Efficacy and safety of modafinil (Provigil®) for the treatment of fatigue in multiple sclerosis: a two centre phase 2 study Phase II study of donepezil in irradiated brain tumor patients: effect on cognitive function, mood, and quality of life. Potential role of levocarnitine supplementation for the treatment of chemotherapy-induced fatigue in non-anaemic cancer patients Epidemiology of chronic non-malignant pain in Denmark Megestrol acetate for anorexia in patients with far-advanced cancer: a double-blind controlled clinical trial. Randomized trial of paroxetine in end-stage COPD. Effect of methylprednisolone sodium succinate on quality of life in preterminal cancer patients: a placebo-controlled, multicenter study. The Methylprednisolone Preterminal Cancer Study Group. A double blind placebo controlled trial of medroxyprogesterone acetate (MPA) in cancer cachexia. Methylprednisolone as palliative therapy for female terminal cancer patients. The Methylprednisolone Female Preterminal Cancer Study Group. Treatment of HIV-related fatigue with armodafinil: a placebo-controlled randomized trial. 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 Randomized clinical trial of adenosine 5'-triphosphate in patients with advanced non-small-cell lung cancer. A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor Amisulpride in the short-term treatment of depressive and physical symptoms in cancer patients during chemotherapies A randomized, double-blind, placebo-controlled trial of psychostimulants for the treatment of fatigue in ambulatory patients with human immunodeficiency virus disease. Modafinil for fatigue in MS Efficacy of dexmethylphenidate for the treatment of fatigue after cancer chemotherapy: a randomized clinical trial. Effects of a supraphysiological dose of testosterone on physical function, muscle performance, mood, and fatigue in men with HIV-associated weight loss. Effect of armodafinil on cognition in patients with HIV/AIDS and fatigue Effect of paroxetine hydrochloride (Paxil®) on fatigue and depression in breast cancer patients receiving chemotherapy A randomised placebo controlled exploratory study of vitamin B-12, lofepramine, and L-phenylalanine (the “Cari Loder regime”) in the treatment of multiple sclerosis Amantadine treatment of fatigue associated with multiple sclerosis. Assessment of tumor necrosis factor alpha blockade as an intervention to improve tolerability of dose-intensive chemotherapy in cancer patients. Randomized study of dexamethasone treatment for delayed emesis, anorexia and fatigue induced by irinotecan Modafinil for the treatment of fatigue in lung cancer: results of a placebo-controlled, double-blind, randomized trial. Methylphenidate associated with narcotics for the treatment of cancer pain. Comparison of the effect of aspirin and amantadine for the treatment of fatigue in multiple sclerosis: a randomized, blinded, crossover study Effects of methylphenidate on fatigue and depression: a randomized, double-blind, placebo-controlled trial. Effects of Treatment for Depression on Fatigue in Multiple Sclerosis Epidural methadone results in dose-dependent analgesia in cancer pain, further enhanced by epidural dexamethasone Effectiveness of megestrol acetate in patients with advanced cancer: a randomized, double-blind, crossover study. Clinically important changes in acute pain outcome measures: a validation study. A double-blind, placebo-controlled trial of testosterone therapy for HIV-positive men with hypogonadal symptoms. Amantadine, fatigue, and multiple sclerosis. Modafinil for the treatment of fatigue in lung cancer: a pilot study A pilot trial of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer. Modafinil effects in multiple sclerosis patients with fatigue 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 Modafinil to treat fatigue in amyotrophic lateral sclerosis: An open label pilot study An open-label study of the effects of bupropion SR on fatigue, depression and quality of life of mixed-site cancer patients and their partners. A double-blind, placebo-controlled trial of amantadine for the treatment of fatigue in patients with the post-polio syndrome. Fatigue therapy in multiple sclerosis Differential effects of paroxetine on fatigue and depression: a randomized, double-blind trial from the University of Rochester Cancer Center Community Clinical Oncology Program. Quality of life is improved in breast cancer patients by Standardised Mistletoe Extract PS76A2 during chemotherapy and follow-up: a randomised, placebo-controlled, double-blind, multicentre clinical trial. Using Modafinil to Treat Fatigue in Parkinson Disease: A Double-Blind, Placebo-Controlled Pilot Study Neurobehavioral Effects of Interferon-α in Cancer Patients: Phenomenology and Paroxetine Responsiveness of Symptom Dimensions Amantadine influences cognitive processing in patients with multiple sclerosis. Fatigue in multiple sclerosis: multidimensional assessment and response to symptomatic treatment [Methylphenidate in palliative care in cancer patient: a double-blind randomised trial versus placebo]. The effects of amantadine and pemoline on cognitive functioning in multiple sclerosis. Amantadine therapy for fatigue in multiple sclerosis. DHEA treatment for HIV+ patients: effects on mood, androgenic and anabolic parameters Modafinil in treatment of 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. Does amantadine have favourable effects on fatigue in Persian patients suffering from multiple sclerosis? L-carnitine supplementation for the management of fatigue in patients with cancer: an eastern cooperative oncology group phase III, randomized, double-blind, placebo-controlled trial. L-carnitine supplementation for the treatment of fatigue and depressed mood in cancer patients with carnitine deficiency: a preliminary analysis. Citalopram reduces endotoxin-induced fatigue Fluoxetine versus placebo in advanced cancer outpatients: a double-blinded trial of the Hoosier Oncology Group. Intravenous L-carnitine increases plasma carnitine, reduces fatigue, and may preserve exercise capacity in hemodialysis patients. The symptoms of advanced cancer: relationship to age, gender, and performance status in 1,000 patients Modafinil treatment of fatigue in patients with ALS: a placebo-controlled study. Effects of celecoxib, medroxyprogesterone, and dietary intervention on systemic syndromes in patients with advanced lung adenocarcinoma: a pilot study. A phase 3 randomized, placebo‐controlled, double‐blind, clinical trial of the effect of modafinil on cancer‐related fatigue among 631 patients receiving chemotherapy Patient-controlled methylphenidate for cancer fatigue: a double-blind, randomized, placebo-controlled trial. A Randomized, Double-blind, 2-Period, Placebo-Controlled Crossover Trial of a Sustained-Release Methylphenidate in the Treatment of Fatigue in Cancer Patients A randomized controlled crossover trial of aspirin for fatigue in multiple sclerosis Modafinil and armodafinil treatment for fatigue for HIV-positive patients with and without chronic hepatitis C Phase III, randomized, double-blind, placebo-controlled study of long-acting methylphenidate for cancer-related fatigue: North Central Cancer Treatment Group NCCTG-N05C7 trial. The effect of donepezil on sedation and other symptoms in patients receiving opioids for cancer pain: a pilot study. A randomized, crossover evaluation of methylphenidate in cancer patients receiving strong narcotics Donepezil for cancer fatigue: a double-blind, randomized, placebo-controlled trial. Methylphenidate in the management of asthenia in breast cancer patients treated with docetaxel: results of a pilot study Reduction of cancer-related fatigue with dexamethasone: a double-blind, randomized, placebo-controlled trial in patients with advanced cancer. Modafinil treatment for fatigue in HIV/AIDS: a randomized placebo-controlled study. Phase III, randomized, double-blind, placebo-controlled study of modafinil for fatigue in patients treated with docetaxel-based chemotherapy A randomized, double-blind, placebo-controlled trial assessing the impact of dexamphetamine on fatigue in patients with advanced cancer. Megestrol acetate in advanced, progressive, hormone-insensitive cancer. Effects on the quality of life: a placebo-controlled, randomised, multicentre trial. Safety, tolerability and symptom outcomes associated with L-carnitine supplementation in patients with cancer, fatigue, and carnitine deficiency: a phase I/II study. Effect of sertraline on symptoms and survival in patients with advanced cancer, but without major depression: a placebo-controlled double-blind randomised trial. The effect of immunomodulatory treatment on multiple sclerosis fatigue Corticosteroid therapy of preterminal gastrointestinal cancer A double‐blind, randomized, crossover trial of pemoline in fatigue associated with multiple sclerosis L-carnitine supplementation in patients with advanced cancer and carnitine deficiency: a double-blind, placebo-controlled study. Testosterone Versus Fluoxetine for Depression and Fatigue in HIV/AIDS: A Placebo-Controlled Trial Effects of medroxyprogesterone acetate on appetite, weight, and quality of life in advanced-stage non-hormone-sensitive cancer: a placebo-controlled multicenter study. Effects of dextroamphetamine on depression and fatigue in men with HIV: a double-blind, placebo-controlled trial.
Objective : To assess the efficacy and safety of modafinil for the treatment of fatigue in multiple sclerosis ( MS ) . Methods : Patients aged 18–65 years with a diagnosis of MS , a stable disability level ≤6 on the Kurtzke extended disability status scale ( EDSS ) , and a mean score > 4 on the fatigue severity scale ( FSS ) were eligible for the 9 week , single blind , phase 2 , two centre study . Exclusion criteria included a diagnosis of narcolepsy , sleep apnoea , or clinical ly significant major systemic disease and recent use of medications affecting fatigue . All patients , who remained blinded for the treatment regimen , received placebo during weeks 1–2 , 200 mg/day modafinil during weeks 3–4 , 400 mg/day modafinil during weeks 5–6 , and placebo during weeks 7–9 . Safety was evaluated by unblinded investigators . Efficacy was evaluated by self rating scales , using the FSS , the modified fatigue impact scale ( MFIS ) , a visual analogue scale for fatigue ( VAS-F ) , and the Epworth sleepiness scale ( ESS ) . Adverse events were recorded . Results : Seventy two patients ( MS type : 74 % relapsing-remitting ; 7 % primary progressive ; 19 % secondary progressive ) received treatment . After treatment with 200 mg/day modafinil for 2 weeks , a significant improvement in fatigue versus placebo run in was demonstrated . Mean scores after treatment with 200 mg/day modafinil were : FSS , 4.7 versus 5.5 for placebo ( p<0.001 ) ; MFIS , 37.7 versus 44.7 ( p<0.001 ) ; and VAS-F , 5.4 versus 4.5 ( p=0.003 ) . Fatigue scores for 400 mg/day modafinil were not significantly improved versus placebo run in . Mean ESS scores were significantly improved ( p<0.001 ) with 200 mg/day modafinil ( 7.2 ) and 400 mg/day ( 7.0 ) versus the score at baseline ( 9.5 ) . Serious adverse events were not found at either dose . The most common adverse events were headache , nausea , and aesthenia . Sixty five patients ( 90 % ) completed the study . Conclusions : These data suggest that 200 mg/day modafinil significantly improves fatigue and is well tolerated in patients with MS PURPOSE A prospect i ve , open-label phase II study was conducted to determine whether donepezil , a US Food and Drug Administration-approved reversible acetylcholinesterase inhibitor used to treat mild to moderate Alzheimer 's type dementia , improved cognitive functioning , mood , and quality of life ( QOL ) in irradiated brain tumor patients . PATIENTS AND METHODS Thirty-four patients received donepezil 5 mg/d for 6 weeks , then 10 mg/d for 18 weeks , followed by a washout period of 6 weeks off drug . Outcomes were assessed at baseline , 12 , 24 ( end of treatment ) , and 30 weeks ( end of wash-out ) . All tests were administered by a trained research nurse . RESULTS Of 35 patients who initiated the study , 24 patients ( mean age , 45 years ) remained on study for 24 weeks and completed all outcome assessment s. All 24 patients had a primary brain tumor , mostly low- grade glioma . Scores significantly improved between baseline ( pretreatment ) and week 24 on measures of attention/concentration , verbal memory , and figural memory and a trend for verbal fluency ( all P < .05 ) . Confused mood also improved from baseline to 24 weeks ( P = .004 ) , with a trend for fatigue and anger ( all P < .05 ) . Health-related QOL improved significantly from baseline to 24 weeks , particularly , for brain specific concerns with a trend for improvement in emotional and social functioning ( all P < .05 ) . CONCLUSION Cognitive functioning , mood , and health-related QOL were significantly improved following a 24-week course of the acetylcholinesterase inhibitor donepezil .  Toxicities were minimal . We are planning a double blinded , placebo-controlled , phase III trial of donepezil to confirm these favorable results Ifosfamide and cisplatin cause urinary loss of carnitine , which is a fundamental molecule for energy production in mammalian cells . We investigated whether restoration of the carnitine pool might improve chemotherapy-induced fatigue in non-anaemic cancer patients . Consecutive patients with low plasma carnitine levels who experienced fatigue during chemotherapy were considered eligible for study entry . Patients were excluded if they had anaemia or other conditions thought to be causing asthenia .  Fatigue was assessed by the Functional Assessment of Cancer Therapy-Fatigue quality of life question naire . Treatment consisted of oral levocarnitine 4 g daily , for 7 days . Fifty patients were enrolled ; chemotherapy was cisplatin-based in 44 patients and ifosfamide-based in six patients . In the whole group , baseline mean Functional Assessment of Cancer Therapy-Fatigue score was 19.7 ( ±6.4 ; st and ard deviation ) and the mean plasma carnitine value was 20.9 μM ( ±6.8 ; st and ard deviation ) . After 1 week , fatigue ameliorated in 45 patients and the mean Functional Assessment of Cancer Therapy-Fatigue score was 34.9 ( ±5.4 ; st and ard deviation ) ( P<.001 ) . All patients achieved normal plasma carnitine levels . Patients maintained the improved Functional Assessment of Cancer Therapy-Fatigue score until the next cycle of chemotherapy . In selected patients , levocarnitine supplementation may be effective in alleviating chemotherapy-induced fatigue . This compound deserves further investigations in a r and omised , placebo-controlled study & NA ; A series of health surveys are conducted every sixth to seventh year in Denmark . In the most recent survey of 2000 , a national r and om sample ( > 16 years ) was drawn from the Danish Central Personal Register . Out of the original sample 12,333 ( 74 % ) were interviewed and of these 10,066 returned a completed question naire ( SF‐36 ) . The present study includes only those who both took part in the interview and the postal question naire . Cancer patients were excluded . Persons suffering from chronic pain ( PG ) were identified through the question ‘ Do you have chronic/long lasting pain lasting 6 months or more ’ ? An overall chronic pain prevalence of 19 % was found −16 % for men and 21 % for women . Prevalence of chronic pain increased with increasing age . Persons ≥67 years had 3.9 higher odds of suffering from chronic pain than persons in the age group 16–24 years . Compared with married persons , divorced or separated persons had 1.5 higher odds of chronic pain . Odds for chronic pain were 1.9 higher among those with an education of less than 10 years compared with individuals with an education of 13 years or more . During a 14‐day period reporters of chronic pain had an average of 0.8 days ( range 0–10 ) lost due to illness compared with an average of 0.4 days ( range 0–10 ) for the control group ( CG ) ( Odds Ratio ( OR ) ) 2.0 ) . Persons with a job which required high physical strain were more likely to report chronic pain compared with those with a sedentary job ( OR 2.2 ) . The odds of quitting one 's job because of ill health were seven times higher among people belonging to the PG . A strong association between chronic pain and poor self‐rated health was also demonstrated . The PG had twice as many contacts with various health professionals compared with the CG , and the health care system was , on average , utilised 25 % more ( overall contacts ) by the PG than by the general population . Among the persons in the PG , 33 % were not satisfied with the examinations carried out in connection with their pain condition and 40 % were not satisfied with the treatment offered . Nearly 130,000 adults , corresponding to 3 % of the Danish population , use opioids on a regular basis . Opioids are used by 12 % of the PG The aim of this study was to evaluate