Fatigue therapy in multiple sclerosis: results of a double-blind, randomized, parallel trial of amantadine, pemoline, and placebo. Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease. Comparison of the effects of acetyl L-carnitine and amantadine for the treatment of fatigue in multiple sclerosis: results of a pilot, randomised, double-blind, crossover trial. A randomised, placebo-controlled, double-blind trial of the effects of d-methylphenidate on fatigue and cognitive dysfunction in women undergoing adjuvant chemotherapy for breast cancer. A randomized, double-blind crossover trial of fluoxetine and amitriptyline in the treatment of fibromyalgia. A double-blind, placebo-controlled trial of amantadine for the treatment of fatigue in patients with the post-polio syndrome. Amantadine treatment of fatigue associated with multiple sclerosis. A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer. Modafinil for fatigue in MS: a randomized placebo-controlled double-blind study. Modafinil effects in multiple sclerosis patients with fatigue. Amantadine therapy for fatigue in multiple sclerosis. A phase III, double-blind, placebo-controlled prospective randomized clinical trial of d-threo-methylphenidate HCl in brain tumor patients receiving radiation therapy. Adjunct modafinil for the short-term treatment of fatigue and sleepiness in patients with major depressive disorder: a preliminary double-blind, placebo-controlled study. A randomized controlled trial of amantadine in fatigue associated with multiple sclerosis. The Canadian MS Research Group. Amantadine, fatigue, and multiple sclerosis. Randomized controlled trial of modafinil for the treatment of fatigue in postpolio patients. Modafinil for treatment of fatigue in post-polio syndrome: a randomized controlled trial. Effect of paroxetine hydrochloride (Paxil) on fatigue and depression in breast cancer patients receiving chemotherapy. A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis. Will improvement in quality of life (QOL) impact fatigue in patients receiving radiation therapy for advanced cancer?
To determine the relative efficacy of amantadine, pemoline, and placebo in treatment of multiple sclerosis (MS)-related fatigue.
                Fatigue is a complication of MS. Both pemoline and amantadine have been used to treat MS fatigue, but their relative efficacy is not known.
                Amantadine, pemoline, and placebo were compared in a randomized, double-blind, placebo-controlled study using a parallel-group design. Ninety-three ambulatory MS patients completed the study. Primary outcome measures were the fatigue severity scale (FSS); the MS-specific fatigue scale (MS-FS); and subjective response determined by verbal self-report. Secondary outcome measures consisted of assessments of sleep, depression, and vitality. Repeated-measures analysis of variance with planned post-hoc contrasts and Fisher's exact test were used to compare treatment response.
                Amantadine-treated patients showed a significantly greater reduction in fatigue, as measured by the MS-FS, than did patients treated with placebo (p = 0.04). By verbal report at the end of the study, 79% of patients treated with amantadine versus 52% treated with placebo and 32% treated with pemoline preferred drug therapy compared with no treatment (p = 0.03). No significant differences in any primary outcome measures were noted between pemoline and placebo. Neither amantadine nor pemoline affected sleep or depression relative to placebo.
                Amantadine was significantly better than placebo in treating fatigue in MS patients, whereas pemoline was not. The benefit of amantadine was not due to changes in sleep, depression, or neurologic disability. To evaluate the effectiveness of patient-controlled methylphenidate as compared with placebo in cancer patients with fatigue, as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue (FACIT-F).
                Patients with a fatigue score of at least 4 on a scale of 0 to 10 (0 = no fatigue, 10 = worst possible fatigue) and hemoglobin level of at least 10 g/dL were included. Patients were randomly assigned to receive 5 mg methylphenidate or placebo every 2 hours as needed (maximum of four capsules a day), for 7 days. Patients completed a daily diary including study drug record and fatigue intensity. A research nurse telephoned patients daily to assess toxicity and fatigue level. All patients were offered open-label methylphenidate for 4 weeks. FACIT-F and the Edmonton Symptom Assessment System (ESAS) were assessed at baseline, and days 8, 15, and 36. The FACIT-F fatigue subscore on day 8 was considered the primary end point.
