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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 25 of 35. This is the beginning of the thread.
Posted by SLS on February 20, 2005, at 7:11:30
I am becoming suspicious that the discontinuation syndrome (withdrawal) is self-reinforcing in a manner similar to the kindling model of epilepsy. If this is true, then one becomes increasingly sensitive to dosage reductions and the severity of the withdrawal symptoms increases over the taper period. The degree to which this occurs would be proportional to the amount of time one spends in the "withdrawal state". Among other things, this might explain why some people describe the persistence of withdrawal symptoms long after the drug has been discontinued. If kindling is operating, it makes it that much more critical to prevent the withdrawal state from emerging in the first place or discontinue the drug as rapidly as possible and endure the syndrome for a shorter period of time while intervening with palliative measures. Strategies might best be designed by taking into account the kindling process.
- Scott
Posted by SLS on February 20, 2005, at 8:15:31
In reply to Kindling?, posted by SLS on February 20, 2005, at 7:11:30
> I am becoming suspicious that the discontinuation syndrome (withdrawal) is self-reinforcing in a manner similar to the kindling model of epilepsy. If this is true, then one becomes increasingly sensitive to dosage reductions and the severity of the withdrawal symptoms increases over the taper period. The degree to which this occurs would be proportional to the amount of time one spends in the "withdrawal state". Among other things, this might explain why some people describe the persistence of withdrawal symptoms long after the drug has been discontinued. If kindling is operating, it makes it that much more critical to prevent the withdrawal state from emerging in the first place or discontinue the drug as rapidly as possible and endure the syndrome for a shorter period of time while intervening with palliative measures. Strategies might best be designed by taking into account the kindling process.
>
>
> - Scott
I just performed a search on Medline using the search terms "kindling" and "withdrawal". I feel pretty smart right about now. :-)
Has anyone discontinued Paxil, Effexor, or a benzodiazepine while taking an anticonvulsant / mood stabilizer? Which one(s)? How would you describe your withdrawal experience?
- Scott
Posted by SLS on February 20, 2005, at 8:21:38
In reply to Re: Kindling?, posted by SLS on February 20, 2005, at 8:15:31
This is exciting.
- Scott
Posted by SLS on February 20, 2005, at 8:43:18
In reply to Re: Kindling?, posted by SLS on February 20, 2005, at 8:21:38
> This is exciting.
It might not be a bad idea to look at glutamatergic activity as being involved in the development and persistence of a withdrawal syndrome. This would expand the number of strategies to investigate.
- Scott
Posted by SLS on February 20, 2005, at 9:00:39
In reply to Re: Kindling?, posted by SLS on February 20, 2005, at 8:43:18
> It might not be a bad idea to look at glutamatergic activity as being involved in the development and persistence of a withdrawal syndrome. This would expand the number of strategies to investigate.
Most of the work looking at the possible role of kindling in withdrawal involves alcohol. It is difficult to know the extent to which any of the results of such investigations can be extrapolated to SRI discontinuation. Still, it would be interesting to know how a drug like memantine or amantadine might modify the withdrawal process.
- Scott
Posted by lunesta on February 20, 2005, at 15:40:47
In reply to Kindling?, posted by SLS on February 20, 2005, at 7:11:30
your right. withdrawl from benzos is very similar to antidepressants, which is clearly the response of a lowered seizure threshold. antidepresant discontinuation is basically a low level seizure state.
Posted by SLS on February 21, 2005, at 10:18:40
In reply to Re: Kindling?, posted by lunesta on February 20, 2005, at 15:40:47
> your right. withdrawl from benzos is very similar to antidepressants, which is clearly the response of a lowered seizure threshold. antidepresant discontinuation is basically a low level seizure state.
I found that many of the symptoms of withdrawal from Effexor and Paxil felt the same as withdrawal from Ativan and Klonopin.
- Scott
Posted by ed_uk on February 21, 2005, at 12:59:18
In reply to Re: Kindling? » lunesta, posted by SLS on February 21, 2005, at 10:18:40
Hi Scott :-)
You suddenly seem to have become very enthusiastic!! Has your depression gone? Did you change your medication?
Best Regards,
Ed.
Posted by ed_uk on February 21, 2005, at 13:06:44
In reply to Re: Kindling? » SLS, posted by ed_uk on February 21, 2005, at 12:59:18
Scott, I think you may find this interesting............
