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Dr. Bob is Robert Hsiung, MD,
bob@dr-bob.orgShown: posts 1 to 9 of 9. This is the beginning of the thread.
Posted by Mitch on June 18, 2001, at 10:20:36
Anybody had any success with this for ADHD or as an augmentor for anergic bipolar depression?? It looks like it might be helpful. Any input would be nice. This is available in the US. Obviously from what I found in the monograph (excerpt below) it isn't an alpha-1 agonist after all. Hmmm.
In vitro, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. In a preclinical model, the wakefulness induced by amphetamine, but not modafinil, is antagonized by the dopamine receptor antagonist haloperidol.
Modafinil does not appear to be a direct or indirect alpha-adrenergic agonist. Although modafinil-induced wakefulness can be attenuated by the a1-adrenergic receptor antagonist, prazosin, in assay systems known to be responsive to a1-adrenergic agonists, modafinil has no activity. Modafinil does not display sympathomimetic activity in the rat vas deferens preparations (agonist-stimulated or electrically stimulated) nor does it increase the formation of the adrenergic receptor-mediated second messenger phosphatidyl inositol in in vitro models. Unlike sympathomimetic agents, modafinil does not reduce cataplexy in narcoleptic canines and has minimal effects on cardiovascular and hemodynamic parameters.
In the cat, equal wakefulness-promoting doses of methylphenidate and amphetamine increased neuronal activation throughout the brain. Modafinil at an equivalent wakefulness-promoting dose selectively and prominently increased neuronal activation in more discrete regions of the brain.The relationship of this finding in cats to the effects of modafinil in humans is unknown.
Posted by SalArmy4me on June 18, 2001, at 12:27:30
In reply to Any success with Provigil (Modafinil) for ADHD?, posted by Mitch on June 18, 2001, at 10:20:36
RUGINO, THOMAS A. M.D.. COPLEY, TERESA C. M.S.. Effects of Modafinil in Children With Attention-Deficit/Hyperactivity Disorder: An Open-Label Study. Journal of the American Academy of Child & Adolescent Psychiatry. 40(2):230-235, Feb 2001:
"Modafinil was administered once a day in the morning to 15 children, 11 (73%) of whom completed the study. Treatment with modafinil resulted in statistically significant improvements in clinical parameters that are commonly used to follow the progress of treatment of children with ADHD. In this study, the positive effect is more pronounced for hyperactive-impulsive features (TOVA impulsivity subscore, p = .006) compared with the inattentive features (TOVA inattention subscore, p = .086).
Modafinil demonstrated an effect duration that lasted past the end of the school day for all but 1 of the 11 subjects who completed the study, suggesting that once-per-day dosing was adequate for maintenance of school-based activities. Adverse events were minor and manageable without medication discontinuance in four of the five children with side effects. The most common adverse event was delayed onset of sleep or sleep disruption which, in two of the three cases, responded favorably to a reduction of dose. This compares well with the rate of adverse events from other stimulants used for management of ADHD (Fox and Reider, 1993). Specifically, methylphenidate and amphetamines are commonly associated with weight loss and appetite suppression during the early course of administration (Klein et al., 1988; Schachar et al., 1997; Schertz et al., 1996). In contrast, no patients given modafinil as part of this study lost weight or experienced decreased appetite..."
Posted by Sulpicia on June 18, 2001, at 18:00:20
In reply to Any success with Provigil (Modafinil) for ADHD?, posted by Mitch on June 18, 2001, at 10:20:36
> Anybody had any success with this for ADHD or as an augmentor for anergic bipolar depression?? It looks like it might be helpful. Any input would be nice. This is available in the US. Obviously from what I found in the monograph (excerpt below) it isn't an alpha-1 agonist after all. Hmmm.
>
> In vitro, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. In a preclinical model, the wakefulness induced by amphetamine, but not modafinil, is antagonized by the dopamine receptor antagonist haloperidol.
