From The Journal of Sleep Research comes a fascinating study on how modafinil (Provigil) work.
Here’s the scientific abstract. To investigate the effects of a wake-promoting drug, modafinil on regional cerebral blood flow (rCBF) in healthy volunteers, we performed (99m)Tc-ethylcysteinate dimer single photon emission computed tomography (SPECT) before and after modafinil or placebo administration. Twenty-one healthy subjects received single doses of 400 mg modafinil or placebo in a double blind randomized crossover study design. Administrations of modafinil or placebo in a subject were separated by a 2-week washout. Brain SPECT was performed twice before and 3 h after modafinil or placebo administration. For statistical parametric mapping analysis, all SPECT images were spatially normalized to the standard SPECT template and then smoothed using a 12-mm full width at half-maximum Gaussian kernel. The paired t-test was used to compare pre- versus post-modafinil and pre- versus post-placebo SPECT images. Differences in rCBF between post-modafinil and post-placebo conditions were also tested.
Modafinil decreased Epworth and Stanford sleepiness scales whereas placebo did not. The post-modafinil condition was associated with increased rCBF in bilateral thalami and dorsal pons, whereas the post-placebo condition showed increased rCBF in a smaller area of the dorsal pons when compared with the drug naïve baseline condition.
Compared with the post-placebo condition, the post-modafinil condition showed higher rCBF in bilateral frontopolar, orbitofrontal, superior frontal, middle frontal gyri, short insular gyri, left cingulate gyrus, left middle/inferior temporal gyri, left parahippocampal gyrus, and left pons. In healthy volunteers, modafinil increased wakefulness and rCBF in the arousal-related systems and in brain areas related to emotion and executive function.
Ref: Joo EY, Tae WS, Jung KY, Hong SB. Cerebral blood flow changes in man by wake-promoting drug, modafinil: a randomized double blind study. J Sleep Res. 2008 Mar;17(1):82-88. Department of Neurology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
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27 Comments
Just curious – was on provigil prescribed by Psych. Hep C became active after 24 years of sobriety – off provigil and antidepressant. After 2 years, Had “alleged” partial complex seizures -3 w/in 10 days – (after mri/2eeg’s) no proof of seizure, per se. Now on Neurontin & Lopressor (for hypetension – long term med) ADHD driving me sideways, doing the best I can – any chance of provigil not being a negative w/the hep c or “alleged” seizures?
What is the effect on dopamine and norepinephrine release?
Have been taking modofinil off and on for years. Does the Amen Clinic have any information on the effects of this drug on their brain scans? I would appreciate any information and/or opinions that you have about this drug.
Thank you, Helen Worcester
Thanks for the post. I’ve been on Provigil for several years now to combat my MS fatigue. I found a great improvement since begining the medication, although I did have to increase my dosage recently. It’s very reassurring to read this study and know that I’m getting a bit more out of it than just being able to keep my eyes open. I believe Provigil along with Effexor XR has helped me live and function better in my daily life. It sure beats sleeping and/or zoning out due to fatigue all day!
Are you aware of any potential harmful effects long term use may cause?
I can’t get my insurance to pay for it. I’ve been buying online but it sometimes seems that the generic isn’t the same. Any suggestions? Thanks
It would be interesting to see the effects of Provigil and in a separate group, Adderall, on symptomatic patients, as it may be that the biochemistry is different. I have been on: first, Provigil, which wasn’t effective for me, and then Adderall, which was effective, to improve wakefulness. I have a history of a “mild” traumatic brain injury (TBI). I’d like to see a double blind study of patients with mild TBI; I think it would be more helpful to know what is happening with symptomatic patients who need treatment. I’m not convinced that the results would be the same as with healthy volunteers. It stands to reason that it is altered brain chemistry from the brain trauma which results in a need for the drug, and therefore, the effect of the drug may also differ from that seen in a healthy subject. Just something to think about….
Was just put on Tenex (Guanfacine). Doc is declaring kids who were on this sometimes deveoped a “sensitivity to slights” (which you described in your book, “Change Your Brain…”) Just thought how could this be? Decreased blood-flow to temporal lobes???
