By: Dr. Geoffrey Modest
The treatment of depression in the elderly can be very difficult. The usual meds (SSRIs) tend to be less effective in the elderly, with some studies not finding much difference from placebo. And psychotherapy, which does help some, is often also less effective, given that many elderly do not have much insight into their condition and many also find it difficult to change. There have been studies in the past showing significant efficacy of stimulants, especially in those with severe depression (eg, a study at Mass General Hosp of 129 geriatric inpatients with severe major depression found 66% with significant improvement within 1-2 days, and only 8% with adverse reactions and none with reduction in appetite. Average doses of dextroamphetamin was 8.2 mg and methylphenidate 8.2 mg (see J Geriatr Psychiatry Neurol. 1990;3(3):146). Other old studies have found an overall response rate of 81%. I am unaware of newer studies).
In this context, a 16 week RCT was done of 143 geriatric outpatients with major depression, comparing methylphenidate to citalopram to the combination of the two (see doi: 10.1176/appi.ajp.2014.14070889). In brief:
–mean age 70, 1/2 women, 75% white, 16 years of education, age at depression onset mean 42 yo, duration of episode mean of 48 months and 80% with >24 months of depression.
–inclusion criteria: unipolar major depressive disorder, score >15 in Hamilton Depression Rating Scale HAM-D (mean in study was 18.9) and >25 on Mini-Mental State Exam (mean was 28.7)
–patients seen weekly for 4 weeks to titrate methyphenidate dose, then every 2 weeks for the 16-week study (ultimate methylphenidate range was 5-40 mg, with average of 16.3 mg in both groups). citalopram started at 20mg, then increased to 40mg after 1 months if insufficient improvement, then 60mg after 7-8 weeks if needed, with average dose of approx 35 mg in both groups.
Results:
–the HAM-D was significantly improved in the combo group within 2 weeks and maintained for the rest of the study (62% remission rate at 16 weeks). the citalopram only group was intermediate (42% at 16 weeks), and the methylphenidate group did the least well (29% at 16 weeks). all of these results were significantly better than placebo for depression severity, assessment of global clinical improvement, and cognitive function (methylphenidate did not add to the improvement of cognitive function).
–the citalopram dose was significantly associated with achieving remission: 29.8% in those without citalopram, 41.9% in those on 20mg, 56.4% in those on 40mg, and 69.2% in those on 60mg. there was no clear dose-response curve in those on methylphenidate.
So, pretty impressive results. the combination therapy was pretty well-tolerated (did not increase the incidence of adverse reactions or the number of people who dropped out of the study — 45 dropped out, for a variety of reasons). The symptom response to the combination was faster (evident within a couple of weeks) and more profound. The issues that come up are:
–The FDA limits the citalopram dosing to 20mg for elderly. I did note in a blog post “there is a pretty dramatic increase in QTc with citalopram, but it is important to note that the actual clinical effect of this prolongation is NOT clear: the FDA looked at a large VA database and found that the risk of ventricular arrhythmias and mortality were LOWER in depressed patients on greater than 40mg citalopram/day, similar results to those found in patients on sertraline”.
–One other concern is that methylphenidate can increase citalopram levels
It would be great to have studies looking at the combo of another, perhaps safer SSRI (eg sertraline) with methylphenidate….