Modafinil/Armodafinil

for Anxiety

Modafinil is a psychostimulant effective in the treatment of excessive sleepiness associated with narcolepsy and in people with 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 effect on fatigue, anxiety, sleep-wake disturbances, and depression in people with cancer.

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 Link: doi: 10.1007/s00520-014-2486-7

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.

Effectiveness Not Established