a low-dose regimen of megestrol acetate ( MA ; 320 mg/day ) on appetite in advanced cancer patients . Out- patients with far-advanced non-hormone responsive tumours and loss of appetite were r and omised in a phase III trial , with two consecutive phases : a 14-day double-blind placebo controlled phase ( phase A ) and a 76-day open phase ( phase B ) . During phase A , patients were treated with MA , two 160 mg tablets/day , or placebo . In phase B , the MA dose was titrated to clinical response in both groups . Appetite , food intake , body weight , performance status , mood and quality of life were evaluated with st and ardised measures ; patients ' global judgement about treatment efficacy was also requested . Of 42 patients entering the study , 33 ( 17 MA and 16 placebo ) were evaluable for efficacy . The appetite score improved significantly with MA after 7 days ( P = 0.0023 ) , and this effect was still significant at 14 days ( P = 0.0064 ) . Patients judged the treatment with MA effective in 88.2 % of cases ( 14th day ) , whilst placebo was considered effective by 25 % ( P = 0.0003 ) . None of the other measures showed significant changes during treatment . The remarkable effect on appetite evident after 7 days , without serious side-effects , shows that MA can produce significant subjective effects at a low-dose even in patients with far-advanced disease BACKGROUND Although the underlying pathology is initially confined to the lungs , the associated emotional responses to chronic obstructive pulmonary disease ( COPD ) contribute greatly to the result ing morbidity . The objective of this study was to examine the effect of an antidepressant drug on disease-specific quality of life in patients with end-stage COPD who present significant depressive symptoms . METHODS We conducted a 12-week , r and omized double-blind placebo-controlled trial of Paroxetine in which quality of life measured by the Chronic Respiratory Question naire ( CRQ ) , an evaluative COPD -specific quality -of-life question naire , was the primary outcome . RESULTS 23 patients were r and omized and 15 completed the trial ( 8 on Paroxetine ; 7 on placebo ) . In the per- protocol analysis , we observed statistically and clinical ly significant improvements favoring the active treatment in 2 of the 4 domains of the CRQ : emotional function ( adjusted mean difference : 1.1 ; 95 % confidence interval [ CI ] : 0.0 - 2.2 ) and mastery ( difference : 1.1 ; CI : 0.4 - 1.8 ) . Dyspnea and fatigue improved , but to an extent that did not reach statistical significance . In the intention-to-treat analysis , none of the differences in CRQ scores was significant . Paroxetine was not associated to any worsening of respiratory symptoms . CONCLUSIONS The results of this small r and omized trial indicated that patients with end-stage COPD may benefit from antidepressant drug therapy when significant depressive symptoms are present . This study underlined the difficulties in conducting experimental studies in frail and elderly patients with COPD The effectiveness of an 8-week , 125 mg/day intravenous course of methylprednisolone sodium succinate ( MPSS ) for improving quality of life in patients with preterminal cancer was investigated in a double-blind , placebo-controlled , multicenter study . Quality of life was assessed using the Nurses ' Observational Scale for Inpatient Evaluation ( NOSIE ) , the Linear Analog Self- Assessment Scale ( LASA ) , and the Physicians ' Global Evaluation . A total of 403 patients were enrolled : 207 were treated with MPSS and 196 were treated with placebo . MPSS was significantly more effective than placebo in improving quality of life as judged by the changes from baseline in the NOSIE and LASA total scores . ( P less than 0.05 ) and by the Physicians ' Global Evaluation ( P less than 0.001 ) . The mortality rate was similar between  MPSS-treated males ( 40.2 % ) ,  placebo-treated  males ( 35.5 % ) , and  MPSS-treated  females ( 40.0 % ) . However , the mortality rate of 27.7 % for female placebo-treated females was significantly lower than for their MPSS-treated counterparts . The reason for lower mortality among placebo-treated females is unknown and warrants further study Patients with breast cancer treated with MPA often report an improvement in appetite . Similar appetite stimulation is seen in patients treated with some corticosteroids , but MPA has a potential advantage over these drugs in that it does not exert a catabolic effect . MPA ( 100 mg tds orally ) has therefore been compared with placebo in 60 patients with advanced malignant disease . Twenty-one patients in the MPA group and 20 in the placebo group were receiving chemotherapy .  Patients were treated for 6 weeks and were assessed at weeks 0 , 3 and 6 for appetite , energy , mood and pain using visual analogue scales . Nutritional status was assessed by the measurement of serum proteins and anthropometrics . Karnofsky score was recorded as a measure of performance status . There was a significant improvement in appetite in the MPA group between weeks 0 ( pre- study ) and 3 ( P = 0.0002 ) and 0 and 6 ( P = 0.015 ) . There was no significant improvement in appetite in the placebo group . Supporting this finding was the significant increase in serum thyroid binding pre-albumin and retinol binding protein in the MPA group between weeks 0 and 3 and 0 and 6 ( P = 0.023 and P = 0.039 respectively ) . These two parameters showed no significant change in the placebo group . There was no change in anthropometric measurements , weight , performance status , energy , mood or pain in either group . These data indicate that there was a significant increase in appetite in anorexic patients with advanced cancer treated with MPA which was reflected in increases in rapid turnover proteins reported to reflect nutritional status . However , this apparent increase in appetite did not result in improved weight , performance status , energy levels , mood or relief of pain . Further studies to investigate the effect of higher doses of  MPA  are indicated A total of 173 female terminal cancer patients were r and omized to treatment with daily 125 mg infusions of methylprednisolone sodium succinate or a matching placebo for a period of 8 consecutive weeks . Data were collected relative to quality of life , investigator assessment of efficacy and cause and time of death within the 8-week treatment period . Significant improvement in quality of life was reported across the 8-week follow-up period in the steroid group . Investigator global assessment of efficacy significantly favored the steroid-treatment patients . There were no significant differences between treatment groups with regard to overall mortality rates or time to death . The total number of reported adverse events did not differ significantly between treatment groups . However , significantly more steroid patients reported gastrointestinal and cardiovascular events . The severity and outcome of these events did not differ from the placebo patients . The results of this study confirm previous reports of steroid efficacy in improving quality of life in terminal cancer patients . The absence of any untoward effect on mortality and the favorable safety profile support the use of methylprednisolone as palliative therapy for terminal cancer patients OBJECTIVE To evaluate the efficacy and safety of armodafinil in the treatment of  fatigue in HIV+ patients , and to assess its effect on depressive symptoms and behavior once fatigue remitted . METHOD HIV+ patients with clinical ly significant fatigue were treated in a placebo-controlled r and omized double-blind trial for 4 weeks . Armodafinil responders and placebo non-responders or relapsers were treated openly for a total of 16 weeks with armodafinil . The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement Scale , supplemented by the Fatigue Severity Scale , the Hamilton Depression Rating Scale , and the Beck Depression Inventory . Safety was assessed with assays of CD4 cell count and HIV RNA viral load and the SAFTEE side effects rating scale . Maximum trial dose of armodafinil was 250 mg/d . RESULTS Seventy patients were enrolled . Attrition was 9 % . In intention-to-treat analyses , fatigue response rate to armodafinil was 75 % and to placebo , 26 % . Armodafinil did not reduce depressive symptoms in the absence of improved energy , but of those patients with an Axis I depressive disorder at study entry whose energy improved , 82 % experienced improved mood as well . Markers of immunologic suppression did not change during treatment . At 6 months , those still taking armodafinil had more energy and fewer depressive symptoms than those who were no longer taking it . CONCLUSIONS As we found in our RCT of modafinil , armodafinil appears effective and well tolerated in treating  fatigue in HIV+ patients . Side effects were minimal and most patients reported substantially improved energy and mood 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 r and omised , 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 BACKGROUND Extracellular adenosine 5'-triphosphate ( ATP ) is involved in the regulation of a variety of biologic processes , including neurotransmission , muscle contraction , and liver glucose metabolism , via purinergic receptors . In nonr and omized studies involving patients with different tumor types including non-small-cell lung cancer ( NSCLC ) , ATP infusion appeared to inhibit loss of weight and deterioration of quality of life ( QOL ) and performance status . We conducted a r and omized clinical trial to evaluate the effects of ATP in patients with advanced NSCLC ( stage IIIB or IV ) . METHODS Fifty-eight patients were r and omly assigned to receive either 10 intravenous 30-hour ATP infusions , with the infusions given at 2- to 4-week intervals , or no ATP . Outcome parameters were assessed every 4 weeks until 28 weeks . Between-group differences were tested for statistical significance by use of repeated- measures analysis , and reported P values are two-sided . RESULTS Twenty-eight patients were allocated to receive ATP treatment and 30 received no ATP .  Mean weight changes per 4-week period were -1.0 kg ( 95 % confidence interval [ CI ] = -1.5 to -0.5 ) in the control group and 0.2 kg ( 95 % CI = -0.2 to + 0.6 ) in the ATP group ( P = .002 ) . Serum albumin concentration declined by -1.2 g/L ( 95 % CI= -2.0 to -0.4 ) per 4 weeks in the control group but remained stable ( 0.0 g/L ; 95 % CI = -0.3 to + 0.3 ) in the ATP group ( P = .006 ) . Elbow flexor muscle strength declined by -5.5 % ( 95 % CI = -9.6 % to -1 . 4 % ) per 4 weeks in the control group but remained stable ( 0.0 % ; 95 % CI= -1.4 % to + 1.4 % ) in the ATP group ( P = .01 ) . A similar pattern was observed for knee extensor muscles ( P = .02 ) . The effects of  ATP  on body weight , muscle strength , and albumin concentration were especially marked in cachectic patients ( P = .0002 , P = .0001 , and P = . 0001 , respectively , for ATP versus no ATP ) . QOL score changes per 4-week period in the ATP group showed overall less deterioration than in the control group-physical scores ( -0.2 % versus -2.4 % ; P = . 0002 ) ; functional scores ( + 0.4 % versus -5.5 % ; P = .02 ) ; psychologic scores ( -0.7 % versus -2.4 % ; P = .11 ) ; overall QOL score ( + 0.1 % versus -3.5 % ; P = .0001 ) . CONCLUSIONS This r and omized trial demonstrates that ATP has beneficial effects on weight , muscle strength , and QOL in patients with advanced NSCLC Limited research is available regarding the efficacy of psychostimulants in treating cognitive function in primary brain tumor patients . An open-label , r and omized , pilot trial examined both the general and differential efficacy of 4 weeks of methylpheni date ( MPH ) and modafinil ( MOD ) in 24 brain tumor patients . Participants completed cognitive tests and self-report measures of fatigue , sleep disturbance , mood and quality of life at baseline and after 4 weeks . Following stimulant treatment , there was evidence of a beneficial effect on test performance in speed of processing and executive function requiring divided attention . Patients with the greatest deficit in executive function at baseline appeared to derive the greatest benefit following stimulant therapy . Inconsistent , differential effects were found on a measure of attention in favor of MPH and on a measure of processing speed in favor of MOD . There was also evidence of a general beneficial effect on patient-reported measures of fatigue , mood , and quality of life , with no statistically significant differences between treatment arms in these measures over time . The results from this small pilot study should be interpreted with caution , but appear to warrant additional research , in larger study sample s , targeting fatigue , processing speed and executive function , and exploring different doses of stimulants . Future studies may also wish to explore the specific patient factors that may be associated with responsiveness to psychostimulant treatment Introduction Amisulpride is a substituted benzamide that , at low doses , selectively blocks D2 and D3 presynaptic dopamine receptors , enhancing dopaminergic transmission in frontal cortex and limbic areas . Many clinical studies versus placebo , tricyclic antidepressants and selective serotonin reuptake inhibitors showed amisulpride antidepressant effect , supporting its safety and rapid onset of action . In oncological population , depression is quite frequent and difficult to treat because of the particular sensitivity of cancer patients to the antidepressants ’ side effects . Goals of workThe aims of this study were to evaluate efficacy , safety and tolerability of low doses of amisulpride ( 50 mg ) in oncological , depressed patients during chemotheraphy . Material s and methods One hundred six consecutive cancer out patients with depressive symptoms were treated in a prospect i ve , intention to treat , 4-week study , and were evaluated in single-blind with Montgomery Asberg rating scale for depression ( MADRS ) , clinical global impression ( CGI ) and dosage record treatment emergent symptom scale ( DOTES ) to assess side effects of treatment . Main results After 4 weeks of treatment , scores of MADRS and CGI significantly improved ( p < 0.002 ; p < 0.001 , respectively ) , with a reduction of depressive symptoms concerning both emotional ( such as apparent sadness , reported sadness , inner tension , etc . ) and physical cluster ( such as lack of appetite , reduction in weight , tiredness and insomnia ) with good tolerability ( only two patients dropped out ) . Conclusions This study is the first trial on the use of amisulpride in a cohort of oncological , depressed patients during chemotherapy . Amisulpride demonstrated high efficacy and safety . Controlled studies are needed to confirm these preliminary data BACKGROUND 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 . OBJECTIVE To compare the efficacy of 2 psychostimulant medications , methylpheni date hydrochloride ( Ritalin ) and pemoline ( Cylert ) , with a placebo intervention for the treatment of fatigue in patients with HIV disease . METHODS In this double-blind trial , 144 ambulatory patients with HIV disease and persistent and severe fatigue were r and omized to treatment with methylpheni date , pemoline , or placebo . Medications were titrated up to a maximum dose of 60 mg of methlypheni date 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 . RESULTS One hundred nine subjects completed the 6-week trial ; 15 patients ( 41 % ) receiving methylpheni date and 12 patients ( 36 % ) receiving pemoline demonstrated clinical ly significant improvement compared with 6 patients ( 15 % ) receiving placebo . Patients receiving methylpheni date 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 methlypheni date 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 . CONCLUSIONS Many patients with HIV- and acquired immunodeficiency syndrome-unrelated fatigue respond favorably to treatment with methylpheni date 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 Objective : To assess whether modafinil , a wakefulness-promoting agent , is useful for fatigue in patients with multiple sclerosis ( MS ) . Methods : 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 r and omized , 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 . Results : 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 . Conclusions : There was no improvement of fatigue in patients with multiple sclerosis treated with modafinil vs placebo according to the Modified Fatigue Impact Scale Cancer and its treatment can induce subjective and objective evidence of diminished functional capacity encompassing physical fatigue and cognitive impairment . Dexmethylpheni date ( D-MPH ; the D-isomer of methylpheni date ) was evaluated for treatment of chemotherapy-related fatigue and cognitive impairment . A r and omized , 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 r and omized 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 clinical ly 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 Testosterone increases fat-free mass ( FFM ) in men infected with human immunodeficiency virus ( HIV ) , but its effects on muscle performance , physical function , mood , and quality of life are poorly understood . Sixty-one HIV-infected men with weight loss were r and omized to receive weekly intramuscular injections of 300 mg of testosterone enanthate or placebo for 16 wk . The primary outcome of interest was physical function ( walking speed , stair-climbing power , and load-carrying ability ) . Secondary outcome measures included body weight and composition , muscle performance , sexual function , mood , and quality of life . Serum nadir free and total testosterone levels increased ( + 188.0 + /- 29.6 and + 720 + /- 86 ng/dl ) in the testosterone , but not placebo , group . Testosterone administration was associated with increased FFM ( 2.8 + /- 0.5 kg ) , which was significantly greater than in the placebo group ( P < 0.0001 ) . Leg press strength increased significantly in testosterone-treated ( P = 0.027 ) , but not placebo-treated , men ; the difference between groups was not significant . Other measures of muscle performance and physical function did not change significantly in either group . Men receiving testosterone demonstrated significantly greater improvements in mental health and quality -of-life scores than those receiving placebo and improvements in fatigue/energy and mood scores that were not significantly different from those receiving placebo .  