Treatments modafinil

The mode of action of modafinil, a new arousal-promoting compound used in the treatment of sleepiness associated with narcolepsy, is not fully understood. 

Modafinil is considered the standard for treatment of excessive daytime sleepiness. Plasma concentrations peak in 2 to 4 hours, and the half-life is 15 hours. Preliminary evidence suggests no tolerance or withdrawal after abrupt discontinuation and no risk of abuse. 

Compiled from US. Modafinil in Narcolepsy Multicenter Study Group and Standard of Practice Committee of the American Sleep Disorders Association. Pradice parameters for the use of stimulants in the treatment of narcolepsy. Seep 1994 17 348-351. 

Substance-Induced Anxiety Disorder. Numerous medicines and drugs of abuse can produce panic attacks. Panic attacks can be triggered by central nervous system stimulants such as cocaine, methamphetamine, caffeine, over-the-counter herbal stimulants such as ephedra, or any of the medications commonly used to treat narcolepsy and ADHD, including psychostimulants and modafinil. Thyroid supplementation with thyroxine (Synthroid) or triiodothyronine (Cytomel) can rarely produce panic attacks. Abrupt withdrawal from central nervous system depressants such as alcohol, barbiturates, and benzodiazepines can cause panic attacks as well. This can be especially problematic with short-acting benzodiazepines such as alprazolam (Xanax), which is an effective treatment for panic disorder but which has been associated with between dose withdrawal symptoms. 

Modafinil (Provigil). The newest stimulant, modafinil, is not, pharmacologically, a true stimulant. Nevertheless, it is an effective treatment for narcolepsy at doses from 200 to 400mg/day. Several studies indicate that modahnil has little potential for abuse and is easier to tolerate than other stimulants. Modafinil has been studied in the treatment of ADHD. Though not approved for marketing by the FDA at the time of this writing, it may gain the indication in the near future. 

Fava M, Judge R, Hoog SL, et al Fluoxetine versus sertraline and paroxetine in major depressive disorder changes in weight with long-term treatment. J Clin Psychiatry 61 863-867, 2000 Fava M, Thase ME, DeBattista C A multicenter, placebo-controlled study of modafinil augmentation in partial responders to selective serotonin reuptake inhibitors with persistent fatigue and sleepiness. J Clin Psychiatry 66 85-93, 2005... 

Modafinil is a stimulant medication used to improve wakefulness in patients with narcolepsy, obstructive sleep apnea/hypopnea syndrome (as adjunct to standard treatments for the underlying disorder), and shift work sleep disorder. Controlled and open trials provided data on the efficacy and safety of modafinil in patients with narcolepsy (Besset et al. 1996 Billiard et al. 1994 Broughton et al. 1997 Mitler et al. 2000 U.S. Modafinil in Narcolepsy Multicenter Study Group 1998, 2000). Modafinil has a long duration of action and low potential for dependence and may be a reasonable first choice in the treatment of mild to moderate narcolepsy (Silber 2001). There is also considerable interest in the potential use of modafinil in the treatment of ADHD, and studies are in progress. 

Besset A, Chetrit M, Carlander B, et al Use of modafinil in the treatment of narcolepsy a long-term follow-up study. Neurophysiol Clin 26 60-66, 1996... 

Broughton RJ, Fleming JA, George CF, et al Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in narcolepsy. Neurology 49 444-451, 1997... 

Mitler MM, Harsh J, Hirshkowitz M, et al Long-term efficacy and safety of modafinil (Provigil) for the treatment of excessive daytime sleepiness associated with narcolepsy. Sleep Med 1 231-243, 2000... 

U.S. Modafinil in Narcolepsy Multicenter Study Group Randomized trial of modafinil as a treatment for the excessive daytime somnolence of narcolepsy. Neurology 54 1166-1175, 2000 Wernicke JF, Kratochvil CJ Safety profile of atomoxetine in the treatment of children and adolescents with ADHD. J Clin Psychiatry 63 (suppl 12) 50-55, 2002... 

Drugs That Interfere with Hormonal Contraceptives Concomitant use of HIV-protease inhibitors, griseofulvin, modafinil, penicillins, rifampin, rifabutin, phenytoin, carbamazepine, or certain herbal supplements such as St. John s wort with hormonal contraceptive agents may reduce the effectiveness of the contraception and up to one month after discontinuation of these concomitant therapies. Therefore, women requiring treatment with one or more of these drugs must use two other effective or highly effective methods of contraception or abstain from heterosexual sexual contact while taking thalidomide... 

U.S. Modafinil in Narcolepsy Multicenter Study Group. Randomized trial of modafmil for the treatment of pathological somnolence in narcolepsy. Ann Neurol 1998 43 88-97. 

The recommended dose of modafinil is 200 mg/day for the treatment of excessive daytime sleepiness associated with narcolepsy however, doses of 400 mg/day are FDA-approved. While there is evidence that the higher dose is well tolerated, it has not been established that it confers additional therapeutic benefit (196). In sleep-deprived subjects, doses of 600 mg/day have been administered, but the preponderance of evidence suggests that 300M00 mg/day is probably sufficient and less likely to produce unwanted side effects. 

The most common adverse reactions to this medication are headache, nausea, nervousness, anxiety, and insomnia (211). Generally, these reactions are mild or moderate. The frequencies with which the most common treatment-emergent whole-body, digestive, respiratory, and nervous-system adverse experiences have occurred with daily 200- and 400-mg doses in patient populations were headache 50%, nausea 13%, rhinitis 11%, and nervousness 8%. Unlike amphetamine, modafinil is not associated with significant cardiovascular stimulation. 

Bastuji H, Jouvet M. Successful treatment of idiopathic hypersomnia and narcolepsy with modafinil. Prog Neuro-psychopharmacol Biol Psychiatry 1988 12 695-700. 

Billiard M. Introduction Modafinil, a new treatment of narcolepsy and idiopathic hypersomnia. Drugs Today 1996 32(suppl I) 1 -5. 

Czeisler CA, Dinges DF, Walsh JK, Roth T, Niebler G. Modafinil for the treatment of excessive sleepiness in chronic shift work sleep disorder. Sleep 2003 26(suppl) A115. 

Black JE, Hirshkowitz M (2005) Modafinil for treatment of residual excessive sleepiness in nasal continuous positive airway pressure-treated obstructive sleep apnea/hypopnea syndrome. Sleep 28 464-471... 

Ivanenko A, Tauman R, Gozal D (2003) Modafinil in the treatment of excessive daytime sleepiness in children. Sleep Med 4 579-582... 

The approval of armodafinil marked a significant advance in the treatment of narcolepsy. In this chapter, the pharmacological profile and syntheses of modafinil 4 and armodafinil 1 are profiled in detail.16... 

The armodafinil development program was very similar to the development program previously undertaken for modafinil (or racemic API). Four double-blind and two opened-label clinical trials (1090 patients enrolled with 645 receiving active treatment with armodafinil and 445 receiving placebo) have evaluated the efficacy and safety of armodafinil for the treatment of excessive sleepiness (ES) associated with obstructive sleep apnea (OSA), shift-work disorder (SWD), and narcolepsy.24... 

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