                Of 112 patients randomly assigned, 52 patients in the methylphenidate and 53 in the placebo group were assessable for analysis. Fatigue intensity improved significantly on day 8 in both the methylphenidate and placebo groups. However, there was no significant difference in fatigue improvement by FACIT-F (P = .31) or ESAS (P = .14) between groups. In open-label phase, fatigue intensity maintained low as compared with baseline. No significant toxicities were observed.
                Both methylphenidate and placebo resulted in significant symptom improvement. Methylphenidate was not significantly superior to placebo after 1 week of treatment. Longer study duration is justified. The role of daily telephone calls from a research nurse should be explored as a palliative care intervention. Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment. Dexmethylphenidate (D-MPH; the D-isomer of methylphenidate) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment. A randomized, double-blind, placebo-controlled, parallel-group study evaluated the potential therapeutic effect and safety of D-MPH in the treatment of patients with chemotherapy-related fatigue. Change from baseline in the Functional Assessment of Chronic Illness Therapy-Fatigue Subscale (FACIT-F) total score at Week 8 was the primary outcome measure. One hundred fifty-four patients (predominantly with breast and ovarian cancers) were randomized and treated. Compared with placebo, D-MPH-treated subjects demonstrated a significant improvement in fatigue symptoms at Week 8 in the FACIT-F (P=0.02) and the Clinical Global Impression-Severity scores (P=0.02), without clinically relevant changes in hemoglobin levels. Cognitive function was not significantly improved. There was a higher rate of study drug-related adverse events (AEs) (48 of 76 [63%] vs. 22 of 78 [28%]) and a higher discontinuation rate because of AEs (8 of 76 [11%] vs. 1 of 78 [1.3%]) in D-MPH-treated subjects compared with placebo-treated subjects. The most commonly reported AEs independent of study drug relationship in D-MPH-treated subjects were headache, nausea, and dry mouth, and in placebo-treated subjects were headache, diarrhea, and insomnia. D-MPH produced significant improvement in fatigue in subjects previously treated with cytotoxic chemotherapy. Further studies with D-MPH or other agents to explore treatment response in chemotherapy-associated fatigue should be considered. Fatigue is a commonly encountered symptom of human immunodeficiency virus (HIV) disease, associated with significant psychological and functional morbidity and poor quality of life. Preliminary studies on the treatment of fatigue from the cancer and multiple sclerosis literature suggest that psychostimulants may be effective in reducing fatigue.
                To compare the efficacy of 2 psychostimulant medications, methylphenidate hydrochloride (Ritalin) and pemoline (Cylert), with a placebo intervention for the treatment of fatigue in patients with HIV disease.
                In this double-blind trial, 144 ambulatory patients with HIV disease and persistent and severe fatigue were randomized to treatment with methylphenidate, pemoline, or placebo. Medications were titrated up to a maximum dose of 60 mg of methlyphenidate hydrochloride, 150 mg of pemoline, or 8 capsules of placebo daily. Fatigue was measured using 2 self-reported rating scales, the Piper Fatigue Scale (PFS) and the Visual Analogue Scale for Fatigue (VAS-F). We also used the timed isometric unilateral straight leg-raising task, a measure of muscular endurance. Quality-of-life and psychological well-being measures included the Beck Depression Inventory, the Brief Symptom Inventory, and the 36-Item Short-Form Medical Outcomes Study Health Status Survey. Side effects were monitored using the Systematic Assessment for Treatment Emergent Events and the Extra-pyramidal Symptom Rating Scale. All measures were rated weekly.
                One hundred nine subjects completed the 6-week trial; 15 patients (41%) receiving methylphenidate and 12 patients (36%) receiving pemoline demonstrated clinically significant improvement compared with 6 patients (15%) receiving placebo. Patients receiving methylphenidate or pemoline demonstrated significantly more improvement in fatigue on several self-reported rating scales (PFS total score, P=.04; affective subscale, P=.008; sensory subscale, P=.04; and VAS-F energy subscale, P=.02). Analysis of the regression slopes by means of hierarchical linear modeling demonstrated a significantly greater rate of improvement in PFS total scores among patients receiving psychostimulants compared with the placebo group (P=.02). There were no significant differences in the efficacy between methlyphenidate and pemoline on any outcome measure studied. Improvement in fatigue was also significantly correlated with improvement in measures of depression, psychological distress, and overall quality of life. Severe side effects were relatively uncommon among this sample, and only hyperactivity or jitteriness occurred significantly more often among subjects receiving active medication.
