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Dr. Bob is Robert Hsiung, MD,
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Posted by AndrewB on August 5, 2000, at 10:24:56
This is my fourth day on Adrafinil. I have tried doses both of both 300mg. or 600mg. in the morning. It gives me a sense of inner tension. In the evenings it gives me a cracker jack headache and heartburn. Anybody get this?
I will try just 150mg. today.
AndrewB
Posted by shar on August 5, 2000, at 12:52:47
In reply to Adrafinil, anyone experience this?, posted by AndrewB on August 5, 2000, at 10:24:56
Andrew,
You and I are on about the same schedule; today is day 6 for me. I go really slow with meds so my body will have a sense of what's coming.I started days at: 150, 150, 150+75, 150 a.m. and 150 about noon, 300, 300. So I am on my second day at a whole 300 at once. I haven't had any of the things you mentioned. However, I believe inner tension is one of the more common side effects mentioned.
I will go on to days at 300+150, 300+150+75, then 600. I will stay at 600 a while to give it a chance. If needed I'll step up slowly some more.
Good luck with yours!
Shar
> This is my fourth day on Adrafinil. I have tried doses both of both 300mg. or 600mg. in the morning. It gives me a sense of inner tension. In the evenings it gives me a cracker jack headache and heartburn. Anybody get this?
>
> I will try just 150mg. today.
>
> AndrewB
Posted by Angela5 on August 5, 2000, at 13:00:48
In reply to Adrafinil, anyone experience this?, posted by AndrewB on August 5, 2000, at 10:24:56
I tried both 300 mg 1x/day and 300 mg 2x/day. It gave me very nasty headaches, but no heartburn or inner tension. I discontinued it mainly because of the headaches, although it had been helping with my concentration.
Angela
Posted by SLS on August 5, 2000, at 19:28:23
In reply to Adrafinil, anyone experience this?, posted by AndrewB on August 5, 2000, at 10:24:56
> This is my fourth day on Adrafinil. I have tried doses both of both 300mg. or 600mg. in the morning. It gives me a sense of inner tension. In the evenings it gives me a cracker jack headache and heartburn. Anybody get this?
>
> I will try just 150mg. today.
>
> AndrewBProvigil produced exactly the same effects with me along with headaches.
I hope it works as well for you as it does for JohnL.
I thought you had already tried adrafinil without success. What's the deal?
By the way, I have again added Neurontin to the Lamictal I have been taking. It is helping some. However, my past experiences with this drug have been equivocal. Keeping my fingers crossed...
- Scott
Posted by AndrewB on August 5, 2000, at 22:06:01
In reply to Re: Adrafinil, anyone experience this?, posted by SLS on August 5, 2000, at 19:28:23
Scott,
Since modafinil is a metabolite of adrafinil, I guesss I shouldn't be surprised you experienced the same thing on Provigil.I don't know how adrafinil works, but these short term effects with adrafinil aren't alpha1 andrenergic agonism, based on my experience with rebox. and Naphazoline. I suspect glutaminergic. This concerns me because excess glutamate is known to be neurotoxic as well as excitatory. I will read up on this issue if I can happen too make adrafinil effective for me.
I am trying adrafinil for the 1st time. Rebox. started to poop out on me. Nice to be free of the sexual side effects of rebox. Rebox. also limited my athletic stamina severely.
Will try ritalin and adderall next as a trial. Possibly provigil. If proper arousal isn't achieved, I have some of Goldstein's arousal agents to try like lamotrigine, TRH spray and cycloserine.
I don't need that much arousal. I'm not that bad off now. Some daytime sleepiness, you know, but not really fatigue. Maybe the selegiline I'm taking has helped me out a bit in respect to arousal. I have concluded that selegiline solidiifes the action of amiuslpride for me, making me not wilt under stress. Also I have less social anxiety, I have an acceptable amount now. No side effects for me on selegiline.
AndrewB
Posted by SLS on August 6, 2000, at 8:00:00
In reply to Scott, posted by AndrewB on August 5, 2000, at 22:06:01
Hi Andrew.
