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Original Research: SARCOIDOSIS |

Double-Blind, Randomized Trial of Dexmethylphenidate Hydrochloride for the Treatment of Sarcoidosis-Associated Fatigue* FREE TO VIEW

Elyse E. Lower, MD; Stacy Harman; Robert P. Baughman, MD
Author and Funding Information

*From the Department of Medicine, University of Cincinnati Medical Center, Cincinnati, OH.

Correspondence to: Elyse E. Lower, MD, 1001 Holmes, Eden Ave, Cincinnati, OH 45267-0565; e-mail: elower@ohcmail.com



Chest. 2008;133(5):1189-1195. doi:10.1378/chest.07-2952
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Published online

Background: Fatigue is a common complaint in patients with sarcoidosis. We studied the effectiveness of dexmethylphenidate hydrochloride (d-MPH) in treating sarcoidosis-associated fatigue.

Methods: This was a double-blind, randomized, placebo-controlled, crossover trial of d-MPH. Patients were seen weekly and completed Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) and Fatigue Assessment Score (FAS) instruments. After a 1-week wash-in period, patients received either d-MPH or placebo. After 8 weeks, the medications were stopped. Following a 2-week wash-out period, patients were crossed over to 8 weeks of the other treatment. FVC and 6-min walk distance (6MWD) were determined initially and after each treatment arm.

Results: Ten patients with sarcoidosis were enrolled: 8 women and 5 African Americans. All were receiving systemic sarcoidosis therapy. Significant improvement in fatigue was reported by patients when receiving d-MPH (FACIT-F, p < 0.001; FAS, p < 0.02). FVC was higher at the end of 8 weeks of d-MPH compared to the baseline values (baseline median, 2.38 L; range, 1.17 to 4.53 L; placebo median, 2.41 L; range, 1.50 to 4.65 L; d-MPH median, 2.56 L; range, 1.50 to 4.96 L; p < 0.01). There was no significant difference in the 6MWD (baseline median, 330 m; range, 60 to 460 m; placebo median, 350 m; range, 180 to 460 m; d-MPH median, 390 m; range, 200 to 460 m). d-MPH was well tolerated.

Conclusions: Treatment with d-MPH was associated with a significant improvement in sarcoidosis-associated fatigue.

Trial registration: Clinicaltrials.gov Identifier: NCT00361387.

Figures in this Article

Sarcoidosis is a multiorgan disease associated with multiple systemic complaints, including fatigue and malaise.1Studies23 using structured questionnaires have identified fatigue in 50 to 80% of sarcoidosis patients. In subgroups treated with either corticosteroids or methotrexate, 50% had fatigue.3

Methylphenidate has been used for the treatment of fatigue in patients with cancer,4HIV infection,5and chronic fatigue syndrome.6In an open-label trial,7 methylphenidate was reported as useful for fatigue associated with sarcoidosis.

Dexmethylphenidate hydrochloride (d-MPH) is the d-threo-methylphenidate hydrochloride isomer of methylphenidate. It is approximately twice as potent as the racemic formulation and appears to have a longer half-life; hence, it can be administered twice daily.8

One trial9 found d-MPH superior to placebo in treating fatigue and memory problems, “chemobrain,” associated with cancer chemotherapy. Based on the prolonged benefit and low toxicity of d-MPH, we performed a double-blind, randomized trial of d-MPH for the treatment of sarcoidosis-associated fatigue. The study was designed to confirm the utility of stimulants in treating sarcoidosis-associated fatigue. It also was designed to document changes in the pulmonary function and respiratory health status during therapy.

All study participants had biopsy-confirmed sarcoidosis with consistent clinical features for > 2 years1 and complained of chronic fatigue with no other identified causes. Patients were excluded from the study if they had uncontrolled hypertension or cardiac arrhythmias. Maintenance systemic therapy without significant change was administered throughout the study. Patients provided written informed consent of a protocol approved by the University of Cincinnati Institutional Review Board.

