Gagnon, B., Low, G., & Schreier, G. (2005). Methylphenidate hydrochloride improves cognitive function in patients with advanced cancer and hypoactive delirium: A prospective clinical study. Journal of Psychiatry Neuroscience, 30, 100–107. Retrieved from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC551162/?tool=pubmed

The study was conducted to investigate the clinical improvement observed in patients with advanced cancer and hypoactive delirium after the administration of methylphenidate hydrochloride (MPH).

First, a 10 mg test dose of MPH was given orally to all participants. If there were no distressing side effects, participants were given 10 mg of MPH twice daily at 8 am and 12 pm. Follow-up was daily for hospital inpatients and every three to four days for patients in the community. Doses of MPH were increased in 5 mg increments to reach the maximum tolerable dose for the patient’s satisfaction and the resolution of delirium.

Measurements were taken before delirium and delusions (T0), at baseline prior to the MPH treatment (T1), one hour after after the MPH dose (T2), and when a stable dose was achieved (T3). 

The Mini-Mental State Examination was used as an assessment tool on a daily basis for inpatients and every three to four days for outpatients.

• All participants had a diagnosis of advanced metastatic cancer. Participants had lung, colon, breast, prostate, cervical, or testicular cancer. 
• The total number of participants was 14.
• Participants were between the ages of 41–80 years.
• 64% of participants were male and 36% were female.

The study utilized a case series design for patients with advanced cancer and hypoactive delirium.

• The Mini-Mental State Examination (MMSE) measured global cognitive function.
• No specific information was provided on the instruments used to assess psychomotor retardation, sleep and drowsiness, absence of delusions, or absence of delirium.

All participants had a positive response to MPH that included increased alertness, partial-to-complete resolution of psychomotor retardation, normalization of slurred speech, and a marked increase in energy levels.

All 14 participants showed improvement in their cognitive function as documented by the MMSE. In 13 patients, the median MMSE score improved to 28 (mean = 27.8, standard deviation = 2.4, p = 0.02) compared with the median score one hour after the first dose of MPH. One patient died before reaching a stable dose of MPH.

The pretreatment MMSE median score was 21 (mean = 20.9, standard deviation = 4.9), which improved to a median of 27 (mean = 24.9, standard deviation = 4.7) after the first dose of MPH (p < 0.001).

MPH improved alertness and general cognitive function in a small sample of patients with advanced cancer. However, due to confounding issues with disease and treatment responses, more research is warranted to determine its effectiveness.

• The study had a small sample size.
• The study was limited to patients with advanced cancer.
• All participants received MPH, so there was no control group.
• The study had a limited measurement of cognitive function, as the MMSE is a global indicator with known practice effects.
• The study did not explain its assessment of psychomotor functioning or its determination of sleep and drowsiness.
• There were confounding issues with brain metastases in 29% of participants.
• There were confounding issues with pain medications in 57% of patients.
• There was no discussion regarding the clinical significance of the changes in MMSE scores.