Sexual function scores did not change in either group . In HIV-infected men with weight loss , a supraphysiological dose of testosterone significantly increased FFM but did not improve self-reported or performance-based measures of physical function . Improvements in mood , fatigue , and quality -of-life measures in the testosterone group , although clinical ly important , need further confirmation Fatigue and cognitive impairment are common in HIV+ adults and may occur independently or be causally linked . This study examined whether alleviation of fatigue with armodafinil in a placebo-controlled double-blind 4-week trial had an effect on cognitive function  among those with and without mild neuropsychological impairment at baseline . Sixty-one patients completed a st and ard battery of neuropsychological tests at study entry and Week 4 : A total of 33 were r and omized to armodafinil and 28 to placebo . While there was a significant effect of active medication on fatigue , cognitive performance measured by a global change score did not differ between treatment groups , or in those on active treatment with or without mild neuropsychological impairment Summary Background . 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 . Methods . We report on a double-blind clinical trial of 94 female breast cancer patients receiving at least four cycles of chemotherapy r and omly 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 question naires 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 ] ) . Results . 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 ) . Conclusions . 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 Objective : To determine whether combination therapy with lofepramine , L-phenylalanine , and intramuscular vitamin B-12 ( the “ Cari Loder regime ” ) reduces disability in patients with multiple sclerosis . Methods : A placebo controlled , double blind , r and omised study carried out in five United Kingdom centres on out patients with clinical ly definite multiple sclerosis , measurable disability on Guy 's neurological disability scale ( GNDS ) , no relapse in the preceding six months , and not on antidepressant drugs . Over 24 weeks all patients received vitamin B-12 , 1 mg intramuscularly weekly , and either lofepramine 70 mg and L-phenylalanine 500 mg twice daily , or matching placebo tablets . Outcome was assessed using the GNDS , the Kurtzke exp and ed disability status scale ; the Beck depression inventory , the Chalder fatigue scale , and the Gulick MS specific symptom scale . Results : 138 patients were entered , and two were lost from each group . There was no statistically significant difference between the groups at entry or at follow up . Analysis of covariance suggested that treated patients had better outcomes on four of the five scales used . Both groups showed a reduction of 2 GNDS points within the first two weeks , and when data from all time points were considered , the treated group had a significant improvement of 0.6 GNDS points from two weeks onwards . Conclusions : Patients with multiple sclerosis improved by 2 GNDS points after starting vitamin B-12 injections . The addition of lofepramine and L-phenylalanine added a further 0.6 points benefit . More research is needed to confirm and explore the significance of this clinical ly small difference 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 can not 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 PURPOSE Maintaining dose-intensity with chemotherapeutic agents is hindered by a number of adverse effects including asthenia/fatigue . Tumor necrosis factor ( TNF ) is one of the cytokines responsible for the fatigue and cachexia associated with malignancies . We used etanercept ( TNF-decoy receptor ) to maintain dose-intensity of weekly docetaxel . PATIENTS AND METHODS Initially , 12 patients with advanced malignancies were r and omly assigned to either docetaxel 43 mg/m2 weekly alone ( cohort A ) or the same docetaxel dose plus etanercept 25 mg subcutaneously twice weekly ( cohort B ) . Subsequently , higher doses of docetaxel in combination with etanercept were evaluated . Pharmacokinetics ( PKs ) , nuclear factor-kappa B ( NF-kappaB ) activation , and intracellular cytokines levels were measured . Patients completed weekly question naires quantifying asthenia/fatigue . RESULTS Twenty-nine of 36 intended docetaxel doses during the first cycle were delivered in cohort A , and 35 of 36 doses were delivered in cohort B ( P = .055 ) . Three cohort B patients received additional cycles in the absence of disease progression or severe toxicity , whereas no patients from cohort A received additional cycles . Escalation to docetaxel 52 mg/m2 weekly with etanercept result ed in neutropenia , not fatigue , as the limiting adverse effect , and the addition of filgrastim permitted the maintenance of dose-intensity in additional patients . Patients r and omly selected to receive etanercept/docetaxel self-reported less fatigue ( P < .001 ) , and docetaxel PKs show no relevant influence of etanercept . NF-kappaB activation and increased expression of TNF-alpha were associated with increments in docetaxel dose . Antitumor activity was noticed exclusively in patients receiving etanercept . CONCLUSION The addition of etanercept is safe and had no impact on docetaxel concentrations . The significant improvement in tolerability and the trend toward preservation of dose-intensity suggests further exploration of TNF blockade as an adjunct to cancer therapies The prevention of post-chemotherapy symptoms such as delayed emesis , anorexia , and fatigue induced by irinotecan has not been studied . We compared the effects of dexamethasone ( Dex ) with those of a placebo on these symptoms in a r and omized study . Seventy patients scheduled to receive irinotecan chemotherapy  were enrolled in the study and r and omly divided into a treatment or a placebo group . In the treatment group , 8 mg of Dex were administered on days 2–4 after the start of chemotherapy . All patients in both groups received Dex and granisetron for prophylaxis against acute emesis on day 1 . We evaluated 68 patients ( 35 receiving Dex , 33 receiving the placebo ) .  Although delayed emesis was completely prevented in most of patients in both groups ( Dex , 82.9 % ; placebo , 78.8 % ) , anorexia and fatigue were more completely prevented in those in the Dex group ( Dex , 62.9 % and 77.1 % , placebo , 39.4 % and 57.6 % , respectively ) . The effect of Dex on improving simultaneous prophylaxis against all three symptoms was almost significant ( Dex , 60.0 % ; placebo , 36.4 % ; P=0.058 ) . The safety profiles of the two groups were not discernibly different . These results suggest that treatment with Dex may be beneficial to reduce post-chemotherapy symptoms induced by irinotecan , specifically anorexia and fatigue , with acceptable toxicities PURPOSE Fatigue is a distressing symptom occurring in more than 60 % of patients with cancer . The CNS stimulants modafinil and methylpheni date are recommended for the treatment of cancer-related fatigue , despite a limited evidence base . We aim ed to evaluate the efficacy and tolerability of modafinil in the management of fatigue in patients with non-small-cell lung cancer ( NSCLC ) . PATIENTS AND METHODS Adults with advanced NSCLC and performance status of 0 to 2 , who were not treated with chemotherapy or radiotherapy within the last 4 weeks , were r and omly assigned to daily modafinil ( 100 mg on days 1 to 14 ; 200 mg on days 15 to 28 ) or matched placebo . The primary outcome was change in Functional Assessment of Chronic Illness Therapy ( FACIT ) -Fatigue score from baseline to 28 days , adjusted for baseline fatigue and performance status . Secondary outcomes included safety and patient-reported measures of depression , daytime sleepiness , and quality of life . RESULTS A total of 208 patients were r and omly assigned , and 160 patients ( modafinil , n = 75 ; placebo , n = 85 ) completed question naires at both baseline and day 28 and were included in the modified intention-to-treat analysis . FACIT-Fatigue scores improved from baseline to day 28 ( mean score change : modafinil , 5.29 ; 95 % CI , 2.57 to 8.02 ; placebo , 5.09 ; 95 % CI , 2.54 to 7.65 ) , but there was no difference between treatments ( 0.20 ; 95 % CI , -3.56 to 3.97 ) . There was also no difference between treatments for the secondary outcomes ; 47 % of the modafinil group and 23 % of the placebo group stated that the intervention was not helpful . CONCLUSION Modafinil had no effect on cancer-related fatigue and should not be prescribed outside a clinical trial setting . Its use was associated with a clinical ly significant placebo effect Thirty-two patients with chronic pain due to advanced cancer were treated with methylpheni date ( 10 mg with breakfast and 5 mg with lunch ) for 3 days , versus placebo , in a r and omized , double-blind , cross-over study design ed to evaluate the capacity of methylpheni date to potentiate the analgesic effect of narcotics and /or to decrease sedation induced by narcotics . In 28 evaluable patients , the intensity of pain ( visual analogue 0 - 100 ) and intake of extra doses of analgesics ( number of doses/day ) were 43 + /- 27 and 2.2 + /- 2.4 during methylpheni date , versus 55 + /- 24 ( P less than 0.02 ) and 2.9 + /- 2.9 ( P less than 0.002 ) during placebo , respectively . Activity and drowsiness ( visual analogue 0 - 100 ) were 57 + /- 25 and 58 + /- 24 after methylpheni date , respectively , versus 41 + /- 26 ( P less than 0.05 ) and 45 + /- 27 ( P less than 0.02 ) after placebo . Upon completion of the study , the investigator and the patient chose methylpheni date blindly as a more useful drug in 23 cases ( 83 % ) and 20 cases ( 70 % ) , respectively ( P less than 0.02 ) . No cases of severe toxicity were observed . We conclude that methylpheni date can increase the analgesic effect and decrease sedation of narcotics in this population Abstract Objectives : The purpose of this study was to compare the relative efficacy of acetylsalicylic acid ( ASA ) and amantadine for the treatment of  fatigue in multiple sclerosis ( MS ) . Methods : A 10-week , r and omized double-blind crossover clinical trial conducted from October 2009 to September 2010 . Fifty-two patients with MS presenting fatigue at 21 to 53 years of age were r and omly allocated to the two treatment groups . The first group received amantadine ( 100 mg twice daily ) for a total of 4 weeks . The second group received ASA ( 500 mg once daily ) for four weeks . After a 2-week washout period , they crossed over to the alternative treatment for 4 weeks . Patients were rated at baseline and the end of each phase with the Fatigue Severity Scale ( FSS ) . Results : ASA appeared to be equivalent in efficacy and safety to amantadine . A significant decrease in FSS occurred in both groups . Of the 26 patients treated with amantadine , the mean ( SD ) of FSS decreased from 4·8 ( 1·4 ) to 4·0 ( 1·4 ) ( P<0·001 ) . In the 26 patients treated with ASA , the mean ( SD ) of FSS decreased from 4·6 ( 1·4 ) to 3·5 ( 1·5 ) ( P<0·001 ) . Discussion : This study demonstrates that both ASA and amantadine significantly reduce MS-related fatigue .  Both ASA and amantadine have previously been shown to reduce fatigue , and we postulate that treatment with ASA and amantadine may have similar benefits CONTEXT Fatigue is highly prevalent in population s with advanced illness and is often associated with depressed mood . The role of psychostimulant therapy in the treatment of these conditions remains ill defined . OBJECTIVES To evaluate the response of fatigue and depression in patients with advanced illness to titrated doses of methylpheni date ( MP ) as compared with placebo . METHODS In a r and omized , double-blind , placebo-controlled trial , 30 hospice patients , both in patients and out patients , who had fatigue scores of at least four on a scale of zero to 10 ( 0=no fatigue and 10=worst fatigue ) , were r and omly assigned to receive either 5 mg of MP at 8 am and 1 pm or placebo . Doses of MP were titrated every three days according to response and adverse effects . Home care patients were monitored daily by telephone and visited by a research nurse on Study Days 0 ( baseline ) , 3 , 7 , and 14 . Fatigue was assessed using the Piper Fatigue Scale as the primary outcome measure and vali date d by the Visual Analogue Scale for Fatigue and the Edmonton Symptom Assessment Scale ( ESAS ) fatigue score .  Subjects in inpatient facilities were interviewed or assessed by staff on an identical schedule . Depressive symptoms were assessed by the Beck Depression Inventory-II , Center for Epidemiologic Studies Depression Scale , and the ESAS depression score . Primary statistical analysis was conducted using repeated- measures multivariate analysis of the variance . RESULTS Both MP- and placebo-treated groups had similar measures of fatigue at baseline . Patients taking MP were found to have significantly lower fatigue scores ( Piper Fatigue Scale , Visual Analogue Scale for Fatigue , and ESAS ) at Day 14 compared with baseline . The improvement in fatigue with MP treatment was dose-dependent ; the mean average effective dose was 10 mg on Day 3 and 20 mg on Day 14 ( dose range of 10 - 40 mg ) . Placebo-treated individuals showed no significant improvement in fatigue . For patients with clinical ly significant depression on Day 0 , treatment with MP was associated with a significant reduction in all test indices for depressed mood . For the placebo group , the changes in measures of depression were less than observed in the treatment group but were inconsistent between assessment tools . No significant toxicities were observed . CONCLUSION MP reduced symptoms of fatigue and depression when compared with placebo . The effect of MP on fatigue was dose-dependent and sustained over the duration of the study Objective : There has long been a belief that depression contributes to fatigue in multiple sclerosis ( MS ) although supporting data are minimal at best . Clinical guidelines for the treatment of fatigue include recommendations for the treatment of depression in the absence of clear empirical support . The goal of this study was to examine the effects of treatment for depression on fatigue in MS . Methods : Sixty patients with a relapsing form of MS and moderate to severe depression were r and omly assigned to one of three vali date d 16‐week treatments for depression : individual cognitive behavioral therapy , group psychotherapy , or sertraline . Assessment s at baseline and treatment cessation included the primary outcome measure , fatigue assessment instrument ( FAI ) , and Beck depression inventory ( BDI ) . Results : The total FAI and the global fatigue severity subscale were significantly reduced over the course of treatment ( p values < .02 ) . Other subscales did not change significantly . Secondary analyses showed change in global fatigue severity was associated with change in BDI ( p = .03 ) but change in total FAI was only marginally related to change in BDI ( p = .05 ) . These relationships were due entirely to change in mood ( p values < .02 ) and not to change in cognitive or vegetative symptoms ( p values > .17 ) . Conclusions : These findings suggest that treatment for depression is associated with reductions in the severity of fatigue symptoms , and that this relationship is due primarily to treatment