> I don't know how adrafinil works, but these short term effects with adrafinil aren't alpha1 andrenergic agonism, based on my experience with rebox. and Naphazoline.
What did you experience when you introduced naphazoline? Are there any NE alpha-1 agonists available that cross the blood-brain barrier?
> I suspect glutaminergic. This concerns me because excess glutamate is known to be neurotoxic as well as excitatory.
I didn't know that. One of the abstracts I came across on Medline hinted that Provigil may exert some neuroprotective effects on striatal dopaminergic neurons and glial cells. Sometimes, I think such conclusions are impelled by wishful thinking. I don't know. Upon which cells is excess glutamate known to be toxic?
> I am trying adrafinil for the 1st time. Rebox. started to poop out on me.
That sucks.
> Nice to be free of the sexual side effects of rebox. Rebox. also limited my athletic stamina severely.
From this, I surmise that you have discontinued reboxetine. I would just point out that you used the phrase "started to poop out". If you retain some positive effect from reboxetine, you may want to consider returning to it as an adjunct if necessary. I'm guessing that you would not have discontinued it if it were not for the unwanted side effects it produces. I know how quickly I want to discontinue a drug that is not producing satisfactory results if it means I can escape its side effects.
> Will try ritalin and adderall next as a trial.
This was my first thought even before I had read this far. However, the thought was to add it as an adjunct to reboxetine. Of course, there have been descriptions on Psycho-Babble of people who find Adderal to be a necessary adjunct to adrafinil to produce a robust improvement. I would make Adderal my first choice.
> I don't need that much arousal. I'm not that bad off now. Some daytime sleepiness, you know, but not really fatigue. Maybe the selegiline I'm taking has helped me out a bit in respect to arousal.
Did reboxetine lose its effect after you added selegiline or before?
> I have concluded that selegiline solidiifes the action of amiuslpride for me, making me not wilt under stress.
This is why I had thought to add sulpiride/amisulpride to Parnate.
> Also I have less social anxiety, I have an acceptable amount now. No side effects for me on selegiline.
May the force be with you...
On a personal note: After the first few days of taking Neurontin, I have begun to see diminishing returns. More importantly, I have experienced the induction of significant cognitive disturbances. This has occurred at a dosage of 900mg. My experiences in the past indicate that this is probably less dosage dependant and more time dependant. My motivation to take Neurontin Tuesday night was to reduce the great anxiety and depression that I was sure would prevent me from driving to my doctor's office for my appointment the next morning. When I found that the anxiety and depression had abated significantly, I decided to continue with it. However, it really wacked me out yesterday evening after taking a 200mg dose that represented a total of 800mg for the day. I have now decided to discontinue it by decreasing the dosage slowly. I am afraid of this drug.
- Scott
Posted by JohnL on August 7, 2000, at 3:59:26
In reply to Adrafinil, anyone experience this?, posted by AndrewB on August 5, 2000, at 10:24:56
Andrew,
Sorry about the rough start. 600mg might be too much, not just now, but in the longrun. I say that because I've been taking Adrafinil for a while now and am doing fine at just 300mg. I've tried higher doses, but 300mg is just right. I've come to believe more is not always better with any drug, that often times more can actually be as bad as not enough. With me anyway.At 600mg I get a low-level headache similar to Provigil, except Provigil was a seriously heavy-duty headache.
My results are not comparable to yours though, I don't think, because I am taking a cocktail. I take 300mg Adrafinil at breakfast, one tab of St Johnswort (New Chapter 10%hyperforin brand) at breakfast, one tab of SAMe mid-morning, and 7.5mg Remeron in early evening. Four ingredients, but all at very low doses, producing better results than any higher dose of a singular ingredient. SAMe and SJW both provide a lot more health side benefits too, besides being useful for depression.
