Clinical Question

What is the comparative effectiveness of citalopram (Celexa), methylphenidate (Ritalin), or both for the treatment of depression among older patients?

Bottom Line

Combined treatment with citalopram plus methylphenidate provided faster improvement of depression symptoms in older patients with unipolar depression. Combined treatment was also more likely than either medication alone to lead to remission of depression at four weeks and 16 weeks. The study was too small to assess clinically meaningful differences in rare adverse drug effects. Because there was no dose-response effect with titration of the methylphenidate, a low dose (e.g., 5 mg twice daily) seems prudent. (Level of Evidence = 1b)

Synopsis

This randomized controlled trial of older patients with depression compared citalopram plus placebo (n = 48), methylphenidate plus placebo (n = 47), and both active treatments (n = 47). Inclusion criteria were unipolar depression by Diagnostic and Statistical Manual of Mental Disorders, 4th ed., text revision criteria, a score of at least 16 on the Hamilton Depression Rating Scale (HAM-D), and a score of at least 22 on the Mini-Mental State Examination. Patients were excluded if they had severe or unstable medical illness, acute suicidal or violent behavior, a history of suicide attempts in the past year, any psychiatric diagnosis other than unipolar depression with or without comorbid anxiety, or other central nervous system diseases.

Methylphenidate (or placebo) was titrated during the first four weeks, as tolerated, starting at 2.5 mg twice daily and increasing to a maximum 20 mg twice daily. If response was insufficient at four weeks, citalopram (or placebo) was also increased from 20 to 40 mg or, in some cases, 60 mg daily. Remission rates were 30% among patients who received placebo instead of citalopram, 42% with 20 mg of citalopram, 56% with 40 mg, and 69% with 60 mg. There was no dose-response gradient with methylphenidate. Change in HAM-D score was greater and faster with combined therapy. Remission was defined as a HAM-D score of 6 or less and was more likely with combined therapy (62%) at 16 weeks, compared with citalopram alone (42%) or methylphenidate alone (29%; chi-squared test = 9.2; P = .001). There were no significant differences between groups in cognitive change, which improved across all groups. Note that the U.S. Food and Drug Administration currently recommends a 20-mg maximum daily dosage of citalopram.

Study design: Randomized controlled trial (double-blinded)

Funding source: Government

Allocation: Concealed

Setting: Outpatient (specialty)

Reference: LavretskyHReinleibMCyrNStSiddarthPErcoliLMSenturkDCitalopram, methylphenidate, or their combination in geriatric depression: a randomized, double-blind, placebo controlled trial. Am J Psychiatry2015; 172( 6): 561– 569.