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.
Effectiveness Not Established
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.doi: 10.1371/journal.pone.0084391
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.
- N (studies) = 5
- SAMPLE RANGE ACROSS STUDIES: 10–62
- TOTAL PATIENTS INCLUDED IN REVIEW: 198
- KEY SAMPLE CHARACTERISTICS: Three studies included mixed tumor types, one was in prostate, and one was in patients with primary brain tumor.
Phase of Care and Clinical Applications:
PHASE OF CARE: Mutliple 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.doi: 10.1200/JCO.20.1.335
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%.
Research Evidence Summaries
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.doi: 10.1177/104990910101800610
A phase II study of methylphenidate for depression in patients with advanced cancer
Intervention Characteristics/Basic Study Process:
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.
- N = 30
- MALES: 50%, FEMALES: 50%
- KEY DISEASE CHARACTERISTICS: Primary cancer sites: breast (5), esophagus (4), head and neck (4), lung (4), pancreas (4), colorectal (2), and other (7)
- OTHER KEY SAMPLE CHARACTERISTICS: Inclusion criterion was the answer of “yes” to the question, “Are you depressed?” with no current or previous antidepressant use.
- SITE: One center was included.
- SETTING TYPE: Inpatients and outpatients were enrolled in the palliative care program.
- Question, “Are you depressed?”
- Other symptoms (anorexia, concentration problems, fatigue, and sedation) were assessed by a categorical rating (none, mild, moderate, or severe) before starting methylphenidate and daily thereafter.
- Pain was assessed using a 0–10 scale.
- Known side effects of methylphenidate also were assessed.
- Satisfaction question: ”Are you satisfied with the way the drug affected your mood?” was asked at the end of the study on day seven.
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.
- Small sample with no randomization
- Long-term efficacy and side effect data are needed.
- Single-site data are less transferable than multi-site data.
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.doi: 10.1016/j.euroneuro.2014.01.016
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
Intervention Characteristics/Basic Study Process:
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.
- N = 88
- MEAN AGE = 59.52 years (group 1), 55.89 years (group 2 [placebo])
- MALES: 78%, FEMALES: 22%
- KEY DISEASE CHARACTERISTICS: Patients diagnosed with a major depressive disorder in the terminal disease stage of any type of cancer
- OTHER KEY SAMPLE CHARACTERISTICS: Receiving palliative care with a life expectancy less than three months; oncology or surgery departments or palliative care units; Malay, Chinese, Indian, and other ethnicities were included; 84% were inpatient in both groups
- SITE: Single-site
- SETTING TYPE: Multiple settings
- LOCATION: University Malaya Medical Centre, Kuala Lumpur, Malaysia
Phase of Care and Clinical Applications:
- PHASE OF CARE: End-of-life care
- APPLICATIONS: Palliative care
Randomized, double-blinded, placebo-controlled study
- Montgomery-Asberg Depression Rating Scale (MADRS): A clinician-rated scale for the assessment of depression that includes 10 items (nine are patient-reported and one is based on observation).
- Clinical Global Impression–Severity Scale (CGI-S): A single-item, clinician-rated scale that reflects the global severity of illness at time of assessment.
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.
- Small sample (< 100)
- Risk of bias (sample characteristics)
- Findings not generalizable
- Subject withdrawals ≥ 10%
- Other limitations/explanation: The percentage of males was higher in the placebo group. There was a high dropout rate, mostly because of death, but side effects and personal reasons also were mentioned. Well-designed, larger studies need to be done. A study using MPH alone would be useful. Some of the symptoms could be related to the disease rather than depression.
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.