I have to admit though, the best ever was 300mg Adrafinil + 50mg Amisulpride. What an awesome combo. It took a while, but I finally narrowed my impotence side effect down to Amisulpride. That's too bad, because Amisulpride was great combined with Adrafinil. I almost felt too good, because I was so motivated and interested in hobbies and activities that I really slacked off at work. With my current cocktail I'm still motivated and interested, though not to an extreme, and have found a good middle ground where I can still enjoy both work and fun, and not be so engrossed in just fun. I'm doing much better in the workplace and still having fun at home.
Anyway, just wanted to say 300mg could be all you need. I've been on and off Adrafinil twice. The first time it took about a week to kick in. The second time it took longer, almost 3 weeks. But once it kicked in, a dose increase was not needed, and actually made things a little worse, not better. So if at all possible, try to stick it out for a few weeks before making any other decisions. And once you are adjusted to it, Amisulpride could be a nice compliment to it. Or, as in my case, low dose SJW and low dose SAMe. Those took about 2 weeks each to kick in. When I added Amisulpride, that also took about 2 weeks.
John
Posted by AndrewB on August 7, 2000, at 11:39:47
In reply to Re: Adrafinil, anyone experience this?, posted by JohnL on August 7, 2000, at 3:59:26
John,
Thanks for all the great advice. I will try to give adrafinil a fair trial.
I am going to halt the adrafinil trial until I receive some propranolol for the headcahes. Then I will go with 150mgs/day to start.
How long does it take for the adrafinil to leave your system? Can you believe it, I felt an arousal effect from adrafinil in a few hours!
Make note that Michael is using bromocriptine successfully to combat adrafinil induced sexual dysfunction. I have also read that bromocriptine is effective for amisulpride sexual dysfunction. Seems to me that if you took bromcriptine you may be able to take both amisulpride and adrafinil together again.
---------------------------
Scott,I don't know if Naphazoline crosses the blood brain barrier. On a related note, I am very interested in the idea of an alphal1 andrenergic agonist being able to be centrally selective in its actions (vs. having both central and periphereal action) as is claimed (hah, hah!) for adrafinil. Reboxetine's effect of severely limiting my athletic stamina and the sexual side effects, I believe are due to periphereal alpha1 agonism. So I would think a centrally acting alpha1 agonist would be great for a lot of people, myself included.
Glutamate opens the calcium channels. Compare this to the calcium channel blocking action of nimodipine. Too much calcium within the cell somehow leads to neuron death. I forgot the speicifics. Anyway, such glutamate induced neuron death is being recognized as a leading factor in a lot mental maladies and other conditions. For example, the greater part of the brain damage caused by a stroke is not due to hypoxia, rather glutamate toxicity. By applying a drug that blocks glutamate's action soon after a stroke, such as a calcium channel blocker, people have been able to recover much better from strokes. It is Memantine's glutamate limiting actions, as an NMDA receptor antagonist, that enables it to be effective in the treatment of dementia, neuropathic pain, Alzheimers, Huntington's disease, Amyotrophic Lateral Sclerosis and glaucoma. The miracles of modern medicine!
Now Scott, let me ask you, how do you think lamotrigine's glutamate lowering action translates into its effectiveness as a mood stabilizer. And is there a relationship between the glutamate effect limiting action of a calcium channel blocker like nimodipine and the calcium channel blocker's effectiveness as an augmenting agent to mood stabilizers. Have you ever considered taking a mood stabilizer?
As far as Provigil and glutamate toxicity, that is just a loose thought of mine. I would be more comfortable with adrafinil and Provigil if their mechanisms of action were better understood.
I'm not sure why reboxetine pooped out. The timing of it though clears selegiline of any association with it. Actually, I quickly built up a tolerance to Naphazoline (the alpha1 agonist) and this tolerance seems also to have crossed over and effected reboxetine's ability to act on these receptors. But, hey, I wouldn't lay money down on that being what really happened.
One final note, Dr. Goldstein lists neurontin as an (indirect) NMDA antagonist.
