Re: New Drug for Narcoleptics

Anders Sandberg (
22 May 1999 16:48:30 +0200

"James D. Wilson" <> writes:

> You are talking about Provigil, and I started taking it as an
> alternative to Ritalin two weeks ago. What do you want to know?

A bit of medline on modafinil (the active substance) below. Overall, it looks fairly safe, does not affect the hormone system too much, might worsen hypertension and might make you think that you are more alert and efficient than you are.

Any bet how quickly use of it for purposes other than narcolepsy will be classed as narcotics? ;-)

Aviat Space Environ Med 1999 May;70(5):493-8

Naps and modafinil as countermeasures for the effects of sleep deprivation on cognitive performance.

Batejat DM, Lagarde DP

Institut De Medecine Aerospatiale du Service De Sante Des Armees, Bretigny sur Orge, France.

Disruptions in wake-sleep rhythms, particularly induced by sleep deprivation are limiting factors for military personnel in operations. The role of sleep and naps in the recovery of performance is generally accepted. Pharmacological aids, for example hypnotic or stimulant substances can also be effective countermeasures. Recently, a new stimulant compound, modafinil (MODIODAL) has also proven effective. Considering the excellent results obtained with napping and modafinil, we have studied the combined effect of these two countermeasures on psychomotor performance under conditions simulating an operational situation. Beneficial effects of a few hours' nap on performance were confirmed. Consequently naps should be encouraged, even if limited and diurnal. Modafinil, which combines wakening and stimulating properties without any known side effects, was useful for longer periods of sleep deprivation and when there was no real possibility of sleep recovery. Modafinil did not prevent sleep if sleep opportunities were available. The combination of naps and modafinil demonstrated the best cognitive performance during sleep deprivation.

Clin Pharmacol Ther 1999 Mar;65(3):328-35

Does short-term treatment with modafinil affect blood pressure in patients with obstructive sleep apnea?

Heitmann J, Cassel W, Grote L, Bickel U, Hartlaub U, Penzel T, Peter JH

Department of Medicine, Marburg University, Germany.

OBJECTIVE: To investigate the effects of modafinil, a central nonamphetamine awakening substance, on blood pressure and heart rate in hypersomnolent patients with obstructive sleep apnea. DESIGN: This double-blind, randomized, placebo-controlled crossover trial was performed over 2 days and 3 nights in a single-center study of hospitalized patients from a referred care center. Twenty-six otherwise healthy men (age range, 30 to 60 years) with mild to moderate obstructive sleep apnea were recruited by the outpatient department of the Marburg University Sleep Laboratory. Patients were given 200 mg oral modafinil in the morning and 100 mg at midday. Placebo was given in the same manner in a crossover design. Mean arterial (radial) blood pressure was monitored continuously during nocturnal sleep and during a series of standardized daytime physical and psychologic performance tests. RESULTS: The difference in the main end point between the treatment with modafinil and placebo was 1.17+/-0.83 (mean +/- SE) mm Hg (95% confidence interval: -0.56 to 2.91 mm Hg). The maximal differences in blood pressure values occurred under loaded conditions (systolic blood pressure, ergometry: 5.62+/-1.13 mm Hg; mental stress test: 6.19+/-1.33 mm Hg). CONCLUSION: Short-term administration of modafinil did not elicit a significant response with regard to the main end point. However, cardiovascular effects during mental and physical load were observed. Longterm studies that include subjects with hypertension are necessary to investigate the clinical relevance of the cardiovascular effects of modafinil.

J Clin Pharmacol 1999 Jan;39(1):30-40

A double-blind, placebo-controlled, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers.

Wong YN, Simcoe D, Hartman LN, Laughton WB, King SP, McCormick GC, Grebow PE

Drug Safety and Disposition, Cephalon, Inc., West Chester, Pennsylvania, USA.

