This is good to hear. Depakote and Trileptal definitely had the opposite effect for me, and I was worried that Keppra would end up being more of the same.
<< Also, I haven't seen you posting that much on babble lately. How are things going for you in general? >>< Not so well, but not horrendous. >
I think this is probably the most positive assessment of your state you've given in a while. I'm glad that there's at least a small uptick for you and hope that the trend continues.
< My lack of posting recently is probably due mostly to PB burnout. >
Understood, and it makes your responses to my posts that much more appreciated. :)
< However, some is due also to a preoccupation with the holidays and a new digital camera I've been playing with. >
New toys are always nice!
<< I'm currently on:
* 2.5 mg selegiline -- positive effect on mood, but makes me sleepy so I'm moving the dose to the evening >>
< Interesting that it should make you sleepy. Does it act to reduce the amount of dreaming you experience? >I'm not sure, but this seems to be clearly a direct effect of the selegiline. I take it and then boom I'm tired an hour later. I've tried moving the dose around in the day to establish cause-and-effect. It's still kind of weird, though, since I thought selegiline's increase in dopamine would be energizing if anything.
<< * 112.5 mg Lithium; in the process of tapering because it made me more anxious; >>
< I've heard of this. It might be an indication that you are adversely affected by serotonergic drugs. Did it cause you to clench your teeth? >No bruxism for me, but I had a pretty bad experience on Lexapro last fall. Somewhat similar increased anxiety and tension. With Lex, though, I also had RLS something aweful. My hypothesis with the Li had to do with it increasing NE release and desensitizing the alpha-2 receptor:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=1645513&query_hl=8&itool=pubmed_docsum
<< I seem to do alright a couple days after each dose reduction; in between I get really tired and depressed. >>
< Similarly, I experienced a rebound antidepressant effect the first time I discontinued lithium. >Actually, I wrote that poorly. I actually get rebound depression for a few days after lowering Li, and then eventually a return to a place slightly less anxious than before the dose reduction, but perhaps a little more melancholy.
<< * 0.75 Klonopin; in the process of a smalll dose reduction because it makes me slow and contributes to my depression >>
< It occurs that some people experience a mild to moderate depressogenic reaction to Klonopin. Personally, I attribute this to its serotonergic effects, although they are not yet well defined. This phenomenon sometimes dissipates over time at a stable dosage and consistent dosing schedule. It might be that the pro-serotonergic effects of both lithium and Klonopin are acting together to create more depression, not less. >
Unfortunately the depressiogenic aspect of Klonopin has been more or less consistent over my time on the drug. The lithium might have actually offset it, to an extent, but at the cost of substantially increased anxiety. Hence the experiment of the double-taper.
<< When that settles down, my pdoc and I are talking about either Neurontin or Keppra for mood stabilization and to help with the rest of the benzo taper. I will definitely keep you and anyone else interested posted. >>< Generally speaking, Neurontin does not make for an effective mood stabilizer unless it is combined with another one like Lamictal. It is used more as an anxiolytic now. Keppra has yet to prove itself. Lamictal is reported to be particularly effective for rapid-cycling. >
I've tried Lamictal, but that's what ended up putting me on the Klonopin in the first place. I had a full-on panic attack for the first time in my life. :( It also was making my muscles horribly tight, indicated a generalized increase in somatic anxiety. This was at 50 mg/day. Perhaps I need to stick it out longer. Or try it combination with Neurontin. At this point, though, I'm inclined to give Keppra (+selegiline) a go first...
I did find the Kaufman paper, as well as another small open on-off study. I'm also intrigued by the anti-kindling aspect of Keppra, although I don't understand quite what that means. I realize you're taking a babble vacation right now, so I can do some poking around the web and/or look for your old posts.
Finally, and you may have already seen this, but FYI it looks like Keppra may have some back-door pro-GABA effects:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=8911659&dopt=Abstract
with (if I'm reading this right) particularly strong effects at the GABA-A complex:
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=12086975&dopt=AbstractAll the best,
cache-monkey
Posted by ed_uk on January 17, 2006, at 15:14:58
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » 4WD, posted by SLS on January 17, 2006, at 9:09:57
Hi Scott
Nice to see you back at p-babble. I always read your posts.
Ed
Posted by ed_uk on January 17, 2006, at 15:17:28
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » SLS, posted by cache-monkey on January 17, 2006, at 13:45:26
Hi CM
A long-acting low potency benzo like Librium might help you taper the clonazepam.