Patients were seen weekly as outpatients in a designated area for research studies during this 20-week, double-blind, randomized, placebo-controlled trial. Vital signs, including pulse and BP, were measured at each visit. The study was divided into two parts. After receiving placebo for 1 week, patients were randomized to receive d-MPH or placebo with an initial twice-daily dose of either 5 mg of d-MPH or placebo. Randomization was performed using a random-sequence generator without blocking or stratification. Randomization and drug dispensing were performed by a research pharmacist who blinded the remaining study personnel from the identity of the drug. The dose of either drug was escalated to a maximum of two tablets bid (total dose, 20 mg of d-MPH) at the discretion of the blinded treating physician, based on the symptoms. After 8 weeks of therapy, followed by 2 weeks of placebo, patients were crossed over to the opposite drug for 8 weeks with doses adjusted by the blinded treating physician. This is summarized in Figure 1 .

At each weekly visit, patients completed instruments to assess fatigue, which included the non–disease-specific Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F)10and the sarcoidosis-specific Fatigue Assessment Score (FAS).11 For FACIT-F, the maximum score is 52; the higher the score, the less the fatigue. For FAS, the maximum score is 50; the higher the score, the more the fatigue.

The Saint George Respiratory Questionnaire (SGRQ) was measured initially and after each treatment arm.12This 76-item questionnaire is composed of three domains, symptoms, activity, and impact, as well as a total score. All four scores are normalized to a score range from 0 to 100, with a lower the number correlating with a better health status. The Sarcoidosis Health Questionnaire (SHQ) is a sarcoidosis-specific health-related quality of life instrument.13 The higher the score, the less severe the impairment in health-related quality of life. Spirometry and distance walked in 6 min were measured during the wash-in period, the wash-out period, and at the end of each treatment period using a previously described protocol.2 To assess toxicity including jitteriness, palpitations, insomnia, chest pain, and headache, a Likert score questionnaire was completed weekly. The Beck Depression Inventory (BDI)-II was self administered at baseline, week 11, and after each treatment.14

A total of 10 patients were chosen based on a prior study9 of the effect of d-MPH and reproducibility of FACIT-F score. Comparisons were made for the paired data using Student paired t test, with a p value of < 0.05 considered significant.

The study was performed between June 2006 and January 2007. Forty-four sarcoidosis patients were screened for the study (Fig 2 ). The two major reasons for not participating were exclusion criteria (not receiving stable therapy or clinically significant cardiac arrythmias) or not available for the 20 weekly visits required by the study. Ten patients were enrolled, and all completed all aspects of the study. The enrolled patients had a median age of 52 years (range, 39 to 74 years). Eight of the patients were women, and five each were African American or white. All patients were receiving one or more systemic agents for sarcoidosis: prednisone (n = 9), hydroxychloroquine (n = 7), methotrexate (n = 6), azathioprine (n = 1), and leflunomide (n = 1). All patients had evidence of pulmonary sarcoidosis with other active organ involvement including skin (n = 4), and one patient each with ocular, neurologic, and extrathoracic lymphadenopathy. At week 8 of d-MPH treatment, four patients were receiving only 15 mg of d-MPH (10 mg in morning, 5 mg in afternoon), and the other six patients were receiving 10 mg bid of d-MPH.

Table 1 demonstrates the median and range of the FAS and FACIT-F scores at the time of study entry and after 1 week of placebo. At baseline, all patients had significant fatigue with FAS score ≥ 22.11 Both FAS and FACIT-F scores changed insignificantly during the 1 week of placebo (FAS, p = 0.0547; FACIT-F, p = 0.0977). Table 1 also shows the subsequent FAS and FACIT-F scores during wash-out period (weeks 10 and 11). Patients were receiving placebo at that time. Patients were aware that there was a transition between the two arms of the study but did not know when active drug was started. The values for week 1 and week 11 were quite similar, with no significant difference between the two time points (p > 0.50).

Figure 3 demonstrates the mean FACIT-F and FAS by week of therapy during either the placebo or d-MPH periods. The scores obtained at week 1 and week 11 are shown as the baseline values of each treatment (baseline). There was a significant difference between d-MPH and placebo for the values measured (FACIT-F, p < 0.001; FAS, p < 0.02). The effect of d-MPH on FACIT-F score was apparent within 2 weeks of therapy, while no difference was seen for the FAS score until week 5.

