Introduction
Methylphenidate (MP) is often recommended for symptom control in advanced cancer. Little is known about its side effects in frail adults.
Objectives
To evaluate MP associated symptoms or side effects (S/E) in three symptom studies among patients with advanced cancer.
Methods
Data was collected from two published prospective cohort series and a phase 2 study of MP for symptom control in advanced cancer. All three reports had identical dosing schedules and symptom assessments. Initial MP doses were 10 mg/d (5 mg at 8 a.m. and at 12 noon) titrated up to a maximum of 30 mg/d. Depression, fatigue, and symptoms identified as possible MP S/E (agitation, anorexia, dizziness, dry mouth, headache, insomnia, nausea, palpitation, tremors, vomiting) were evaluated for presence (prevalence) and for severity (using categorical scales) before MP (day 0) and on days 3, 5 and 7 thereafter. The categorical scale used was none, mild, moderate, and severe. For this analysis all who received at least one dose of MP were evaluable for potential S/E, and those who completed 7 consecutive days therapy were evaluable for efficacy.
Results
62 patients were enrolled. 50 completed 7 days of MP with a median age of 69 (range 30-90) years. Thirty-five received MP 10 mg/day, one 15 mg/day, thirteen 20 mg/day, and one 30 mg/d of MP by day 7. Most (96 %) had improvement in depression and/or fatigue. Amongst the 62 patients new symptom prevalence throughout the study was; agitation (16%), insomnia (16%), dry mouth (15%), nausea (10%), tremors (6%), anorexia (5%), headache (3%), palpitations (2%), and vomiting (2%). Patients could have more than one symptom simultaneously. Seven patients (11%) withdrew due to MP S/E. Moderate symptoms occurred in 10 people during the study period, but none had severe symptoms. Some symptoms present before MP showed significant improvement during MP therapy; agitation [0.48±0.68 to 0.32±0.55 (P<0.029)], anorexia [0.86±1.00 to 0.67±0.83 (P<0.008)], and dizziness [0.14±0.40 to 0.06±0.31 (P<0.011)].
Conclusions
1) Treatment with MP (10-20 mg/d) in advanced cancer is well tolerated; only 11% withdrew due to MP S/E. 2) S/E symptoms occurring with MP appeared to improve spontaneously despite continued MP therapy. The commonest new symptoms after MP started were agitation (16%), insomnia (16%), and dry mouth (15%). 3) Depression and fatigue improved at doses lower than those recommended in other clinical conditions. 4) MP improved depression and fatigue, and some secondary symptoms associated with them. Methylphenidate (MP) appears safe when used in the treatment of depression and fatigue in advanced cancer.