Best wishes to the both of you,
AndrewB
Posted by SLS on August 8, 2000, at 17:44:18
In reply to Re: Adrafinil: John, Scott, posted by AndrewB on August 7, 2000, at 11:39:47
Hi Andrew.
> I don't know if Naphazoline crosses the blood brain barrier.I believe naphazoline enters the brain through the eye, as the eye lies on the brain side of the blood-brain barrier.
> On a related note, I am very interested in the idea of an alphal1 andrenergic agonist being able to be centrally selective in its actions (vs. having both central and periphereal action) as is claimed (hah, hah!) for adrafinil.
I tried looking for such a drug a few months back, but came up empty. I really didn't invest that much energy into it. I guess naphazoline is the closest thing to it, and is probably why Dr. Goldstein has come to rely on it.
By the way, what URLs are available for Dr. Goldstein? My guess is that you utilize more than one resource. His ideas to use different drugs (substances) as biological probes are exciting and in accord with my own. I've suggested this type of algorithm in the past, but didn't know that anyone had actually put them into practice. Have you thought to contact him?
> Reboxetine's effect of severely limiting my athletic stamina and the sexual side effects, I believe are due to periphereal alpha1 agonism. So I would think a centrally acting alpha1 agonist would be great for a lot of people, myself included.
What mechanisms are proposed for why NE alpha-1 agonism affects your athletic performance? What exactly do you experience? Are you sure it is not related to sympathetic/cardiac effects?
> Glutamate opens the calcium channels. Compare this to the calcium channel blocking action of nimodipine. Too much calcium within the cell somehow leads to neuron death. I forgot the speicifics. Anyway, such glutamate induced neuron death is being recognized as a leading factor in a lot mental maladies and other conditions. For example, the greater part of the brain damage caused by a stroke is not due to hypoxia, rather glutamate toxicity.
I am too anergic to do the homework, but aren't there other substances (peptides?) released by the traumatized tissue that is responsible for much of the neuronal damage? Ornithine something-or-other. Years ago, I read of a strategy intended to prevent the secretion of or inactivate these substances. It was critical to intervene within hours of the event. This did not involve increasing cerebral blood flow via CA-channel blockade. Aside from L-type CA-channel blockade, what other properties does nimodipine possess?
> It is Memantine's glutamate limiting actions, as an NMDA receptor antagonist, that enables it to be effective in the treatment of dementia, neuropathic pain, Alzheimers, Huntington's disease, Amyotrophic Lateral Sclerosis and glaucoma. The miracles of modern medicine!
What are some of the main functions and pathways involved with NMDA receptors?
> Now Scott, let me ask you, how do you think lamotrigine's glutamate lowering action translates into its effectiveness as a mood stabilizer.By inhibiting the release of glutamate, lamotrigine (Lamictal) allows the glutamate/GABA balance to shift in favor of GABA. GABA receptors and neurons are responsible for preventing the overactivity of excitatory pathways. One of Depakote's properties is to increase GABA activity. Neurontin (gabapentin), an anolog of GABA, was thought to increase the synthesis of GABA. (The NMDA explanation you describe may be a more viable explanation). Tiagabine (Gabitril), another anticonvulsant proposed as a mood stabilizer, potentiates GABA neurotransmission by acting as a GABA uptake inhibitor. Topiramate (Topomax) may act more like lamotrigine in that it probably inhibits glutamate activity by inhibiting the NMDA receptor.
As for mood stabilization per se, I don't know enough to report specifics. As for anti-manic potential, I have come across some abstracts detailing the role of GABA pathways in reducing the activity of DA neurons in the nucleus accumbens in a manner antagonistic of glutamatergic input.
> Have you ever considered taking a mood stabilizer?
So far, lamotrigine is the only one that consistently produces some relief from depression. However, it does not seem particularly effective as an antimanic drug for me as it did not prevent a Nardil discontinuation-induced mixed state that I experienced a year ago. My guess is that the antidepressant properties of lamotrigine are distinct from its mood stabilization properties and may involve dopaminergic phenomena. One of the early studies reported some pro-dopaminergic activity.
