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Stimulant May Speed Antidepressant Response Time in Elderly

Nancy A. Melville

March 04, 2015

The combination of the methylphenidate (multiple brands) and the antidepressant citalopram (multiple brands) may
accelerate the rate of response in elderly patients with depression, new research suggests.
A randomized, placebo-controlled study conducted by investigators at the University of California, Los Angeles
(UCLA) showed that most patients who responded to the treatment achieved remission within the first month.
Importantly, the investigators note, the combined therapy did not increase side effects.
"The combination can shorten time to remission to 1 to 4 weeks in patients who are depressed," lead author Helen
Lavretsky, MD, professor of psychiatry in residence and director of the Late- Life Mood, Stress, and Wellness
Research Program at UCLA's Geffen School of Medicine, told Medscape Medical News.
The study was published online February 13 in the American Journal of Psychiatry.
Slower Response
Elderly patients with depression have a slower response to antidepressants sometimes as long as 12 to 16 weeks
as well as lower rates of remission.
"Methylphenidate and other stimulants have had a known fast onset of action, up to 72 hours in depressed patients,
and that was a rationale for use in this study," said Dr Lavretsky.
The study is the first randomized, placebo-controlled trial to evaluate the combination of methylphenidate and the
selective serotonin reuptake inhibitor (SSRI) citalopram for depression in the elderly in comparison with monotherapy
with either drug, the authors noted.
For the double-blind trial, 143 outpatients whose average age was 69.7 years and who were diagnosed with major
depression in accordance with DSM-IV-TR criteria were randomly assigned to one of three treatment groups:
methylphenidate plus placebo (n = 48), citalopram plus placebo (n = 48), and the combination of citalopram plus
methylphenidate (n = 47).
Patients were treated with daily doses ranging from 20 mg to 60 mg for citalopram (mean, 32 mg) and from 5 mg to
40 mg for methylphenidate (mean, 16 mg).
At 16 weeks, all groups met the primary outcome measure of significant improvement in depression severity (P <
.01), as assessed by Hamilton Depression Rating Scale (HAM-D) score.
However, improvement was more significant in the combination methylphenidate plus citalopram group compared with
the other two (P < .05), as were Clinical Global Impression scores (P < .001).
Scores on the Short Form 36-Item Health Survey for well-being were also higher in the combination treatment group
compared with the monotherapy groups (P = .01).
Importantly, the rate of improvement in the HAM-D depression scores was significantly higher in the combination
therapy group in the first 4 weeks of the trial compared with the monotherapy groups (P < .05).
There were no significant differences between the treatment groups in terms of cognitive improvement or side effects.
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"We found that the combination of methylphenidate and citalopram was well tolerated, better than methylphenidate
alone, [and that] the number of side effects did not differ per group," Dr Lavretsky said.
She noted that there were also fewer dropouts only two because of side effects in the combination group
compared with seven in each monotherapy group.
Dosing Caution
The most typical expected side effects related to methylphenidate are increased anxiety and insomnia, and there are
some concerns of cardiac side effects, Dr Lavretsky said.
With citalopram, the most expected side effects are sexual dysfunction and gastrointestinal problems. The authors
underscored the fact that potential cardiac side effects should be considered among elderly patients.
"Our results with regard to citalopram dosing should be interpreted cautiously and with consideration of the 2011 US
Food and Drug Administration recommendation that citalopram dosing be limited to 40 mg/day in younger adults and
20 mg/day in the elderly because of potential cardiac side effects, as well as recently published data confirming an
increase in the QTc interval with citalopram use in older patients with dementia," they write.
Clinicians may consider different options for methylphenidate therapy, on the basis of patients' individual needs, Dr
Lavretsky noted. Patients with long-standing depression, for instance, may benefit from the combination therapy,
whereas medically ill patients with depression of recent onset as a reaction to a medical disorder may benefit from
methylphenidate alone.
"Caution is needed in patients with psychotic depression, in those with underlying and unstable heart disease, or in
those with stroke," she said.
The findings nevertheless point to a potentially effective approach in addressing the significant challenges of
managing depression in the elderly, the authors conclude.
"Overall, the outcomes are encouraging for mental health providers, given the limited number of successful treatment
strategies available to enhance antidepressant response with additional benefits in function in geriatric depression,"
they write.
Valuable Insight
Commenting on the findings for Medscape Medical News, Martha Sajatovic, MD, professor of psychiatry and
neurology and director of the Neurological and Behavioral Outcomes Center at University Hospitals Case Medical
Center, in Cleveland, Ohio, said the study provides valuable insights into the treatment of depression in the elderly.
"This is an important study for a number of reasons. First, depression is a significant problem in the elderly, and we
know that depressed elders tend to have a variety of health complications that cause personal burden to them and
higher medical costs in general.
"Second, with the pullback of funding and support for medication treatment clinical trials from both the US government
and pharma, there are fewer studies like this using currently available compounds that can help guide the practicing
clinician in the trenches who is doing his or her best to help older people with depression," she said.
Dr Sajatovic cautioned that combining drugs has the potential risk of increasing side effects, and "clinicians that treat
older people always need to carefully balance and consider benefit vs burdens of treatment."
That said, efforts to find improved treatments to address the challenges in treating the elderly are important, she
noted.
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"There is a clear need for antidepressant treatments that are quick, well-tolerated, practical, and associated with
sustained response in older people with depression."
Also commenting on the study, Melinda S. Lantz, MD, chief of geriatric psychiatry at Mount Sinai Beth Israel Medical
Center in New York City, agreed that the risks and benefits need to be considered when combining drugs to treat
depression in the elderly.
"I think the study was well conducted, and it does show a small benefit in response in the first 4 weeks, but in the
end, clinicians need to ask if it is worth the side effects," she said, referring to issues such as anxiety, insomnia, and
potential cardiac risks associated with stimulants.
She noted that in many cases, efforts to treat depression in the elderly fail simply because antidepressant doses are
not adequate.
"The big issue and this study really demonstrates this is you have to pay attention to the dose of the drug," she
told Medscape Medical News.
"In clinical practice, most geriatric patients are undertreated with their primary antidepressant they will be started
on a low dose of perhaps 10 mg of an SSRI, and the dose isn't adjusted rapidly enough, if at all."
The study received support from National Institutes of Health (NIH) grants MH077650 and MH086481 to Dr Lavretsk y.
Dr Lavretsk y reports having received research support from the Forest Research Institute and the Alzheimer's
Research and Prevention Foundation. Dr Sajatovic has received research grants from Pfizer, Merck , Ortho-McNeilJanssen, Janssen, the Reuter Foundation, the Woodruff Foundation, the Reinberger Foundation, the NIH, and the
Centers for Disease Control and Prevention, and she has been a consultant for Brack et, Prophase, Otsuk a, Pfizer,
Amgen, and Sunovion. Dr Lantz reports no relevant financial relationships.
Am J Psychiatry. Published online February 13, 2015. Abstract
Medscape Medical News 2015 WebMD, LLC
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Cite this article: Stimulant May Speed Antidepressant Response Time in Elderly. Medscape. Mar 04, 2015.

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