Lundorff, L.E., Jonsson, B.H., & Sjøgren, P. (2009). Modafinil for attentional and psychomotor dysfunction in advanced cancer: A double-blind randomised, cross-over trial. Palliative Medicine, 23, 731–738.

The study's primary aim was to assess the effectiveness of single-dose modafinil on cognitive function in patients with advanced cancer treated in palliative care settings. Its secondary aim was to assess the effectiveness of modafinil on other symptoms.

On day 1, patients were randomly assigned to receive either 200 mg of modafinil or an oral placebo. On day 4, each patient group was given the alternative treatment that was not dispensed on day 1.

• The number of participants was 28.
• The median participant age was 62, with a range of 40–79.
• 57% of the participants were male and 43% were female.
• All participants had advanced cancer, with a variety of hematologic and solid tumors.
• All participants had a tiredness score fo 50 mm on the Edmonton System Assessment Scale and a score range of 40–70 on the Karnofsky Performance Status Scale. 

The study took place in the palliative care department of Herning Hospital in Denmark.

The study was a double-blind, randomized, cross-over, single-dose trial.

• The Finger Tapping Test (FTT) is well-validated test of psychomotor speed that is used for detecting lateral cerebral lesions and unspecific psychomotor impairment.
• The Trail Making Test, Part B (TMT-B) is a test of visual information processing used to assess visual search skills, scanning, speed of processing, mental flexibility, attention, and psychomotor speed. 
• The Edmonton System Assessment Scale assesses nine symptoms common in patients with cancer: pain, tiredness, nausea, depression, anxiety, drowsiness, appetite, well-being, and shortness of breath.
• The Karnofsky Performance Status Scale measures general well-being. Scores range from 0 (death) to 100 (perfect health with no complaints or signs of disease).

Patients on the modafinil treatment group saw statistically significant improvements in psychomotor speed with the dominant hand (as measured by the FTT) and speed of processing (as measured by the TMT-B), as compared with the placebo group (p = 0.006). The modafinil treatment group also showed statistically significant improvements in depression and drowsiness as compared with the placebo group (p = 0.042).

The frequency and intensity of side effects were similar on both treatments, and no statistically significant differences were reported. However, four patients experienced disrupted sleep and vivid dreams after modafinil treatment.

Modafinil improved attention and psychomotor speed and diminished depression and drowsiness.

• The number of participants was small, but was in congruence with priori power analyses.
• The study design had limited administration of the medication (only one single dose) and follow-up; therefore, no conclusions can be made about long-term usage of modafinil.
• The authors reported that patients were allowed to use supplemental doses of short-acting opioids for breakthrough pain throughout the study, except before testing on study days. The holding of as-needed opioids is an ethical concern for patient comfort. Although opioid use was controlled, patients may have been in pain, which would confound cognitive results.
• No information regarding pain prior to cognitive testing was noted.
• The authors did not address practice effects with repeated administration of the TMT-B.