> Modafinil does not appear to be a direct or indirect alpha-adrenergic agonist. Although modafinil-induced wakefulness can be attenuated by the a1-adrenergic receptor antagonist, prazosin, in assay systems known to be responsive to a1-adrenergic agonists, modafinil has no activity. Modafinil does not display sympathomimetic activity in the rat vas deferens preparations (agonist-stimulated or electrically stimulated) nor does it increase the formation of the adrenergic receptor-mediated second messenger phosphatidyl inositol in in vitro models. Unlike sympathomimetic agents, modafinil does not reduce cataplexy in narcoleptic canines and has minimal effects on cardiovascular and hemodynamic parameters.
> In the cat, equal wakefulness-promoting doses of methylphenidate and amphetamine increased neuronal activation throughout the brain. Modafinil at an equivalent wakefulness-promoting dose selectively and prominently increased neuronal activation in more discrete regions of the brain.The relationship of this finding in cats to the effects of modafinil in humans is unknown.Mitch--
the trials in adults failed [and the co.'s stock dropped!] --
you should be able to find the reference[s] to this at the ADD site at
About.com. Just search for provigil.
Regarding the ped study, aside from 15 being a *very* small number, I would be
interested to find out how old the children were. It's no biggie to control hyperactivity:
caffeine does this for many with ADHD. Inattention is the crucial problem which pstims address successfully.
I wonder about their ages in terms of their ability to recognize the difference between the effect of an agent
that works primarily on alertness versus one more narrowly targeted on attention.
My daughter [16 y/o] tried this both as an ADD med and an add-on AD with no result save a headache.
And it's pricey too.
At the university where our pdoc works they are in month 8 or 9 of a 1 year trial of provigil as an
AD add-on and the preliminary results are not great -- tho that may change.
A doc friend with ADD tried it and said it woke him up but did little for focus/attention.
The pdoc, looking at the pharmacology [or reading the tea leaves] opined that provigil would selectively
work on the centers of alertness in the brain, rather than the specific areas [and dopamine issues] involved in
ADHD.
Good luck with this -- I don't have to tell you that what doesn't work for one person may work for another.
S.
Posted by Andy123 on June 18, 2001, at 19:56:26
In reply to Any success with Provigil (Modafinil) for ADHD?, posted by Mitch on June 18, 2001, at 10:20:36
Provigil made me feel like total poo! I don't recommend it to anyone predisposed to dysphoria! I'd throw in pemoline to that list of stimulants that make me feel yucky.
Posted by Mitch on June 18, 2001, at 23:22:31
In reply to Re: Any success with Provigil (Modafinil) for ADHD? » Mitch, posted by SalArmy4me on June 18, 2001, at 12:27:30
> RUGINO, THOMAS A. M.D.. COPLEY, TERESA C. M.S.. Effects of Modafinil in Children With Attention-Deficit/Hyperactivity Disorder: An Open-Label Study. Journal of the American Academy of Child & Adolescent Psychiatry. 40(2):230-235, Feb 2001:
>
> "Modafinil was administered once a day in the morning to 15 children, 11 (73%) of whom completed the study. Treatment with modafinil resulted in statistically significant improvements in clinical parameters that are commonly used to follow the progress of treatment of children with ADHD. In this study, the positive effect is more pronounced for hyperactive-impulsive features (TOVA impulsivity subscore, p = .006) compared with the inattentive features (TOVA inattention subscore, p = .086).
>
> Modafinil demonstrated an effect duration that lasted past the end of the school day for all but 1 of the 11 subjects who completed the study, suggesting that once-per-day dosing was adequate for maintenance of school-based activities. Adverse events were minor and manageable without medication discontinuance in four of the five children with side effects. The most common adverse event was delayed onset of sleep or sleep disruption which, in two of the three cases, responded favorably to a reduction of dose. This compares well with the rate of adverse events from other stimulants used for management of ADHD (Fox and Reider, 1993). Specifically, methylphenidate and amphetamines are commonly associated with weight loss and appetite suppression during the early course of administration (Klein et al., 1988; Schachar et al., 1997; Schertz et al., 1996). In contrast, no patients given modafinil as part of this study lost weight or experienced decreased appetite..."thanks Sal,
Mitch
Posted by Mitch on June 18, 2001, at 23:39:07
In reply to Re: Any success with Provigil (Modafinil) for ADHD? » Mitch, posted by Sulpicia on June 18, 2001, at 18:00:20
> > Anybody had any success with this for ADHD or as an augmentor for anergic bipolar depression?? It looks like it might be helpful. Any input would be nice. This is available in the US. Obviously from what I found in the monograph (excerpt below) it isn't an alpha-1 agonist after all. Hmmm.