                Many patients with HIV- and acquired immunodeficiency syndrome-unrelated fatigue respond favorably to treatment with methylphenidate or pemoline. Both psychostimulants appear to be equally effective and significantly superior to placebo in decreasing fatigue severity with minimal side effects. Moreover, improvement of fatigue was significantly associated with improved quality of life and decreased levels of depression and psychological distress. Treatment with acetyl L-carnitine (ALCAR) has been shown to improve fatigue in patients with chronic fatigue syndrome, but there have been no trials on the effect of ALCAR for treating fatigue in multiple sclerosis (MS). To compare the efficacy of ALCAR with that of amantadine, one of the drugs most widely used to treat MS-related fatigue, 36 MS patients presenting fatigue were enrolled in a randomised, double-blind, crossover study. Patients were treated for 3 months with either amantadine (100 mg twice daily) or ALCAR (1 g twice daily). After a 3-month washout period, they crossed over to the alternative treatment for 3 months. Patients were rated at baseline and every 3 months according to the Fatigue Severity Scale (FSS), the primary endpoint of the study. Secondary outcome variables were: Fatigue Impact Scale (FIS), Beck Depression Inventory (BDI) and Social Experience Checklist (SEC). Six patients withdrew from the study because of adverse reactions (five on amantadine and one on ALCAR). Statistical analysis showed significant effects of ALCAR compared with amantadine for the Fatigue Severity Scale (p = 0.039). There were no significant effects for any of the secondary outcome variables. The results of this study show that ALCAR is better tolerated and more effective than amantadine for the treatment of MS-related fatigue. Women who receive adjuvant chemotherapy for breast cancer develop fatigue, and a subset reports cognitive impairment. Methylphenidate is reported to improve fatigue and to decrease cognitive impairment in other populations.
                Women were randomised early during their chemotherapy to receive d-methylphenidate (d-MPH), a form of methylphenidate, or an identical appearing placebo. All participants took placebo for one cycle to ensure compliance and then study medication until completion of chemotherapy. Subjects were assessed at baseline, end of chemotherapy and at approximately 6 months follow-up with the High Sensitivity Cognitive Screen (HSCS) and the Hopkins Verbal Learning Test-Revised (HVLT-R). They also completed the self-report Functional Assessment of Cancer Therapy-General (FACT-G) and FACT-F (F = fatigue) questionnaires, evaluating quality of life and fatigue.
                A total of 57 evaluable women were randomised: 29 to d-MPH and 28 to placebo; the study did not meet its accrual goal of 170 patients, mainly because women were reluctant to take additional medication in general and methylphenidate in particular. Groups were well matched for age (median, 50 years) and education. d-MPH and placebo were well tolerated. There were no significant differences between the randomised groups in classification of cognitive function by HSCS or in summed FACT-F fatigue scores (the primary endpoints of the study) at any of the assessments. There were also no differences in HLTV-R scores or quality of life.
                This study is underpowered, but there are no trends to suggest that d-MPH, taken concurrently with adjuvant chemotherapy, improves quality of life or fatigue. To study the effect of fluoxetine (FL) and amitriptyline (AM), alone and in combination, in patients with fibromyalgia (FM).
                Nineteen patients with FM completed a randomized, double-blind crossover study, which consisted of 4 6-week trials of FL (20 mg), AM (25 mg), a combination of FL and AM, or placebo. Patients were evaluated on the first and last day of each trial period. Outcome measures included a tender point score, the Fibromyalgia Impact Questionnaire (FIQ), the Beck Depression Inventory (BDI) scale, and visual analog scales (VAS) for global well-being (1 completed by the physician and 1 by the patient), pain, sleep trouble, fatigue, and feeling refreshed upon awakening.