Average mean ± SD values for the FACIT-F and FAS scores during the placebo arm were 24.3 ± 5.41 and 33.6 ± 4.43, respectively. Power calculations based on this variation for the FACIT-F score indicated that 10 patients would be able to detect at least a 30% difference from placebo with α = 0.05 and β = 0.05. From the FAS variation, power calculations indicated that 10 patients would be able to detect at least a 25% difference from placebo with α = 0.01 and β = 0.05.

The baseline values for the SGRQ are shown in Table 2 . For the SGRQ, the lower the score, the healthier the patient feels. Compared to a healthy population, a score ≥ 20 was associated with lung diseases such as COPD or asthma.15 The SGRQ score was elevated in all patients with no significant difference noted between baseline and either therapy. There was a significant difference between SGRQ symptoms score between d-MPH (median, 54) and placebo treatment (median, 61; p < 0.02), consistent with a worse symptoms score while receiving placebo therapy. There was no significant difference in the total SGRQ score.

The SHQ total score was lower at the baseline than after either therapy (Table 2). For the SHQ, the higher the score, the less affected the individual.13 There was no significant difference between the SHQ total scores obtained after placebo or d-MPH therapy. There was no difference in the various components of the SHQ score (data note shown).

Pulmonary function studies were performed prior to and at the end of each treatment arm. Table 3 shows the results of these studies. The FVC and FVC percentage of predicted were higher at the end of 8 weeks of d-MPH compared to the baseline studies (p < 0.01 and p < 0.05, respectively). The small increase in FVC and FVC percentage of predicted during placebo therapy was not significant. There was no significant difference in the 6-min walk distance (6MWD) throughout the study.

A BDI-II score ≥ 21 is associated with significant depression.14 The BDI-II at baseline was significantly higher than after either treatment arm (baseline, 22.5; range, 5 to 29; d-MPH, 13; range, 1 to 25 [p < 0.005]; placebo, 13; range, 1 to 28 [p < 0.005]). However, the BDI-II score at week 11 (during placebo wash-out period), the score was significantly lower than baseline (12; range, 1 to 26). There was no difference between the d-MPH or placebo treatment values and those obtained during the washout values obtained at week 11.

No patient discontinued the study because of toxicity, but four patients were receiving a lower afternoon dose while receiving d-MPH. No patient required a reduced dose while receiving placebo. Heart rate and BP remained stable throughout the study. Overall, the Likert scales for jitteriness, palpitations, headache, and chest pain were similar for patients while receiving placebo or d-MPH, and there was no significant correlation between these symptoms and the dose of d-MPH (Fig 4 ). There was no difference in the Likert scores for insomnia.

Fatigue is a common complaint expressed by many patients with chronic diseases. In one study3 of unselected sarcoidosis patients, fatigue was noted in > 70% of patients, compared to only 20% of a control population. This high frequency has been reported in other sarcoidosis populations.2,16 As in other chronic diseases, including cancer, the cause of the fatigue can be multifactorial. Fatigue is not associated with most other clinical markers of disease activity in sarcoidosis.3 However, patients reporting higher levels of fatigue may walk shorter 6MWDs.2 Sleep apnea occurs with increased frequency in sarcoidosis patients.1718 Tumor necrosis factor-α is released at increased levels in patients with sarcoidosis. Infliximab, a specific tumor necrosis factor inhibitor, can be effective for the treatment of chronic pulmonary sarcoidosis19and has been used successfully in the treatment of a sarcoidosis patient with debilitating fatigue.20 However, infliximab is associated with high cost and significant toxicity. In the current study, despite systemic therapy for sarcoidosis, all patients continued to complain of fatigue.

