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 Link

Study Purpose

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.

Sample Characteristics

  • 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

Setting

  • 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 

Study Design

Randomized, double-blinded, placebo-controlled study

Measurement Instruments/Methods

  • 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.

Results

The MADRS scores at baseline did not differ between the groups; however, the MTZ+MPH group had a greater reduction in MADRS scores by day 28. These differences were noted from day 3 and were significant. The number of patients who responded to treatment also differed between the groups and was significantly greater in the MTZ+MPH group by day 28. There also were significant differences in the changes of CGI-S scores between the groups from day 3 till the end of the study.
 
Notably, adverse events of nervous system were seen in the MTZ+MPH group although most were mild. The high dropout rate was not statistically significant between the groups. The most common reasons for dropouts were death, neuropsychiatric symptoms, and personal reasons.

Conclusions

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.

Limitations

  • 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.

Nursing Implications

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.