Modafinil/Armodafinil

Modafinil/Armodafinil

PEP Topic 
Depression
Description 

Modafinil is a psychostimulant effective in the treatment of excessive sleepiness associated with narcolepsy and shift-work sleep disorder. It is used to increase wakefulness and capacity for attention, to brighten mood, and to enhance memory. Modafinil comes as a tablet for oral intake and has been evaluated in patients with cancer for fatigue and cognitive impairment.

Armodafinil is a similar drug with a slightly different chemical configuration also used as a wakefulness-promoting agent. Armodafinil reaches peak concentration in the blood later after administration than modafinil.   Armodafinil has been studied for its effects on fatigue, anxiety, sleep-wake disturbances, and depression in patients with cancer.

Effectiveness Not Established

Research Evidence Summaries

Berenson, J.R., Yellin, O., Shamasunder, H.K., Chen, C.S., Charu, V., Woliver, T.B., . . . Vescio, R. (2014). A phase 3 trial of armodafinil for the treatment of cancer-related fatigue for patients with multiple myeloma. Supportive Care in Cancer. Advance online publication. 

doi: 10.1007/s00520-014-2486-7
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Study Purpose:

To study effects of armodafinil on cancer-related fatigue in patients with multiple myeloma

Intervention Characteristics/Basic Study Process:

Patients were randomly assigned to study groups in this crossover design study. One group was a treatment-only arm that got armodafinil, and the other was a placebo-first arm that received a placebo followed by armodafinil. Patients received armodafinil 150 mg once daily for 56 days in the treatment-only group. In the other group, patients received a placebo for 28 days and armodafinil on days 29–56. Assessments were done at baseline and at days 15, 28, 43, and 56. Five variations of study assessments were used to address potential memorization effects, and the order in which versions were used was varied.

Sample Characteristics:

N = 50  
 
MEAN AGE = 65 years (range = 43–85 years)
 
MALES: 58%, FEMALES: 42%
 
KEY DISEASE CHARACTERISTICS: All had multiple myeloma
 
OTHER KEY SAMPLE CHARACTERISTICS: All had to satisfy the International Statistical Classification of Diseases and Related Health Problems (ICD10) criteria for fatigue and demonstrate at least moderate fatigue with a Brief Fatigue Inventory (BFI) score < 36 to be eligible

Setting:

  • SITE: Multi-site    
  • SETTING TYPE: Not specified    
  • LOCATION: California

Phase of Care and Clinical Applications:

  • PHASE OF CARE: Active antitumor treatment

Study Design:

Double-blind, randomized, crossover-controlled trial

Measurement Instruments/Methods:

  • Brief Fatigue Inventory (BFI)
  • Hospital Anxiety and Depression Scale (HADS)
  • Epworth sleepiness scale
  • Trail Making Test (TMT) version B
  • Symbol Digits Modalities Test (SDMT)
  • Digit span test
  • Functional Assessment of Chronic Illness Scale–Fatigue (FACIT-F)
  • Functional Assessment of Cancer Therapy–General (FACIT-G)

Results:

Adverse effects observed during armodafinil treatment were similar between groups. Fatigue as measured by the BFI scale decreased significantly for both groups over time with no difference between groups. Outcomes measured by FACIT scores increased significantly in the placebo-first group by day 28, and FACIT fatigue scores improved significantly in both groups. Anxiety decreased significantly from baseline in both groups. Depression scores only declined significantly in the placebo-first group by day 28. Degree of sleepiness decreased significantly in the placebo group. There were no significant changes in study measures between day 28 and day 56 in which all patients received armodafinil.

Conclusions:

Armodafinil was not shown to significantly improve symptoms of fatigue, anxiety, or depression in patients with multiple myeloma.

Limitations:

  • Small sample (< 100)
  • Other limitations/explanation: 20% drop-out rate prior to day 56; more patients in the treatment-only group dropped out.

Nursing Implications:

Armodafinil, a medication similar to modafinil, was not shown to be effective for the reduction of fatigue, anxiety, or depression.

Gehring, K., Patwardhan, S. Y., Collins, R., Groves, M. D., Etzel, C. J., Meyers, C. A., & Wefel, J. S. (2012). A randomized trial on the efficacy of methylphenidate and modafinil for improving cognitive functioning and symptoms in patients with a primary brain tumor. Journal of Neuro-Oncology, 107, 165–174.

doi: 10.1007/s11060-011-0723-1
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Study Purpose:

To compare the effectiveness of immediate-release and sustained-release methylphenidate versus modafinil in improving cognitive function in patients with primary brain tumors.

