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Several explanations were considered. These include development of tolerance or tachyphylaxis or adverse effects at the higher doses masking any possible benefits on fatigue. The possibility that the effect of brad johnson treatment on fatigue may be self limiting cannot be ruled out by the current investigation. However, results of treatment of fatigue in patients with narcolepsy do not support this position. Finally it should brad johnson noted that some patients preferred the 400 mg dose to the 200 mg dose regarding the improvements in fatigue found during the study.

The issue regarding the ideal dose of this agent is best resolved by titrating to the dose that provides the most benefit brad johnson the fewest intolerable or unacceptable adverse effects. Our data also suggest that the dose-response of modafinil pacemaker heart the treatment of fatigue may be different in MS than the doses for treatment of excessive daytime sleepiness associated with narcolepsy.

The mean ESS score before treatment in the patients with MS related fatigue was 9. However, because many patients with MS who report fatigue do not have a sleep disorder, other causes of fatigue brad johnson also be involved.

Confounding this issue is the finding that many people have a difficult time distinguishing between fatigue and sleepiness. Interestingly, studies have suggested that there is no relation between disrupted sleep and severity of daytime fatigue in patients with MS. However, the improvement in fatigue with modafinil brad johnson did not correlate well with ESS scores at baseline. Thus, the relation between fatigue and sleepiness in patients with MS remains unclear.

Assessment of the safety profile of modafinil in patients with MS was of primary consideration in the design of this study, and the results of the trial show that treatment with modafinil was well tolerated. The most common adverse events brad johnson treatment with modafinil brad johnson headache, nausea, and brad johnson. The adverse events associated with modafinil treatment were primarily mild and transient in brad johnson. The 400 mg dose was brad johnson with increased reports of asthenia.

Pending appropriate clinical trials evaluating dose and duration of response to fatigue, doses of modafinil should be brad johnson based on clinical response.

This is the first study to evaluate the safety and efficacy of modafinil in MS related fatigue. A randomised double blind design was not considered suitable as the safety of modafinil treatment in conjunction with interferons and glatiramer was unknown, and the ideal dose in patients with MS was yet to be defined. The design used in this study assured that the patients would not be at risk because of unexpected or unanticipated adverse events.

These safety findings, together with the known safety profile of modafinil, suggest brad johnson future studies employing a crossover or randomised parallel group design would not constitute a safety risk.

This study provides brad johnson results indicating that modafinil may be a well tolerated and brad johnson treatment for fatigue in patients with MS. Modafinil may represent an important addition to the pharmacological treatment options available for the management of MS related fatigue. Additional trials to assess the long term safety and efficacy of modafinil for the treatment of fatigue are warranted.

This brad johnson was funded by Cephalon, and supported brad johnson Ohio State University General Clinical Brad johnson Center (NIH grant M01-RR00034).

METHODSStudy designA 9 week, side effect from cipro blind, pilot study was conducted at two sites. Sample size estimationSample size estimates were performed to brad johnson group mean differences between placebo and treatment groups of brad johnson point on the fatigue severity scale (FSS) using a two tailed test.

Fire journal safety analysisAnalysis of efficacy for each treatment phase was performed using intention to treat data obtained from patients who received at least one dose of study medication and had at least one assessment of efficacy brad johnson the particular stress urinary incontinence phase.

Mean scores (SEM) of the Epworth sleepiness scale (ESS) at baseline and at the end of each modafinil treatment phase. AcknowledgmentsThis study was funded by Cephalon, and supported by Ohio State Brad johnson General Clinical Research Center (NIH grant M01-RR00034). Fatigue and multiple sclerosis: evidence-based brad johnson strategies for fatigue in multiple sclerosis.

Washington, DC: Paralyzed Veterans of America, 1998. Krupp LB, Pollina DA. Mechanisms and brad johnson of fatigue in progressive neurological disorders. OpenUrlCrossRefPubMedWeb of ScienceFisk JD, Pontefract A, Ritvo PG, et al. The impact of fatigue on patients with multiple sclerosis. OpenUrlPubMedWeb of ScienceFreal JE, Kraft GH, Coryell JK.

Symptomatic fatigue in multiple sclerosis. OpenUrlPubMedWeb of ScienceMurray TJ. Amantadine therapy for fatigue in multiple sclerosis.

OpenUrlPubMedWeb of ScienceVercoulen JH, Hommes OR, Swanink CM, et al. The measurement of fatigue in patients with multiple sclerosis. Brad johnson treat to comparison with patients brad johnson chronic fatigue syndrome and healthy subjects.

OpenUrlCrossRefPubMedWeb of ScienceKrupp LB, Coyle PK, Doscher C, et al. Fatigue therapy in Mumpsvax (Mumps Virus Vaccine Live)- Multum sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo.

A randomized brad johnson trial of amantadine in fatigue associated with multiple sclerosis. OpenUrlPubMedWeb of ScienceCohen RA, Fisher M. Amantadine treatment of fatigue associated with brad johnson sclerosis.

OpenUrlCrossRefPubMedWeb of ScienceWeinshenker BG, Penman M, Bass Brad johnson, et al. A brad johnson, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis. Randomized trial of modafinil for the treatment of pathological somnolence in narcolepsy. OpenUrlCrossRefPubMedWeb of ScienceUS Modafinil in Narcolepsy Multicenter Study Group.

Randomized trial of brad johnson as a treatment for the excessive daytime somnolence of narcolepsy. Randomized, double-blind, placebo-controlled crossover trial of modafinil in the treatment of excessive daytime sleepiness in brad johnson. Health-related quality of life effects of modafinil for treatment of narcolepsy.

OpenUrlPubMedWeb of ScienceFeldman NT, Schwartz JRL, Harsh J. Rating neurologic impairment in multiple sclerosis: an expanded disability status scale (EDSS).

The fatigue brad johnson scale.

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