related changes in mood Background : This study was design ed to evaluate the role of epidural methadone-lidocaine in cancer pain combined or not to epidural dexamethasone . Methods : In all , 72 cancer patients , 32- to 67-year-old were r and omized to six groups ( n=12 ) and prospect ively studied to examine analgesia and adverse effects for 3 weeks . Patients received single-dose protocol epidural test drugs : Control group ( CG ) received epidural 40-mg lidocaine diluted to 10-ml volume with saline . Dexamethasone group ( DG ) 40-mg lidocaine plus 10-mg dexamethasone . The 2.5MetG 2.5-mg epidural methadone with 40-mg lidocaine ; the 5MetG , 5-mg epidural methadone plus 40-mg lidocaine , the 7.5MetG , 7.5-mg epidural methadone plus 40-mg lidocaine and finally the 7.5Met-DexG , 7.5-mg methadone with 40-mg lidocaine and 10-mg dexamethasone . Results : Groups CG , DG and 2.5MetG were similar regarding analgesia and side effects . Patients from 5MetG and 7.5MetG took 3±1 and 5±1 days , respectively , to restart oral morphine . Patients from 7.5MetDG took 14±2 to restart oral morphine  ( P<0.001 ) . Daily somnolence and appetite improved in the 7.5MetDG during 2-week evaluation ( P<0.005 ) . Fatigue improved for both DG and 7.5MetDG during 2-week evaluation ( P<0.005 ) . By the third week of evaluation , all patients were similar . Conclusions : Epidural methadone plus lidocaine result ed in dose-dependent analgesia , further improved by epidural dexamethasone , which also improved fatigue PURPOSE To evaluate the effect of megestrol acetate at a lower dose than previously investigated on the symptoms of cachexia in patients with advanced cancer . METHODS A total of 84 patients with advanced , solid tumours not responsive to hormone therapy were enrolled in this double-blind , crossover study . During phase 1 , patients were r and omly assigned to receive megestrol acetate ( 160 mg 3 times daily ) for 10 days or placebo . During phase 2 , after a 2-day washout period , patients received the alternate treatment for 10 days . Patients underwent daily assessment s of activity , nausea , appetite and well-being by means of a visual analogue scale ( VAS ) . In addition , nutritional status ( weight , tricep skinfold measure , arm muscle circumference ) , energy intake , fatigue ( Piper Fatigue Scale ) and quality of life ( Functional Living Index-Cancer [ FLIC ] ) were assessed . RESULTS Among the 53 evaluable patients  megestrol acetate result ed in a significant improvement in appetite ( p = 0.005 ) , activity ( p = 0.007 ) and well-being ( p = 0.03 ) . There was no significant change in the intensity of nausea , nutritional parameters , energy intake or FLIC scores . There was a significant improvement in 2 of the 3 factors measured by the Piper Fatigue Scale and in the overall fatigue score . Upon completion of the study , while still blind to the treatment condition , 30 patients indicated that they felt better overall after megestrol , 15 said they felt better after placebo , and 10 indicated no preference ( p = 0.001 ) . CONCLUSION Treatment with megestrol acetate results in rapid and significant improvement of symptoms in terminally ill patients at lower doses than previously reported . The effects are not secondary to nutritional changes . The FLIC quality -of-life question naire was unable to detect these changes The purpose of this study was to vali date the changes in acute pain measurement scales that are most strongly associated with a patient-determined indicator of clinical importance . Measures of pain intensity and pain relief are commonly used outcomes in therapeutic clinical trials . Recent studies of the properties of acute pain measures have provided data defining the cut-off points that are best associated with clinical ly important differences . Validation of these findings in another clinical trial data set is important . Data were obtained from the titration phase of a recently conducted r and omized controlled clinical trial of oral transmucosal fentanyl citrate ( OTFC ) , which compared OTFC to immediate release morphine sulfate ( MSIR ) for the treatment of cancer-related acute breakthrough pain .  Changes in pain intensity and pain relief were recorded every 15 minutes for 60 minutes and global medication performance recorded at the end of each study pain episode . At any titration step , if the patient felt that the first dose of the study medication did not provide adequate relief within 30 minutes , an additional rescue medication could be taken . To find the level of each pain scale best associated with this measure of the adequacy of pain relief , the calculated sensitivity , specificity , and accuracy for different cut-off points of the measured pain scales were compared to whether or not the patient needed rescue medication . The overall ability of the pain measures to discriminate episodes for which a rescue was not needed was calculated using area under the receiver operating characteristics ( ROC ) curves . Data were analyzed from 134 OTFC-naive patients who collected data on 1307 episodes of breakthrough pain . Using the criteria of a balanced sensitivity and specificity , the best cut-off points were determined to be : 33 % for the percent pain intensity difference ; > or = 2 for the raw pain intensity difference on a 0 - 10 numeric rating scale ; > or = 2 ( i.e. , moderate or better ) for pain relief ; > or = 33 % for the percent maximum total pain relief ; and > or = 2 ( good or better ) for global medication performance . ROC area under the curve ranged from 0.839 to 0.862 for each of the pain measures listed above , calculated at 60 minutes . These data indicate that the pain scale cut-off points that are best associated with a patient-derived measure of a clinical ly important difference closely approximate those found in an earlier study . ROC analysis provided evidence that the overall pain measures were strongly associated with not requiring an " additional dose of rescue medication . " Thus , the cut-off points determined for these pain scales provide a good surrogate measure of a patient-determined clinical ly important response . This provides support for the usefulness of these values in future clinical trials of pain therapy BACKGROUND The goal was to evaluate the efficacy of testosterone in alleviation of hypogonadal symptoms ( diminished libido , depressed mood , low energy , and depleted muscle mass ) in men with symptomatic human immunodeficiency virus illness . METHODS Seventy-four patients were enrolled in a double-blind , placebo-controlled 6-week trial with bi-weekly testosterone injections , followed by 12 weeks of open-label maintenance treatment . Major outcome measures were Clinical Global Impressions Scale ratings for libido , mood , energy , and erectile function ; Hamilton Depression Rating Scale scores , and Chalder Fatigue Scale scores . Body composition changes were assessed with bioelectric impedance analysis . RESULTS Seventy men completed the 6-week trial . Response rates , defined as much or very much improved libido , were 74 % ( 28/38 ) for patients r and omized to testosterone , and 19 % ( 6/32 ) for placebo-treated patients ( P<.001 ) . Of the 62 completers with fatigue at baseline , 59 % ( 20/34 ) receiving testosterone and 25 % ( 7/28 ) receiving placebo reported improved energy ( P<.01 ) . Among the 26 completers with an Axis I depressive disorder at baseline , 58 % of the testosterone-treated patients reported improved mood compared with 14 % of placebo-treated patients ( Fisher exact test = .08 ) . With testosterone treatment , average increase in muscle mass over 12 weeks was 1.6 kg for the whole group , and 2.2 kg for the 14 men with wasting at baseline . Improvement on all parameters was maintained during subsequent open-label treatment for up to 18 weeks . CONCLUSION Testosterone is well tolerated and effective in the short-term treatment of symptoms of clinical hypogonadism in men with symptomatic human immunodeficiency virus illness , restoring libido and energy , alleviating depressed mood , and increasing muscle mass 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 Cancer-related fatigue is the most prevalent and distressing symptom experienced by patients with advanced cancer . Central nervous system stimulants have been shown to relieve fatigue in nonmalignant disease . Modafinil is a stimulant with a selective site of action in the brain that is better tolerated than traditional stimulants , such as methylpheni date . The aim of this study was to determine the feasibility of conducting a r and omised controlled trial to assess the efficacy and safety of modafinil for the treatment of fatigue in patients with lung cancer . Twenty patients with non-small cell lung cancer were recruited to this open-label study . Modafinil was taken in a fixed dose-titration schedule of 100 mg daily for 7 days followed by 200 mg daily for 7 days . Fifteen patients completed the study . During the study period , there was a rapid and statistically significant reduction in the primary outcome , fatigue ( P = 0.001 ) and the secondary outcomes of daytime sleepiness and depression/anxiety . This improvement in fatigue was also clinical ly significant . Ten patients chose to continue modafinil after the study and the drug was well-tolerated . It would be both feasible and worthwhile to conduct a definitive r and omised controlled trial to determine the role of modafinil in the treatment of cancer-related fatigue Abrupt onset of hot flashes poses a significant problem for women treated with chemotherapy for breast cancer . Alternatives to hormone replacement , such as the use of the selective serotonin re-uptake inhibitor ( SSRI ) paroxetine hydrochloride , are being explored as therapies for hot flashes in this patient population . The present study investigated the efficacy of paroxetine for the treatment of hot flashes and associated symptoms in women with breast cancer . This study included 13 patients who were seen in the Psychosocial Clinic at Moffitt Cancer Center . They were referred by their medical oncologist after reporting complaints of significant difficulty with hot flashes . Baseline question naires were completed and a structured diagnostic interview for clinical depression was conducted , all of which were repeated 5 weeks after the paroxetine 20 mg daily was started . Significant improvements were seen in the ratings of hot flash severity ( P = 0.002 ) . In addition , significant improvements were observed in general , emotional , and mental fatigue . Rates of clinical ly significant depressive symptomatology also decreased and sleep quality improved significantly as well . Finally , the incidence of clinical depression improved from 39 % at baseline to 8 % after treatment . These preliminary data suggest that the antidepressant paroxetine can be helpful in the treatment of hot flashes and associated fatigue , sleep disturbance , and depression in women with breast cancer treated with chemotherapy . Further controlled studies are needed to more fully evaluate the efficacy of the SSRIs for hot flashes in women with breast cancer Background To investigate the effects of Modafinil on focused attention , motor function and motor excitability in patients with multiple sclerosis ( MS ) and fatigue . Methods 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 . Results 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 duration s remained unchanged . Conclusions 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 Background Women who receive adjuvant chemotherapy for breast cancer develop fatigue , and a subset reports cognitive impairment . Methylpheni date is reported to improve fatigue and to decrease cognitive impairment in other population s. Material s and methods Women were r and omised early during their chemotherapy  to receive d-methylpheni date ( d-MPH ) , a form of methylpheni date , 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 ∼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 ) question naires , evaluating quality of life and fatigue . Results A total of 57 evaluable women were r and omised : 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 methylpheni date 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 r and omised 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 assessment s. There were also no differences in HLTV-R scores or quality of life . Conclusions 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 An open label trial of modafinil was conducted to determine whether it would be tolerated and effective in treating fatigue for people with amyotrophic lateral sclerosis ( ALS ) . Fifteen patients with ALS were treated for two weeks with either 200 mg or 400 mg of modafinil . Reported side effects of the medication were mild and included diarrhea , headache , nervousness , and insomnia . Side effects did not result in any study dropouts . Following treatment , mean scores on the Fatigue Severity Scale ( FSS ) decreased from 51.3 ( SD 9.2 ) to 42.8 ( SD 10.2 ) . On the Epworth Sleepiness Scale ( ESS ) , mean scores decreased from 8.2 ( SD 2.0 ) to 4.5 ( SD 2.4 ) . Reductions in both the FSS and the ESS were significant at p < 0.001 . Mean scores on the self-report version of the Functional Independence Measure ( FIM-SR ) increased from 115.2 ( SD 5.6 ) to 118.1 ( SD 5.4 ) , with p < 0.01 . This pilot study suggests that modafinil is well-tolerated and may reduce symptoms of fatigue in ALS . Further blinded , controlled studies of modafinil in larger numbers of ALS patients are warranted This preliminary study investigated whether bupropion sustained release ( SR ) improved symptomatic fatigue , depression and quality of life in cancer patients and caregiver quality of life .  The sample consisted of a prospect i ve open case series of 21 cancer patients , with fatigue and with or without depression at moderate to severe levels , referred for psychiatric assessment from a tertiary care cancer centre . Both patient symptom ratings and caregiver ratings were measured before and after 4 weeks of treatment with the maximally tolerated dose of bupropion in the range of 100 - 300 mg per day . At trial completion , significant improvement was found for symptoms of fatigue and depression . Subjects were divided into two groups : depressed and non-depressed ( based on a cut-off score of 17 on the Hamilton Depression Rating Scale ) . Both groups reported improvement for fatigue and depressive symptoms . Depressed subjects and their caregivers did not experience any change in quality of life , while the non-depressed subjects and their caregivers reported improvements . Results from this small group of patients suggest that bupropion may have potential as an effective pharmaceutical agent for treating cancer-related  fatigue .  A r and omized , placebo-controlled trial with this medication is indicated 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 Objective To determine the relative efficacy of amantadine , pemoline , and placebo in treatment of multiple sclerosis (MS)-related fatigue .  Background Fatigue is a complication of MS . Both pemoline and amantadine have been used to treat MS fatigue , but their relative efficacy is not known . Methods Amantadine , pemoline , and placebo were compared in a r and omized , double-blind , placebo-controlled study using a parallel-group design . Ninety-three ambulatory MS patients completed the study . Primary outcome measures were the fatigue seventy scale ( FSS ) ; the MS-specific fatigue scale ( MS-FS ) ; and subjective response determined by verbal self-report . Secondary outcome measures consisted of assessment s 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 . Results 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 . Conclusion 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 PURPOSE Fatigue and depression typically occur together in cancer patients , suggesting a common etiology , perhaps based on serotonin . This r and omized clinical trial tested whether paroxetine , a selective serotonin reuptake inhibitor antidepressant known to modulate brain serotonin , would reduce fatigue in cancer patients and whether any reduction was related to depression . PATIENTS AND METHODS Cancer patients undergoing chemotherapy for the first time were assessed for fatigue .  Of 704 patients who reported fatigue at their second chemotherapy cycle , 549 patients were r and omly assigned to receive either 20 mg of oral paroxetine hydrochloride daily or placebo for 8 weeks . The assessment s of fatigue and depression were performed at cycles 3 and 4 of chemotherapy . RESULTS A total of 244 patients treated with paroxetine and 235 patients treated with placebo  provided assessable data . No difference was detected in fatigue between patient groups . At the end of the study , there was a difference between groups in the mean level of depression ( Center for Epidemiologic Studies Depression scores , 12.0 v 14.8 , respectively ; P < .01 ) . CONCLUSION Paroxetine had no influence on fatigue in patients receiving chemotherapy .  