I think lithium may be helpful in the future, but I hate the affect-flattening effect and passivity it produces. Depakote makes me feel moderately worse in the long-run, although it can produce an improvement initially and acutely. Neurontin affects me in a similar manner, but really whacks me out within a week or two. I have discovered this past week that the exacerbation of depression and the cognitive disturbances it produces is time-dependant and not dosage-dependant. A few months ago, it left me in a worsened state for at least three weeks after discontinuation. I am a bit frightened by Neurontin.
> I'm not sure why reboxetine pooped out. The timing of it though clears selegiline of any association with it. Actually, I quickly built up a tolerance to Naphazoline (the alpha1 agonist)
I didn't know that you had gleaned a positive effect from naphazoline. What did it do for you and how long did it last?
> and this tolerance seems also to have crossed over and effected reboxetine's ability to act on these receptors. But, hey, I wouldn't lay money down on that being what really happened.
Receptor dynamics can be permanently changed by drug exposure, particularly if it is repeated and intermittant.
I would like to comment on a description JohnL recently offered. He sait that it took adrafinil longer to produce an adequate response once he discontinued it and later restarted it.
> One final note, Dr. Goldstein lists neurontin as an (indirect) NMDA antagonist.
Topiramate (Topomax) is thought to be a direct-acting antagonist of the NMDA receptor. This is in addition to its GABAergic potentiation properties. I hope I eventually get around to learning more about glutamate, NMDA, and sigma receptors - to name a few. I wish I had more of my wits to be able to. I also wish I were closer to a medical school library.
> Best wishes to the both of you
As always, the sentiments are reciprocal.
Take care.
- Scott
Posted by AndrewB on August 9, 2000, at 10:51:12
In reply to Re: Adrafinil: John, Scott » AndrewB, posted by SLS on August 8, 2000, at 17:44:18
Scott,
Thank you for again giving me so much useful information. You have a very special mind (even if it is mushy!).
I'm sorry but I really can't answer the questions you asked (i.e. NMDA receptor pathways and actions). I would have to research the answers and I'm unfortunately too bogged down with other stuff to do this. I have to admit that sometimes when I mention things to you in a post, for example 'glutamate toxicity', I see it as a bit like fishing for information, because I hope the responses I get back from you will contain information on the subject I hadn't known before, and so often that is what ends up happenning, you educating me. Thanks again.
My approach lately is to determine if a drug has any potential to help me and if it is safe and tolerable for a short term trial. I don't go much beyond that now as far as research. Now that it seems that selegiline at a low dose has had such a positve effect, I will research the drug further, epecially relating to its long term health effects and drug interactions.
I've been feeling great the last 4 days. My energy, mood and cognition are better than an average person's! In repsonse to this blessed event, first I need to carve an idol- from the hip bone of a snake- in the image of that mercurial god of drug reactions, then bow before it and pray for continued response! Secondly, I need to find out why I am feeling so good. I'm taking the amisulpride with selegiline (and no reboxetine) but also lately I've been taking .5 or 1mg of klono. in the evening to improve sleep quality and have been taking memantine during the day. It shouldn't take too long to sort this out.
By the way, I responded to Naph. for about 3 days before receptor tolerance occurred. The effect if gave me was about the same effect I felt with reboxetine.
AndrewB
Posted by Rick on August 9, 2000, at 17:22:32
In reply to Scott, posted by AndrewB on August 5, 2000, at 22:06:01
While I haven't used adrafinil, some of you know that I added modafinil (Provigil) to my effective Klonopin/Serzone regimen to help with motivation and occasional fatigue. And you know that, while this did indeed work for the intended purpose, it further enhanced my non-depressive Generalized Social Anxiety treatment by adding extra confidence and a good measure of sociability. In other words, it took me a step beyond eliminating the core anxiety symptoms.