Paroxetine, Panorama and user reporting of
ADRs: Consumer intelligence matters in
clinical practice and post-marketing drug
surveillance
Abstract. We systematically analysed two complementary samples of emails relating to patients’ problems with the popular
SSRI antidepressant, paroxetine. These mainly concerned serious mood disorders and drug withdrawal symptoms. 1,374 emails
were immediate responses to a major BBC-TV documentary programme. These were contrasted with 862 messages on similar
themes sent to a website discussion forum over a period of nearly three years. Despite the limitations of most individual email
reports, we judged their collective weight to be profound. We also suggest that the value of “immersion” in a large body of such
data may be greater than continuing exposure to a variable trickle of reports.We discuss the significance of these data in relation
to the patient–prescriber relationship and pharmacovigilance. We suggest that the Internet offers unparalleled opportunities
for soliciting and monitoring patients’ reports of adverse drug reactions, and propose practical initiatives to capture peoples’
experiences and thereby promote safer and more effective drug use.Here is an extract from the article........
NB. Paroxetine (Paxil) is sold as Seroxat in the UK.
Nine reports suggested sensitisation, again providing evidence that numerical analysis could not show.
In these cases, an initial course of treatment and withdrawal was uneventful, though subsequent exposure
led to severe reactions.
“I have taken Seroxat on two different occasions in my life. The first time I stopped taking them the
side effects were minimal, and I was quite happy to be prescribed them the second time . . . This time
was totally different. I was very ill for about a week when I started to take them (nauseous, faint,
totally unable to care for myself – I was hardly able to get out of bed). After about 6–9 months . . . I
began to get a strange whooshing feeling in my head. The GP told me it would not be the tablets –
although wasn’t keen to find out what it could be! I decided I would gradually reduce the tablets in
order to come off them, but found it extremely hard.” (993)
“Seroxat is in my view a very good drug and has helped me to get back to my usual self. Six months
after starting them, I came off ‘cold turkey’ with no side effects whatsoever but the panic attacks
returned and so I was put back on them about five months later. Since then I have tried to come off
them and haven’t been able to due to the common side effect: head shocks. I’ve tried to wean myself
off but still get this horrible sensation.”
Posted by SLS on February 21, 2005, at 13:34:49
In reply to Re: Kindling? » SLS, posted by ed_uk on February 21, 2005, at 12:59:18
> Hi Scott :-)
>
> You suddenly seem to have become very enthusiastic!! Has your depression gone? Did you change your medication?
>
> Best Regards,
> Ed.
Unfortunately, my depression isn't really any better. Parnate helps give me more mental energy to work with, but not a hell of a lot. It probably shows though.My enthusiasm comes from the potential that exists with PB to tackle such a pervasive problem like drug discontinuation withdrawal syndromes. I don't think it is asking too much for people to quickly list along the same thread what strategies have worked for them. It would be immensely helpful.
Another thing that has me excited is that I believe I have identified an important concept to explain the phenomenology of the withdrawal syndrome. Kindling. To recognize this and use it to our advantage in proposing strategies to more easily discontinue drugs like Paxil, Effexor, and benzodiazepines might be a real breakthrough. Wishful thinking, perhaps.
- Scott
Posted by SLS on February 21, 2005, at 13:43:20
In reply to Re: Kindling?, posted by ed_uk on February 21, 2005, at 13:06:44
> Scott, I think you may find this interesting............
Yes. Another major consequence of a kindling model is that the withdrawal syndrome becomes more severe with repeated exposures. I decided not to mention it previously because I didn't want to introduce too many concepts at once.
- Scott
Posted by Minnie-Haha on February 21, 2005, at 15:24:30
In reply to Re: Kindling?, posted by SLS on February 20, 2005, at 8:15:31
> Has anyone discontinued Paxil, Effexor, or a benzodiazepine while taking an anticonvulsant / mood stabilizer? Which one(s)? How would you describe your withdrawal experience?
I got off of Effexor while I was on a mood stabilizer. I can't remember now whether it was Depakote (my first MS) or Trileptal (my second/current MS), but I just don't remember having severe problems. I gradually decreased my Effexor dose and slowly started up on Wellbutrin.
Posted by Minnie-Haha on February 21, 2005, at 15:26:14
In reply to Re: Kindling?, posted by SLS on February 20, 2005, at 8:43:18
> It might not be a bad idea to look at glutamatergic activity as being involved in the development and persistence of a withdrawal syndrome...
You completely lose me when you talk like this, but I like that there are people here who understand this stuff enough to ask what appear to be really good questions.