Interest exists for the use of stimulants in treating fatigue in patients with chronic conditions, including cancer4, HIV infection,5 multiple sclerosis,21 and chronic fatigue syndrome.6 While several studies reported a positive response, most of these studies were not performed in a blinded fashion or compared to placebo. There have been some placebo-controlled trials demonstrating improvement of fatigue with methylphenidate vs placebo.5,22 Although methylphenidate has been the most commonly studied drug,46 it has a short half-life and is associated with toxicity such as jitteriness, palpitations, and headache. Studies of d-MPH vs methylphenidate for attention deficit disorder have demonstrated equal efficacy with less toxicity and longer duration of activity for d-MPH.8A double-blind randomized study9 demonstrated significant improvement with d-MPH in the treatment of fatigue associated with cancer chemotherapy. Although these drugs are generally well tolerated, a small risk for cardiac arrhythmias and sudden death has been reported.23 In this study, no significant difference in toxicity was reported during the placebo and d-MPH treatment periods.

This study supports the use of stimulants for fatigue in patients with sarcoidosis.7 The improvement in fatigue at week 8 for the d-MPH group vs placebo was 36%, similar to the 33% improvement in fatigue observed with d-MPH for cancer chemotherapy-related fatigue.9 In this small study, no difference in toxicity was noted between drug and placebo. A prior study7 of methylphenidate for sarcoidosis-associated fatigue showed significant improvement in symptoms. However, because the study with methylphenidate was not placebo controlled, some of the improvement could have been a placebo effect. While a placebo effect was noted between week 0 and week 1 for both FAS and FACIT-F, the changes in scores were not significant. The blinded nature of the study led to stable FAS and FACIT-F scores during the placebo wash-in and wash-out periods of the study (weeks 1, 10, and 11), as shown in Table 1. While the study sample was relatively small, the FACIT-F and FAS results were fairly reproducible during the weekly visits throughout the placebo arm of the study. Our power calculations indicated that by studying 10 patients we would be able to detect a significant difference in fatigue. Thus we were fairly confident that the changes in fatigue found in this study were not the results of a type 1 error.

To determine the effect of fatigue on the respiratory quality of life of our patients, we administered the SGRQ and SHQ before and after each treatment arm. Compared to a healthy population, a SGRQ total score ≥ 20 was associated with lung diseases such as COPD or asthma.15 Patients recruited for clinical trials of pharmacologic agents for COPD had a median SGRQ score ≥ 40, and a ≥ 4-point-greater change was associated with clinical significance.2425 In the current study, nine patients had a score > 40, which is a higher proportion than reported by previous sarcoidosis studies.2,26 In the prior studies,2,26 the surveys represented all sarcoidosis patients, while this study focused on those with fatigue. The overall effect of d-MPH on SGRQ was fairly mild. The only significant difference from placebo treatment was in the SGRQ symptoms component.

Significant changes associated with d-MPH were not seen for the sarcoidosis health questionnaire. There was an improvement in the SHQ from baseline after treatment with either placebo or d-MPH. The SHQ is a relatively new questionnaire,13 and the degree of change that is associated with clinically significant improvement has yet to be determined.

A previous study2 reported that the FAS score negatively correlates with pulmonary function and 6MWD. In this small study, improvement in fatigue was associated with some improvement in pulmonary function. With d-MPH therapy, there was a significant improvement in the FVC compared to baseline. These changes were for both the absolute and percentage of predicted FVC. A similar improvement, although not clinically significant, was also seen with the 6MWD. One report27found that methylphenidate was a respiratory stimulant and increased the vital capacity of a patient with primary alveolar hypoventilation. However, it seems more likely that these small changes in pulmonary function were the result of feeling less fatigued at the time of performing the tests. Subjective fatigue has been shown to correlate with pulmonary function in patients with chronic obstructive lung disease.28 In this study, the small changes in the vital capacity by itself were not likely to have been the cause of the changes in SGRQ and FAS scores.

Depression is commonly reported by sarcoidosis patients.2930 Methylphenidate, the racemic form of d-MPH, has been reported to be effective for medically ill patients with depression.3132 It also may be synergistic with antidepressants.3334 At time of entry into the study, the BDI-II score was higher than 21 in half of the patients, consistent with clinically significant depression.14 However, the score fell during the placebo wash-in and wash-out periods. There was only one patient who had a score > 21 while receiving placebo in the wash-out period. Likewise, the BDI-II score was low during both treatment arms of this study. Therefore, any improvement in the fatigue seen in this study does not seem to be as an antidepressant.