A randomized, double-blind, placebo-controlled, ascending-dose study was conducted to evaluate the pharmacokinetic and safety profiles of increasing modafinil doses (200 mg, 400 mg, 600 mg, 800 mg) administered orally over a 7-day period in normal healthy male volunteers. Eight subjects (six modafinil; two placebo) were randomized to each of the four dose groups. Modafinil or a placebo was administered once daily for 7 days. Serial blood samples were obtained following administration of the day 1 and day 7 doses for characterization of pharmacokinetics, and trough samples were obtained prior to dosing on days 2 through 6 to assess the time to reach the steady state. Pharmacokinetic parameters were calculated using noncompartmental methods. Modafinil steady state was reached after three daily doses. Modafinil pharmacokinetics were dose and time independent over the range of 200 mg to 800 mg. Steady-state pharmacokinetics of modafinil were characterized by a rapid oral absorption rate, a low plasma clearance of approximately 50 mL/min, a volume of distribution of approximately 0.8 L/kg, and a long half-life of approximately 15 hr. Modafinil was primarily eliminated by metabolism. Modafinil acid was the major urinary metabolite. Stereospecific pharmacokinetics of modafinil were demonstrated. The d-modafinil enantiomer was eliminated at a threefold faster rate than 1-modafinil. Modafinil 200 mg, 400 mg, and 600 mg doses were generally well tolerated. The modafinil 800 mg dose panel was discontinued after 3 days of treatment due to the observation of increased blood pressure and pulse rate. The safety data from this study suggest that the maximum tolerable single daily oral modafinil dose, without titration, may be 600 mg.

J Sleep Res 1998 Jun;7(2):105-14

Effect of modafinil on plasma melatonin, cortisol and growth hormone rhythms, rectal temperature and performance in healthy subjects during a 36 h sleep deprivation.

Brun J, Chamba G, Khalfallah Y, Girard P, Boissy I, Bastuji H, Sassolas G, Claustrat B

Service de Radiopharmacie et Radioanalyse, Centre de Medecine Nucleaire, Hopital NeuroCardiologique, Lyon, France.

Modafinil is an alerting substance which has been used successfully to treat narcolepsy. Nothing is known about its effect on hormone secretions. For this purpose, eight healthy young men were enrolled in a double blind trial to test the effects of modafinil on daily plasma melatonin, cortisol and growth hormone (GH) rhythms. Blood was sampled for hormone assays, every hour during the daytime and every 30 min during the nighttime. In addition, rectal temperature and mental performances were determined during the study which comprised 3 sessions, two weeks apart: a 24 h control session including a night with sleep (S1) and two 48 h sessions S2 and S3 with a sleep-deprived night (N1) followed by a recovery night (N2). Modafinil (300 mg x 2) or placebo were randomly attributed during N1 at 22 h and 8 h. As expected, performance was improved after modafinil administration and body temperature was maintained or increased. Plasma melatonin and cortisol profiles were similar after modafinil and placebo administration. The levels observed during the recovery and the control nights (N2) displayed no difference. For GH, during both sleep deprived nights, secretion was dramatically reduced compared with the control one, although the number of secretory episodes was unchanged. These data show that the alerting property of modafinil is not related to an alteration of hormone profiles and suggest that the acute modafinil administration is devoid of short-term side-effects.

J Sleep Res 1997 Jun;6(2):84-91

Self-monitoring cognitive performance during sleep deprivation: effects of modafinil, d-amphetamine and placebo.

Baranski JV, Pigeau RA

Information Processing Sector, Defence and Civil Institute of Environmental Medicine, North York, Ontario, Canada.

Self-monitoring refers to the ability to assess accurately one's own performance in a specific environment. The present study investigated the effects of the stimulating drugs modafinil (300 mg) and d-amphetamine (20 mg) on the ability to self-monitor cognitive performance during 64 h of sleep deprivation (SD) and sustained mental work. Two cognitive tasks were investigated: a visual (perceptual) judgement task and a complex mental addition task. Subjects in the placebo condition displayed marked circadian and SD effects on cognitive task performance but their self-monitoring was substantively undisturbed by SD. Subjects performing under the influence of d-amphetamine likewise displayed highly proficient self-monitoring throughout the SD period. In contrast, modafinil had a disruptive effect on self-monitoring, inducing a reliable 'overconfidence' effect (i.e. an overestimation of actual cognitive performance), which was particularly marked 2-4 h post-dose. Although modafinil has proven to be a safe and effective countermeasure to the effects of extensive SD on cognitive task performance, we encourage a more comprehensive understanding of the relation between its subjective and performance enhancing effects before the drug is recommended as a viable fatigue countermeasure.

Anders Sandberg                                      Towards Ascension!                  
GCS/M/S/O d++ -p+ c++++ !l u+ e++ m++ s+/+ n--- h+/* f+ g+ w++ t+ r+ !y