A possible explanation is that cancer-related fatigue does not involve a reduction in brain 5-HT levels The objective of this r and omised , multicentre , double-blind clinical trial was to investigate the impact of PS76A2 , an aqueous mistletoe extract st and ardised to mistletoe lectins , on quality of life ( QoL ) in breast cancer patients . A total of 352 patients were r and omly allocated to 2 groups receiving PS76A2 ( 15 ng mistletoe lectin/0.5 ml ) or matching placebo twice weekly for 4 to 6 cycles of CMF ( cyclophosphamide , methotrexate , fluorouracil ) chemotherapy followed by 2 months follow-up . The primary efficacy end-point was the change from baseline of 3 FACT-G subscales ( physical , emotional and functional well-being ) during the fourth CMF cycle . Secondary measures included GLQ-8 ( 8 linear analogue self- assessment scales ) , Spitzer 's uniscale and haematological variables . The main variables of safety analysis were adverse events , including injection site reactions and clinical laboratory tests . The results showed that physical , emotional and functional well-being improved upon PS76A2 , but deteriorated following placebo . The treatment differences were statistically significant for the 3 subscales as well as for the summary score FACT-G , which was analysed as O'Brien 's rank sum of its 3 subscales : The total score increased by 4.40 + /- 11.28 , indicating a higher QoL after PS76A2 , but decreased by 5.11 + /- 11.77 with placebo ( p<0.0001 ) . The GLQ-8 sum of 8 LASA scales was analysed as a summary score of GLQ-5 ( sum of item nos. 1 , 5 , 6 , 7 , 8) and GLQ-3 ( sum of item nos. 2 , 3 , 4 ) . GLQ-5 characterises typical aspects of QoL , while GLQ-3 consists of 3 side-effects of CMF ( feeling sick , numbness or pins and needles , loss of hair ) . GLQ-5 decreased by 42.9 + /- 125.0 upon PS76A2 , indicating an improvement in QoL , but increased by 60.3 + /- 94.0 upon placebo ( p<0.0001 ) . GLQ-3 deteriorated in both groups ( PS76A2 : 13.9 + /- 52.4 ; placebo : 34.5 + /- 57.0 ) , but the differences in favour of PS76A2 were , nevertheless , statistically significant ( p=0.0007 ) . The total score GLQ-8 improved by 28.9 + /- 154.6 after PS76A2 and deteriorated by 94.8 + /- 141.1 after placebo ( p<0.0001 ) . Spitzer 's uniscale improved by 12.2 + /- 30.7 upon PS76A2 and deteriorated by 10.8 + /- 26.1 with placebo ( p<0.0001 ) . After follow-up without chemotherapy , a significant treatment difference in favour of PS76A2 was determined by means of FACT-G , GLQ-8 and Spitzer 's uniscale . PS76A2 was well tolerated in this trial , with the exception of slight local reactions in 17.6 % of the PS76A2 group . In conclusion , PS76A2 ( 15 ng mistletoe lectin/0.5 ml twice weekly ) was shown to be safe and effective in improving QoL in breast cancer patients during chemotherapy and follow-up Background : Fatigue is a major nonmotor symptom in Parkinson disease ( PD ) . It is associated with reduced activity and lower quality of life . Objective : To determine if modafinil improves subjective fatigue and physical fatigability in PD . Methods : Nineteen PD patients who reported significant fatigue in the Multidimensional Fatigue Inventory ( MFI ) participated in this 8-week study . Subjects took their regular medications and were r and omly assigned to the treatment group ( 9 subjects , modafinil 100-mg capsule BID ) or placebo group ( 10 subjects ) . We used the MFI to measure subjective fatigue and used finger tapping and intermittent force generation to evaluate physical fatigability . Subjects also completed the Epworth Sleepiness Scale ( ESS ) and the Center of Epidemiological Study -Depression Scale . Results : There were no significant differences at baseline and at 1 month in finger tapping and ESS between the modafinil and placebo groups . At 2 months , the modafinil group had a higher tapping frequency ( P < 0.05 ) , shorter dwell time ( P < 0.05 ) , and less fatigability in finger tapping and tended to have lower ESS scores ( P < 0.12 ) than the placebo group . However , there was no difference between groups over time for any dimension of the MFI . Conclusions : This small study demonstrated that although modafinil may be effective in reducing physical fatigability in PD , it did not improve fatigue symptoms We have previously shown that the risk of major depression in patients with malignant melanoma undergoing interferon-α ( IFN-α ) therapy  can be reduced by pretreatment with the antidepressant , paroxetine . Using dimensional analyses , the present study assessed the expression and treatment responsiveness of specific clusters of neuropsychiatric symptoms over the first three months of IFN-α therapy .  Forty patients with malignant melanoma eligible for IFN-α treatment  were r and omly assigned to receive either paroxetine or placebo in a double-blind design . Neuropsychiatric assessment s were conducted at regular intervals during the first twelve weeks of IFN-α therapy and included the 21-item Hamilton Depression Rating Scale , the 14-item Hamilton Anxiety Rating Scale and the Neurotoxicity Rating Scale . Neurovegetative and somatic symptoms including anorexia , fatigue and pain appeared within two weeks of IFN-α therapy in a large proportion of patients . In contrast , symptoms of depressed mood , anxiety and cognitive dysfunction appeared later during IFN-α treatment and more specifically in patients who met DSM-IV criteria for major depression . Symptoms of depression , anxiety , cognitive dysfunction and pain were more responsive , whereas symptoms of fatigue and anorexia were less responsive , to paroxetine treatment . These data demonstrate distinct phenomenology and treatment responsiveness of symptom dimensions induced by IFN-α , and suggest that different mechanisms mediate the various behavioral manifestations of cytokine-induced “ sickness behavior . We investigated the effect of amantadine on cognitive processing in patients with multiple sclerosis ( MS ) and fatigue with objective electrophysiological measures . Behavioral methods ( Reaction Time , RT ) and two different Event Related Potential ( ERP ) components measuring i ) stimulus selection ( Selection Negativity , SN ) and ii ) response selection ( Lateralized Readiness Potential , LRP ) were employed . Twenty-four patients with clinical definite MS ( 10 relapsing remitting and 14 secondary progressive ) and confirmed fatigue in the past three months ( Fatigue Severity Scale ( FSS ) > 4 ) were included . Patients were r and omized in a double-blind , placebo-controlled cross-over design . We found a difference between the two treatments for ERP measures to stimuli with relevant colour starting at about 200 ms . This negativity had a higher amplitude during amantadine treatment regardless of treatment order . The RT did not differ significantly between the treated and untreated groups . Additional analysis indicated that patients with a disease duration of less than 7 years had a significant test position ( practice effect ) , but no treatment effect , while patients with a longer MS duration showed no practice effect , but rather an improved reaction speed and increased ERP amplitude effects when treated with amantadine . The present findings suggest that amantadine exerts beneficial effects on early cognitive processes in patients with MS , but appears to be limited to subjects with a longer duration of the disease Sixty relapsing-remitting multiple sclerosis ( MS ) patients were selected on the basis of their score on the Fatigue Severity Scale ( FSS ) and formed two groups : 40 patients ( fatigued MS ; MSf ) scored above the 75th percentile of a previously assessed representative MS sample ( 100 patients ) , and 20 age- and sex-matched patients ( nonfatigued MS patients ; MSnf ) scored below the 25th percentile . The patients underwent clinical evaluation ( Exp and ed Disability Status Scale ( EDSS ) ) , further assessment of fatigue ( Fatigue Impact Scale ) , scales evaluating depression ( Hamilton Depression Rating Scale ( HDRS ) and Beck ’s Depression Inventory ( BDI ) ) and neuropsychological tests . All patients were evaluated for muscle fatigability and central activation by means of a biomechanical test of sustained contraction ; they also underwent somatosensory evoked potentials ( SSEPs ) and transcranial magnetic stimulation ( TMS ) . The patients of the MSf subgroup were then r and omized to one of the following two treatments : 4-aminopyridine ( 4-AP ) 24 mg/day and fluoxetine ( FLX ) 20 mg/day . After a one-week titration this treatment proceeded for 8 weeks . At the end of the treatment , EDSS , fatigue and depression scores were further evaluated . At baseline , fatigue test scores consistently correlated with depression and cognitive test scores , but not with the fatigability test . Fatigue scores decreased in both treatment groups in a similar way . Due to the design of the study , this can not be disjoined from a placebo effect . The changes of fatigue scores could not be predicted in the FLX group , whereas in the 4-AP group higher basal fatigability test scores were associated with greater reduction in fatigue scores The amphetamine , methylpheni date ( Ritaline ) has been proposed as being of interest in the treatment of asthenia in patients with advanced cancer . To evaluate this hypothesis a r and omised controlled double-blind parallel-group national multi-centre trial is proposed versus placebo . Three previous r and omised controlled studies and one open study have suggested that the administration of methylpheni date may be of interest in the palliative care of asthenic cancer patients . However , these studies do not permit a definitive conclusion to be drawn . This article presents the protocol of our new trial . The primary objective is to evaluate the anti-asthenic effect of methylpheni date using a visual analogue scale ( VAS ) after 7 days of treatment of cancer patients in palliative care , i.e. when the cancer is considered to be rapidly evolving or as terminal . One hundred and ten patients are treated for 28 days at a starting dose of 20 mg/day , and adjustment of the dose is possible . It is important to stress that only the concerted efforts of an interdisciplinary team ( somatologues , psychiatrists , psychologists , paramedical carers and social workers ) can tackle the challenges posed by the difficult symptom of asthenia . The medical treatment is only one element of the approach to caring for these patients BACKGROUND Amantadine hydrochloride and pemoline , both frequently used to treat the fatigue of multiple sclerosis ( MS ) , may also improve attention and other cognitive functions in MS . To our knowledge , these agents have never been compared in a placebo-controlled trial of patients with MS . OBJECTIVE To evaluate the effects of amantadine and pemoline on cognitive functioning in MS . METHODS A total of 45 ambulatory patients with MS and severe fatigue were treated for 6 weeks with amantadine , pemoline , or placebo using a parallel group design . They underwent comprehensive neuropsychological testing to determine treatment effects on cognitive functioning . Primary outcome measures were tests of attention ( Digit Span , Trail Making Test , and Symbol Digit Modalities Test ) , verbal memory ( Selective Reminding Test ) , nonverbal memory ( Benton Visual Retention Test ) , and motor speed ( Finger Tapping Test ) . RESULTS Fatigue did not significantly correlate with any of the neuropsychological outcome measures at baseline or after treatment . All three treatment groups improved on tests of attention ( P < .003 ) , verbal memory ( P < .001 ) , and motor speed ( P < .002 ) . There were no significant differences between amantadine , pemoline , and placebo . CONCLUSIONS Cognitive functioning in MS is independent of fatigue . Neither amantadine nor pemoline enhances cognitive performance in MS compared with placebo 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 cl aim ed 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 goal of this pilot study was to evaluate the effect of dehydroepi and rosterone ( DHEA ) on  depressed mood and fatigue in HIV+ men and women , unselected for baseline DHEA level . Secondary questions concerned treatment effects on libido and body cell mass , on serum testosterone levels , and elicitation of short-term side effects . Treatment consisted of an open-label 8-week trial using DHEA doses from 200 to 500 mg/day . Mood responders were maintained for another 4 weeks , then r and omized to a double blind placebo controlled 4-week discontinuation trial . Forty-five patients , including six women , entered the trial . Of 32 week 8 completers , mood was much improved in 72 % , and 81 % were rated responders with respect to fatigue . Response on either parameter was unrelated to baseline serum DHEA level . Twenty-one patients entered the double blind discontinuation phase . No differences in relapse rate between placebo and DHEA groups were observed for either mood or fatigue . Body cell mass increased significantly by week 8 , and this improvement was maintained throughout the double blind phase for patients in both treatment conditions . Libido increased significantly as well . DHEA therapy did not have an effect on CD4 cell count or on serum testosterone levels in men . In conclusion , DHEA may be a promising treatment for HIV+ patients with depressed mood and fatigue  , although persistence of response even in placebo-treated patients during the discontinuation phase leaves unresolved questions . A parallel group double blind clinical trial is indicated as the next step to more clearly identify therapeutic efficacy Background Modafinil is a unique wake-promoting agent that is chemically distinct from traditional stimulants . Results of a placebo-controlled study showed it to improve fatigue in multiple sclerosis ( MS ) at a dose of 200 mg daily , but not at a dose of 400 mg daily . Objective To establish the efficacy , safety and appropriate dose of modafinil in the treatment of fatigue and sleepiness in patients with multiple sclerosis . Method A total of 50 patients diagnosed with MS ( mean age 40.4 ± 10.3 years , 30 females/20 males ; MS type : 36 relapsing remitting , 1 primary progressive , 13 secondary progressive ; mean disability level 3.8 ± 1.5 on the Kurtzke EDSS ) and complaining of chronic fatigue were enrolled in a prospect i ve 3-month , two-center , open-label study . Efficacy was evaluated with the Fatigue Severity Scale ( FSS , score range 0 - 42 ) , the Epworth Sleepiness Scale ( ESS , score range 0 - 24 ) and by subjective patient appraisal of change of fatigue , quality of life and overall satisfaction with treatment . Adverse effects ( AEs ) were recorded throughout the study . Treatment was started with a single daily dose of 100 mg in all patients . In non-responders the dose was increased by 100 mg increments up to a maximum daily dose of 400 mg . Results Three patients discontinued modafinil because of AEs ( nervousness , dizziness ) . Two patients ( 4 % ) were treated with 50 mg , 25 ( 50 % ) with 100 mg , 21 ( 42 % ) with 200 mg and 2 ( 4 % ) with 300 mg daily . No patient required 400 mg daily . Mean FSS scores were 30.3 ± 8.5 at baseline and 25.4 ± 3.7 at 3 months ( p < 0.0001 ) . Mean ESS scores were 9.7 ± 3.9 at baseline and 4.9 ± 2.9 at 3 months ( p < 0.0001 ) . Self- appraisal of change of fatigue showed clear improvement in 41 patients ( 87.2 % ) , some improvement in 4 ( 8.5 % ) and no change in 2 ( 4.3 % ) . Overall clinical condition was clearly improved in 43 patients ( 91.5 % ) , somewhat improved in 1 patient ( 2.1 % ) , and unchanged in 3 patients ( 6.4 % ) . No patient reported worsening of overall clinical condition . Conclusions Treatment with modafinil significantly improves fatigue and sleepiness and is well tolerated by patients with MS . Unlike the higher dose regimen required in narcolepsy , a low-dose regimen of modafinil is effective in MS PURPOSE 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-methylpheni date HCl ( d-MPH ) , a central nervous system ( CNS ) stimulant on QOL and cognitive function in patients undergoing RT . METHODS AND MATERIAL S Sixty-eight patients with primary or metastatic brain tumors were r and omly 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 . RESULTS 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 . CONCLUSIONS Prophylactic use of d-MPH in brain tumor patients undergoing RT did not result in an improvement in QOL BACKGROUND AND PURPOSE Fatigue is a frequent symptom in multiple sclerosis ( MS ) , recognized as the most unpleasant symptom by 50 - 60 % of patients . Amantadine is one of the medications prescribed for fatigue in MS . Some previous studies have demonstrated a positive influences of amantadine on fatigue in MS . The aim of this study was to determine the efficacy of amantadine on Persian MS patients . MATERIAL AND METHODS This prospect i ve study took