Over the last few years I have been inspired by you to go on to study Neuroscience at U.T.D. in TX.
Hey everyone – if you need a place to share and chat about ADD/ADHD and even the amenlinic – come check out our new ADD forum.
There you will see scotts personal blog and get to meet all kinds of great people who are also dealing with ADD.
Look forward to seeing you there!!!
the scottsaddforum team
One physician assistant (P.A.) I know strongly opposes prescribing Provigil — he has told at least one of my clients (I’m an MFT) that “It’s addictive! It’s nothing but speed!” I don’t want to risk a professional conflict with him (because I’ve sent several clients to him with the suggestion that Provigil might help them), but I wish I could inform him that it’s not “speed.” I’ve printed your current pages article and might mail it to him… can you say anymore about the “addictive” and “speed” impressions?
I am a pharmacist who has had a major post TBI/MS. I was started on Ritalin after, then changed to Provigil. Not because one worked better but because DR’s have been made t be afraid to prescribe and thought Provigil sounded better since I was in health care. I think Adderral XR should be tested aginst Provigil. First, I do not believe you would see a significant difference in outcome desired. They both help with fatigue and concentration in this case. Key is Adderall is GENERIC and cheap. But the drug companies do not want you to know that. Then there is the new VYVANCE which is the same as Adderrall XR. However it’s delivery system prevents it from being abused. So if abuse is not a concern and being able to afford it try the generic. I am tired of DR’s being so affraid of the use of Contolled Drugs they prefer to do nothing than try to help. YET ARE SO WILLING TO OVER PRESCRIBE FOR CHILDREN. ADULTS WITH DISABILITIES NEED A VOICE AND INFORMATION.
My psychiatrist told me that Provigil would be her first choice for my ADD and age, (61),but ins.co. will not pay for that drug for ADD dx. So, she prescribed generic Ritalin,having to increase the dose several times, I reached the maximin dose, 60mg. daily. I have now been on methylin (long-acting) 60mg. daily, along with Effexor 225mg daily which I’ve been taking 10yrs for my severe depression. I feel that I need more methylin, but my psych. won’t go above the recommended daily amt. I’ve been taking the methylin for 3yrs and have become tolerant to it. I do think my brain operates better and maybe only thinks I need more. I’m more organized, do better at work, get along better with friends and generally feel more satisfied with my life. I still struggle with procrastination, and low energy. On the topic of addiction, I was a drug addict and alchoholic the first half of my life, and suffered terrible depression sober. Since my diagnosis of ADD, I have lost all cravings and desire for alcohol or drugs. I had been sober for 14yrs. when I found out I have ADD. I can tell by others reactions to me, that I function much better in the last 3yrs than before.
Provigil helps me get into “the flow” when working and performing analytical tasks, where adderall helps me with large motor tasks “housework.” I have come to believed that I am wrong in assuming that I could function well on one or the other drugs. I do really well when I take both adderall and provigil. I have fibromyalgia and sjogren’s syndrome. Both conditions cause “brain fog” and fatigue.
In response to the first poster (Kathie, reactivation of latent Hep C), adrafanil, the pro-drug of modafanil and available in Europe for a number of years, has been known to precipitate hepatotoxicity in individuals so treated. Labelling for modafanil states abnormal liver function tests are rarely associated with administration and that severe hepatic disease is a “possibly significant” drug-disease interaction.
Also, modafanil inhibits some hepatic metabolic enzymes and induces others, so check with your doctor or pharmacist for any significant drug-drug interactions.
Unfortunately, the other non-amphetamine alternative for ADHD, atomoxetine, has also been associtated with sever liver toxicity, albeit rarely.
Duloxetine, a dual re-uptake inhibitor with FDA approved indications for depression and diabetic neuropathy, and that may find utility for ADHD via the auspices of weak dopamine re-uptake inhibition, is not recommended for use in individuals with any form of hepatic dysfunction.
Bupropion, also an antidepressant that may help with symptoms of ADHD, is contraindicated in patients with a history of seizure disorder.