In the current double-blind study, d-MPH significantly improved reported fatigue in chronic sarcoidosis patients compared to placebo, as reported by a higher FACIT-F score throughout the 8 weeks of use, and a lower FAS score for the second month of treatment (Fig 3). This is the first known study to compare these two measures of fatigue in sarcoidosis patients. The fact that fatigue was improved with d-MPH by both instruments supports the value of d-MPH in treating sarcoidosis-associated fatigue.

Abbreviations: BDI = Beck Depression Inventory; d-MPH = dexmethylphenidate hydrochloride; FACIT-F = Functional Assessment of Chronic Illness Therapy-Fatigue; FAS = Fatigue Assessment Score; SGRQ = Saint George Respiratory Questionnaire; SHQ = Sarcoidosis Health Questionnaire; 6MWD = 6-min walk distance

The authors have no conflicts of interest to disclose.

Figure Jump LinkFigure 1. Overall scheme of the trial. After a 1-week wash-in period, patients were randomly assigned to receive either d-MPH or placebo in treatment 1. They received 2 weeks of placebo as a washout. During treatment 2, patients received placebo or d-MPH (opposite of treatment 1) for 8 more weeks.Grahic Jump Location
Figure Jump LinkFigure 2. Flow diagram for patients evaluated for study. Of 44 patients assessed for eligibility, 10 participated in the study.Grahic Jump Location
Table Graphic Jump Location
Table 1. Fatigue Levels During Wash-in and Wash-out Periods
* 

Baseline obtained during no therapy. Weeks 1, 10, 11 obtained while patient was receiving placebo in a single-blind fashion.

Figure Jump LinkFigure 3. The median FACIT-F (left, A) and FAS (right, B) by week of therapy during either the placebo or d-MPH period. Baseline values represent the scores obtained at week 1 and week 11 before the respective treatments. There was a significant difference between the values measured (FACIT-F, p < 0.001; FAS, p < 0.02).Grahic Jump Location
Table Graphic Jump Location
Table 2. Respiratory Health Status During Treatment*
* 

Data are presented as median (range).

 

Significantly different from placebo (p < 0.05).

 

Significantly different from placebo (p < 0.01) and d-MPH (p < 0.02).

Table Graphic Jump Location
Table 3. Pulmonary Function During Treatment*
* 

Data are presented as median (range).

 

Differs from baseline (p < 0.01).

 

Differs from baseline (p < 0.05).

Figure Jump LinkFigure 4. Likert scores reported by patients for insomnia, jitteriness, palpitations, and chest pain while receiving either placebo or d-MPH. Scale was 1 to 5. There was no difference in the responses between the two treatment arms. The central box represents the values from the lower to upper quartile (25 to 75 percentile). The middle line represents the median. The horizontal line extends from the minimum to the maximum value, excluding “outside” and “far out” values that are displayed as separate points.Grahic Jump Location
Hunninghake, GW, Costabel, U, Ando, M, et al (1999) ATS/ERS/WASOG statement on sarcoidosis: American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders.Sarcoidosis Vasc Diffuse Lung Dis16,149-173. [PubMed]
 
Baughman, RP, Sparkman, BK, Lower, EE Six-minute walk test and health status assessment in sarcoidosis.Chest2007;132,207-213. [PubMed] [CrossRef]
 
de Vries, J, Rothkrantz-Kos, S, Dieijen-Visser, MP, et al The relationship between fatigue and clinical parameters in pulmonary sarcoidosis.Sarcoidosis Vasc Diffuse Lung Dis2004;21,127-136. [PubMed]
 
Bruera, E, Driver, L, Barnes, EA, et al Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report.J Clin Oncol2003;21,4439-4443. [PubMed]
 
Breitbart, W, Rosenfeld, B, Kaim, M, et al A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease.Arch Intern Med2001;161,411-420. [PubMed]
 
Blockmans, D, Persoons, P, Van, HB, et al Does methylphenidate reduce the symptoms of chronic fatigue syndrome?Am J Med2006;119,167-130
 
