Provigil (modafinil) has several unique properties that make it a more advantageous choice than straight-forward stimulants like amphetamines. Still, like the amphetamines, Provigil works primarily by increasing dopamine and norepinephrine activity. This is mainly why it is designated a C-IV, controlled substance in the U.S. It will, at the least, cause some activity in the pleasure center(s) of the human brain in addition to increasing awareness, alertness, heart rate, etc. Provigil also has shown some SSRI activity, so it will not only add to the SSRI effect of the Seroquel (which, granted, is not Seroquel's primary action in the brain), but also Provigil will reduce the rate of metabolism of the two drugs you are already taking (Provigil is also broken down in the liver by the class of enzymes referred to as Cytochrome P450), and just as giving 2 different chefs, 2 different dinners to prepare, adding a 3rd dinner to prepare means that the chefs will take longer, overall, to prepare each of the others - I hope this analogy made sense to you. In the end, my point is that readjusting the dosage of your Seroquel (quetiapine) 300mg (daily) and your Klonopin (clonazepam) 1mg (daily?) may be necessary; if anything, taking the same dose of these drugs will have a stronger effect on you than they did before adding the Provigil.
Unlike the amphetamines however, Provigil also increases histamine activity especially in the hypothalamus which is a very targeted approach to increasing wakefulness. The amphetamines do not have such an effect. Unfortunately, if you have severe allergies, they will be worsened by taking Provigil, and you will also have a greater allergic (histaminergic) response in general (seasonal allergies, ant bites, etc.) due to this property of the drug.
Also unlike the amphetamine class of stimulants, Provigil has been found to increase the overall activity, or amplitude, of those neurons that are "connected" to each other by what's called, "electrotonic coupling." While most neurons send chemoelectric signals to neighboring neurons over a gap (called the synapse), there exists a minority of neurons that are coupled, physically, at these neuronal "intersections." The overall effect of this lacking a spatial gap is such that when the first neuron fires, the following neuron firing of these neurons attached by this electrotonic coupling, is virtually simultaneous with, or even synchronous with, the firing of the initial neuron. How this is accomplished is not known. It is still one of the many neurological mysteries over which many researchers scratch their heads. Also relevant, due to the increased activity of neurons employing this type of coupling, overall levels of anxiety (partly due to the GABAergic pathways for these neurons not having the same sedating effect) will increase.
Finally (though I could go on and on in this part of my response about the *how* of this drug), Provigil differs from the amphetamines in that it inhibits the release of the natural GABA agonist neurotransmitters in the brain. The GABA class of receptors are those to which benzodiazapenes (your clonazepam, for example) attach to and which trigger the cell processes that lead to sedation and anti-anxiety (i.e. anxiolytic) effects. So, and this is a considerable warning and potential reason why Provigil may be difficult for you to tolerate, your natural, inherent level of anxiety will, unfortunately, increase. Whether or not the effectiveness of your clonazepam will be lessened is unknown; the evidence suggests only that your overall anxiety will increase, but that any benzodiazepine, based solely on this evidence, should still work just as well at sedating and relaxing you.
So, I've summed up the basics of the "how-it-works" part of this drug, Provigil. What I haven't done, yet, is applied its neurochemical activity to how it might benefit someone with bipolar disorder, who feels a bit over-sedated and sleepy, that is already taking Seroquel 300mg (a very common and appropriate dose for bipolar disorder) and clonazepam 1mg (I would neither recommend any benzos to be taken in conjunction with a drug in the class of that of Seroquel's, nor for bipolar disorder, but, alas, I am not your doctor).
For full-blown bipolar disorder, granted every case is different, you are really missing a drug specifically designed primarily as a mood stabilizer like Depakote (valproic acid), or the older drug, Lithium (lithium carbonate, and other ionic forms), which makes me wonder if you are still occasionally experiencing the classic, manic episodes that accompany bipolar's pathology. What I would most recommend is adding a drug that is designed primarily as a mood stabilizer, whether or not it is also used as an anticonvulsant (a very common “sharing” of uses for mood-stablizing drugs).
Provigil is currently undergoing studies for applications to several psychiatric disorders. Right now, since you are taking both a major tranquilizer (also known as an atypical antipsychotic), Seroquel, and a minor tranquilizer (known, in this case, to be a benzodiazapene), Klonopin, I would recommend phasing out the Klonopin altogether and seeing how that works for you WITHOUT taking Provigil. If, during the time of coming off of it (and by coming off of it, I mean religiously following a reduced dosage schedule, such as: First, reducing dosage to 0.75mg for the first 4 days, to 0.5mg for the following 6 days, and finally 0.25mg for the last 10 days), you find yourself having panic attacks, then I would return to the same dosage of Klonopin and try reducing the Seroquel slightly.
However, there is the inconvenient fact that the at, and near, the 300mg strength of Seroquel, the drug achieves a level of total saturation with the appropriate dopaminergic receptor subtypes in the brain, and the tangible effects of sedation are actually lessened compared to taking 100mg or even 200mg of Seroquel. In other words, and I know this is counter-intuitive, a dosage of 300mg of Seroquel every night at bedtime will actually cause less sedation, slurring of words, sleepiness during the day, etc, than will a lesser dose of Seroquel (again due to the nature of the drug and the effects of Seroquel's receptor saturation in the brain). Therefore, reducing the dosage of Seroquel will probably not help you better tolerate its sedative effects. HOWEVER, if you are taking Seroquel *XR* (as many bipolar patients do), the first thing to try is simply to take Seroquel, normal release and NOT take the *XR* form. The XR, or extended release, form of this drug is tolerated by only a very few since the high level of sedation of the Seroquel continues well into the daytime than than does the normal release version.
The main reason I would not try Provigil is due to its opposite mechanisms of action in areas of the brain that would overlap with the drugs you are already taking. This overlap would apply to both Seroquel and Klonopin. Still, there is a possibility that Provigil will help you reach a level of wakefulness and alertness - without the anxiety! - that you cannot currently experience while taking the Seroquel and Klonopin. However, it is always better to take fewer drugs overall than to take more medication to compensate for the effects of others. Be sure to keep that universal truth in mind as you attempt to find the solution.
Kind regards and best wishes,
Francisco Fernandez
Pre-med graduate, B.S. Biology, CPhT; Emory University
LaurieShay