place in Isfahan , Iran and included 42 MS patients with fatigue who were divided r and omly into two groups . Twenty-one patients received amantadine and all others placebo . The Fatigue Severity Scale ( FSS ) was used to determine the severity of the fatigue . FSS scores at baseline and two months later were compared in the two groups . RESULTS Mean ( SD ) baseline FSS score was 5.27 ( 1.11 ) in the amantadine group and 4.89 ( 1.13 ) in the placebo group ( p > 0.05 ) . Mean FSS at the end of study was 4.00 ( 1.02 ) in the amantadine group and 4.24 ( 1.03 ) in the placebo group ( p > 0.05 ) ; however , the FSS change ( the difference between FSS scores at the end of the study and at the beginning of the study ) in amantadine and placebo groups was -1.27 ( 0.53 ) and -0.66 ( 0.33 ) , respectively , which was significant ( p < 0.05 ) . CONCLUSIONS Our findings demonstrate a significant drop on the fatigue severity scale in MS patients after treatment with amantadine ; nevertheless , more studies on a larger scale with longer duration are needed to confirm this finding PURPOSE L-carnitine , a popular complementary and alternative medicine product , is used by patients with cancer for the treatment of fatigue , the most commonly reported symptom in this patient population . The purpose of this study was to determine the efficacy of L-carnitine supplementation as a treatment for fatigue in patients with cancer . PATIENTS AND METHODS In this double-blind , placebo-controlled trial , patients with invasive malignancies and fatigue were r and omly assigned to either 2 g/d of L-carnitine oral supplementation or matching placebo . The primary end point was the change in average daily fatigue from baseline to week 4 using the Brief Fatigue Inventory ( BFI ) . RESULTS Three hundred seventy-six patients were r and omly assigned to treatment with L-carnitine supplementation or placebo . L-carnitine supplementation result ed in significant carnitine plasma level increase by week 4 . The primary outcome , fatigue , measured using the BFI , improved in both arms compared with baseline ( L-carnitine : -0.96 , 95 % CI , -1.32 to -0.60 ; placebo : -1.11 , 95 % CI -1.44 to -0.78 ) . There were no statistically significant differences between arms ( P = .57 ) . Secondary outcomes , including fatigue measured by the Functional Assessment of Chronic Illness Therapy-Fatigue instrument , depression , and pain , did not show significant difference between arms . A separate analysis of patients who were carnitine-deficient at baseline did not show statistically significant improvement in fatigue or other outcomes after L-carnitine supplementation . CONCLUSION Four weeks of 2 g of L-carnitine supplementation did not improve fatigue in patients with invasive malignancies and good performance status Nutritional factors are among the postulated causes of fatigue , a highly prevalent symptom in the cancer population , with serious impact on patients ' quality of life . Deficiency of the micronutrient carnitine may play a role by reducing energy production through fatty acid oxidation . We present preliminary data of an open-label , dose-finding study to determine safety and maximally tolerated dose ( MTD ) of 1 week of L-carnitine supplementation in cancer patients with fatigue and carnitine deficiency . Patients who met inclusion /exclusion criteria underwent carnitine level determination . Eighty-three percent of these patients ( 15/18 ) had carnitine deficiency . Preliminary data analysis of 13 patients showed that total carnitine increased from 30.0 + /- 6.9 to 41.0 + /- 12.1 ( mean + /- SD ) after 1 week of supplementation ( P = 0.01 ) , and free carnitine increased from 24.3 + /- 6.1 to 33.8 + /- 9.8 ( P = 0.004 ) . Outcome measures were fatigue ( BFI score ) , depression ( CES-D ) , sleep disruption ( ESS ) , and performance status ( Karnofsky ) . Median ( min , max ) BFI score at baseline was 73 ( 46 , 82 ) versus 50 ( 3 , 82 ) after 1-week supplementation ( P = 0.009 ) . CES-D score at baseline was 29 ( 16 , 42 ) and 22 ( 8 , 32 ) after 1 week ( P = 0.028 ) . ESS at baseline was 46.5 ( 0 , 69 ) and 30.4 ( 0 , 72 ) after 1 week ( P = 0.015 ) . Karnofsky score did not change significantly ( P = 0.38 ) . We are currently conducting a r and omized , double-blind , placebo-controlled study to rigorously assess the role of L-carnitine for the treatment of fatigue and depression in cancer patients Increased levels of inflammatory cytokines such as tumor necrosis factor ( TNF ) and interleukin-6 ( IL-6 ) may play a role in depression . Mild depressive-like symptoms can be induced in humans through activation of the innate immune system with endotoxin . Whether preventive treatment with antidepressants can reduce endotoxin-induced symptoms has never been tested . In a double-blind , r and omized , placebo-controlled , cross-over study , we administered intravenous low-dose endotoxin ( 0.8 ng/kg ) or placebo to 11 healthy subjects who had received oral pre-treatment with citalopram ( 10 mg twice a day ) or placebo for 5 days . The Montgomery-Åsberg Depression Rating Scale , the State and Trait Anxiety Inventory , and a visual analog scale were used to measure depressive and anxiety symptoms and social anhedonia . Serum levels of TNF and IL-6 were measured with immunoassays . Compared to placebo , endotoxin administration increased serum levels of TNF and IL-6 , and caused mild depressive-like symptoms , in particular lassitude and social anhedonia . While citalopram pre-treatment had no effect on the innate immune response to endotoxin , it reduced the endotoxin-induced MADRS total score by 50 % , with a moderate effect size ( Cohen 's d=0.5 ) . Most of the MADRS total score was due to the lassitude item , and citalopram pre-treatment specifically reduced endotoxin-induced lassitude with a large effect size ( Cohen 's d=0.9 ) . These results suggest that subchronic pre-treatment with the serotonin-reuptake inhibitor citalopram blunts mood symptoms induced by acute immune system activation with endotoxin without inhibiting the peripheral immune response PURPOSE To determine whether fluoxetine improves overall quality of life ( QOL ) in advanced cancer patients with symptoms of depression revealed by a simple survey . PATIENTS AND METHODS One hundred sixty-three patients with an advanced solid tumor and expected survival between 3 and 24 months were r and omly assigned in a double-blinded fashion to receive either fluoxetine ( 20 mg daily ) or placebo for 12 weeks . Patients were screened for at least minimal depressive symptoms and assessed every 3 to 6 weeks for QOL and depression .  Patients with recent exposure to antidepressants were excluded . RESULTS The groups were comparable at baseline in terms of age , sex , disease distribution , performance status , and level of depressive symptoms . One hundred twenty-nine patients ( 79 % ) completed at least one follow-up assessment . Analysis using generalized estimating equation modeling revealed that patients treated with fluoxetine exhibited a significant improvement in QOL as shown by the Functional Assessment of Cancer Therapy-General , compared with patients given placebo ( P = .01 ) . Specifically , the level of depressive symptoms expressed was lower in patients treated with fluoxetine ( P = .0005 ) , and the subgroup of patients showing higher levels of depressive symptoms on the two- question screening survey were the most likely to benefit from treatment . CONCLUSION In this mix of patients with advanced cancer who had symptoms of depression as determined by a two- question bedside survey , use of fluoxetine was well tolerated , overall QOL was improved , and depressive symptoms were reduced Exercise capacity in patients with end-stage renal disease ( ESRD ) remains impaired despite correction of anemia . Carnitine insufficiency may contribute to impaired exercise and functional capacities in patients with ESRD . Two r and omized placebo-controlled trials were conducted to test whether intravenous L-carnitine improves exercise capacity ( assessed by maximal rate of oxygen consumption [ VO(2max ) ] ) and quality of life ( measured by the Kidney Disease Question naire [ KDQ ] ) in patients with ESRD . In study A , patients were administered L-carnitine , 20 mg/kg ( n = 28 ) , or placebo ( n = 28 ) intravenously at the conclusion of each thrice-weekly dialysis session for 24 weeks . In study B , a dose-ranging study , patients were administered intravenous L-carnitine , 10 mg/kg ( n = 32 ) , 20 mg/kg ( n = 30 ) , or 40 mg/kg ( n = 32 ) , or placebo ( n = 33 ) as in study A. The prospect i ve primary statistical analysis evaluated changes in VO(2max ) in each study and specified that changes in the KDQ were assessed only in the combined population s. L-Carnitine supplementation increased plasma carnitine concentrations , but did not affect VO(2max ) in either study . Because change in VO(2max ) showed significant heterogeneity , a secondary analysis using a mixture of linear models approach on the combined study population s was performed . L-Carnitine therapy ( combined all doses ) was associated with a statistically significant smaller deterioration in VO(2max ) ( -0.88 + /- 0.26 versus -0.05 + /- 0.19 mL/kg/min , placebo versus L-carnitine , respectively ; P = 0.009 ) . L-Carnitine significantly improved the fatigue domain of the KDQ after 12 ( P = 0.01 ) and 24 weeks ( P = 0.03 ) of treatment compared with placebo using the primary analysis but did not significantly affect the total score ( P = 0.10 ) or other domains of the instrument ( P > 0.11 ) . Carnitine was well tolerated , and no drug-related adverse effects were identified . Intravenous L-carnitine treatment increased plasma carnitine concentrations , improved patient-assessed fatigue , and may prevent the decline in peak exercise capacity  in hemodialysis patients .  VO(2max ) in the primary analysis and other assessed end points were unaffected by carnitine therapy Abstract A multivariate analysis of the data was conducted to evaluate the effects of age , gender , and performance status on symptom profile . A comprehensive prospect i ve analysis of symptoms was conducted in 1,000 patients on initial referral to the Palliative Medicine Program of the Clevel and Clinic . The median number of symptoms per patient was 11 ( range 1–27 ) . The ten most prevalent symptoms were pain , easy fatigue , weakness , anorexia , lack of energy , dry mouth , constipation , early satiety , dyspnea , and greater than 10 % weight loss . The prevalence of these 10 symptoms ranged from 50 % to 84 % . Younger age was associated with 11 symptoms : blackout , vomiting , pain , nausea , headache , sedation , bloating , sleep problems , anxiety , depression , and constipation . Gender was associated with 8 symptoms . Males had more dysphagia , hoarseness , > 10 % weight loss and sleep problems ; females , more early satiety , nausea , vomiting , and anxiety . Performance status was associated with 14 symptoms . Advanced cancer patients are polysymptomatic . Ten symptoms are highly prevalent . Symptom prevalence for 24 individual symptoms differs with age , or gender , or performance status Our objective was to determine whether modafinil alleviates fatigue in patients with amyotrophic lateral sclerosis ( ALS ) . A placebo controlled trial with a 3:1 modafinil : placebo r and omization in doses up to 300 mg/day for 4 weeks was followed by 8 weeks of open maintenance treatment . The primary endpoint was the Clinical Global Impressions-Improvement Scale . Secondary endpoints were the Fatigue Severity Scale , Epworth Sleepiness Scale , Beck Depression Inventory , Role Function Scale , and visual analog scales . Analysis of covariance was used to assess change at Week 4 . Thirty-two patients were r and omized ; 29 completed the 4-week trial . In intention to treat ( ITT ) analysis , the response was 76 % for modafinil versus 14 % for placebo . In a completer analysis , the modafinil response rate was 86 % , and the placebo response rate remained 14 % . The number needed to treat was 1.6 ( ITT ) . No medically serious adverse events were reported . Modafinil may be a promising intervention for fatigue in ALS patients . Replication in a larger study is needed Systemic syndromes characterized by a persistent activity of circulating mediators ( cytokines ) are frequently present with advanced cancer . We grouped under the general heading of " Systemic Immune-Metabolic Syndrome ( SIMS ) " a particular variety of distressing systemic syndrome characterized by dysregulation of the psycho-neuro-immune-endocrine homeostasis , with overlapping clinical manifestations . SIMS may include cachexia , anorexia , nausea , early satiety , fatigue , tumor fever , cognitive changes and superinfection . The aim of this study was to ameliorate some of the SIMS symptoms in a homogeneous group of lung adenocarcinoma patients using a multitargeted therapy .  Fifteen patients with evidence of SIMS were studied . SIMS was defined as the presence of weight loss , anorexia , fatigue performance status>/=2 and acute-phase protein response . Patients received medroxyprogesterone ( MPA ) ( 500 mg twice daily ) , celecoxib ( 200 mg twice daily ) , plus oral food supplementation for 6 weeks . After treatment , 13 patients either had stable weight ( + /- 1 % ) or had gained weight . There were significant differences in improvement of body-weight-change rate , nausea , early satiety , fatigue , appetite and performance status .  Patients who had any kind of lung infection showed higher levels of IL-10 compared to non-infected patients ( P=0.039 ) . Our results suggest that patients with advanced lung adenocarcinoma , treated with MPA , celecoxib and dietary intervention , might have considerable improvement in certain SIMS outcomes . This multitargeted symptomatic approach deserves further study Cancer‐related fatigue is a debilitating symptom affecting psychosocial functioning and quality of life in 70 % to 100 % of cancer patients during and after treatment . The authors examined the effect of 200 mg of modafinil daily on the severity of  cancer‐related fatigue PURPOSE To evaluate the effectiveness of patient-controlled methylpheni date as compared with placebo in cancer patients with fatigue  , as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue ( FACIT-F ) . PATIENTS AND METHODS 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 r and omly assigned to receive 5 mg methylpheni date 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 methylpheni date 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 . RESULTS Of 112 patients r and omly assigned , 52 patients in the methylpheni date and 53 in the placebo group were assessable for analysis . Fatigue intensity improved significantly on day 8 in both the methylpheni date 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 . CONCLUSION Both methylpheni date and placebo result ed in significant symptom improvement .  Methylpheni date 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 Purpose This study assessed the efficacy of methylpheni date versus placebo for  cancer-related fatigue reduction .  Other objectives were to analyze cytokine levels and to determine the effects of methylpheni date on other symptoms , cognitive function , work yield , and patients ’ perceptions and preferences . Methods Patients were r and omly assigned ( 1:1 ) to receive methylpheni date -placebo or placebo-methylpheni date for 4 weeks . Patients crossed over after 2 weeks . Wilcoxon signed rank tests and McNemar tests were used to assess continuous and categorical variables . The primary efficacy endpoint was change in the level of worst fatigue on the Brief Fatigue Inventory ( BFI ) at the end of each 2-week period . Results The mean baseline BFI score was moderate ( 5.7 ) . Methylpheni date treatment did not affect patients ’ worst level of fatigue or other symptoms . Results from the Wechsler Adult Intelligence Scale Digit Symbol Test and the Hopkins Verbal Learning Test with BFI interference questions and BFI activity questions showed significant improvement in the methylpheni date -treated patients ’ verbal learning , memory , visual perception , analysis , and scanning speed . Patients treated with methylpheni date missed significantly fewer work hours owing to health reasons and worked significantly more hours . After 4 weeks , 64 % of patients reported that methylpheni date improved their cancer-related fatigue , and 58 % wanted to continue treatment . Significant difference in interleukin 6R ( positive ) , interleukin 10 ( negative ) , and tumor necrosis factor & agr ; ( positive ) was noted between the methylpheni date and the placebo group . Conclusions Low-dose methylpheni date did not improve  cancer-related fatigue .  