                Both FL and AM were associated with significantly improved scores on the FIQ and on the VAS for pain, global well-being, and sleep disturbances. When combined, the 2 treatments worked better than either medication alone. Similar, but nonsignificant, improvement occurred in the BDI scale, the physician global VAS, and the VAS for fatigue and feeling refreshed upon awakening. Trends were less clear for the tender point score.
                Both FL and AM are effective treatments for FM, and they work better in combination than either medication alone. Because amantadine has been shown to reduce fatigue in patients with multiple sclerosis, we performed a double-blind, placebo-controlled study to assess its efficacy in the disabling symptom of post-polio fatigue. Twenty-three patients completed six weeks of therapy. Fatigue was measured by the patients using visual analogue scales (twice per day) and numerical fatigue severity scales (once per week) and by overall impression (at end of therapy). Formal neuropsychological testing and serum drug levels were performed to assess compliance. On all measures, no significant difference was found between treatment and placebo groups. Fifty-four percent of patients given amantadine and 43% given placebo reported a decrease in fatigue; however, the visual analogue scales and fatigue severity scales failed to reflect any improvement. Several patients in the treatment group elected to continue amantadine therapy after the study was completed. Our findings suggest that amantadine is not significantly better than placebo in reducing the sensation of fatigue in post-polio syndrome, and that the measures we employed were insensitive to capture the subjective response experienced by a few patients. Fatigue is a common symptom of multiple sclerosis (MS) that is without an effective treatment. A double-blind, controlled study of fatigue treatment was conducted to evaluate the efficacy of amantadine hydrochloride in treating MS-associated fatigue. Since fatigue cannot be characterized by a single symptom or behavior, a variety of neuropsychological, behavioral, and self-report measures were used to monitor changes across different systems. According to patients' daily diary ratings, amantadine produced small but statistically significant improvements in fatigue across four of seven dimensions (overall energy level, concentration, problem solving, and sense of well-being). In addition, patients with MS who were taking amantadine performed slightly better on the Stroop Interference Test, an attentional measure of freedom from distracting information. Although retrospective reports by patients with MS did not confirm the degree of improvement recorded on a daily basis, the study's results suggested that amantadine may offer modest benefits in alleviating the day-to-day subjective experience of fatigue. Fatigue is very common in patients with cancer. Current guidelines suggest that psychostimulants are "reasonable to consider for severe fatigue." This randomized, double-blind, placebo-controlled trial investigated the hypothesis that dexamphetamine in fatigued patients with advanced cancer would produce a clinically significant improvement with minimal side effects. Fifty patients with advanced cancer, who were receiving palliative care, were randomized to dexamphetamine 10mg twice daily or placebo for eight days. Effectiveness was assessed using the Brief Fatigue Inventory and the McGill Quality-of-Life Questionnaire. The side effects were recorded. The results were analyzed on an intention-to-treat basis. The baseline demographics, fatigue levels, and quality-of-life scores were similar between the two arms. Patients were elderly, had impaired performance status (Eastern Cooperative Oncology Group score=3), and were taking a range of neurologically active medications. Thirty-nine patients completed the trial. There was a transient improvement in the fatigue levels on day 2, but no significant difference in fatigue (P=0.267) or quality of life (P=0.579) by the end of the study. Statistical modeling did not reveal any significant predictors of response to dexamphetamine. These results suggest that dexamphetamine 20mg daily, although well tolerated, does not significantly improve fatigue or quality of life in patients with advanced cancer, as measured by the selected instruments. To assess whether modafinil, a wakefulness-promoting agent, is useful for fatigue in patients with multiple sclerosis (MS).
                Patients with MS with stable disability, and a baseline score of 45 or more on the Modified Fatigue Impact Scale (MFIS), were eligible for the 5-week randomized, double-blind, placebo-controlled, parallel group study. The initial daily dose of modafinil was 200 mg for 1 week. Depending on tolerance, the dose was increased by 100 mg every week up to 400 mg/day and remained unchanged between day 21 and day 35. The primary outcome variable was the change of MFIS score at day 35.