Wagner, MT, Marion, SD, Judson, MA The effects of fatigue and treatment with methylphenidate on sustained attention in sarcoidosis [letter].Sarcoidosis Vasc Diffuse Lung Dis2005;22,235. [PubMed]
 
Wigal, S, Swanson, JM, Feifel, D, et al A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d, l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder.J Am Acad Child Adolesc Psychiatry2004;43,1406-1414. [PubMed]
 
Lower, EE, Fleishman, S, Cooper, A, et al Efficacy of dexamethylphenidate for the treatment of fatigue following cancer chemotherapy: a randomized clinical trial [abstract].J Clin Oncol2005;23,8000
 
Yellen, SB, Cella, DF, Webster, K, et al Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system.J Pain Symptom Manage1997;13,63-74. [PubMed]
 
de Vries, J, Michielsen, H, van Heck, GL, et al Measuring fatigue in sarcoidosis: the Fatigue Assessment Scale (FAS).Br J Health Psychol2004;9,279-291. [PubMed]
 
Jones, PW, Quirk, FH, Baveystock, CM, et al A self-complete measure of health status for chronic airflow limitation: the St. George’s Respiratory Questionnaire.Am Rev Respir Dis1992;145,1321-1327. [PubMed]
 
Cox, CE, Donohue, JF, Brown, CD, et al The sarcoidosis health questionnaire: a new measure of health-related quality of life.Am J Respir Crit Care Med2003;168,323-329. [PubMed]
 
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Michielsen, HJ, De, VJ, Drent, M, et al Psychometric qualities of the Fatigue Assessment Scale in Croatian sarcoidosis patients.Sarcoidosis Vasc Diffuse Lung Dis2005;22,133-138. [PubMed]
 
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Fouchier, SM, Moller, GM, Van Santen-Hoeufft, M, et al Successful treatment with infliximab of a patient with refractory sarcoidosis [in Dutch].Ned Tijdschr Geneeskd2004;148,2446-2450. [PubMed]
 
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Cox, CE, Donohue, JF, Brown, CD, et al Health-related quality of life of persons with sarcoidosis.Chest2004;125,997-1004. [PubMed]
 
Putnam, JS, Kaufman, LV, Michaels, RM, et al Methylphenidate therapy in primary alveolar hypoventilation.Chest1973;64,137-140. [PubMed]
 
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Chang, B, Steimel, J, Moller, DR, et al Depression in sarcoidosis.Am J Respir Crit Care Med2001;163,329-334. [PubMed]
 
Drent, M, Wirnsberger, RM, Breteler, MH, et al Quality of life and depressive symptoms in patients suffering from sarcoidosis.Sarcoidosis Vasc Diffuse Lung Dis1998;15,59-66. [PubMed]
 
Wallace, AE, Kofoed, LL, West, AN Double-blind, placebo-controlled trial of methylphenidate in older, depressed, medically ill patients.Am J Psychiatry1995;152,929-931. [PubMed]
 
Homsi, J, Nelson, KA, Sarhill, N, et al A phase II study of methylphenidate for depression in advanced cancer.Am J Hosp Palliat Care2001;18,403-407. [PubMed]
 
Lavretsky, H, Park, S, Siddarth, P, et al Methylphenidate-enhanced antidepressant response to citalopram in the elderly: a double-blind, placebo-controlled pilot trial.Am J Geriatr Psychiatry2006;14,181-185. [PubMed]
 
Patkar, AA, Masand, PS, Pae, CU, et al A randomized, double-blind, placebo-controlled trial of augmentation with an extended release formulation of methylphenidate in outpatients with treatment-resistant depression.J Clin Psychopharmacol2006;26,653-656. [PubMed]
 