Patients taking methylpheni date had better cognition and were able to work more hours . Patients tolerated methylpheni date well , and the majority felt better and wanted to continue treatment Pharmacotherapeutic options for multiple sclerosis (MS)-related fatigue are limited . Thirty patients were r and omly 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 is prevalent among patients with hepatitis C virus ( HCV ) and with HIV/AIDS but there are no established fatigue treatments for either condition or their combination . We analysed data from three trials of modafinil or armodafinil for HIV-positive patients with fatigue , including 36 co-infected with HCV , to compare treatment response and safety parameters related to HCV status . One hundred and twenty patients received active drug and 70 were r and omized to placebo .  Fatigue response rate to modafinil/armodafinil was 100 % for patients with HCV ( 18/18 ) and 73 % ( 74/102 ) for patients without HCV .  Placebo response rate was 28 % ( 5/18 ) and 29 % ( 15/52 ) , respectively . Depressive symptoms improved only when energy improved . Viral load declined from baseline after 12 and 26 weeks of active medication . CD4 cell count did not change , nor did alanine transaminase and aspartate aminotransferase for patients with HCV . Patients with haematocrit below the reference range responded , as well as patients whose values were within the reference range . Modafinil and armodafinil appear effective and well tolerated for treating fatigue among both HCV-positive and HCV-negative patients with HIV/AIDS , suggesting that they may hold promise for HIV-positive patients considering alpha interferon/ribavirin treatment for HCV . Further investigation in a focused trial is warranted PURPOSE Fatigue is one of the most common symptoms experienced by patients with cancer . This trial was developed to evaluate the efficacy of long-acting methylpheni date for improving cancer-related fatigue and to assess its toxicities . PATIENTS AND METHODS Adults with cancer were r and omly assigned in a double-blinded manner to receive methylpheni date ( target dose , 54 mg/d ) or placebo for 4 weeks . The Brief Fatigue Inventory was the primary outcome measure , while secondary outcome measures included a Symptom Experience Diary ( SED ) , the Short Form-36 ( SF-36 ) Vitality Subscale , a linear analog self- assessment , the Pittsburgh Sleep Quality Index , and the Subject Global Impression of Change . RESULTS In total , 148 patients were enrolled . Using an area under the serum concentration-time curve analysis , there was no evidence that methylpheni date , as compared with placebo , improved the primary end point of cancer-related fatigue in this patient population ( P = .35 ) . Comparisons of secondary end points , including clinical ly significant changes in quality -of-life variables and cancer-related fatigue change from baseline , were similarly negative . However , a subset analysis suggested that patients with more severe fatigue and /or with more advanced disease did have some fatigue improvement with methylpheni date ( eg , in patients with stage III or IV disease , the mean improvement in usual fatigue was 19.7 with methylpheni date v 2.1 with placebo ; P = .02 ) . There was a significant difference in self-reported toxicities ( SED ) , with increased levels of nervousness and appetite loss in the methylpheni date arm . CONCLUSION This clinical trial was unable to support the primary pre study hypothesis that the chosen long-acting methylpheni date product would decrease cancer-related fatigue Opioid-induced sedation is a major complication in patients with cancer pain . This study assessed the effectiveness of donepezil in opioid-induced sedation and related symptoms in patients with cancer pain . Twenty-seven patients who were receiving strong opioids for pain and reported sedation were enrolled .  Donepezil 5 mg was given every morning for 7 days . Changes between baseline and Day 7 in sedation , pain , fatigue and other symptoms were evaluated using the Edmonton Symptom Assessment Scale . Fatigue was also measured using the Functional Assessment of Chronic Illness Therapy-Fatigue ( FACIT-Fatigue ) . Overall usefulness of donepezil was measured by the patient at the end of the study . In 20 evaluable patients , sedation , fatigue , anxiety , well-being , depression , anorexia and problems with sleep were significantly improved . Side effects included nausea , vomiting , diarrhea , muscle and abdominal cramps , and anorexia . Overall , however , the treatment was well tolerated .  Donepezil appears to improve sedation and fatigue in patients receiving opioids for cancer pain . R and omized controlled trials of this agent are justified Sedation may be a doselimiting side-effect of opioid therapy in some cancer patients . This study was design ed to evaluate further the use of the psychostimulant , methylpheni date , an agent that has been reported to counteract opioid-induced sedation , in patients with cancer-related pain . Patients receiving a stable dose of an opioid for cancer-related pain were recruited for this r and omized , double-blind , crossover clinical trial . In addition to their regular dose of narcotics , they received 5 days of methylpheni date followed by 5 days of placebo , or vice versa . Our data did not definitively demonstrate any statistically significant benefit for methylpheni date , but did suggest that this drug could mildly decrease narcotic-induced drowsiness and could increase night-time sleep . These data , in conjunction with other published data , suggest that methylpheni date can counteract narcotic-induced daytime sedation to a limited degree PURPOSE To evaluate the effectiveness of donepezil compared with placebo in cancer patients with fatigue as measured by the Functional Assessment for Chronic Illness Therapy-Fatigue ( FACIT-F ) . PATIENTS AND METHODS Patients with fatigue score > or= 4 on a scale of 0 to 10 ( 0 = no fatigue , 10 = worst possible fatigue ) for more than 1 week were included . Patients were r and omly assigned to receive donepezil 5 mg or placebo orally every morning for 7 days . A research nurse contacted the patients by telephone daily to assess toxicity and fatigue level . All patients were offered open-label donepezil during the second week . FACIT-F and /or the Edmonton Symptom Assessment System ( ESAS ) were assessed at baseline , and days 8 , 11 , and 15 . The FACIT-F fatigue subscale score on day 8 was considered the primary end point . RESULTS Of 142 patients r and omly assigned to treatment , 47 patients in the donepezil group and 56 in the placebo group were assessable for final analysis . Fatigue intensity improved significantly on day 8 in both donepezil and placebo groups . However , there was no significant difference in fatigue improvement by FACIT-F ( P = .57 ) or ESAS ( P = .18 ) between groups . In the open-label phase , fatigue intensity continued to be low as compared with baseline . No significant toxicities were observed . CONCLUSION Donepezil was not significantly superior to placebo in the treatment of cancer-related fatigue Summary Background The objectives of this pilot study were to evaluate the safety and efficacy of the central nervous system stimulant methylpheni date in the management of asthenia in breast cancer patients treated with docetaxel . Patients and methods Patients with early breast cancer who presented asthenia > 3 on the Visual Analogue Scale ( VAS ) after the first cycle of docetaxel-based chemotherapy were included . Patients received two additional cycles of chemotherapy , one with methylpheni date ( 10 mg bid ) and the other without methylpheni date .  Asthenia was evaluated using VAS and the Functional Assessment of Cancer Therapy-Fatigue ( FACT-F ) scale . Distress was assessed using the Hospital Anxiety and Depression Scale ( HADS ) , and quality of life using FACT-F. Results Ten patients were included and evaluated for efficacy and safety . Overall , cycles with methylpheni date were better tolerated than those without methylpheni date in terms of asthenia ( VAS , p = 0.004 ; FACT-F , p = 0.027 ) and quality of life ( FACT-F , p = 0.047 ) . No significant differences were observed in terms of distress ( HADS , p = 0.297 ) . Six ( 60 % ) patients continued with methylpheni date after study end . Main adverse events during study were palpitations and insomnia ( 30 % of patients each ) . Conclusions This pilot study suggests that methylpheni date may reduce asthenia and improve quality of life in breast cancer patients treated with docetaxel PURPOSE Cancer-related fatigue ( CRF ) is the most common symptom in patients with advanced cancer . The primary objective of this prospect i ve , r and omized , double-blind , placebo-controlled study was to compare the effect of dexamethasone and placebo on CRF . PATIENTS AND METHODS Patients with advanced cancer with ≥ three CRF-related symptoms ( ie , fatigue , pain , nausea , loss of appetite , depression , anxiety , or sleep disturbance ) ≥ 4 of 10 on the Edmonton Symptom Assessment Scale ( ESAS ) were eligible . Patients were r and omly assigned to either dexamethasone 4 mg or placebo orally twice per day for 14 days . The primary end point was change in the Functional Assessment of Chronic Illness-Fatigue ( FACIT-F ) subscale from baseline to day 15 . Secondary outcomes included anorexia , anxiety , depression , and symptom distress scores . RESULTS A total of 84 patients were evaluable  ( dexamethasone , 43 ; placebo , 41 ) . Mean ( ± st and ard deviation ) improvement in the FACIT-F subscale at day 15 was significantly higher in the dexamethasone than in the placebo group ( 9 [ ± 10.3 ] v 3.1 [ ± 9.59 ] ; P = .008 ) . The improvement in FACIT-F total quality -of-life scores was also significantly better for the dexamethasone group at day 15 ( P = .03 ) . The mean differences in the ESAS physical distress scores at day 15 were significantly better for the dexamethasone group ( P = .013 , respectively ) . No differences were observed for ESAS overall symptom distress ( P = .22 ) or psychological distress score ( P = .76 ) . Frequency of adverse effects was not significantly different between groups ( 41 of 62 v 44 of 58 ; P = .14 ) . CONCLUSION Dexamethasone is more effective than placebo in improving CRF and quality of life in patients with advanced cancer OBJECTIVE To evaluate the efficacy and safety of modafinil in the treatment of fatigue in patients with human immunodeficiency virus/acquired immune deficiency syndrome ( HIV/AIDS ) and to assess effect on depressive symptoms . METHOD Patients who were HIV+ and had clinical ly significant fatigue ( according to the Fatigue Severity Scale [ FSS ] ) were included in a 4-week r and omized , placebo-controlled , double-blind trial . This was followed by an additional 8 weeks of open-label treatment for modafinil responders and 12 weeks for placebo nonresponders . The primary outcome measure for fatigue and depression was the Clinical Global Impressions-Improvement scale , supplemented by the FSS , Hamilton Depression Rating Scale , and Beck Depression Inventory . Safety was assessed with assays of CD4 cell count and HIV ribonucleic acid ( RNA ) viral load . Visits were weekly for 4 weeks , then biweekly , with a follow-up visit at 6 months . Maximum trial dose of modafinil was 200 mg/d . Data for this study were collected between December 2004 and December 2008 . RESULTS 115 patients were r and omly assigned . In intention-to-treat analyses , fatigue response rate to modafinil was 73 % and to placebo , 28 % . Attrition was 9 % . Modafinil did not have an effect on mood alone in the absence of improved energy . At week 4 , CD4 cell counts did not change significantly ; HIV RNA viral load showed a trend decline for patients taking modafinil but not for those taking placebo . At 6 months , those still taking modafinil had more energy and fewer depressive symptoms than patients who were not taking modafinil , and only those still taking modafinil showed a significant decline from baseline in their HIV RNA viral load . CONCLUSIONS Modafinil appears to be effective and well tolerated in treating fatigue in HIV+ patients . Consideration of its use is warranted considering the high prevalence of fatigue in the HIV community , its minimal side effects , and overall patient acceptance . TRIAL REGISTRATION clinical trials.gov Identifier : NCT00118378 Purpose Modafinil has been reported to benefit a subgroup of patients suffering severe fatigue while undergoing chemotherapy . Docetaxel is associated with fatigue that may lead to premature therapy withdrawal . We investigated whether modafinil could reduce fatigue during docetaxel chemotherapy . Methods This multicenter , r and omized , double-blind , placebo-controlled study evaluated the efficacy of modafinil in patients with metastatic prostate or breast cancer undergoing docetaxel chemotherapy ( every 21 days ; minimum dose 50 mg/m2 ) . At the start of their third or subsequent chemotherapy cycle , patients with significant docetaxel-associated fatigue were r and omized to receive concurrent modafinil 200 mg/day or placebo for 15 days ( “ treatment periods ” ( TP ) ) . Docetaxel was continued for up to four further cycles . Fatigue was evaluated with the fatigue component of the MD And erson Symptom Inventory ( MDASI ) . The primary endpoint was cumulative MDASI area under the curve ( AUC ) during the first 7 days of study medication during TP1 and TP2 . Results Evaluable data were available from 83 patients ( 65 with prostate cancer ) . There was no statistically significant difference between the two treatment arms for the primary endpoint ( MSADI AUC3–10 35.9 vs 39.6 ; 95 % confidence interval −8.9 , 1.4 ; P = 0.15 ) . Overall toxicity was comparable between treatment groups ; however , the incidence of grade ≤2 nausea and vomiting was higher in the modafinil arm ( 45.4 vs 25 % ) . Conclusions Assessing and managing chemotherapy-related fatigue remains a major challenge . There was a lack of difference between the two arms in the planned primary endpoint . However , there was a modest but consistent trend towards improvement of docetaxel-related fatigue in those treated with modafinil . Based on the study findings , modafinil for the treatment of fatigue associated with docetaxel chemotherapy elicits modest improvements . Larger , longer term , r and omized , controlled studies are required to clarify the exact role of modafinil in the treatment of docetaxel-related fatigue Fatigue is very common in patients with cancer . Current guidelines suggest that psychostimulants are " reasonable to consider for severe fatigue . " This r and omized , double-blind , placebo-controlled trial investigated the hypothesis that  dexamphetamine  in fatigued patients with advanced cancer would produce a clinical ly significant improvement with minimal side effects . Fifty patients with advanced cancer , who were receiving palliative care , were r and omized to dexamphetamine 10 mg twice daily or placebo for eight days . Effectiveness was assessed using the Brief Fatigue Inventory and the McGill Quality -of-Life Question naire . 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 20 mg daily , although well tolerated , does not significantly improve fatigue or quality of life in patients with advanced cancer , as measured by the selected instruments A r and omised double-blind placebo-controlled multicentre trial was performed to investigate the effects of megestrol acetate ( MA ) on the quality of life ( QoL ) , appetite , weight and survival of patients with advanced , incurable , hormone-insensitive cancer .  QoL was assessed at the start of treatment and at 4 , 8 and 12 weeks , using the EORTC-QLQ-C30 instrument . 255 patients were r and omised to 320 mg of MA daily or placebo  for 12 weeks . 