Perhaps you don't need a mood stabiliser? Perhaps you will find an AD which suits you?
Ed
Posted by 4WD on January 17, 2006, at 22:24:33
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » 4WD, posted by SLS on January 17, 2006, at 9:09:57
Thanks, Scott. No more question, just appreciation.
I wasn't manic, just hypomanic - in a bad sort of way. Mixed states. Hyper, agitated, jittery and couldn't calm myself. Wired and nervous and ten things going at once and no ability whatsoever to calm myself. And frequently deeply depressed at the same time.
Pdoc says Depakote is good for mixed states. Lamictal helped but couldn't tolerate side effects.
Anyway, thanks so much. I am picturing you in your beach chair.
Marsha
Posted by cache-monkey on January 18, 2006, at 19:39:41
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » cache-monkey, posted by ed_uk on January 17, 2006, at 15:17:28
Hey Ed,
Thanks for the response! :)
I will definitely look into a longer half-life benzo. But I want to get through this last tiny dose reduction first...
Do you have a reason for suggesting Librium instead of the traditional Valium? They seem to have the same long-acting metabolite, based on what I can tell from Ashton's manual. But the half life of Valium itself seems to be longer than Librium. I'm wondering if this might cause a difference in reaction to tapering...
I don't know if I need a mood stabilizer, but based on a critical review of my emotional history something that helps with my sometimes extreme (and usually negative) emotional reactivity might help. Also, I feel like it might help to have some additional bolster for the benzo taper. The one caveat is that I don't want to increase depression and/or experience the horrible cogntitive dulling, both of which I had on Trileptal and Depakote.
I've seen references (from Scott and others) to "anti-kindling" properties of Keppra. Do you know anything about this? My hunch says that might be beneficial in terms of the substantial emotional reactivity, but I'm not sure.
Best,
cache-monkey
> Hi CM
>
> A long-acting low potency benzo like Librium might help you taper the clonazepam.
>
> Perhaps you don't need a mood stabiliser? Perhaps you will find an AD which suits you?
>
> Ed
Posted by ed_uk on January 19, 2006, at 14:25:35
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » ed_uk, posted by cache-monkey on January 18, 2006, at 19:39:41
Hi CM
>Do you have a reason for suggesting Librium instead of the traditional Valium?
I thought your doc might be more comfortable with it. Valium seems to have aquired a particularly bad reputation in the US. Silly really.
>They seem to have the same long-acting metabolite, based on what I can tell from Ashton's manual. But the half life of Valium itself seems to be longer than Librium. I'm wondering if this might cause a difference in reaction to tapering...
I think you'd find them similarly effective for tapering. Valium is the 'traditional' drug for doing benzo tapers in the UK, but probably not in the US. Librium is the 'traditional' drug for treating alcohol withdrawal symptoms, probably because of its (apparantly) lower 'street value'.
>I've seen references (from Scott and others) to "anti-kindling" properties of Keppra. Do you know anything about this?
Keppra is very 'experimental' in psychiatry. There's no good evidence that it's actually effective in treating any psychiatric disorder. It's only really established as an antiepileptic. I'm not saying that it doesn't work, just that it's unproven.
Regards
Ed
Posted by yxibow on January 21, 2006, at 3:56:57
In reply to Re: Keppra for benzo taper and/or mood stabilizer... ? » cache-monkey, posted by ed_uk on January 19, 2006, at 14:25:35
>I thought your doc might be more comfortable with it. Valium seems to have aquired a particularly bad reputation in the US. Silly really.
Especially since Valium has a long half life.
> I think you'd find them similarly effective for tapering. Valium is the 'traditional' drug for doing benzo tapers in the UK, but probably not in the US. Librium is the 'traditional' drug for treating alcohol withdrawal symptoms, probably because of its (apparantly) lower 'street value'.
And being the first benzodiazepine, not as targeted as its followers and a weaker agent.
> Keppra is very 'experimental' in psychiatry. There's no good evidence that it's actually effective in treating any psychiatric disorder. It's only really established as an antiepileptic. I'm not saying that it doesn't work, just that it's unproven.
And from what I've heard worsens psychosis. Or at least from what my psychopharmacologist has seen in his patients. Always looking for the next one :/...
This is the end of the thread.
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