The good news is that pre-existing SUD in not a contraindication for stimulant therapy, and neither is controlled hypertension. Also, reports that amphetamine and congeners are likely to precipitate seizures in sensitive individuals have not been well borne out in clinical studies.
Troy, no effect on NE or DA release or re-uptake. Modafanil’s mechanism of action is most probably mediated via interaction with the orexin/hypocretin system. Orexin/hypocretin is/are (depending on who you ask) involved in tonal maintenance of the reticular activating system. Any effect modafanil has on NE transmission is downstream of this system.
Nancy, modafanil is a schedule IV controlled substance, an classification which ostensibly implies a high threshold for subjective “liking” (ie low abuse potential). Unfortunately, in the facist political clime that faces American citizens today, any level of controlled scheduling is taken as an excuse by many practitioners to abandon their oath and deny efficacious therapy to their patients. Perhaps you should take your colleauge aside and inform him to get with the program or go be a plumber (also a licensed profession where, perhaps, his small minded hypocrisy will do less harm to the public at large). The last thing our beleagured profession needs is yet one more small minded, punitive asshole who thinks he’s on a mission from God to educate the savages. Seriously. Don’t get me started.
Whew.
Now that that’s over, Nancy, modafnil has substantially less abuse potential than amphtamines and congeners (which are surprisingly safe when used as prescribed and for conditions in which they have some beneficial therapeutic role), and is not “speed”, nor does modafanil share a common mechanism of action with those pharmacotherapies more traditionally identified as CNS stimulants (see comment to Troy above). When used in an appropriate manner, there is no shame in prescribing or consuming Provigil. You tell him I said so.
JMc
Hello!
I tried Modafinil for a few days, but suffered some type of reaction (itchiness over entire body). I did not get a chance to really try this drug for my adult attention deficit disorder, and I would like to but fear the itchiness is an anaphylactic response of some kind? Have you ever heard of this?
I do take other supplements and Dexamphetamine. I did not wait a specific number of days after discontinuing the Dex to move to the Modafinil. Is it possible that was the reason for the reaction?
I would like to be off of amphetamines, because the side effects for me are:
1) Huge decrease in healing time
2) A desire to withdraw from society
3) Growing depression in direct proportion to the length of time the drug is taken
I have taken Straterra for a few days and had a complete emotional melt-down within two days (not like me at all), so I stopped that asap.
So, the Modafinil….any chance I would avoid the itchy reaction somehow if I tried again?
Sorry, Victoria, I meant to address your concern vis a vis insurance not covering modafanil (which they won’t often).
The type drug of this class is actually adrafanil, a pro-drug (means the body converts it) of modafanil. Adrafanil is not FDA approved for use in the US. It is, however, available online through various (reputable and perhaps less so) suppliers, and at a substantial discount relative to modafanil. The brand name is Olmifon, and it can be had from a reliable source for about a dollar (U.S.) per. That compares to modafanil, which comes in at about $5 per tablet. Yikes. Also, adrafanil is associated with higher incidence of liver toxicity than is modafanil, though not significant enough to require its withdrawal in international markets (not blanket, anyhoo).
I can’t legally recommend this course of action as Federal law is something of a gray area in this regard, and state laws (of which I am intimately familiar with only one, state, that is) don’t always clear the waters. In fact they usually muddy them a bit more. I merely mention in passing to inform. Were you able to secure insurance funding for modafanil, that would be the way to go. If not, well, necessity is the mother of dissension, as they say.
JMc
PS An aside – my insurance company won’t cover a medication for me in patch form because (and I do quote) “this delivery sytem has not been proven to be MORE efficacious (my emphasis, significant because it also hasn’t proven LESS efficacious), and also because active ingredient remains in the dosage form when disposed (and this is significant because a gradient driven patch wouldn’t work if there WASN’T active ingredient remaining when the patch was removed, just the nature of the beast)”. So, instead of paying $150 a month for this new, “unproven” medication, my insurance company turned around and now they pay $1500 a month for a suitable alternative. Penny wise, but pound foolish.
PPS The scary thing about this mentality is that it’s not much of a leap for the insurer to say, by extentsion, “because this medication is not 100% bioavailable (ie your body is “wasting” active medication by not absorbing or “over” metabolizing or what have you), we will not cover the cost of this medication.”