244 patients were assessable at baseline , 190 at 4 weeks ( placebo 94 ; MA 96 ) , 150 at 8 weeks ( placebo 69 ; MA 81 ) and 112 at 12 weeks ( placebo 55 ; MA 57 ) . A beneficial effect of MA on appetite loss was observed at week 4 ( P < 0.0001 ) and possibly at week 8 ( P = 0.058 ) . Further weight loss during treatment was significant only in the placebo group . In the first 8 weeks , changes in mean global QoL were small and similar in both groups . By 12 weeks the decrease in mean global QoL was more pronounced in the MA group ( P = 0.028 ) , which was related to a deterioration in physical function , while psychosocial function was not affected . Survival was not affected by MA , and side-effects were mild . The results show that MA has a beneficial effect on appetite and that it may retard weight loss with no adverse impact on survival and with mild toxicity . However , MA does not appear to improve global QoL as measured by the EORTC QLQ-C30 Carnitine deficiency is among the many metabolic disturbances that may contribute to fatigue in patients with cancer . Administration of exogenous L-carnitine may hold promise as a treatment for this common symptom . Little is known about L-carnitine  safety , tolerability , and dose-response in patients with cancer . We conducted a Phase I/II open-label trial to assess the safety and tolerability of exogenous L-carnitine and clarify the safe dose range associated with symptom effects for future controlled trials . Adult patients with advanced cancer , carnitine deficiency ( free carnitine < 35 for males or < 25 microM/L for females , or acyl/free carnitine ratio > 0.4 ) , moderate to severe fatigue , and a Karnofsky Performance Status ( KPS ) score > or = 50 were entered by groups of at least three into a st and ard maximum tolerated dose design . Each successive group received a higher dose of L-carnitine ( 250 , 750 , 1250 , 1750 , 2250 , 2750 , 3000 mg/day , respectively ) , administered in two daily doses for 7 days . To compare symptom outcomes before and after supplementation , patients completed vali date d measures of fatigue ( Brief Fatigue Inventory [ BFI ] ) , depressed mood ( Center for Epidemiologic Studies Depression Scale [ CES-D ] ) , quality of sleep ( Epworth Sleeplessness Scale [ ESS ] ) , and KPS at baseline and 1 week later . Of the 38 patients screened for carnitine levels , 29 were deficient ( 76 % ) . Twenty-seven patients participated ( " intention to treat , ITT " ) ( 17 males , 10 females ) , and 21 completed the study ( " completers " ) ; 17 of these patients ( " responders , " mean+/-[SD ] age=57.9+/-15 ) had increased carnitine levels at the end of the supplementation period . The highest dose achieved was 3000 mg/day . No patient experienced significant side effects and no toxicities were noted . Analysis of all the patients accrued ( ITT , n=27 ) showed a total carnitine increase from 32.8+/-10 to 54.3+/-23 microM/L ( P<0.001 ) and free carnitine increase from 26.8+/-8 to 44.1+/-17 microM/L ( P<0.001 ) . BFI decreased significantly , from 66+/-12 to 39.7+/-26 ( P<0.001 ) ; ESS decreased from 12.9+/-12 to 9+/-6 ( P=0.001 ) ; and CES-D decreased from 29.2+/-12 to 19+/-12 ( P<0.001 ) . A separate analysis of the 17 " responders " showed a dose-response relationship for total- ( r=0.54 , P=0.03 ) , free-carnitine ( r=0.56 , P=0.02 ) levels , and fatigue ( BFI ) scores ( r=-0.61 , P=0.01 ) . These findings suggest that l-carnitine may be safely administered at doses up to 3000 mg/day and that positive effects may be more likely at relatively higher doses in this range . This study provides the basis for the design of future placebo-controlled studies of l-carnitine supplementation for cancer-related fatigue BACKGROUND Depression , anxiety , fatigue , and impaired wellbeing are common , important , and closely related in advanced cancer . We aim ed to identify the effects of an established antidepressant on these symptoms and survival in patients with advanced cancer who did not have major depression as assessed by clinicians . METHODS Between July , 2001 , and February , 2006 , 189 patients with advanced cancer were r and omly assigned sertraline 50 mg ( n=95 ) , or placebo ( n=94 ) , once per day . The primary outcome was depression as assessed by the Centre for Epidemiologic Studies Depression scale ( CES-D ) ; the main secondary outcomes were : anxiety as assessed by Hospital Anxiety and Depression Scales ( HADS-A ) ; overall quality of life and fatigue as assessed by Functional Assessment of Cancer Therapy General and Fatigue scales ( FACT-G and FACT-F , respectively ) ; and clinicians ' ratings of quality of life by use of Spizter 's Quality of Life Index ( SQLI ) . Multiple measures were used for corroboration of the most important outcomes . Primary analyses were done by intention to treat and were based on scale scores at 4 weeks and 8 weeks . The benefits of sertraline compared with placebo are expressed on a range from + 100 ( ie , maximum benefit ) to -100 ( ie , maximum harm ) ; a difference of 10 was deemed clinical ly significant . This clinical trial is registered at Current Controlled Trials website http://www.controlled-trials.com/IS RCT N72466475 . FINDINGS Sertraline had no significant effect ( scale , benefit over placebo [ 95 % CI ] ) on depression ( CES-D 0.4 [ -2.6 to 3.4 ] ) , anxiety ( HADS-A 2.0 [ -1.5 to 5.5 ] ) , fatigue ( FACT-F 0.3 [ -4.3 to 4.9 ] ) , overall quality of life ( FACT-G 1.7 [ -1.3 to 4.7 ] ) , or clinicians ' ratings ( SQLI 2.0 [ -2.5 to 6.5 ] ) , and the 95 % CI ruled out a clinical ly significant benefit for all main outcomes . Sertraline was discontinued more often and earlier than was placebo ( hazard ratio 1.46 [ 1.03 - 2.06 ] , p=0.03 ) . Recruitment was stopped after the first planned interim analysis in February 2006 ( n=150 ) showed that survival was longer in patients assigned placebo than in patients assigned sertraline ( unadjusted hazard ratio 1.60 [ 95 % CI 1.04 - 2.45 ] , log-rank p=0.04 ; adjusted hazard ratio 1.62 [ 1.06 - 2.41 ] , Cox model p=0.02 ) . However , at the final analysis in July 2006 of all patients ( n=189 ) and with longer follow-up , survival did not differ significantly between the treatment groups ( unadjusted hazard ratio 1.35 [ 0.95 - 1.91 ] , log-rank p=0.09 ; adjusted hazard ratio 1.27 [ 0.87 - 1.84 ] , Cox model p=0.20 ) . The trial was closed because it had ruled out a significant benefit of sertraline . INTERPRETATION Sertraline did not improve symptoms , wellbeing , or survival in patients with advanced cancer who do not have major depression , and should be reserved for those with a proven indication Objective : To assess the effects of glatiramer acetate and β interferon on  fatigue in multiple sclerosis . Methods : Fatigue was measured at baseline and six months using the fatigue impact scale ( FIS ) . Groups ( glatiramer acetate and β interferon ) were evaluated for the proportion improved , using Fisher ’s exact test . Logistic regression analysis assessed the relation between treatment group and improvement and controlled for confounding variables . Results : Six month paired FIS assessment s were available for 218 patients ( 76 % female ) . Ages ranged between 19 and 61 years , with 86 % having relapsing-remitting disease . Glatiramer acetate was used by 61 % and β interferon by 39 % . At baseline , total FIS and subscale scores were comparable in the two groups . More patients improved on glatiramer acetate than on β interferon  on total FIS ( 24.8 % v 12.9 % , p = 0.033 ; adjusted odds ratio = 2.36 , 95 % confidence interval 1.03 to 5.42 ) , and on physical ( 28.6 % v 14.1 % , p = 0.013 ) and cognitive subscales ( 21.1 % v 10.6 % , p = 0.045 ) . Logistic regression analysis confirmed the association between glatiramer acetate use and improved fatigue , after accounting for baseline group differences . Conclusions : The odds of reduced multiple sclerosis fatigue were around twice as great with glatiramer acetate treatment as with β interferon . Confirmation of this result is required In a controlled double blind study involving 116 patients with far‐advanced gastrointestinal cancer , dexamethasone at dosages of 0.75 and 1.5 mg four times daily produced improved appetite and sense of well‐being in comparison to placebo treatment . This symptomatic palliation , however , was not accompanied by weight gain or improved performance status . Survival of the steroid treated patients was essentially identical to that of the placebo treated patients . Cancer 33:1607–1609 , 1974 Fatigue occurs in a majority of patients with MS and is generally independent of measurable neurologic disability . Few options for treatment are available . We conducted a double-blind , placebo-controlled , crossover trial for each of two 4-week treatment periods . Forty-six eligible patients entered and five dropped out due to concurrent exacerbations . Nineteen patients ( 46.3 % ) experienced excellent or good relief of fatigue with pemoline , and eight patients ( 19.5 % ) with placebo ( p = 0.06 , Fisher 's exact test ) . One-fourth of patients did not tolerate the drug well , and 7 % had to discontinue pemoline during the study due to side effects . The most common side effects were anorexia , irritability , and insomnia .  Pemoline may be an effective short-term treatment for fatigue associated with MS , but its adverse effects are not well tolerated by many patients Carnitine deficiency is prevalent in population s with chronic illness , including cancer . In a recent open-label study , L-carnitine supplementation was well tolerated and appeared to improve fatigue and other outcomes in cancer patients . To further evaluate this finding , adult patients with advanced cancer , carnitine deficiency ( free carnitine more than 35 micromol/L for males or less than 25 micromol/L for females , or acyl/free carnitine ratio of more than 0.4 ) , moderate to severe fatigue , and a Karnofsky Performance Status ( KPS ) score of 50 or more , were r and omly assigned to receive either L-carnitine ( 0.5 g/day for two days , followed by 1g/day for two days , and then 2g/day for 10 days ) or placebo . This double-blind phase was followed by an open-label phase , during which all patients received L-carnitine supplementation for two weeks . Outcomes included the fatigue subscale of the Functional Assessment of Cancer Therapy-Anemia ( FACT-An ) , the Linear Analog Scale Assessment s ( LASA ) , the Mini-Mental State Exam ( MMSE ) , and the KPS .  Twenty-nine patients ( 12 placebo , 17 L-carnitine )  were included in the intent-to-treat ( ITT ) analysis . From baseline to the end of the double-blind phase , serum total and free L-carnitine increased from 32.9+/-3.8 to 56.6+/-20.5 ( P=0.004 ) , and from 22.9+/-19.4 to 45.3+/-17.2 ( P=0.004 ) , respectively , in the L-carnitine-treated group , and from 28.2+/-10.2 to 36.2+/-8.7 ( P = ns ) , and from 22.6+/-7.9 to 28.7+/-8.6 ( P = ns ) in the placebo group , respectively . The planned ITT analysis revealed no significant improvement in any of the study 's endpoints , and these negative findings were not different when data from two patients who did not adhere to the protocol were eliminated . However , an exploratory covariate analysis that excluded these two protocol violators and included outcome data from both the double-blind and open-label phases demonstrated significantly improved fatigue on the FACT-An fatigue subscale ( P<0.03 ) , and significantly improved FACT-An functional well-being subscale ( P<0.03 ) , and KPS ( P<0.003 ) , in the group that started with L-carnitine during the double-blind phase . These data do not support the conclusion that L-carnitine in the doses tested reverses cancer-related fatigue in carnitine-deficient patients . However , L-carnitine supplementation does increase L-carnitine serum levels , and the positive findings in an exploratory analysis justify a larger study to determine if this strategy could be of benefit for a sub population of cancer patients Background : While testosterone 's ameliorative effects on depressive disorders and fatigue in HIV-positive patients have been suggested in the literature , no placebo-controlled trial selecting for depressive disorders and including a st and ard antidepressant has been conducted . Accordingly , this double-blind trial was design ed to determine whether testosterone , as well as fluoxetine , is superior to placebo for depression , fatigue , or both . Method : One hundred twenty-three men with HIV/AIDS with a Diagnostic and Statistical Manual of Mental Disorders , Fourth Edition depressive disorder entered the 8-week trial and were r and omized to testosterone ( up to 400 mg IM testosterone cypionate biweekly ) , fluoxetine ( up to 60 mg/d ) , or double placebo . Outcome variables were the Clinical Global Impressions Scale for mood and for fatigue , the Hamilton Rating Scale for Depression , and the Chalder Fatigue Scale . Results : Ninety men completed the trial . In intention-to-treat analyses , mood response rates were 54 % , 47 % , and 44 % for fluoxetine , testosterone , and placebo , respectively . Among completers , mood response rates were 70 % , 57 % , and 53 % , respectively ; in neither analysis were differences between treatments statistically significant . In contrast , testosterone was superior to fluoxetine and placebo for completers regarding fatigue . In intention-to-treat analysis , response rates were 39 % , 56 % , and 42 % for fluoxetine , testosterone , and placebo , respectively , and for study completers , 41 % , 63 % , and 52 % , respectively , ( P < 0.05 ) , Conclusion : While over 50 % of patients treated with testosterone reported improved mood , this rate was not statistically superior to placebo . Thus , our findings do not support prescription of testosterone as a first-line treatment for depressive disorders  in HIV-positive men . However , if vali date d in additional studies , testosterone may be a useful option for medically ill men experiencing significant fatigue as well as depression PURPOSE To investigate the effects of medroxyprogesterone acetate ( MPA ) on appetite , weight , and quality of life ( QL ) in patients with advanced-stage , incurable , non-hormone-sensitive cancer . PATIENTS AND METHODS Two hundred six eligible patients were r and omized between double-blind MPA 500 mg twice daily or placebo .  Appetite ( 0 to 10 numerical rating scale ) , weight , and QL ( European Organization for Research and Treatment of Cancer Quality of Life Question naire [ EORTC-QLQ-C30 ] ) were assessed before the start of treatment ( t = 0 ) , and 6 weeks ( t = 6 ) and 12 weeks ( t = 12 ) thereafter . RESULTS One hundred thirty-four patients ( 68 MPA and 66 placebo ) were assessable at t = 6 and 99 patients ( 53 MPA and 46 placebo ) at t = 12 . A beneficial effect of MPA on appetite was observed after both 6 weeks ( P = .008 ) and 12 weeks ( P = .01 ) of treatment . After 12 weeks , a mean weight gain of 0.6 + /- 4.4 kg was seen in the MPA , versus an ongoing mean weight loss of 1.4 + /- 4.6 kg in the placebo group . This difference of 2.0 kg was statistically significant ( P = .04 ) . During the study , several areas of QL deteriorated in the total group of patients . With the exception of an improvement in appetite and possible also a reduction in nausea and vomiting , no measurable beneficial effects of MPA on QL could be demonstrated . The side effects profile of MPA was favorable : only a trend toward an increase in ( usually mild ) peripheral edema was observed . CONCLUSION In weight-losing , advanced-stage non-hormone-sensitive cancer patients , MPA exhibits a mild side effects profile , has a beneficial effect on appetite , and may prevent further weight loss . However , general QL in the present study was not measurably influenced by MPA treatment BACKGROUND This report documents findings from a small placebo-controlled trial of dextroamphetamine for depression and fatigue in men with the human immunodeficiency virus ( HIV ) .  Dextroamphetamine offers the potential for rapid onset of effect and activation properties , both of which are important to persons with medical illness and an uncertain , but limited , life expectancy . METHOD Primary inclusion criteria included the presence of a DSM-IV depressive disorder , debilitating fatigue , and no history of dependence on stimulants . The study consisted of a 2-week r and omized , placebo-controlled trial , with the blind maintained until week 8 for responders , followed by open treatment through the completion of 6 months . RESULTS Of 23 men who entered the study , 22 completed the 2-week trial . Intent-to-treat analysis indicated that 73 % of patients ( 8/11 ) r and omly assigned to dextroamphetamine reported significant improvement in mood and energy , compared with 25 % ( 3/12 ) among placebo patients ( Fisher exact test , p < .05 ) . Both clinician- and self-administered measures indicated significantly improved mood , energy , and quality of life among patients taking dextroamphetamine . There was no evidence of the development of tolerance of , abuse of , or dependence on the medication . CONCLUSION These results suggest that dextroamphetamine is a potentially effective , fast-acting antidepressant treatment for HIV patients with depression and debilitating fatigue
BACKGROUND This review up date s the original review , ' Pharmacological treatments for fatigue associated with palliative care ' and also incorporates the review ' Drug therapy for the management of cancer-related fatigue'.In healthy individuals , fatigue is a protective response to physical or mental stress , often relieved by rest .
By contrast , in palliative care patients ' fatigue can be severely debilitating and is often not counteracted with rest , thereby impacting daily activity and quality of life .
Fatigue frequently occurs in patients with advanced disease ( e.g. cancer-related fatigue ) and modalities used to treat cancer can often contribute .
Further complicating issues are the multidimensionality , subjective nature and lack of a consensus definition of fatigue .
The pathophysiology is not fully understood and evidence -based treatment approaches are needed .
OBJECTIVES To evaluate the efficacy of pharmacological treatments for fatigue in palliative care , with a focus on patients at an advanced stage of disease , including patients with cancer and other chronic diseases .