Methylphenidate is a type of psychostimulant used to treat attention-deficit hyperactivity disorder and narcolepsy. Methylphenidate is closely related to amphetamine and is a schedule II drug. It is taken by mouth and available by numerous different brand names. It can be habit-forming, and individuals can develop tolerance to its effects. Methylphenidate use for patients with cancer has been evaluated in anxiety, depression, fatigue, and cognitive impairment. Methylphenidate has been evaluated alone and as part of multimodal approaches combined with other interventions such as exercise.
Gong, S., Sheng, P., Jin, H., He, H., Qi, E., Chen, W., . . . Hou, L. (2014). Effect of methylphenidate in patients with cancer-related fatigue: A systematic review and meta-analysis. PloS One, 9(1), e84391.
To assess the safety and efficacy of methylphenidate for cancer-related fatigue. Secondary outcomes included depression, cognition, and adverse effects.
TYPE OF STUDY: Meta-analysis and systematic review
DATABASES USED: PubMed. EMBASE, PsycINFO, Cochrane Collaboration
KEYWORDS: Methylphenidate, dimethylphenidate, Ritalin, cancer, fatigue, asthenia, tiredness, and randomized controlled trial
INCLUSION CRITERIA: Randomized controlled trials, adults older than 18 years, the trial examined efficacy of methylphenidate on fatigue, and results were sufficient to calculate effect sizes
EXCLUSION CRITERIA: None specified
TOTAL REFERENCES RETRIEVED: N = 374
EVALUATION METHOD AND COMMENTS ON LITERATURE USED: The Jadad scale was used for quality assessment.
PHASE OF CARE: Multiple phases of care
Meta-analysis was done with studies grouped according to the measure of fatigue that was used. In studies using the FACT-F (three studies), results showed a favorable effect of methylphenidate with a mean difference of -3.13 and a signficant overall effect (p -0.01). In studies using the BFI, results showed a favorable effect with mean difference of -0.69, but the Z test of overall effect was not significant. Methylphenidate had no effect on depression (two studies) or cognitive impairment (two studies). Studies varied widely in terms of the duration of treatment. Treatment for greater than four weeks was superior compared to placebo. However, treatment for less than four weeks did not show a significant effect compared to placebo. Rates of adverse effects between those getting methylphenidate and those getting a placebo were not significantly different. Those receiving methylphenidate had significantly more vertigo, anxiety, and nausea.
Results suggest that treatment with methylphenidate for at least four weeks is effective in reducing cancer-related fatigue and is not associated with a high rate of adverse effects. Treatment with methylphenidate did not improve depression or cognitive impairment. Use of different methods of measurement of fatigue showed different results.
Few studies were included, and some of these had very small sample sizes. Included studies did not provide sufficient information on relevant concomitant conditions of patients, such as sleep disorders and anxiety. Dosages and dosage increase approaches with methylphenidate varied.
Findings suggest that treatment with methylphenidate for at least four weeks can be helpful in managing cancer-related fatigue. However, the most appropriate dosages are not clear. Patients can experience side effects, and if methylphenidate is used, nurses need to monitor patients for side effects. Further large studies are needed to strengthen evidence related to effects and side effects of methylphenidate.
Rozans, M., Dreisbach, A., Lertora, J.J., & Kahn, M.J. (2002). Palliative uses of methylphenidate in patients with cancer: A review. Journal of Clinical Oncology, 20, 335–339.
DATABASES USED: MEDLINE
COMMENTS ON LITERATURE USED: Articles published from 1966–2000 related to methylphenidate use in patients with cancer or in palliative care
FINAL NUMBER STUDIES USED = 49
The evidence in the review found that methylphenidate is useful for the treatment of depression in a variety of malignancies, with more than 80% improvement in depression and side effects in less than 20%.
Centeno, C., Sanz, A., Cuervo, M.A., Ramos, D., Hernansanz, S., Gonzalez, J., . . . Pascual, A. (2012). Multicentre, double-blind, randomised placebo-controlled clinical trial on the efficacy of methylphenidate on depressive symptoms in advanced cancer patients. BMJ Supportive and Palliative Care, 2, 328–333.