Posted by SLS on February 21, 2005, at 16:32:34
In reply to Re: Kindling?, posted by Minnie-Haha on February 21, 2005, at 15:24:30
Hi Minnie
Your contribution was EXTREMELY helpful. Thank you.
> > Has anyone discontinued Paxil, Effexor, or a benzodiazepine while taking an anticonvulsant / mood stabilizer? Which one(s)? How would you describe your withdrawal experience?
> I got off of Effexor while I was on a mood stabilizer. I can't remember now whether it was Depakote (my first MS) or Trileptal (my second/current MS), but I just don't remember having severe problems. I gradually decreased my Effexor dose and slowly started up on Wellbutrin.Have you ever needed to discontinue an SSRI (Prozac, Zoloft, Paxil, Luvox, Celexa, Luvox)? Were you on a mood stabilizer at the time? What was your experience?
> > It might not be a bad idea to look at glutamatergic activity as being involved in the development and persistence of a withdrawal syndrome...
> You completely lose me when you talk like this,That's OK. I get lost often when I try to make heads or tails of what the neuroscientists are talking about. Out of necessity, I have been learning this stuff - VERY SLOWLY - over the course of many years. I think that applies to a great many people here who would just as soon not know anything about medicine at all should there never have been a need to.
Thanks again.
- Scott
Posted by Minnie-Haha on February 22, 2005, at 13:57:38
In reply to Re: Kindling? » Minnie-Haha, posted by SLS on February 21, 2005, at 16:32:34
> Have you ever needed to discontinue an SSRI (Prozac, Zoloft, Paxil, Luvox, Celexa, Luvox)? Were you on a mood stabilizer at the time? What was your experience?
Actually, the first AD I ever had to get off of was Zoloft. I had taken it once for 4-6 months for depression, so when I had depression again a couple of years later it was RXd again. However, this second time, after I'd been on it for some months, I started to feel really weird... agitated. As I look back on it now, I think it may have been largely anxiety, but as I'd never experienced anxiety like that before, I didn't recognize it. (Oh, for those long-gone, innocent days.) Anyway, I was immediately put on Depakote and phased off of Zoloft and onto Effexor. Once again, I don't recall this being particularly problematic.
Are you hypothesizing that being on a mood stabilizer may make starting/stopping an AD easier? (I know some use benzos to help with withdrawals, maybe MSs could be helpful, too? I don't know.)
Posted by SLS on February 22, 2005, at 16:07:47
In reply to Re: Kindling?, posted by Minnie-Haha on February 22, 2005, at 13:57:38
Hi.
> Are you hypothesizing that being on a mood stabilizer may make starting/stopping an AD easier?:-)
We'll see...
Thanks for responding.
- Scott
Posted by SLS on March 6, 2005, at 8:05:21
In reply to Re: Kindling?, posted by SLS on February 22, 2005, at 16:07:47
Hi.
I'm not entirely sure that kindling can account for the length of time withdrawal symptoms can persist for weeks and months after drug discontinuation. I would love for there to be a study on this. Will a taper schedule that prevents a withdrawal syndrome from appearing also prevent it from persisting? This is a question that is crucial to have answered.
An alternative explanation is that the changes in gene expression that occur during treatment persist as the altered dynamics between second messengers and nuclear events remain chronic. This would really suck. However, I would not give up on the idea that this situation could not be remedied pharmacologically. I would be interested to know how lithium might affect withdrawal. It might help reduce the excitability of the neuron by reducing the expression of G-protein coupled serotonin receptors.
Any takers?
- Scott
Posted by SLS on April 30, 2005, at 10:41:26
In reply to Re: Kindling?, posted by SLS on February 22, 2005, at 16:07:47
Has anyone tried to discontinue an antidepressant or benzodiazepine while taking an anticonvulsant mood-stabilizer? Which one(s)? How would you describe your withdrawal experience?
Depakote
Tegretol
Trileptal
Neurontin
Zonegren
Gabitril
Dilantin
Topamax
Lamictal
Keppra
Lyrica
- Scott
Posted by Declan on April 30, 2005, at 21:13:24
In reply to Re: Kindling?, posted by SLS on March 6, 2005, at 8:05:21
When tapering off methadone I took low dose Dilantin at night, 30-60mg. The idea was to minimise those convulsion-like spasms that came during sleep onset. Didn't notice anything really, but I did manage to reduce methadone to 1.25mg/d. Which is really difficult.
