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Its binding affinity to DAT is lower than Bupropion. This interaction with DAT and the subsequent increase in a dopaminergic tone is central to its wake-promoting effects. It has no direct or indirect effects on dopamine receptors. However, research also shows evidence that modafinil similarly binds to the norepinephrine transporter (NET) and that it has additional effects on several other CNS systems such as GABA, glutamate, histamine, and orexin pathways.

Overall, Modafinil increases HA, NE, 5-HT, and DA levels in the brain. Mechanism of Enhancing Wakefulness: Histamine, serotonin, and norepinephrine tone is directly related to the arousal state and that neurons releasing these chemicals are almost silent in REM sleep.

The peptide orexin (ORX) released from neurons of the lateral hypothalamus plays an important role in the maintenance of vigilance. It may also account for the observed clinical effect of armodafinil. Armodafinil (Nuvigil): 150 mg or 250 mg given once daily in the morning Obstructive sleep apnea-hypopnea syndrome (OSAHS) : Modafinil: In OSAHS, modafinil is indicated as an adjunct to continuous positive airway pressure (CPAP).

Clinicians should make a maximal effort to treat OSAHS with CPAP for an adequate period Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA time before initiating modafinil. If modafinil is used adjunctively with CPAP, encouraging CPAP and periodic assessment of CPAP compliance is necessary. Armodafinil: The recommended dose of Armodafinil for patients with OSAHS is 150 mg or 250 mg, given once daily in the morning.

Moderate to Severe Chronic Shift Work Sleep Disorder Modafinil: 200 mg daily as a single dose approximately Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA hour before the start of the work shift. Armodafinil: 150 mg daily approximately 1 hour before the start of their work shift. SAFETY PROFILE Modafinil and armodafinil are well tolerated, with most adverse events classified as mild or moderate in severity. Patients with a history of substance use should be closely monitored as modafinil and armodafinil produce psychoactive Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA euphoric effects and feelings consistent with other scheduled CNS stimulants.

Drug interactions Modafinil has displayed some interactions in vitro with the CYP isoenzyme system, although it is less apparent in vivo. As such, there is potential for modafinil to interact with substrates Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA CYP2C19, which includes diazepam, phenytoin, and omeprazole.

Although caution is advised, a clinically significant effect is likely to be low with substrates of CYP2C19. Clomipramine concentrations were significantly higher after treatment with modafinil; however, this patient was genotyped as a CYP2D6 poor metabolizer. Please read our detailed article on pharmacogenomics with tables of medications that affect CYP enzymes in psychiatry. CLINICAL EVIDENCE Modafinil and Armodafinil are evidence-based in the treatment of: Narcolepsy Obstructive Sleep Apnoea as an adjunct to continuous positive airway pressure (CPAP) Moderate to Severe Chronic Shift Work Sleep Disorder Treatment-resistant Depression Negative symptoms of Schizophrenia Bipolar Depression: Multiple trials and a pooled analysis noted decreased depression and fatigue and improved cognition in patients receiving modafinil augmentation than mood stabilisers or antidepressants in bipolar depression.

Cognitive Function Improvement: Modafinil and armodafinil are regularly used off-label as cognitive enhancers after translational experiments reported promising results. An update on the pharmacotherapy of excessive daytime sleepiness and cataplexy Mignot E An update on the pharmacotherapy of excessive daytime Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA and cataplexy. The efficacy and safety of armodafinil as treatment for adults with excessive sleepiness associated with narcolepsy Harsh J et al.

A systematic review of modafinil: Potential clinical uses and Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA of action Ballon J and Feifel D. Modafinil: a review of neurochemical actions and effects on cognition Minzenberg M and Carter C. Mechanisms of modafinil: a review of current research Gerrard, P. Clinical pharmacokinetic profile of modafinil Robertson P and Hellriegel E.

A double-blind, combodart, ascending-dose evaluation of the pharmacokinetics and tolerability of modafinil tablets in healthy male volunteers Wong Y et al.

Pharmacodynamic effects on alertness of single doses of armodafinil in healthy subjects during a nocturnal period of acute sleep loss Dinges D et al. Pharmacokinetic profile of armodafinil in healthy subjects: pooled analysis of data from three randomized studies Darwish M et al.

Comparison of steady-state plasma concentrations of armodafinil and modafinil late in the day following morning administration: post hoc analysis of two randomized, Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA, placebo-controlled, multiple-dose studies in healthy male subjects Darwish M et al. In vitro inhibition and induction of human hepatic cytochrome P450 enzymes by modafinil Robertson P et al.

Interaction profile of armodafinil with medications metabolized by cytochrome P450 enzymes 1A2, 3A4 and 2C19 in healthy subjects Darwish M et al. Single-dose pharmacokinetics of modafinil and methylphenidate given alone or in combination in healthy male volunteers Wong Y et al. Efficacy and safety of adjunctive armodafinil in adults with major depressive episodes associated with bipolar I disorder: A randomized, double-blind, placebo-controlled, multicenter trial Calabrese JR, Frye MA, Yang R, Ketter TA Armodafinil Treatment Trial Study Network.

Markovitz Provocholine (Methacholine Chloride)- FDA, Wagner S. Modafinil: preclinical, clinical, and post-marketing surveillance--a review of Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA liability issues Myrick H et al. Cognitive enhancing effects of modafinil in healthy volunteers Turner D et al.

Modafinil and unconstrained motor activity in schizophrenia: double-blind crossover placebo-controlled trial Farrow T et al. Cognitive enhancers in the treatment of substance use disorders: clinical evidence Brady K et al. Mechanisms Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA modafinil: A review of current research Gerrard P and Malcolm R.

S2377Jonathan RL SchwartzINTEGRIS Sleep Disorders Center and University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The wake-promoting agent modafinil is approved for the treatment of excessive sleepiness associated with obstructive sleep apnea (OSA), shift work disorder (SWD), and narcolepsy.

In OSA, modafinil is recommended for use as an adjunct to standard therapies that treat the underlying airway obstruction. This article reviews the literature on modafinil (pharmacology, pharmacokinetics, efficacy, tolerability, and abuse potential), with bayer ch on use of modafinil in the treatment of excessive sleepiness in patients with OSA, SWD, and narcolepsy.

In large-scale, double-blind, placebo-controlled studies, modafinil improved objectively determined sleep latency, improved overall clinical condition related to severity of sleepiness, and reduced patient-reported sleepiness.

In patients with SWD, diary data showed modafinil reduced the maximum level of sleepiness during night shift work, level of sleepiness during the commute home, and incidence of accidents or near-accidents during the commute home when compared with placebo. Modafinil was well Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA, without adversely affecting cardiovascular parameters or scheduled sleep.

These findings and those of extension studies which reported improvements were maintained suggest modafinil has a beneficial effect on daily life and well-being in patients with excessive sleepiness associated with OSA, SWD, or narcolepsy.

Keywords: Measles and Rubella Virus Vaccine Live (M-R-Vax)- FDA, excessive sleepiness, wakefulness, obstructive sleep apnea, shift work disorder, narcolepsy This work is published and licensed by Dove Medical Press Limited. S2377 Jonathan RL SchwartzINTEGRIS Sleep Disorders Center and University of Oklahoma Health Sciences Center, Oklahoma City, OK, USAAbstract: The wake-promoting agent modafinil is approved for the treatment of excessive sleepiness associated with obstructive sleep apnea (OSA), shift work disorder (SWD), and narcolepsy.

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