                A total of 115 patients with MS were enrolled in the study and in the intention to treat analysis. The mean MFIS score at baseline was 63 +/- 9 in the placebo group and 63 +/- 10 in the modafinil group. MFIS scores improved between day 0 and day 35 in both placebo-treated and modafinil-treated groups, but no significant difference was detected between the two groups. There was no major safety concern.
                There was no improvement of fatigue in patients with multiple sclerosis treated with modafinil vs placebo according to the Modified Fatigue Impact Scale. To investigate the effects of Modafinil on focused attention, motor function and motor excitability in patients with multiple sclerosis (MS) and fatigue.
                21 MS patients with fatigue were enrolled in this double-blind placebo-controlled study. Modafinil (MOD) or placebo (PL) was administered for 8 weeks. The d2 alertness test, the Nine Hole Peg Test (9HPT) and several transcranial magnetic stimulation (TMS) techniques were applied prior to and after the first drug ingestion and well as after 8 weeks of drug intake.
                Prior to the first drug intake, the two groups were comparable. After the first drug ingestion, fatigue as measured by the Fatigue Severity Scale (FSS), performance of the d2 test and the 9HPT improved significantly in the MOD group and remained better than in the PL group after 8 weeks of treatment. Patients in the MOD group made fewer mistakes in the D2 test without being slower. They completed the 9HPT faster. Motor evoked potential amplitudes produced by paired pulse TMS were larger in the MOD group than the PL group. Motor thresholds and silent period durations remained unchanged.
                Compared to PL, MOD improved fatigue, focused attention and dexterity and enhanced motor cortex excitability in this group of patients. MOD may be helpful in MS patients with fatigue to improve cognitive and motor abilities. We carried out a double blind control study of fatigue in 32 patients with multiple sclerosis, comparing amantadine hydrochloride 100 mg twice a day and placebo. On amantadine 31% had marked improvement; 15.6% moderate improvement; 15.6% mild improvement; and 36.5% unchanged. On placebo, none noted marked improvement; one claimed moderate improvement on either amantadine or placebo. 18.7% reported mild improvement on placebo; and most of them had similar or more response to amantadine. No patient selected placebo over amantadine at the end of the trial. Overall improvement was seen in 62.5% of patients on amantadine and 21.8% on placebo. Additional experience up to two years suggests continued benefit but common and important side-effects. The quality of life (QOL) and neurocognitive function of patients with brain tumors are negatively affected by the symptoms of their disease and brain radiation therapy (RT). We assessed the effect of prophylactic d-threo-methylphenidate HCl (d-MPH), a central nervous system (CNS) stimulant on QOL and cognitive function in patients undergoing RT.
                Sixty-eight patients with primary or metastatic brain tumors were randomly assigned to receive d-MPH or placebo. The starting dose of d-MPH was 5 mg twice daily (b.i.d.) and was escalated by 5 mg b.i.d. to a maximum of 15 mg b.i.d. The placebo was administered as one pill b.i.d. escalating three pills b.i.d. The primary outcome was fatigue. Patients were assessed at baseline, the end of radiation therapy, and 4, 8, and 12 weeks after brain RT using the Functional Assessment of Cancer Therapy with brain and fatigue (FACIT-F) subscales, as well as the Center for Epidemiologic Studies Scale and Mini-Mental Status Exam.
                The Mean Fatigue Subscale Score at baseline was 34.7 for the d-MPH arm and 33.3 for the placebo arm (p = 0.61). At 8 weeks after the completion of brain RT, there was no difference in fatigue between patient groups. The adjusted least squares estimate of the Mean Fatigue Subscale Score was 33.7 for the d-MPH and 35.6 for the placebo arm (p = 0.64). Secondary outcomes were not different between the two treatment arms.
                Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL. Fatigue and sleepiness are primary symptoms of depression that may not resolve with antidepressant therapy. Modafinil is a novel agent that has been shown to improve wakefulness and lessen fatigue in a variety of conditions. In this study, we examined the utility of modafinil as an adjunct therapy to treat fatigue and sleepiness in patients with major depression who are partial responders to antidepressants.
