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

• Published in: European neuropsychopharmacology Vol. 24; no. 4; pp. 491 - 498
• Main Authors: Ng, Chong Guan, Boks, Marco P.M., Roes, Kit C.B., Zainal, Nor Zuraida, Sulaiman, Ahmad Hatim, Tan, Seng Beng, de Wit, Niek J.
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.04.2014
• Subjects: Academic Medical Centers; Aged; Antidepressive Agents - adverse effects; Antidepressive Agents - therapeutic use; Cancer; Depression; Depressive Disorder, Major - drug therapy; Diagnostic and Statistical Manual of Mental Disorders; Double-Blind Method; Drug Resistance; Drug Therapy, Combination - adverse effects; Female; Humans; Internal Medicine; Malaysia; Male; Methylphenidate; Methylphenidate - adverse effects; Methylphenidate - therapeutic use; Mianserin - adverse effects; Mianserin - analogs & derivatives; Mianserin - therapeutic use; Middle Aged; Mirtazapine; Neoplasms - psychology; Neoplasms - therapy; Palliative; Palliative Care; Patient Dropouts; Pharmacotherapy; Psychiatric Status Rating Scales; Psychiatry; Terminally Ill - psychology; Malaysia; Pharmacotherapy; Mirtazapine; Depression; Palliative; Methylphenidate; Cancer
• ISSN: 0924-977X; 1873-7862; 1873-7862
• DOI: 10.1016/j.euroneuro.2014.01.016

This is a 4 week, randomized, double-blind, placebo-controlled study to examine the effects of methylphenidate as add-on therapy to mirtazapine compared to placebo for treatment of depression in terminally ill cancer patients. It involved 88 terminally ill cancer patients from University of Malaya Medical Centre, Kuala Lumpur, Malaysia. They were randomized and treated with either methylphenidate or placebo as add on to mirtazapine. The change in Montgomery-Åsberg Depression Rating Scale (MADRS) score from baseline to day 3 was analyzed by linear regression. Changes of MADRS and Clinical Global Impression-Severity Scale (CGI-S) over 28 days were analyzed using mixed model repeated measures (MMRM). Secondary analysis of MADRS response rates, defined as 50% or more reduction from baseline score. A significantly larger reduction of Montgomery-Åsberg Depression Rating Scale (MADRS) score in the methylphenidate group was observed from day 3 (B=4.14; 95% CI=1.83–6.45). Response rate (defined as 50% or more reduction from baseline MADRS score) in the methylphenidate treated group was superior from day 14. Improvement in Clinical Global Impression-Severity Scale (CGI-S) was greater in the methylphenidate treated group from day 3 until day 28. The drop-out rates were 52.3% in the methylphenidate group and 59.1% in the placebo group (relative risk=0.86, 95%CI=0.54–1.37) due to cancer progression. Nervous system adverse events were more common in methylphenidate treated subjects (20.5% vs 9.1%, p=0.13). In conclusions, methylphenidate as add on therapy to mirtazapine demonstrated an earlier antidepressant response in terminally ill cancer patients, although at an increased risk of the nervous system side effects.