> >
> > In vitro, modafinil binds to the dopamine reuptake site and causes an increase in extracellular dopamine, but no increase in dopamine release. In a preclinical model, the wakefulness induced by amphetamine, but not modafinil, is antagonized by the dopamine receptor antagonist haloperidol.
> > Modafinil does not appear to be a direct or indirect alpha-adrenergic agonist. Although modafinil-induced wakefulness can be attenuated by the a1-adrenergic receptor antagonist, prazosin, in assay systems known to be responsive to a1-adrenergic agonists, modafinil has no activity. Modafinil does not display sympathomimetic activity in the rat vas deferens preparations (agonist-stimulated or electrically stimulated) nor does it increase the formation of the adrenergic receptor-mediated second messenger phosphatidyl inositol in in vitro models. Unlike sympathomimetic agents, modafinil does not reduce cataplexy in narcoleptic canines and has minimal effects on cardiovascular and hemodynamic parameters.
> > In the cat, equal wakefulness-promoting doses of methylphenidate and amphetamine increased neuronal activation throughout the brain. Modafinil at an equivalent wakefulness-promoting dose selectively and prominently increased neuronal activation in more discrete regions of the brain.The relationship of this finding in cats to the effects of modafinil in humans is unknown.
>
> Mitch--
> the trials in adults failed [and the co.'s stock dropped!] --
> you should be able to find the reference[s] to this at the ADD site at
> About.com. Just search for provigil.
> Regarding the ped study, aside from 15 being a *very* small number, I would be
> interested to find out how old the children were. It's no biggie to control hyperactivity:
> caffeine does this for many with ADHD. Inattention is the crucial problem which pstims address successfully.
> I wonder about their ages in terms of their ability to recognize the difference between the effect of an agent
> that works primarily on alertness versus one more narrowly targeted on attention.
> My daughter [16 y/o] tried this both as an ADD med and an add-on AD with no result save a headache.
> And it's pricey too.
> At the university where our pdoc works they are in month 8 or 9 of a 1 year trial of provigil as an
> AD add-on and the preliminary results are not great -- tho that may change.
> A doc friend with ADD tried it and said it woke him up but did little for focus/attention.
> The pdoc, looking at the pharmacology [or reading the tea leaves] opined that provigil would selectively
> work on the centers of alertness in the brain, rather than the specific areas [and dopamine issues] involved in
> ADHD.
> Good luck with this -- I don't have to tell you that what doesn't work for one person may work for another.
> S.Sulpicia,
Thanks for that information. I actually have more troubles with inattention than I do with hyperactivity/impulsivity. Dopamine agonists (pergolide) helped somewhat, but made me too sleepy (esp. Mirapex). It looks like a couple of months of nortriptyline again this year! Although you did say the crucial word ("wake-up"), and that is the problem I have when I cycle into this seasonal major depressive episode (I term it the "sleeping sickness"). I just want to sleep ALL THE TIME. I get up just in time to go to work in the afternoon-feel sleepy there all nite, and then go home and crash and SLEEP AND SLEEP AND SLEEP. Don't want to go ANYWHERE, am not interested in doing ANYTHING. It really sucks.
Maybe I can get some samples, I don't know.
Mitch
Posted by Sulpicia on June 19, 2001, at 0:04:19
In reply to Re: Any success with Provigil (Modafinil) for ADHD? » Sulpicia, posted by Mitch on June 18, 2001, at 23:39:07
> > >Mitch --
samples of provigil seem to be everywhere. Look up the manufacturer
and send the contact info to your doc and have him/her request it.