                Patients with partial response to anti-depressant therapy given for at least a 6-week period for a current major depressive episode (DSM-IV criteria) were enrolled in this 6-week, randomized, double-blind, placebo-controlled, parallel-group, multicenter study. Patients received once-daily doses (100-400 mg) of modafinil or matching placebo as adjunct treatment to ongoing antidepressant therapy. The effects of modafinil were evaluated using the Hamilton Rating Scale for Depression (HAM-D), the Fatigue Severity Scale (FSS), the Epworth Sleepiness Scale (ESS), the Clinical Global Impression of Change (CGI-C), and the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36). Adverse events were monitored throughout the study.
                One hundred thirty-six patients were randomized to treatment, with 118 patients (87%) completing the study. Most patients (82%) were fatigued, and one half of patients (51%) were sleepy. Modafinil rapidly improved fatigue and daytime wakefulness, with significantly greater mean improvements from baseline than placebo in fatigue (FSS) scores at week 2 (p < .05) and sleepiness (ESS) scores at week 1 (p < .01); the differences between modafinil and placebo at week 6 were not statistically significant. Assessment of the augmentation effects of modafinil (HAM-D, CGI-C, and SF-36) did not significantly distinguish modafinil from placebo. Modafinil was well tolerated in combination with a variety of antidepressants.
                Modafinil may be a useful adjunct therapy for the short-term management of residual fatigue and sleepiness in patients who are partial responders to antidepressant therapy. One hundred and fifteen patients with definite multiple sclerosis (M.S.) and chronic persistent fatigue were studied. This ten-week cross-over study consisted of a 2-week baseline period and two 3-week treatment periods separated by a 2-week washout. Patients received either amantadine 100 mg bid or matching placebo capsules. Fatigue, the effect of fatigue on an individually pre-selected activity and its effect on activities of daily living, were evaluated. Amantadine produced a small but statistically significant decrease in fatigue. An important placebo effect was noted. Mean fatigue during the washout period was lower than during the placebo run-in period, independently of which treatment had been given first. Side effects were numerous both on amantadine and on placebo. Only insomnia was significantly more common with amantadine. In a double-blind placebo-controlled crossover study of ten patients with multiple sclerosis, we found amantadine hydrochloride therapy to be effective in improving fatigability in six. Administration of the drug was associated with significantly higher levels of beta-endorphin-beta-lipotropin and responders had significantly higher levels than nonresponders. Lactate levels were significantly higher and pyruvate levels lower in nonresponders. Amantadine given for fatigue to patients with multiple sclerosis is associated with measurable changes in levels of metabolites and peptides in the circulation. The purpose of this study was to test whether modafinil is effective in alleviating the symptoms of fatigue in postpolio patients, because it has been helpful for such symptoms in other neurologic disorders. Using a double-blind, randomized, placebo-controlled cross-over design, 14 postpolio patients with moderate to severe fatigue were assigned to receive modafinil or placebo first. Piper Fatigue Scale, Epworth Sleepiness Scale, digit span, and reaction time tests were done at baseline and then at weekly intervals. The Piper Fatigue Scale scores improved by 27 +/- 40% (mean +/- SD) following modafinil and by 43 +/- 36% following placebo. Scores for most of the other tests did not change during the study. Therefore, we conclude that modafinil was not effective in alleviating the symptoms of fatigue in postpolio patients. To determine if modafinil can improve fatigue in patients with post-polio syndrome.
                We used a randomized, placebo-controlled crossover trial. Intervention with modafinil (400 mg/day) and placebo occurred over 6-week periods. Primary endpoint (fatigue) was assessed using the Fatigue Severity Scale as the main outcome measure. Other measures included the Visual Analog Scale for Fatigue and the Fatigue Impact Scale. Secondary endpoint (health-related quality of life) was assessed using the 36-Item Short-Form. Analysis of variance for repeated measures was applied to assess treatment, period, and carryover effects.
                Thirty-six patients were randomized, 33 of whom (mean age: 61 years) completed required interventions. Treatment with modafinil was safe and well-tolerated. After adjusting for periods and order effects, no difference was observed between treatments.