Which would get them off the hook for every single orally administered medication on the books. Isn’t that fun?
PJ,
Yep, modafanil use has been associated with serious epidermal toxicities, which have been on very rare occasions serious enough to require medical intervention. If modafanil gives you a rash or makes you itch, I’d recommend against it just to be on the safe side. You could try rechallenge and see where that gets you, but I’d say it warrants caution.
By the by folks, my postings represent my personal, not necessarily professional, opinion, and should in no way substitute for consultation with your physician or other local health care professionals. Their opinions may be partially or entirely at odds with my own, and that’s OK, too. Since they have access to your complete medical work up, and I don’t, I’d say their advice trumps mine every time, OK? It’s only fun until someone loses an organ.
I was on 7mg. Ritalin from age 6 to age 12.No other treatment was given back in the dark ages of the 70’s. In fact, when it was suddenly stopped at age 12, normal everyday sensory stimuli became so overwhelming that I began to cut class. I would go home & close all the curtains to just sit in a quiet and less bright environment. No one had bothered to inform me of my ADHD, but I knew that I was not crazy, and that I was meeting a legitimate need, even if I found it bewildering.
Long story short, in the middle of college, I was tested for Learning Disorders. Ta Da! What a relief! Here was the reason that I could be so smart yet do so much worse than my peers ! lI self-treated succesfully with exercise, inositol choline, my prescribed homeopathic remedy (HUGE difference with that!) etc. It was OK for other classes, but got back on Ritalin for the Math (I have dyscalcula [math dyslexia],and regular dyslexia)Also some expressive language challenges,etc.).The Ritalin made all the difference, along with continued tutoring and adjusted test times, & environment(non-stimulating, ability to get up and move, etc.)
My dose for Ritalin now, at 135# is still 7mg. Ritalin/4 hours. More Ritalin does not make me high. It makes me overwhelmingly exhausted, bradycardia(slow heartbeat) with chest pain, and miserable.I do find that it needs to be increased to 10mg. if my weight goes up to 140-165(all-time heaviest). I come from a family of chemically dependent people, yet have no history of substance abuse, never even have been drunk. Don’t like caffeine either. So, that is one example of the innacuracy of some of the “information” floating around re. ADD/ADHD.
One more thing, in 2005,I stopped the Ritalin & just dealt with being “lesss” of me-less sharp, harder to focus, decide, think, and relax/sleep. I thought it was better for my liver not to be on long-term meds if possible. After 3 months, an undiagnosed pain condition (Fibromyalgia) surfaced with such intensity that it stopped me from being able to work. In addition to sustained, intense trauma, Dr. said that discontinuing the Ritalin had everything to do with my pain levels, and re-started it for treatment of Fibro pain.To this day, I can still forget to take my Ritalin, but the pain will increase so much that it reminds me to take it! It helps tremendously, medical science has yet to explain why.The theory that makes the most sense to me is that it occupies some of the pain receptor sites and thus inhibits the transfer of pain signals within the brain. I also need to stop the Ritalin when going to the dentist, as it makes me almost unaffected by the Novacaine-another confirmation that it has to do with neurotransmitter reception/neural synapses. As you may know, Provigil is also reccomended for Fibro pain. Why am I not on it? Because I am uninsured & it is hugely expensive. Also, I am horribly prone to medication side-effects, and don’t wish to go through that when the Ritalin does just fine.I tend to be a bit more prone to migraine, but that is my only Ritalin side effect.I take Milk Thistle and many other complementary theraputic things to cope with the meds, illness & accompanying depression and sleep disorders-SAMe, 5-HTP, St. John’s Wort, Albizia, mild dose anti-seizure med for bedtime, etc. This is all in cooperation with my homeopathic MD, and tons of research. One day I would like to be able to go to Dr. Amen’s clinic for the SPECT and other evaluations. I hope all of this is helpful to somebody, I surely do realize how challenging these issues are.
Best of health to you all, if you are on this site, you are looking in the right direction!