The daughter I mentioned has bipolar II and ADHD.
Her current [and effective] coctail is lamictal, welbutrin and adderall.
Needless to say, mania has never been an issue for her -- just horrible depression
the worst of which was severe hypersomnia. No seasonality tho.
Have you tried the pstims as add-ons?
S.
Posted by Mitch on June 19, 2001, at 10:48:31
In reply to Re: Any success with Provigil (Modafinil) for ADHD? » Mitch, posted by Sulpicia on June 19, 2001, at 0:04:19
> > > >Mitch --
> samples of provigil seem to be everywhere. Look up the manufacturer
> and send the contact info to your doc and have him/her request it.
> The daughter I mentioned has bipolar II and ADHD.
> Her current [and effective] coctail is lamictal, welbutrin and adderall.
> Needless to say, mania has never been an issue for her -- just horrible depression
> the worst of which was severe hypersomnia. No seasonality tho.
> Have you tried the pstims as add-ons?
> S.Sulpicia,
YEP, was on 5mg Adderall in the morning during my late fall/early winter seasonal episode (I have two episodes a year about two months long a piece for about 24 years now). The Adderall worked great for the ADHD and I slept a very consistent 7-8 hrs. a nite-got up right away (no slapping the snooze bar a dozen times!) and I had no trouble going to sleep, my mood cycling even settled down (the embedded three week cycles)and I had NO depression during that time (wow!).BUT, I always complained about too much anxiety with it and after a couple of months (I took Neurontin with it too)I got panicky and then a thyroid tumor and the Adderall got stopped. My Mom has epilepsy and had thyroid cancer-so half my thyroid got whacked out. So, my pdoc attempts to treat the ADHD less directly now-with the Neurontin and a little Zoloft.
I just had so many positive things happen taking the stimulant-but I got baggage I didn't want. I was just wondering if there was another way to approach the ADHD without using the usual pstims. Antidepressants-especially SSRI's keep the rapid-cycling going on-but I am not panicky. I am beginning to wonder if anybody can figure this crap out. The nortriptyline worked better than SSRI for the ADHD. Desipramine worked even better but made me clearly hypomanic.
Mitch
Posted by Sulpicia on June 19, 2001, at 14:37:52
In reply to Re: Any success with Provigil (Modafinil) for ADHD? » Sulpicia, posted by Mitch on June 19, 2001, at 10:48:31
> > >It's a tricky act at best to deal with ADHD and mood issues: seemingly what works on
one issue aggravates the other -- horribly.I don't know how your research skills are but you might benefit from searching the medical
literature on a few topics. PubMed is a good starting place. If you're totally lost I imagine
any librarian would be delighted to give you tips.Some ideas: welbutrin and effexor show some efficacy with ADHD -- in bipolar caution re: mania.
Lamictal is becoming more widely recognized for it's AD potential in addition to mood stabilization --
downside, activation of mania in susceptible people.
the older TCAs show some efficacy in ADHD -- desipramine is a common choice in certain pediatric cases;
personally I found partial relief of my ADHD with the TCA tofranil, tho I only deal with unipolar depression
and can't speak to issues of mania.
Find the references for A. Stoll [Harvard] and his study of essential fatty acid supplementation in bipolar disorder;
look at his book [title? Omega Nutrition, but available on amazon.com] and see what sort of evidence there is that might
help you -- do this with an excelllent clinician: the biology is extremely complex and the likelihood of triggering severe
depression is significant with a bumbling or hit or miss approach.
look around for studies on exercise and depression -- there is a good body of work on how exercise raises glucagon levels
and so *can* help with depression.
I imagine you've done the light therapy for the seasonal stuff?
a good experienced therapist and an adult support group for ADHD will make a difference. It's amazing how much you can
learn from how others adapt to ADHD. Try the CHADD web site for details.
I would expressly warn you away from the alt med stuff for ADHD. At best you'll only loose $, at worst, well... I don't have
to tell a person with your history and apparent education not to take ANYthing marketed by some scam artist.
Best,
S.
This is the end of the thread.
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