Declan
Posted by River1924 on May 1, 2005, at 12:40:56
In reply to Re: Kindling?, posted by SLS on April 30, 2005, at 10:41:26
I haven't time to read thru all these posts but, if you mind, what withdrawal symptoms would anti-convulsants prevent when stopping anti-depressants? I always take stimulants (or extra stimulants or provigal) to avoid this extraordinary dopiness I feel when I stop zoloft or effexor (Ordinarily, I just hop full dose from one anti-depressant to another and hope for the best.) The four anti-convulsants I've tried have been sedating and depressing. Just curious. Peace, River.
Posted by SLS on May 2, 2005, at 7:04:51
In reply to Re: Kindling? » SLS, posted by River1924 on May 1, 2005, at 12:40:56
> I haven't time to read thru all these posts but, if you mind, what withdrawal symptoms would anti-convulsants prevent when stopping anti-depressants?
I am not sure. I am just beginning to explore what role an anti-kindling medication might play in the course of withdrawal from antidepressants or benzodiazepines. My hope is that it would help prevent most of the withdrawal symptoms reported, including anxiety and "brain zaps".
- Scott
Posted by Slinky on May 5, 2005, at 23:08:23
In reply to Re: Kindling?, posted by SLS on May 2, 2005, at 7:04:51
After my dose of 200mg of Tegretol the brain zaps are reduced..not entirely but more bearable.
I've just ceased Paxil.Slinky
Posted by Chairman_MAO on May 8, 2005, at 13:48:50
In reply to Re: Kindling?, posted by SLS on May 2, 2005, at 7:04:51
For what it's worth, years ago I took Effexor with Dexedrine. When I started withdrawing from Effexor, I found that taking the Dexedrine (30-40mg at a time) eliminated all withdrawal symptoms from the Effexor.
I think kindling is relevant to withdrawal from benzodiazepines but not antidepressants. I had a pdoc tell me once that withdrawal from benzos was WORSE than barbiturates because seizures can occur up to 14 days after detoxification, which is unheard of with barbiturates. Antidepressants lower the seizure threshold (while benzos obviously raise it), so I would think that kindling upon withdrawal would be a nonissue, no? If you want I can ask a pharmacologist.
Posted by SLS on May 9, 2005, at 7:38:17
In reply to Re: Kindling? » SLS, posted by Chairman_MAO on May 8, 2005, at 13:48:50
> For what it's worth, years ago I took Effexor with Dexedrine. When I started withdrawing from Effexor, I found that taking the Dexedrine (30-40mg at a time) eliminated all withdrawal symptoms from the Effexor.
>
> I think kindling is relevant to withdrawal from benzodiazepines but not antidepressants. I had a pdoc tell me once that withdrawal from benzos was WORSE than barbiturates because seizures can occur up to 14 days after detoxification, which is unheard of with barbiturates. Antidepressants lower the seizure threshold (while benzos obviously raise it), so I would think that kindling upon withdrawal would be a nonissue, no? If you want I can ask a pharmacologist.
It would appear that withdrawal from SRIs phenomenologically appears like withdrawal from benzodiazepines in that it gets worse the longer it is allowed to continue. If the many reports of extended withdrawal syndrome lasting for months after the last dose of the offending agent can be believed, it looks like those experiencing the worst scenarios are those whom discontinued the SRI abruptly - "cold turkey".I'm too lazy to research it and make a case for a true kindling physiology of these phenomena, but it seems that they can be understood or managed as if they were - a virtual kindling if nothing else. If anything, something might be precipitating a resistance on the part of 5-HT neurons from reregulating themselves due to a lack of change of postsynaptic second messenger and nuclear events despite the loss on reuptake inhibition. The nerves remain hyperexcitable.
Do you happen to know what the physiology is behind the kindling of seizures? I'm not really clear on that.
- Scott
Posted by River1924 on May 10, 2005, at 1:59:19
In reply to Re: Kindling? » Chairman_MAO, posted by SLS on May 9, 2005, at 7:38:17
I think the "brain zap" phenomenon must get a better name. I've never experienced it but I'm willing to say it exists. I doubt if most people outside the psychobabble community would take anyone seriously if he or she said they had withdrawal "brain zaps." Do you think this problem is common?
On another note, would a drug like tianeptine help or a supplement like l-tryptophan? Could these brain zaps be a result of vitamin/amino acid/mineral deficiency?
Peace, River.
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Dr. Bob is Robert Hsiung, MD,
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