Figures

Figure Jump LinkFigure 1. Overall scheme of the trial. After a 1-week wash-in period, patients were randomly assigned to receive either d-MPH or placebo in treatment 1. They received 2 weeks of placebo as a washout. During treatment 2, patients received placebo or d-MPH (opposite of treatment 1) for 8 more weeks.Grahic Jump Location
Figure Jump LinkFigure 2. Flow diagram for patients evaluated for study. Of 44 patients assessed for eligibility, 10 participated in the study.Grahic Jump Location
Figure Jump LinkFigure 3. The median FACIT-F (left, A) and FAS (right, B) by week of therapy during either the placebo or d-MPH period. Baseline values represent the scores obtained at week 1 and week 11 before the respective treatments. There was a significant difference between the values measured (FACIT-F, p < 0.001; FAS, p < 0.02).Grahic Jump Location
Figure Jump LinkFigure 4. Likert scores reported by patients for insomnia, jitteriness, palpitations, and chest pain while receiving either placebo or d-MPH. Scale was 1 to 5. There was no difference in the responses between the two treatment arms. The central box represents the values from the lower to upper quartile (25 to 75 percentile). The middle line represents the median. The horizontal line extends from the minimum to the maximum value, excluding “outside” and “far out” values that are displayed as separate points.Grahic Jump Location

Tables

Table Graphic Jump Location
Table 1. Fatigue Levels During Wash-in and Wash-out Periods
* 

Baseline obtained during no therapy. Weeks 1, 10, 11 obtained while patient was receiving placebo in a single-blind fashion.

Table Graphic Jump Location
Table 2. Respiratory Health Status During Treatment*
* 

Data are presented as median (range).

 

Significantly different from placebo (p < 0.05).

 

Significantly different from placebo (p < 0.01) and d-MPH (p < 0.02).

Table Graphic Jump Location
Table 3. Pulmonary Function During Treatment*
* 

Data are presented as median (range).

 

Differs from baseline (p < 0.01).

 

Differs from baseline (p < 0.05).

References

Hunninghake, GW, Costabel, U, Ando, M, et al (1999) ATS/ERS/WASOG statement on sarcoidosis: American Thoracic Society/European Respiratory Society/World Association of Sarcoidosis and other Granulomatous Disorders.Sarcoidosis Vasc Diffuse Lung Dis16,149-173. [PubMed]
 
Baughman, RP, Sparkman, BK, Lower, EE Six-minute walk test and health status assessment in sarcoidosis.Chest2007;132,207-213. [PubMed] [CrossRef]
 
de Vries, J, Rothkrantz-Kos, S, Dieijen-Visser, MP, et al The relationship between fatigue and clinical parameters in pulmonary sarcoidosis.Sarcoidosis Vasc Diffuse Lung Dis2004;21,127-136. [PubMed]
 
Bruera, E, Driver, L, Barnes, EA, et al Patient-controlled methylphenidate for the management of fatigue in patients with advanced cancer: a preliminary report.J Clin Oncol2003;21,4439-4443. [PubMed]
 
Breitbart, W, Rosenfeld, B, Kaim, M, et al A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease.Arch Intern Med2001;161,411-420. [PubMed]
 
Blockmans, D, Persoons, P, Van, HB, et al Does methylphenidate reduce the symptoms of chronic fatigue syndrome?Am J Med2006;119,167-130
 
Wagner, MT, Marion, SD, Judson, MA The effects of fatigue and treatment with methylphenidate on sustained attention in sarcoidosis [letter].Sarcoidosis Vasc Diffuse Lung Dis2005;22,235. [PubMed]
 
Wigal, S, Swanson, JM, Feifel, D, et al A double-blind, placebo-controlled trial of dexmethylphenidate hydrochloride and d, l-threo-methylphenidate hydrochloride in children with attention-deficit/hyperactivity disorder.J Am Acad Child Adolesc Psychiatry2004;43,1406-1414. [PubMed]
 
Lower, EE, Fleishman, S, Cooper, A, et al Efficacy of dexamethylphenidate for the treatment of fatigue following cancer chemotherapy: a randomized clinical trial [abstract].J Clin Oncol2005;23,8000
 
Yellen, SB, Cella, DF, Webster, K, et al Measuring fatigue and other anemia-related symptoms with the Functional Assessment of Cancer Therapy (FACT) measurement system.J Pain Symptom Manage1997;13,63-74. [PubMed]
 
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