But I've been taking Provigil awhile now, and have found myself frequently switching from 100mg/day to 200, and vice-versa. Finally, the pattern is becoming clearer:
Let's say I'm on 200. Everything's going wonderful, but after a few days, I find a little bit of my core Social Anxiety symptoms creeping back (manifested by symptoms like occasional voice shakiness). This is especially likely when I'm facing a lot of everyday stress, e.g., "fire drills" at work. So I'll cut the Provigil down to 100, and everything will go great again SA-wise (especially if the everday stresses have abated). Then, after four-five days, I'll start feeling a little less motivated/sociable, and a little bit more fatigued (which, for me, can actually add to Social Anxiety symptons: Fatigue --- > less assertiveness and less forceful speech --- > a bit more prone to nervousness/shakiness/intimidation. So then I'll go back to 200, and will feel fabulous for a few days. Then the cycle starts all over again.
Yesterday I returned from a five-day trip that would have traditionally been rife with Social Anxiety-causing situations. I temporarily upped my Klonopin a little (to 2mg/day, divided into three doses instead of two), but kept the Provigil at the 100 mg I had been taking most recently. I did incredibly well, but on the final morning of the trip started getting very tired and seeing a bit of anxiety return. Today I'm back to 200 mg of Provigil, and feel great. But, I'm betting that within a few days, I'll go back to 100.
I haven't quite thought through the implications of all of this, but I'm working on it. Fortunately, I'm not desperate to optimze. I'm thinking about trying a regular 100-200-100 switching pattern (with 100 predominating); or trying daily 150 mg (THAT will be fun to accomplish with 200mg pills!); or adjusting doses based on daily life events; or maybe some other approach.
Perhaps precise and/or systematically-fluctuating dosing could be a key to maintaining the optimal psychotropic effects of Provigil -- and likely adrafinil. Indeed, I wonder if this observation could account for some of the inconsitent results, side-effects, and/or poop-out many (most?) Babblers seem to have encountered with both of these meds.
Rick
Posted by JohnL on August 10, 2000, at 3:49:26
In reply to Possible insight into afinil dosing?, posted by Rick on August 9, 2000, at 17:22:32
I noticed the same kind of phenomenon when I used to take Zoloft. When I was increasing dosage, I would do it in an alternating step patterm like 25mg one day, 50mg the next, 25mg, 50mg and so on. Then 50mg for a while. Then 50mg a day, 75mg the next, 50mg the next, 75, and so on.
None of the SSRIs ended up being right for me, but I do recall that this fluctuating dose pattern with Zoloft worked much better than a steady dose pattern.
I wonder how you would respond at say 100mg one day, 200 the next, then 100 the next, 200, 100, etc?
Cutting pills into custom size pieces isn't easy sometimes, but as you mentioned perhaps 150mg might be the way to go. The natural variation of dosage size due to the slight inaccuracies of handcutting the pills might work to your benefit. I take 7.5mg Remeron each night as part of my cocktail. I have to divide a 30mg pill into four pieces with a large sharp knife. But the pieces hardly ever come exactly the size I want. I might actually get 5mg one day, 7.5mg the next, 6mg the next, and such. There is always just a little bit of fluctuation. I've always felt that a little daily fluctuation in dosage works better than a steady state dose. I don't know why. It's just one of those weird subtle phenomenons I've noticed by accident over the years.
John
Posted by Rick on August 10, 2000, at 19:48:08
In reply to Re: Possible insight into afinil dosing? Rick, posted by JohnL on August 10, 2000, at 3:49:26
Very intersting thoughts, John L. Your experiences lend some support to what I'm seeing, and I'll add your suggestions to my experimentation list.
I'll be especially curious to see if the 100-200-100 approach leads to consistent results. The effectiveness of this approach will be of greatest interest/concern on certain days, e,g when I'm really zonked because of getting to bed late the night before, or during the infrequent extra-challenging periods when I temporarily take a little extra Klonopin. Fortunately, whatever happens I'll be able to handle it a lot better than pre-meds. This is fine-tuning.
Rick
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