To study the efficacy of methylphenidate for relief of depressive symptoms in patients with advanced cancer.
Patients who indicated some depressive symptoms from screening were randomized to receive methylphenidate ranging from 10-45 mg daily for 28 days. Doses were adjusted according to individual patient need and toxicity evaluation according to a protocol established for the study. Patient visits and evaluation occurred at days 0, 2, 7, 14, 21, and 28 either in the clinic or the patients’ homes. Patients who completed at least eight days of involvement were included in intent-to-treat analysis using the last measure carried forward.
Methylphenidate administration was not significantly better than placebo for symptoms of depression or anxiety and was associated with more adverse events. The evidence regarding efficacy of methylphenidate is inconclusive.
This study sample was not large enough to enable firm conclusions from this individual study; however, findings did not show a benefit of methylphenidate and showed more adverse events that may be associated with methylphenidate. These results are not supportive for use of methylphenidate in the management of anxiety and depressive symptoms in patients with advanced cancer.
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.
To compare the effectiveness of immediate-release and sustained-release methylphenidate versus modafinil in improving cognitive function in patients with primary brain tumors.
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.
Patients were undergoing multiple phases of care.
The study was a randomized, clinical trial.
Objective Cognitive Function Instruments
Subjective Anxiety Instruments
Subjective Depression Instruments
Subjective Fatigue Instruments
Subjective Sleep-Wake Disturbance Instrument
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).
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.
Homsi, J., Nelson, K.A., Sarhill, N., Rybicki, L., LeGrand, S.B., Davis, M.P., & Walsh, D. (2001). A phase II study of methylphenidate for depression in advanced cancer. American Journal of Hospice and Palliative Care, 18, 403–407.
A phase II study of methylphenidate for depression in patients with advanced cancer
Patients who were identified as being depressed by a palliative medicine attending physician were treated with methylphenidate twice daily. Doses were titrated per regimen until response was obtained. Patients were assessed during a telephone call or bedside interview. The study timeframe was seven days.
Depression was resolved in all patients, most on day three. The maximum daily dose needed was 20 mg. Other symptoms also improved, mean pain scores significantly decreased, and all who responded to treatment were satisfied with therapy.
Ng, C.G., Boks, M.P., Roes, K.C., Zainal, N.Z., Sulaiman, A.H., Tan, S.B., & de Wit, N.J. (2014). Rapid response to methylphenidate as an add-on therapy to mirtazapine in the treatment of major depressive disorder in terminally ill cancer patients: A four-week, randomized, double-blinded, placebo-controlled study. European Neuropsychopharmacology, 24, 491–498.
To evaluate whether adding methylphenidate to mirtazapine in the treatment of depression in terminally ill patients with cancer will cause an earlier antidepressant response compared to patients receiving mirtazapine and a placebo
Patients initially were interviewed by a psychiatrist to confirm the diagnosis of major depressive symptoms using the Mini-International Neuropsychiatric Inventory. Patients were randomized and double-blinded (1:1) to receive either methylphenidate (MPH) or a placebo with mirtazapine (MTZ). Patients taking MTZ received a fixed dosage while MPH was first dosed at 5 mg BID then increased, if needed, after day 3. Outcomes were assessed at baseline and at six subsequent follow-up visits during the double-blind treatment on days 3, 6, 9, 14, 21, and 28. Assessments included the Montgomery-Asberg Depression Rating Scale and the Clinical Global Impression–Severity scale.
Randomized, double-blinded, placebo-controlled study
Although this was a small-scale study and the dropout rate was high, this study has implications for a small subset of patients. The addition of MPH to the standard treatment of depression may improve the response rates of terminally ill patients with cancer, beginning as early as three days after starting treatment. MPH must be used with caution due to side effects.
Psychosocial assessment, which includes depression, is extremely important to the nursing profession. For those who care for terminally ill patients with cancer, having options to improve quality of life for a patient suffering from depression can have significant clinical implications. Using MPH may be one option to consider when seeking quick results in treating a major depressive disorder in terminally ill patients. MPH must be used with caution due to potential side effects, and the need for further research in this population is indicated.