                Based on the utilized measures of outcome modafinil was not superior to placebo in alleviating fatigue or improving quality of life in the studied post-polio syndrome population. Fatigue can significantly interfere with a cancer patient's ability to fulfill daily responsibilities and enjoy life. It commonly co-exists with depression in patients undergoing chemotherapy, suggesting that administration of an antidepressant that alleviates symptoms of depression could also reduce fatigue.
                We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy randomly assigned to receive either 20 mg of the selective serotonin re-uptake inhibitor (SSRI) paroxetine (Paxil, SmithKline Beecham Pharmaceuticals) or an identical-appearing placebo. Patients began their study medication seven days following their first on-study treatment and continued until seven days following their fourth on-study treatment. Seven days after each treatment, participants completed questionnaires measuring fatigue (Multidimensional Assessment of Fatigue, Profile of Mood States-Fatigue/Inertia subscale and Fatigue Symptom Checklist) and depression (Profile of Mood States-Depression subscale [POMS-DD] and Center for Epidemiologic Studies-Depression [CES-D]).
                Repeated-measures ANOVAs, after controlling for baseline measures, showed that paroxetine was more effective than placebo in reducing depression during chemotherapy as measured by the CES-D (p = 0.006) and the POMS-DD (p = 0.07) but not in reducing fatigue (all measures, ps > 0.27).
                Although depression was significantly reduced in the 44 patients receiving paroxetine compared to the 50 patients receiving placebo, indicating that a biologically active dose was used, no significant differences between groups on any of the measures of fatigued were observed. Results suggest that modulation of serotonin may not be a primary mechanism of fatigue related to cancer treatment. Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited. Thirty patients were randomly assigned to aspirin (ASA) 1,300 mg/day or placebo in a double-blind crossover study. Results favored ASA for the main clinical outcomes: Modified Fatigue Impact Scale scores (p = 0.043) and treatment preference (p = 0.012). There were no significant adverse effects. The results warrant further study and support a role for ASA-influenced mechanisms, perhaps immunologic, in the generation of MS-related chronic fatigue. Fatigue has a significant impact on the quality of life (QOL) of cancer patients. Recent research has suggested that physical activity can reduce fatigue in patients receiving active cancer treatment. In this project, we examined the impact that participation in a randomized controlled trial of a multidisciplinary intervention designed to impact overall QOL had on fatigue for advanced cancer patients actively receiving treatment.
                Patients with newly diagnosed cancer were randomly assigned to an 8-session structured multidisciplinary intervention or a standard-care arm at the beginning of their course of radiotherapy (RT) designed to impact QOL. Ninety-minute sessions were led by either a psychiatrist or psychologist, collaborating with a nurse, physical therapist, chaplain, or social worker, depending on the session's theme. The fatigue assessments used in this trial included the Linear Analogue Self Assessment (LASA), the Profile of Mood States (POMS), Spielberger's State-Trait Anxiety Inventory (STAI), and the Symptom Distress Scale (SDS).
                There were 115 participants enrolled and the 2 randomization arms were well balanced in terms of baseline characteristics and treatment received except for increased commuting distance for the patients in the intervention arm (P = 0.042). Most of scores indicated less fatigue (higher score) in the standard treatment group, but there were no statistically significant differences found at baseline and weeks 4, 8, and 27 except for SDS at week 8 (P = 0.018) with less patients reporting significant fatigue in the standard treatment arm. For the entire participant population, fatigue levels initially worsened with radiotherapy, stabilized at week 8, and returned to baseline by week 27. Disease site, chemotherapy use, and radiotherapy dose did not have a significant impact on fatigue levels.
                Radiotherapy initially caused a worsening of fatigue but with time fatigue levels returned to baseline. Clinically, this structured multidisciplinary intervention had no impact on fatigue, and there was the suggestion the multiple sessions may have contributed to worse fatigue during active cancer treatment.
Based on limited evidence, we cannot recommend a specific drug for treatment of fatigue in palliative care patients. Surprisingly, corticosteroids have not been a research focus for fatigue treatment, although these drugs are frequently used. Recent fatigue research seems to focus on modafinil, which may be beneficial although there is no evidence currently. Amantadine and methylphenidate should be further examined. Consensus regarding fatigue assessment in advanced disease is needed.