I have tried adderall, ritalin, and provigil. I felt much better on adderall and ritalin, but I seemed to get more frustrated and argumentitive, so my doctor stopped them. Provigil didn’t seem to work for me, but what is the recommended dosage ? Maybe I wasn’t on a high enough dose. Now I am on nothing. Exercise helps me, but I am so tired after a full nights sleep that I am having trouble getting around to that. Any suggestions ? Frankly, I am sick and tired of being sick and tired. I wouldn’t wish depression on my worst enemy.
I am a wife to a chronic sufferer of Depression. About 3 months ago his psychiatrist put him on Provigil. It was amazing how different he was on this medication. He was able to get up in the morning, he was able to have the energy he needs and seemed as normal as I would hope. As the medication was running out we found out the psychiatrist said she can no longer prescribe Provigil as it is meant for sleep apnea and this is not in her realm. When he just had 4 pills left, he had been in bed for 2 weeks and tired of having no engery so took one and was able to go to work. We have gone through 5 general doctors in trying to get them to prescribe this and NO ONE will allow or approve for its use. Why is it so hard to get prescribed? I have been told it is meant to be for short term use but this Provigil is the difference of quality of life verses being in bed and not being able to get up. I am quite frustrated that the medical system does not work more with us. Does anyone have any ideas as to how to get PROVIGIL prescribed without so much problems?
is there a provigil that is not time released? It has taken 6 to 8 hours to kick in. k
provigil not time released? I heard that breaking up the pills can ruin the time release factor. Ever hear of that? k. hogan
Also, have been taking it 300 mg once or twice a week for severe fatigue due to brain tumor. I wonder what is most effective? kh
MY diagnosis is fibromyalgia and My rhematologist asked me to try Provigal I take 2 capsulte each day and I am fairly lively during the day but I was told to take elavil to promote lower levels of pain and to feel sleepy these neruochemicals do theri work I am functioning af a much lower level than I once was functioning I do not work due to chroic pain and lapses of concsiousness Provigal helped me function without major side effects how ever I do not know what things will be like over the next 10 years I wonder if it is a short term support but what if I stay on these drugs so long that my own brain waves with be less ble to do their jobs What else can I do
I was recently diagnosed with Complex Partial Seizures and have been on Provigil for a year for a misdiagnosis of Idiopathic Hypersomnia, EDS Disorder. The EEG revealed a distinct seizure pattern within the temperal lobe, however the Provigil only helps between seizures. I have also been on Ritalin, Dexadrine and phentermine. All of which helped (Ritalin the most though). My question is this, will my neurologist prescribe a “stimulant” type medication to combat my post-ictal symptoms, which quite honestly are worse than the seizures themselves?
We need to join together in our fight for our quality of life, we pay for our insurance companys to cover this and it should not be such a hassle if our doctors say we need it . Who do this insurance people think they are they are not doctors they are just a buch of money hungry jerks!!! I need this medaction ( Provigal ) i am so tried it is hard to me to do anything .. It is so bad that i fall asleep driving and i have three children to take care of … I mean come on what is it gonna take, i have had this same insurance company for 6 years and i pay a pretty large sum for it every month . I am at such a loss … I really need help and any one that can offer any kind of help it would be soooo wonderful . Thank you for taking the time to read this .
Erica, I have been diagnosed with Unspecified Connective Tissue Disease. I have battled with fatigue every single day. My doctor prescribed Provigil and, like you, my insurance company said no. If I were you, honestly, I would order the generic form (modafinil) online from Canada. It is about a fifth the price. It has made a world of difference for me. Just make sure you get it from a reputable site that requires a Doc. RX
I have a heart arrythmia. I get very tire after my heart beats to fast. well as probably most of us do I didn’t notice I was sleeping more and more. sometimes not even to keep my eyes open after being up an hour. Depression has also been a problem. I saw both my doctors before going on Provigil. today is my first day of taking it has been only a few hours ago and I could take a nap. I am hoping as the day wears on and the weeks pass it will get better. I have become a hermit in my home sleep, computer, tv, read, housework and believe me not all in 1 day. Il give it some time and see how it works.