Intervention Characteristics/Basic Study Process:

Patients were randomized to receive one of the following three interventions for a total of four weeks:  immediate-release methylphenidate, 10 mg twice daily; sustained-release methylphenidate, 18 mg daily; or modafinil, 200 mg daily. Neurocognitive tests were performed prior to the intervention and were repeated approximately 30 days later, after completion of the intervention.

Sample Characteristics:

  • Twenty-four patients with primary brain tumors were included.
  • Mean age was 44.98 years.
  • The sample was 54% male and 46% female.
  • Most (62.5%) of patients’ tumors were in the left hemisphere.
  • Prior treatment history included radiation therapy (83%) and chemotherapy (87.5%). Of all the participants, 62.5% received chemotherapy during the study.

Setting:

  • Single site
  • Outpatient
  • MD Anderson Cancer Center, Houston, Texas

Phase of Care and Clinical Applications:

Patients were undergoing multiple phases of care.

Study Design:

The study was a randomized, clinical trial.

Measurement Instruments/Methods:

Objective Cognitive Function Instruments

  • Wechsler Adult Intelligence Scale, third edition (WAIS-III) Digit Span and Digit Symbol subtests
  • Trail Making Test (TMT) Parts A and B
  • Hopkins Verbal Learning Test (HVLT) Immediate Recall, Delayed Recall, and Delayed Recognition Trials
  • Multilingual Aphasia Examination Controlled Oral Word Association (MAE COWA) category
  • Lafayette Instrument Grooved Pegboard Test

Subjective Anxiety Instruments

  • State-Trait Anxiety Inventory (STAI) to measure state and trait anxiety  
  • Profile of Mood States (POMS) to measure tension and anxiety

Subjective Depression Instruments

  • Beck Depression Inventory (BDI)
  • Profile of Mood States (POMS) Questionnaire, Depression-Dejection Scale

Subjective Fatigue Instruments

  • Brief Fatigue Inventory (BFI)
  • POMS questionnaire, Fatigue-Inertia Scale

Subjective Sleep-Wake Disturbance Instrument

  • Brief Sleep Disturbance Scale (BSDS)

Results:

  • Over time, no differences were found in cognitive function in regard to attention or motor function.
  • Over time, mixed results were found in regard to the speed of processing:
    • The WAIS-III Digit Symbol subtest showed significant improvement (p = 0.02), but TMT Part A did not.
    • The HVLT Delayed Recognition Trial showed a signficiant decline (p = 0.03) in memory, but the other memory-related trials did not.
  • In regard to the use of either stimulant and executive function over time, the TMT Part B score improved significantly (p = 0.02); however, the MAE COWA score declined significantly (p = 0.02).
  • In regard to differences between the methylphenidate and modafinil treatment groups over time, researchers found the following:
    • A significant difference (p = 0.05) in attention. Attention-related scores of patients taking methylphenidate were stable on the WAIS-III Digit Span subtest; the scores of patients taking modafinil worsened over time.
    • A difference in the speed of processing as measured by TMT Part A. Patients using modafinil improved in comparison to patients taking methylphenidate, whose scores either remained stable or declined slightly (p = 0.05).
  • In regard to subjective measures of other symptoms, researchers noted, with use of either stimulant over time:
    • Significant improvement (p < 0.01) of depression, as measured by the BDI and POMS Depression-Dejection Scale.
    • Significant improvement (p = 0.04) of fatigue, as measured by the BFI.
    • Significant improvement of fatigue (p < 0.01), as measured by the POMS Fatigue-Inertia Scale.
    • Significant improvement (p = 0.03) of anxiety, as measured by the state subtest of the STAI.
  • No differences were found over time in regard to sleep-wake disturbances.
  • No differences were found between treatment groups in subjective symptom measures over time.

Conclusions:

Although this study revealed some improvements in specific cognitive domains over time (e.g., executive function, speed of processing), it is unclear whether these improvements were due to the use of a stimulant; a specific medication (modafinil versus methylphenidate); or other variables, such as practice effects related to the absence of alternative neuropsychological tests. Making definitive interpretations based on this small study is difficult because the findings were confounded by the use of two stimulants (one with two different dosage schedules) and the lack of a control group (patients who were not receiving stimulants).

Limitations:

  • The study had a small sample size, with less than 30 participants.
  • The study had risks of bias due to no control group and no blinding.
  • Participant withdrawals were 10% or greater.
  • The investigators were unable to achieve the sample size recommended by the power analysis due to poor accrual and a high drop-out rate (29%). Treatment groups differed significantly in regard to age (p = 0.02) and gender (p = 0.03). Age and gender influence neuropsychological test results.

Nursing Implications:

No evidence was provided to support the use of stimulants to improve cognitive function. The study supports the conduct of future research of this topic in studies with larger sample sizes and in randomized, clinical trials with a nonintervention arm.

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